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Sample records for chronic niacin overload

  1. Chronic niacin overload may be involved in the increased prevalence of obesity in US children

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate nicotinamide’s action on glucose metabolism, and the association between niacin consumption and obesity prevalence. METHODS: Dynamic nicotinamide’s effect on plasma hydrogen peroxide and glucose metabolism was in- vestigated using oral glucose tolerance tests with or without nicotinamide in the same five healthy subjects.Lag-regression analysis was used to examine the association between the niacin consumption and the obesity prevalence among US children using the data from the Economic ...

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

    Science.gov (United States)

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

    2010-02-25

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

  3. Niacin

    Science.gov (United States)

    ... your blood and to increase the amount of high density lipoprotein (HDL; ''good cholesterol''). Niacin can be used in a number of situations including the following: alone or in combination with other ... attack in patients with high cholesterol who have had a heart attack; to ...

  4. Niacin as potential treatment for dyslipidemia and hyperphosphatemia associated with chronic renal failure: the need for clinical trials.

    Science.gov (United States)

    Ahmed, Mohamed H

    2010-06-01

    Niacin has profound and unique effects on lipid metabolism. In addition to increasing high-density lipoprotein cholesterol, it is also known to decrease total cholesterol, low-density lipoprotein cholesterol, and triglyceride. Interestingly, the plasma concentration of lipoprotein(a) [Lp(a)], which has been suggested to play a role as an independent risk factor for coronary heart disease, is also decreased by niacin. Therefore, it is not surprising that in the literature it was given unique description as broad-spectrum lipid drug. Its impact is referred to as desirable normalization of a range of cardiovascular risk factors. However, its clinical use is limited due to harmless but unpleasant unique side effect of cutaneous flushing. Interestingly, recent experimental and clinical studies suggest the potential benefit of niacin as a treatment of dyslipidemia and high plasma phosphate associated with chronic kidney disease (CKD). Both dyslipidemia and high serum phosphate levels are shown to be associated with higher cardiovascular mortality. Furthermore, niacin administration improves renal tissue lipid metabolism, renal function and structure, hypertension, proteinuria, and histological tubulointerstitial injury. Further studies are required before the use of niacin for the treatment of both dyslipidemia and hyperphosphatemia with CKD advocated. PMID:20486851

  5. 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

    Background Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy. Methods A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation. Results Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users. Conclusions The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient. PMID:27442587

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

    Directory of Open Access Journals (Sweden)

    Yusra Habib Khan

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

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

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

    2006-07-01

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

  8. Eccentric overload training in patients with a chronic Achilles tendinopathy: a systematic review.

    NARCIS (Netherlands)

    Kingma, J.J.; Knikker, R. de; Wittink, H.M.; Takken, T.

    2007-01-01

    Background: Eccentric overload training seems to be a promising conservative intervention in patients with chronic Achilles tendinopathy. The efficacy of eccentric overload training on the outcome measures of pain and physical functioning are not exactly clear. Study design: Systematic review of the

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

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    Gao C

    2014-04-01

    Full Text Available Chong Gao, Li Li, Baoan Chen, Huihui Song, Jian Cheng, Xiaoping Zhang, Yunyu SunDepartment of Hematology and Oncology, Key Department of Jiangsu Medicine, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaBackground: The purpose of this study was to evaluate the clinical outcomes of transfusion-associated iron overload in patients with chronic refractory anemia.Methods: Clinical manifestations, main organ function, results of computed tomography (CT, endocrine evaluation, and serum ferritin levels were analyzed retrospectively in 13 patients who were transfusion-dependent for more than 1 year (receiving >50 units of red blood cells to determine the degree of iron overload and efficacy of iron-chelating therapy.Results: Serum ferritin levels increased to 1,830–5,740 ng/mL in all patients. Ten patients had abnormal liver function. The CT Hounsfield units in the liver increased significantly in eleven patients, and were proportional to their serum ferritin levels. Skin pigmentation, liver dysfunction, and endocrine dysfunction were observed in nine patients with serum ferritin >3,500 ng/mL, eight of whom have since died. Interestingly, serum ferritin levels did not decrease significantly in nine transfusion-dependent patients who had received 15–60 days of iron-chelating therapy.Conclusion: Transfusion-dependent patients may progress to secondary iron overload with organ impairment, which may be fatal in those who are heavily iron-overloaded. The CT Hounsfield unit is a sensitive indicator of iron overload in the liver. Iron chelation therapy should be initiated when serum ferritin is >1,000 ng/mL and continued until it is <1,000 ng/mL in transfusional iron-overloaded patients.Keywords: anemia, aplastic, iron overload, myelodysplastic syndromes

  10. Binding of serum ferritin to concanavalin A in patients with iron overload and with chronic liver disease.

    OpenAIRE

    Chapman, R W; Gorman, A; Laulicht, M; Hussain, M.A.; Sherlock, S; Hoffbrand, A V

    1982-01-01

    Total serum ferritin and the proportion of serum ferritin binding to concanavalin A (glycosylated ferritin) was measured in 18 healthy volunteers and in 84 patients, eight with primary haemochromatosis, 43 with beta-thalassaemia major and secondary iron overload and 33 with chronic liver diseases without iron overload. The total serum ferritin was either equally or even more closely related than either the non-binding or the concanavalin A binding ferritin, to the liver iron concentration in ...

  11. The Role of Iron and Iron Overload in Chronic Liver Disease

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    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

  12. The Role of Iron and Iron Overload in Chronic Liver Disease.

    Science.gov (United States)

    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

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

    Science.gov (United States)

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

    2011-06-01

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

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

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

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

    Science.gov (United States)

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

    2013-12-10

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

  16. Persistent atrial fibrillation in a goat model of chronic left atrial overload.

    NARCIS (Netherlands)

    Remes, J.; Brakel, T.J. van; Bolotin, G.; Garber, C.; Jong, MM de; Veen, FH van der; Maessen, J.G.

    2008-01-01

    OBJECTIVES: Atrial dilatation predisposes to atrial fibrillation. Although several animal models focus on the initiating mechanisms of atrial fibrillation in dilated atria, a model of left atrial overload resulting in persistent atrial fibrillation in nonanesthetized animals has not been presented t

  17. [Niacin deficiency and cutaneous immunity].

    Science.gov (United States)

    Ikenouchi-Sugita, Atsuko; Sugita, Kazunari

    2015-01-01

    Niacin, also known as vitamin B3, is required for the synthesis of coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Niacin binds with G protein-coupled receptor (GPR) 109A on cutaneous Langerhans cells and causes vasodilation with flushing in head and neck area. Niacin deficiency due to excessive alcohol consumption, certain drugs or inadequate uptake in diet causes pellagra, a photosensitivity dermatitis. Recently several studies have revealed the mechanism of photosensitivity in niacin deficiency, which may pave a way for new therapeutic approaches. The expression level of prostaglandin E synthase (PTGES) is up-regulated in the skin of both pellagra patients and niacin deficient pellagra mouse models. In addition, pellagra is mediated through prostaglandin E₂-EP4 (PGE₂-EP4) signaling via reactive oxygen species (ROS) production in keratinocytes. In this article, we have reviewed the role of niacin in immunity and the mechanism of niacin deficiency-induced photosensitivity. PMID:25765687

  18. Frequency of primary iron overload and HFE gene mutations (C282Y, H63D and S65C) in chronic liver disease patients in north India

    Institute of Scientific and Technical Information of China (English)

    Barjinderjit Kaur Dhillon; Reena Das; Gurjeewan Garewal; Yogesh Chawla; RK Dhiman; Ashim Das; Ajay Duseja; GR Chandak

    2007-01-01

    AIM: To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y,H63D, and S65C) in patients with chronic liver disorders (CLD) and controls.METHODS: To identify patients with iron overload (transferrin saturation > 45% in females and > 50% in males and serum ferritin > 1000 ng/mL) we evaluated 236 patients with CLD, including 59 with non-alcoholic steatohepatitis (NASH), 22 with alcoholic liver disease (ALD), 19 of cirrhosis due to viruses (HBV, HCV), and 136 with cryptogenic cirrhosis. Mutations of the HFE gene were analyzed by PCR-RE. hundred controls were screened for iron status and the mutations.RESULTS: Seventeen patients with CLD showed evidence of iron overload. Fifteen cases of iron overload had cryptogenic cirrhosis and two had ALD. None of the controls showed iron overload. We did not find any individual with 282Y or 65C either in the cases or in the controls. The prevalence of H63D heterozygosity was 12% in normal individuals, 14.8% in 236 patients (16.9% in NASH, 13.6% in ALD, 26.3% in viral and 12.5% in cryptogenic cirrhosis) and the overall prevalence was 13.98%. Only two of the 17 patients with primary iron overload were heterozygous for H63D. One patient with NASH and one normal individual who were homozygous for H63D showed no iron overload.CONCLUJSION: Primary iron overload in Indians is nonHFE type, which is different from that in Europeans and further molecular studies are required to determine the defect in various iron regulatory genes.

  19. Effects of Functional Limb Overloading on Symmetrical Weight Bearing, Walking Speed, Perceived Mobility, and Community Participation among Patients with Chronic Stroke

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    Sami S. Alabdulwahab

    2015-01-01

    Full Text Available Background. Stroke is a leading cause for long-term disability that often compromises the sensorimotor and gait function accompanied by spasticity. Gait abnormalities persist through the chronic stages of the condition and only a small percentage of these persons are able to walk functionally in the community. Material and Method. Patients with chronic stroke were recruited from outpatient rehabilitation unit at Department of Neurology & Neurosurgery, All India Institute of Medical Sciences, having a history of first stroke at least six months before recruitment, with unilateral motor deficits affecting gait. The patients were randomly assigned to either the functional limb overloading (FLO or Limb Overloading Resistance Training (LORT group and provided four weeks of training. Result. We found that there was an improvement in gait performance, weight bearing on affected limb, and perceived mobility and community participation. Conclusion. To the best of our knowledge, this is the first study that has evaluated the effects of functional limb overloading training on symmetric weight bearing, walking ability, and perceived mobility and participation in chronic hemiplegic population. The study demonstrated a beneficial effect of training on all the outcomes, suggesting that the functional limb overloading training can be a useful tool in the management of gait problems in chronic stroke patients.

  20. Niacin requirements for genomic stability.

    Science.gov (United States)

    Kirkland, James B

    2012-05-01

    Through its involvement in over 400 NAD(P)-dependent reactions, niacin status has the potential to influence every area of metabolism. Niacin deficiency has been linked to genomic instability largely through impaired function of the poly ADP-ribose polymerase (PARP) family of enzymes. In various models, niacin deficiency has been found to cause impaired cell cycle arrest and apoptosis, delayed DNA excision repair, accumulation of single and double strand breaks, chromosomal breakage, telomere erosion and cancer development. Rat models suggest that most aspects of genomic instability are minimized by the recommended levels of niacin found in AIN-93 formulations; however, some beneficial responses do occur in the range from adequate up to pharmacological niacin intakes. Mouse models show a wide range of protection against UV-induced skin cancer well into pharmacological levels of niacin intake. It is currently a challenge to compare animal and human data to estimate the role of niacin status in the risk of genomic instability in human populations. It seems fairly certain that some portion of even affluent populations will benefit from niacin supplementation, and some subpopulations are likely well below an optimal intake of this vitamin. With exposure to stressors, like chemotherapy or excess sunlight, suraphysiological doses of niacin may be beneficial.

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

    Science.gov (United States)

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

    2016-04-01

    The aim of this study was to investigate cardiac functional status in pregnancy using a comprehensive approach taking into account the simultaneous changes in loading and geometry, as well as maternal age and anthropometric indices. This was a prospective cross-sectional study of 559 nulliparous pregnant women assessed at 4 time points during pregnancy and at 1 year postpartum. All women underwent conventional echocardiography and tissue Doppler velocities and strain rate analysis at multiple cardiac sites. Mean arterial pressure and total vascular resistance index significantly decreased (both Pmaladaptation to the volume-overloaded state in some apparently normal pregnancies. These unexpected cardiovascular findings have important implications for the management of both normal and pathological pregnancy states. PMID:26962206

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

    Institute of Scientific and Technical Information of China (English)

    Katarzyna Sikorska; Piotr Stalke; Tomasz Romanowski

    2013-01-01

    BACKGROUND: 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. METHODS: 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. RESULTS: 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

  3. The importance of trabecular hypertrophy in right ventricular adaptation to chronic pressure overload.

    Science.gov (United States)

    van de Veerdonk, Mariëlle C; Dusoswa, Sophie A; Marcus, J Tim; Bogaard, Harm-Jan; Spruijt, Onno; Kind, Taco; Westerhof, Nico; Vonk-Noordegraaf, Anton

    2014-02-01

    To assess the contribution of right ventricular (RV) trabeculae and papillary muscles (TPM) to RV mass and volumes in controls and patients with pulmonary arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP) during follow-up. 50 patients underwent cardiac magnetic resonance (CMR) and right heart catheterization at baseline and after one-year follow-up. Furthermore 20 controls underwent CMR. RV masses were assessed with and without TPM. TPM constituted a larger proportion of total RV mass and RV end-diastolic volume (RVEDV) in PAH than in controls (Mass: 35 ± 7 vs. 25 ± 5 %; p TPM mass was related to the RVFW mass in patients (baseline: R = 0.65; p TPM from the assessment resulted in altered RV mass, volumes and function than when included (all p TPM mass (β = 0.44; p = 0.004) but not the changes in RVFW mass (p = 0.095) were independently related to changes in PAP during follow-up. RV TPM showed a larger contribution to total RV mass in PAH (~35 %) compared to controls (~25 %). Inclusion of TPM in the analyses significantly influenced the magnitude of the RV volumes and mass. Furthermore, TPM mass was stronger related to changes in PAP than RVFW mass. Our results implicate that TPM are important contributors to RV adaptation during pressure overload and cannot be neglected from the RV assessment.

  4. Longitudinal MRI and Ferritin Monitoring of Iron Overload in Chronically Transfused and Chelated Children With Sickle Cell Anemia and Thalassemia Major.

    Science.gov (United States)

    Aubart, Mélodie; Ou, Phalla; Elie, Caroline; Canniffe, Carla; Kutty, Shelby; Delos, Vincent; Graffigne, Christine; de Montalembert, Mariane; Brousse, Valentine

    2016-10-01

    Iron overload is an ineluctable complication in chronically transfused children warranting accurate assessment to avoid related morbidity. We investigated longitudinally the relationships between ferritin levels and hepatic and cardiac T2* magnetic resonance imaging (MRI) in a cohort of chronically transfused children receiving chelation therapy. Thirty children with sickle cell anemia (SCA) and 7 with thalassemia major (TM) chelated similarly by deferasirox were analyzed. Sex ratio, age, median duration of transfusion programs (5 y; range, 2 to 14 y), median transfusion iron intake 0.54 mg/kg/d (range, 0.27 to 0.74 mg/kg/d), and median ferritin level (1550 mg/L; range, 184 to 6204 mg/L) were comparable in TM and SCA. A significant relation was found between ferritin level and transfusion iron intake (P<0.001) despite chelation therapy. Analysis of 73 hepatic T2* MRI performed yearly demonstrated severe hepatic iron overload (≥14 mg/g) in 38.3% cases and a strong relationship between serum ferritin level and liver iron content both in SCA and TM (P<0.001). Analysis of 55 cardiac T2* MRI measurements found no cardiac overload in patients with SCA. Cardiac iron overload was moderate in 4 cases and severe in 1 case of TM. In almost half the cases, ferritin trend correctly predicted hepatic iron trend, both in patients with SCA and TM but failed to predict cardiac iron trend, notably in TM patients. Despite chelation therapy, iron burden in chronically transfused patients remains a threat. Ferritin levels are associated with liver iron overload in chelated children with SCA and TM, but iron burden should be best monitored with MRI whenever the setting allows it. PMID:27548334

  5. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    Institute of Scientific and Technical Information of China (English)

    Massimo; Sartori; Silvano; Andorno; Angelo; Rossini; Renzo; Boldorini; Cristina; Bozzola; Stefania; Carmagnola; Mario; Del; Piano; Emanuele; Albano

    2010-01-01

    AIM:To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C(CHC). METHODS:We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to,or unsuitable for,antiviral therapy who underwent mild iron depletion(ferritin≤70 ng/mL) by long-term phlebotomy.Histological improvement,as defined by at least one point reduction in the staging score or,in case...

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

    Directory of Open Access Journals (Sweden)

    Maria L Watson

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

  7. Cartilage contact pressure elevations in dysplastic hips: a chronic overload model

    Directory of Open Access Journals (Sweden)

    Grosland Nicole M

    2006-10-01

    Full Text Available Abstract Background Developmental dysplasia of the hip (DDH is a condition in which bone growth irregularities subject articular cartilage to higher mechanical stresses, increase susceptibility to subluxation, and elevate the risk of early osteoarthritis. Study objectives were to calculate three-dimensional cartilage contact stresses and to examine increases of accumulated pressure exposure over a gait cycle that may initiate the osteoarthritic process in the human hip, in the absence of trauma or surgical intervention. Methods Patient-specific, non-linear, contact finite element models, constructed from computed tomography arthrograms using a custom-built meshing program, were subjected to normal gait cycle loads. Results Peak contact pressures for dysplastic and asymptomatic hips ranged from 3.56 – 9.88 MPa. Spatially discriminatory cumulative contact pressures ranged from 2.45 – 6.62 MPa per gait cycle. Chronic over-pressure doses, for 2 million cycles per year over 20 years, ranged from 0.463 – 5.85 MPa-years using a 2-MPa damage threshold. Conclusion There were significant differences between the normal control and the asymptomatic hips, and a trend towards significance between the asymptomatic and symptomatic hips of patients afflicted with developmental dysplasia of the hip. The magnitudes of peak cumulative contact pressure differed between apposed articular surfaces. Bone irregularities caused localized pressure elevations and an upward trend between chronic over-pressure exposure and increasing Severin classification.

  8. Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

    Science.gov (United States)

    Piloni, Natacha E; Perazzo, Juan C; Fernandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2016-02-01

    This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation. PMID:26677163

  9. 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. PMID:24908908

  10. Niacin for dairy cattle: a review.

    Science.gov (United States)

    Niehoff, Inka-Donata; Hüther, Liane; Lebzien, Peter

    2009-01-01

    Due to the incorporation of niacin into the coenzymes NAD and NADP, niacin is of great importance for the metabolism of man and animals. Apart from niacin in feed and endogenous formation, microbial niacin synthesis in the rumen is an important source for dairy cows. But the amount synthesised seems to differ greatly, which might be influenced by the ration fed. Many studies revealed a positive impact of a niacin supplementation on rumen protozoa, but microbial protein synthesis or volatile fatty acid production in the rumen showed inconsistent reactions to supplemental niacin. The amount of niacin reaching the duodenum is usually higher when niacin is fed. However, not the whole quantity supplemented reaches the duodenum, indicating degradation or absorption before the duodenal cannula. Furthermore, supplementation of niacin did not always lead to a higher niacin concentration in blood. Effects on other blood parameters have been inconsistent, but might be more obvious when cows are in a tense metabolic situation, for example, ketosis or if high amounts are infused post-ruminally, since ruminal degradation appears to be substantial. The same is valid for milk parameters. In the few studies where blood niacin and milk parameters have been investigated, enhanced niacin concentrations in blood did not necessarily affect milk production or composition. These results are discussed in the present review, gaps of knowledge of niacin's mode of action on the metabolism of dairy cows are identified and directions for future research are suggested.

  11. Niacin and niacinamide (Vitamin B3)

    Science.gov (United States)

    Niacin and niacinamide are forms of Vitamin B3. Vitamin B3 is found in many foods including yeast, meat, fish, milk, eggs, green vegetables, beans, and cereal grains. Niacin and niacinamide are also found in many vitamin B complex ...

  12. 21 CFR 582.5530 - Niacin.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Niacin. 582.5530 Section 582.5530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... § 582.5530 Niacin. (a) Product. Niacin. (b) Conditions of use. This substance is generally recognized...

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

    OpenAIRE

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

    2013-01-01

    Skeletal muscle mass loss and dysfunction have been linked to many diseases. Conversely, resistance exercise, mainly by activating mammalian target of rapamycin complex 1 (mTORC1), promotes skeletal muscle hypertrophy and exerts several therapeutic effects. Moreover, mTORC1, along with peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), regulates skeletal muscle metabolism. However, it is unclear whether PGC-1α is required for skeletal muscle adaptations after overload. Here...

  14. Pathology of hepatic iron overload

    Institute of Scientific and Technical Information of China (English)

    Yves Deugnier; Bruno Turlin

    2007-01-01

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

  15. Vascular endothelium derived endothelin-1 is required for normal heart function after chronic pressure overload in mice.

    Directory of Open Access Journals (Sweden)

    Susi Heiden

    Full Text Available BACKGROUND: Endothelin-1 participates in the pathophysiology of heart failure. The reasons for the lack of beneficial effect of endothelin antagonists in heart failure patients remain however speculative. The anti-apoptotic properties of ET-1 on cardiomyocytes could be a reasonable explanation. We therefore hypothesized that blocking the pro-apoptotic TNF-α pathway using pentoxifylline could prevent the deleterious effect of the lack of ET-1 in a model for heart failure. METHODS: We performed transaortic constriction (TAC in vascular endothelial cells specific ET-1 deficient (VEETKO and wild type (WT mice (n = 5-9 and treated them with pentoxifylline for twelve weeks. RESULTS: TAC induced a cardiac hypertrophy in VEETKO and WT mice but a reduction of fractional shortening could be detected by echocardiography in VEETKO mice only. Cardiomyocyte diameter was significantly increased by TAC in VEETKO mice only. Pentoxifylline treatment prevented cardiac hypertrophy and reduction of fractional shortening in VEETKO mice but decreased fractional shortening in WT mice. Collagen deposition and number of apoptotic cells remained stable between the groups as did TNF-α, caspase-3 and caspase-8 messenger RNA expression levels. TAC surgery enhanced ANP, BNP and bcl2 expression. Pentoxifylline treatment reduced expression levels of BNP, bcl2 and bax. CONCLUSIONS: Lack of endothelial ET-1 worsened the impact of TAC-induced pressure overload on cardiac function, indicating the crucial role of ET-1 for normal cardiac function under stress. Moreover, we put in light a TNF-α-independent beneficial effect of pentoxifylline in the VEETKO mice suggesting a therapeutic potential for pentoxifylline in a subpopulation of heart failure patients at higher risk.

  16. Acute Liver Failure Secondary to Niacin Toxicity

    Directory of Open Access Journals (Sweden)

    Marc A. Ellsworth

    2014-01-01

    Full Text Available A 17-year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. He was recently released from an alcohol treatment center with acute onset of chest pain. Cardiac workup was negative but he was found to have abnormal coagulation studies and elevated liver transaminases. Other evaluations included a normal toxicology screen and negative acetaminophen level. Autoimmune and infectious workups were normal providing no identifiable cause of his acute liver failure. He initially denied any ingestions or illicit drug use but on further query he admitted taking niacin in an attempt to obscure the results of an upcoming drug test. Niacin has been touted on the Internet as an aid to help pass urine drug tests though there is no evidence to support this practice. Niacin toxicity has been associated with serious multisystem organ failure and fulminant hepatic failure requiring liver transplantation. Pediatric providers should be aware of the risks associated with niacin toxicity and other experimental medical therapies that may be described on the Internet or other nonreputable sources.

  17. Information overload and data overload in lexicography

    DEFF Research Database (Denmark)

    Tarp, Sven; Gouws, Rufus H.

    2016-01-01

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

  18. Low-dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson’s disease symptoms without side effects

    Science.gov (United States)

    Wakade, Chandramohan; Chong, Raymond; Bradley, Eric; Morgan, John C

    2015-01-01

    Key Clinical Message A 65-year-old male, Parkinson’s disease patient, was evaluated for GPR109A expression, niacin index, UPDRS scale, handwriting test, and quality of sleep with and without niacin treatment. The evaluation was repeated 3 months after niacin was stopped. Niacin modulated the abovementioned parameters and showed the overall improvement without side effects. PMID:26273459

  19. Low-dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson’s disease symptoms without side effects

    OpenAIRE

    Wakade, Chandramohan; Chong, Raymond; Bradley, Eric; Morgan, John C.

    2015-01-01

    Key Clinical Message A 65-year-old male, Parkinson’s disease patient, was evaluated for GPR109A expression, niacin index, UPDRS scale, handwriting test, and quality of sleep with and without niacin treatment. The evaluation was repeated 3 months after niacin was stopped. Niacin modulated the abovementioned parameters and showed the overall improvement without side effects.

  20. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Vinod Pullarkat

    2010-01-01

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

  1. Effects of Micronutrient Niacin on Treatment Efficiency of Textile Wastewater

    Institute of Scientific and Technical Information of China (English)

    LIANG Wei; HU Hongying; GU Xin; CHE Yuling; WANG Hui; GUO Yufeng; SONG Yudong

    2006-01-01

    Textile wastewater is well known as one of the wastewaters to be most difficultly treated. The effects of niacin on textile wastewater niacin, the physical and chemical indexes of the water samples, such as COD, ammonia and dehydrogenase activities, were analyzed every day with standard methods, and obvious improvement in wastewater treatcould improve the COD removal efficiency signifcantly with removal rates mental condition, addition of niacin had almost no effect on the removal of ase by 130%. It proved that the biological treatment performance of textile wastewater treatment system probably could be optimized through micronutrient niacin supplement.

  2. Iron overload and immunity

    Institute of Scientific and Technical Information of China (English)

    Gra(c)a Porto; Maria De Sousa

    2007-01-01

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

  3. Design and evaluation of niacin microspheres

    Directory of Open Access Journals (Sweden)

    Maravajhala Vidyavathi

    2009-01-01

    Full Text Available Present study aims to prepare and evaluate niacin microspheres. Niacin-ethyl cellulose microspheres were prepared by water-in-oil-in-oil double emulsion solvent diffusion method. Spherical, free flowing microspheres having an entrapment efficiency of 72% were obtained. The effect of polymer-drug ratio, surfactant concentration for secondary emulsion process and stirring speed of emulsification process were evaluated with respect to entrapment efficiency, in vitro drug release behavior and particle size. FT-IR and DSC analyses confirmed the absence of drug-polymer interaction. The in vitro release profile could be altered significantly by changing various processing and formulation parameters to give a controlled release of drug from the microspheres. The percentage yield was 85%, particle size range was 405 to 560 µm. The drug release was controlled for 10 h. The in vitro release profiles from optimized formulations were applied on various kinetic models. The best fit with the highest correlation coefficient was observed in Higuchi model, indicating diffusion controlled principle. The in vitro release profiles of optimized formulation was studied and compared with commercially available niacin extended release formulation.

  4. Scientific Opinion on Dietary Reference Values for niacin

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA

    2014-07-01

    Full Text Available Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA derived Dietary Reference Values (DRVs for niacin. Niacin is a generic term for nicotinic acid and nicotinamide. Niacin can be synthesised in the human body from the indispensable amino acid tryptophan. Approximately 60 mg of tryptophan yields 1 mg of niacin defined as 1 mg niacin equivalent (NE. Long-term inadequate intake of tryptophan and niacin can lead to the development of pellagra. In the absence of new scientific data, the Panel endorses the Average Requirement (AR for adults of 1.3 mg NE/MJ (5.5 mg NE/1 000 kcal adopted by the Scientific Committee for Food (1993, based on data on urinary excretion of niacin metabolites as an endpoint. The Population Reference Intake (PRI of 1.6 mg NE/MJ (6.6 mg NE/1 000 kcal is derived from the AR assuming a coefficient of variation of 10 %. For infants aged 7-11 months, children and adolescents, as well as for pregnant and lactating women, the Panel considers that there is no evidence that the relationship between niacin requirement and energy requirement differs from that of adults; therefore, the AR and PRI for adults are also applied to these age and life stage groups.

  5. HFE gene in primary and secondary hepatic iron overload

    Institute of Scientific and Technical Information of China (English)

    Giada Sebastiani; Ann P Walker

    2007-01-01

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

  6. Transfusion associated circulatory overload

    Directory of Open Access Journals (Sweden)

    Naveen Agnihotri

    2014-01-01

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

  7. Prooxidant Mechanisms in Iron Overload Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ching-Feng Cheng

    2013-01-01

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

  8. 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

    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-indu...... relevance as a constraint on platelets during niacin therapy.......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....... 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...

  9. Radiometric microbiologic assay for the biologically active forms of niacin

    Energy Technology Data Exchange (ETDEWEB)

    Kertcher, J.A.; Guilarte, T.R.; Chen, M.F.; Rider, A.A.; McIntyre, P.A.

    1979-05-01

    A radiometric microbiologic assay has been developed for the determination of niacin in biologic fluids. Lactobacillus plantarum produced /sup 14/CO/sub 2/ from L-(U-/sup 14/C) malic acid in quantities proportional to the amount of niacin present. The assay is specific for the biologically active forms of niacin in humans. Thirty normal hemolysates were analyzed and the values ranged from 13.0 to 17.8 ..mu..g niacin/ml RBC (mean = 15.27 +- 1.33 s.d.). Good recovery and reproducibility studies were obtained with this assay. On thirty blood samples, correlation was excellent between the radiometric and the conventional turbidimetric assays.

  10. Niacin and cholesterol: role in cardiovascular disease (review).

    Science.gov (United States)

    Ganji, Shobha H; Kamanna, Vaijinath S; Kashyap, Moti L

    2003-06-01

    Niacin has been widely used as a pharmacologic agent to regulate abnormalities in plasma lipid and lipoprotein metabolism and in the treatment of atherosclerotic cardiovascular disease. Although the use of niacin in the treatment of dyslipidemia has been reported as early as 1955, only recent studies have yielded an understanding about the cellular and molecular mechanism of action of niacin on lipid and lipoprotein metabolism. In brief, the beneficial effect of niacin to reduce triglycerides and apolipoprotein-B containing lipoproteins (e.g., VLDL and LDL) are mainly through: a) decreasing fatty acid mobilization from adipose tissue triglyceride stores, and b) inhibiting hepatocyte diacylglycerol acyltransferase and triglyceride synthesis leading to increased intracellular apo B degradation and subsequent decreased secretion of VLDL and LDL particles. The mechanism of action of niacin to raise HDL is by decreasing the fractional catabolic rate of HDL-apo AI without affecting the synthetic rates. Additionally, niacin selectively increases the plasma levels of Lp-AI (HDL subfraction without apo AII), a cardioprotective subfraction of HDL in patients with low HDL. Using human hepatocytes (Hep G2 cells) as an in vitro model system, recent studies indicate that niacin selectively inhibits the uptake/removal of HDL-apo AI (but not HDL-cholesterol ester) by hepatocytes, thereby increasing the capacity of retained HDL-apo AI to augment cholesterol efflux through reverse cholesterol transport pathway. The studies discussed in this review provide evidence to extend the role of niacin as a lipid-lowering drug beyond its role as a vitamin.

  11. Effects of isoniazid and niacin on experimental wound-healing

    DEFF Research Database (Denmark)

    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....

  12. Effect of graded levels of niacin supplementation of a semipurified diet on energy and nitrogen balance, growth performance, diarrhea occurrence, and niacin metabolite excretion by growing swine.

    Science.gov (United States)

    Ivers, D J; Veum, T L

    2012-01-01

    Thirty-six crossbred barrows with an average initial age of 42 d and BW of 13.8 kg were placed in individual metabolism crates in a 35-d experiment to evaluate the supplementation of a semipurified diet with graded levels of crystalline niacin. Response criteria were energy and N balance, growth performance, occurrence of niacin deficiency diarrhea, and urinary excretion of the niacin metabolite N(1)-methyl-2-pyridone-5-carboxylamide (PYR). The basal diet met the true ileal Trp requirement of growing swine, and supplementation with 6, 10, 14, 18, 22, or 44 mg of niacin/kg made 6 treatments. Pigs were observed for scours twice daily, and pig BW and feed consumption were determined weekly. Total urine collections and fecal grab samples were made twice daily from each pig from d 28 to 35. Pigs fed the diet containing 14 mg of niacin/kg absorbed and retained more (P niacin/kg, and pigs fed the diet containing 10 mg of niacin/kg were intermediate in ADG. There were no additional improvements in the response criteria with niacin supplementation greater than 14 mg/kg. Urinary PYR criteria (mg/L and mg/d) were greater (P niacin/kg than for pigs fed the diets containing 6 to 22 mg of niacin/kg. However, urinary PYR criteria for pigs fed the diets containing 6 to 22 mg of niacin/kg did not differ from each other, indicating that PYR was not a sensitive indicator of niacin status for growing swine. Niacin treatment did not affect the percentages of N retained/N absorbed, N retained/N intake, DE, or ME. In conclusion, 14 mg of crystalline niacin/kg of semipurified diet adequate in Trp was the minimum concentration of niacin that maximized N utilization and growth performance, and prevented niacin deficiency diarrhea of growing swine in the current experiment. Because practical feed ingredients may be sources of available endogenous niacin, supplementation of practical diets with 100% of the current NRC requirement for niacin should provide adequate niacin for growing swine.

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

    Science.gov (United States)

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

    2016-10-01

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

  14. Immediate release niacin effect at stratified lipid levels

    Directory of Open Access Journals (Sweden)

    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.

  15. Effects of Extended-Release Niacin and Extended-Release Niacin/Laropiprant on the Pharmacokinetics of Simvastatin in Healthy Subjects.

    Science.gov (United States)

    Lauring, Brett; Dishy, Victor; De Kam, Pieter-Jan; Crumley, Tami; Wenning, Larissa; Liu, Fang; Sisk, Christine; Wagner, John; Lai, Eseng

    2015-01-01

    The use of multiple lipid-modifying agents with different mechanisms of action is often required to regulate lipid levels in patients with dyslipidemia. During combination therapy, alterations in the pharmacokinetics of any of the drugs used and their metabolites may occur. Three separate open-label, randomized, crossover studies evaluated the potential for pharmacokinetic interaction between extended-release niacin (with and without concomitant laropiprant) and simvastatin in healthy subjects. Study 1 used single doses of extended-release niacin and simvastatin; study 2 used multiple-dose coadministration of extended-release niacin/laropiprant and simvastatin in healthy subjects; and study 3 used single doses of both extended-release niacin and the coadministration of extended-release niacin/laropiprant and simvastatin in healthy Chinese subjects. During each treatment period, plasma samples were collected predose and at prespecified postdose time points for pharmacokinetic analyses. The safety and tolerability of simvastatin with and without coadministered extended-release niacin (or extended-release niacin/laropiprant) were assessed by clinical evaluation of adverse experiences. In 2 studies in healthy subjects, modest increases in exposure to simvastatin acid (by ∼60%) by extended-release niacin and extended-release niacin/laropiprant were observed. Based on the clinical experience with simvastatin, these effects are not believed to be clinically meaningful. In the third study on healthy Chinese subjects, no statistically meaningful increases in exposure to simvastatin by extended-release niacin and extended-release niacin/laropiprant were observed. In all populations examined in these studies, the coadministration of extended-release niacin and simvastatin was generally well tolerated. PMID:24832384

  16. Death by information overload.

    Science.gov (United States)

    Hemp, Paul

    2009-09-01

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

  17. Dietary Fat Overload Reprograms Brown Fat Mitochondria

    Directory of Open Access Journals (Sweden)

    DANIELE eLETTIERI BARBATO

    2015-09-01

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

  18. Niacin restriction upregulates NADPH oxidase and ROS in human keratinocytes

    OpenAIRE

    Benavente, Claudia A.; Jacobson, Elaine L.

    2007-01-01

    NAD+ is a substrate for many enzymes, including poly(ADP-ribose) polymerases and sirtuins, which are involved in fundamental cellular processes including DNA repair, stress responses, signaling, transcription, apoptosis, metabolism, differentiation, chromatin structure, and life span. Because these molecular processes are important early in cancer development, we developed a model to identify critical NAD-dependent pathways potentially important in early skin carcinogenesis. Removal of niacin...

  19. True Niacin Deficiency in Quinolinic Acid Phosphoribosyltransferase (QPRT) Knockout Mice.

    Science.gov (United States)

    Shibata, Katsumi

    2015-01-01

    Pyridine nucleotide coenzymes (PNCs) are involved in over 500 enzyme reactions. PNCs are biosynthesized from the amino acid L-tryptophan (L-Trp), as well as the vitamin niacin. Hence, "true" niacin-deficient animals cannot be "created" using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected in qprt(-/-)mice. The qprt(+/+), qprt(+/-) or qprt(-/-) mice (8 wk old) were fed a complete diet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. When qprt(-/-)mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt(+/+) and the qprt(+/-) mice. On the other hand, in the qprt(-/-) mice fed the NiA-free diet, food intake and body weight were reduced to 60% (pniacin such as blood and liver NAD concentrations were also lower in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice. Urinary excretion of quinolinic acid was greater in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice (pniacin-deficient mice.

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

    Institute of Scientific and Technical Information of China (English)

    Philip Hilgard; Guido Gerken

    2005-01-01

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

  1. The C57BL/6 genetic background confers cardioprotection in iron-overloaded mice

    Science.gov (United States)

    Musumeci, Marco; Maccari, Sonia; Sestili, Paola; Massimi, Alessia; Corritore, Elisa; Marano, Giuseppe; Catalano, Liviana

    2013-01-01

    Background Chronic transfusion therapy causes a progressive iron overload that damages many organs including the heart. Recent evidence suggests that L-type calcium channels play an important role in iron uptake by cardiomyocytes under conditions of iron overload. Given that beta-adrenergic stimulation significantly enhances L-type calcium current, we hypothesised that beta-adrenergic blocking drugs could reduce the deleterious effects of iron overload on the heart. Methods Iron overload was generated by intraperitoneal injections of iron dextran (1g/kg) administered once a week for 8 weeks in male C57bl/6 mice, while propranolol was administered in drinking water at the dose of 40 mg/kg/day. Cardiac function and ventricular remodelling were evaluated by echocardiography and histological methods. Results As compared to placebo, iron injection caused cardiac iron deposition. Surprisingly, despite iron overload, myocardial function and ventricular geometry in the iron-treated mice resulted unchanged as compared to those in the placebo-treated mice. Administration of propranolol increased cardiac performance in iron-overloaded mice. Specifically, as compared to the values in the iron-overloaded group, in iron-overloaded animals treated with propranolol left ventricular fractional shortening increased (from 31.6% to 44.2%, P =0.01) whereas left ventricular end-diastolic diameter decreased (from 4.1±0.1 mm to 3.5±0.1 mm, P =0.03). Propranolol did not alter cardiac systolic function or left ventricular sizes in the placebo group. Conclusions These results demonstrate that C57bl/6 mice are resistant to iron overload-induced myocardial injury and that treatment with propranolol is able to increase cardiac performance in iron-overloaded mice. However, since C57bl/6 mice were resistant to iron-induced injury, it remains to be evaluated further whether propranolol could prevent iron-overload cardiomyopathy. PMID:22790263

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

    Institute of Scientific and Technical Information of China (English)

    汤召兵; 苟欣; 王明; 何卫阳; 刘朝东; 邓远忠

    2011-01-01

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

  3. The therapeutic role of niacin in dyslipidemia management.

    Science.gov (United States)

    Boden, William E; Sidhu, Mandeep S; Toth, Peter P

    2014-03-01

    There is abundant epidemiologic evidence to support the independent, inverse relationship between low levels of high-density lipoprotein cholesterol (HDL-C) and incident cardiovascular (CV) risk, the clinical importance of which is underscored by the high prevalence of low HDL-C in populations with coronary heart disease (CHD), with or without elevated levels of low-density lipoprotein cholesterol (LDL-C). The National Cholesterol Education Program recommended that optimal treatment for high-risk patients includes both lowering LDL-C and non-HDL-C to risk stratified levels and raising HDL-C when it is <40 mg/dL, although no target level for the latter lipoprotein was suggested. Niacin is the most powerful agent currently available for raising low levels of HDL-C. It also induces significant reductions in triglycerides, lipoprotein(a), and LDL-C levels while also favorably altering LDL particle size and number. In the Coronary Drug Project, niacin treatment was associated with significant reductions in CV events and long-term mortality, similar to the reductions seen in the statin monotherapy trials. In combination trials, niacin plus a statin or bile acid sequestrant produces additive reductions in CHD morbidity and mortality and promotes regression of coronary atherosclerosis. Recently, 2 clinical outcome trials (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes [AIM-HIGH] and Second Heart Protection Study [HPS-2 THRIVE]) failed to show a reduction in CV events in patients treated to optimally low levels of LDL-C. Despite favorable effects on HDL-C and triglycerides, these studies did not demonstrate incremental clinical benefit with niacin when added to simvastatin, although notable limitations were identified in each of these trials. Thus, there is insufficient evidence from clinical trials to recommend HDL-targeted therapy for additional event reduction at the present time. However, niacin

  4. 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. Mater

  5. Hepcidin in iron overload disorders

    OpenAIRE

    Papanikolaou, George; Tzilianos, Michalis; Christakis, John I.; Bogdanos, Dionisios; Tsimirika, Konstantina; MacFarlane, Julie; Goldberg, Y. Paul; Sakellaropoulos, Nikos; Ganz, Tomas; Nemeth, Elizabeta

    2005-01-01

    Hepcidin is the principal regulator of iron absorption in humans. The peptide inhibits cellular iron efflux by binding to the iron export channel ferroportin and inducing its internalization and degradation. Either hepcidin deficiency or alterations in its target, ferroportin, would be expected to result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. Indeed, hepcidin deficiency has been reported in hereditary hemochromatosis and attributed to mutations in ...

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

    Directory of Open Access Journals (Sweden)

    Desiree Wanders

    Full Text Available AIMS: To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  7. The discovery of niacin, biotin, and pantothenic acid.

    Science.gov (United States)

    Lanska, Douglas J

    2012-01-01

    The aim was to describe the discovery of niacin, biotin, and pantothenic acid. By the 1920s, it became apparent that 'water-soluble B' (vitamin B) is not a single substance. In particular, fresh yeast could prevent both beriberi and pellagra, but the 'antipolyneuritis factor' in yeast is thermolabile, while the antipellagra factor is heat stable, suggesting that there are at least two water-soluble vitamins. Various terms were proposed for these water-soluble factors, but vitamins B(1) and B(2) were most widely used to refer to the thermolabile and heat-stable factors, respectively. Although vitamin B(1) proved to be a single chemical substance (thiamin), vitamin B(2) was ultimately found to be a complex of several chemically unrelated heat-stable factors, including niacin, biotin, and pantothenic acid. Recognition that niacin is a vitamin in the early 20th century resulted from efforts to understand and treat a widespread human disease - pellagra. American epidemiologist and US Public Health Service officer Joseph Goldberger (1874-1929) had been instrumental to elucidating the nutritional basis for pellagra. Goldberger conducted a classic series of observational and experimental studies in humans, combined with an extensive series of experiments with an animal model of the condition (black tongue in dogs). In contrast, recognition that biotin and pantothenic acid are vitamins occurred somewhat later as a result of efforts to understand microbial growth factors. The metabolic roles in humans of these latter substances were ultimately elucidated by human experiments using particular toxins and by studies of rare inborn errors of metabolism. Symptomatic nutritional deficiencies of biotin and pantothenic acid were, and continue to be, rare.

  8. Final report of the safety assessment of niacinamide and niacin.

    Science.gov (United States)

    2005-01-01

    Niacinamide (aka nicotinamide) and Niacin (aka nicotinic acid) are heterocyclic aromatic compounds which function in cosmetics primarily as hair and skin conditioning agents. Niacinamide is used in around 30 cosmetic formulations including shampoos, hair tonics, skin moisturizers, and cleansing formulations. Niacin is used in a few similar product types. The concentration of use of Niacinamide varies from a low of 0.0001% in night preparations to a high of 3% in body and hand creams, lotions, powders and sprays. Niacin concentrations of use range from 0.01% in body and hand creams, lotions, powders and sprays to 0.1% in paste masks (mud packs). Both ingredients are accepted for use in cosmetics in Japan and the European Union. Both are GRAS direct food additives and nutrient and/or dietary supplements. Niacinamide may be used in clinical treatment of hypercholesteremia and Niacin in prevention of pellegra and treatment of certain psychological disorders. Both ingredients are readily absorbed from skin, blood, and the intestines and widely distribute throughout the body. Metabolites include N1-methylnicotinamide and N1-methyl-4-pyridone-3-carboxamide. Excretion is primarily through the urinary tract. While Niacinamide is more toxic than Niacin in acute toxicity studies, both are relatively non-toxic. Short-term oral, parenteral, or dermal toxicity studies did not identify significant irreversible effects. Niacinamide, evaluated in an in vitro test to predict ocular irritation, was not an acute ocular hazard. Animal testing of Niacinamide in rabbits in actual formulations produced mostly non-irritant reactions, with only some marginally irritating responses. Skin irritation tests of up to 2.5% Niacinamide in rabbits produced only marginal irritation. Skin sensitization tests of Niacinamide at 5% during induction and 20% during challenge were negative in guinea pigs. Neither cosmetic ingredient was mutagenic in Ames tests, with or without metabolic activation

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Radiometric-microbiologic assay of niacin using Kloeckera brevis: analysis of human blood and food

    Energy Technology Data Exchange (ETDEWEB)

    Guilarte, T.R.; Pravlik, K.

    1983-12-01

    Kloeckera brevis, a yeast, was used as the test organism for the development of a radiometric-microbiologic (RMA) assay for niacin. The assay was determined to be sensitive to the 2 ng niacin per vial level and specific for the biologically active forms of this vitamin. The method was shown to be simple, accurate, and precise in the analysis of niacin in human blood and food. The application of the radiometric technique eliminates some of the problems encountered with conventional turbidimetric-microbiologic assay.

  11. Niacin as a drug repositioning candidate for hyperphosphatemia management in dialysis patients

    Directory of Open Access Journals (Sweden)

    Shin S

    2014-10-01

    Full Text Available Sooyoung Shin, Sukhyang LeeAjou University College of Pharmacy, Yeongtong-gu, Suwon-si, Gyeonggi-do, Korea Abstract: Nearly all patients with end-stage renal disease develop hyperphosphatemia. These patients typically require oral phosphate binders for life-long phosphorus management, in addition to dietary restrictions and maintenance dialysis. Recently, niacin, a traditional antilipemic agent, drew attention as an experimental treatment for hyperphosphatemia. The purpose of this article was to report on new findings regarding niacin’s novel effects and to review the possibility of repurposing niacin for hyperphosphatemia treatment in dialysis patients by elucidating its safety and efficacy profiles along with its synergistic clinical benefits. Following approval from the Institutional Review Board, we tracked the yearly trends of order frequency of niacin in comparison with statins and sevelamer in a tertiary care hospital. Also, a Cochrane Library and PubMed literature search was performed to capture prospective clinical trials on niacin’s hypophosphatemic effects in dialysis patients. Niacin use in clinical settings has been on the wane, and the major contribution to that originates from the wide use of statins. Niacin use rates have further plummeted following a trial failure which prompted the suspension of the niacin-laropiprant (a flushing blocker combination product in the global market. Our literature search identified ten relevant articles. Overall, all studies demonstrated that niacin or nicotinamide (the metabolite form reduced serum phosphorus levels as well as Ca-P products significantly. Additive beneficial effects on lipid parameters were also observed. Sevelamer appeared superior to niacin in a comparative study, but the study design had several limitations. The intervention dosage for niacin ranged from 375 to 1,500 mg/day, with the average daily dose of approximately 1,000–1,500 mg. Niacin can be a patient

  12. Intelligent overload control for composite web services

    NARCIS (Netherlands)

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

    2009-01-01

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

  13. Echocardiographic features of right ventricular volume overload

    Directory of Open Access Journals (Sweden)

    Shah Lilam

    1979-01-01

    Full Text Available Interventricular septal motion is studied in sixty tow cases clas-sified into 3 groups; Gr. 1-right ventricular volume overload (RVVO; Gr. II-combined right ventricular volume overload and left ventricular volume overload (RVVO + LVVO; Gr. III-com-bined right ventricular volume overload and right ventricular pres-sure overload (RVVO + RVPO. A linear relationship was obtained between the right ventricu-lar dimension index (RVDI obtained echocardiographically and the magnitude of the left to right shunt at the atrial level (Qn/Qs. Two rare instances of false negatives in a hemodynamically in-significant left to right shunt and in a large ASD are reported. Modification of abnormal septal motion in Gr. II and Gr. III is studied. Lesion specific features of certain anomalies i.e. Ebstein′s ano-maly, total anomalous pulmonary venous return (TAPVR and en-docardial cushion defects (ECD are discussed.

  14. Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats.

    Science.gov (United States)

    Silva de Paula, Eloisa; Carneiro, Maria Fernanda Hornos; Grotto, Denise; Hernandes, Lívia Cristina; Antunes, Lusânia Maria Greggi; Barbosa, Fernando

    2016-01-01

    This study investigates the potential beneficial effects of niacin (NA; vitamin B3) supplementation in rats chronically exposed to methylmercury (MeHg). Animals were randomly assigned to one of 4 groups (n = 6): Group I, control, received distilled water by gavage; Group II, received MeHg (100 µg/kg/d) by gavage; Group III, received NA (50 mg/kg/d) in drinking water; Group IV, received MeHg (100 µg/kg/d) by gavage + NA (50 mg/kg/d) in drinking water. Biochemical parameters levels of glucose, triglycerides, total cholesterol and fractions, and enzyme activities aspartate transaminase (AST) and alanine transaminase (ALT) were determined. Further, oxidative stress markers activity of glutathione peroxidase (GPx) and catalase (CAT) activity, as well as levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide, were examined, and the comet assay was performed, using blood/plasma. Hg levels were measured in blood, brain, and kidneys of animals. Our results demonstrated that NA reduced adverse effects produced by MeHg. The mechanism underlying these effects appears to be related to the intrinsic antioxidant potential of NA. Considering the beneficial effects attributed to NA following MeHg exposure and that fish are the main source of both NA and MeHg, future studies need to evaluate the potential counteractive effect of NA against the adverse consequences of MeHg exposure in fish-eating populations.

  15. Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats.

    Science.gov (United States)

    Silva de Paula, Eloisa; Carneiro, Maria Fernanda Hornos; Grotto, Denise; Hernandes, Lívia Cristina; Antunes, Lusânia Maria Greggi; Barbosa, Fernando

    2016-01-01

    This study investigates the potential beneficial effects of niacin (NA; vitamin B3) supplementation in rats chronically exposed to methylmercury (MeHg). Animals were randomly assigned to one of 4 groups (n = 6): Group I, control, received distilled water by gavage; Group II, received MeHg (100 µg/kg/d) by gavage; Group III, received NA (50 mg/kg/d) in drinking water; Group IV, received MeHg (100 µg/kg/d) by gavage + NA (50 mg/kg/d) in drinking water. Biochemical parameters levels of glucose, triglycerides, total cholesterol and fractions, and enzyme activities aspartate transaminase (AST) and alanine transaminase (ALT) were determined. Further, oxidative stress markers activity of glutathione peroxidase (GPx) and catalase (CAT) activity, as well as levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide, were examined, and the comet assay was performed, using blood/plasma. Hg levels were measured in blood, brain, and kidneys of animals. Our results demonstrated that NA reduced adverse effects produced by MeHg. The mechanism underlying these effects appears to be related to the intrinsic antioxidant potential of NA. Considering the beneficial effects attributed to NA following MeHg exposure and that fish are the main source of both NA and MeHg, future studies need to evaluate the potential counteractive effect of NA against the adverse consequences of MeHg exposure in fish-eating populations. PMID:26914397

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

    Science.gov (United States)

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

    1996-01-01

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

  17. Estudos sobre a dosagem microbiologica das vitaminas do complexo B - II. Niacina Microbiological assay for niacine

    Directory of Open Access Journals (Sweden)

    Gilberto G. Villela

    1945-02-01

    Full Text Available The microbiological assay method of Snell and Wright for niacine was studied and some modifications of the basal medium were proposed. A maximal growth of the "Lactobacillus arabinosus" was obtained by the addition to the basal medium of 25 mg % asparagine and increasing the percentages of glucose and sodium acetate. Liver and yeast extracts were assayed satisfactory and the niacine added was recovered quantitatively.

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

    OpenAIRE

    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. Materials and methods: A survey on past week's dietary intake (food frequency questionnaire)was completed by N = 509 Dutch university students (20.8 years old). The SLEEP-50 questionnaire subscale on in...

  19. Combination treatment with atorvastatin plus niacin provides effective control of complex dyslipidemias: a literature review.

    Science.gov (United States)

    McKenney, James M

    2012-01-01

    Patients with dyslipidemia receive a cardiovascular benefit from lowering low-density lipoprotein cholesterol (LDL-C). Atorvastatin is currently one of the most effective approved medications for lowering LDL-C, and has been shown to significantly reduce cardiovascular risk in many patient groups. However, even with substantial lowering of LDL-C with atorvastatin, patients still have a residual risk for coronary heart disease. Elevated triglyceride levels and low high-density lipoprotein cholesterol (HDL-C) levels may contribute to this risk. Approved medications targeting these secondary lipid parameters include fibrates, omega-3 fatty acids, and niacin. Among these medications, niacin provides the optimal increase in HDL-C levels and has efficacy similar to the other medications in lowering triglyceride levels. However, there are challenges to adherence with niacin treatment. The most common challenge during niacin treatment is flushing, although it typically decreases with ongoing use and can be ameliorated by pretreatment with aspirin and counseling by the prescriber. A combination of atorvastatin and niacin may provide more complete normalization of the lipid profile and increased cardiovascular benefits. A literature review of the PubMed and Embase databases was conducted for clinical studies that reported on the lipid-modifying efficacy of the atorvastatin plus niacin combination. Identified studies involved patients at risk for coronary heart disease and patients with established coronary heart disease. Overall, the studies were small but indicated that atorvastatin in combination with niacin was efficacious in normalizing lipid parameters. Larger lipid studies as well as studies evaluating cardiovascular outcomes during atorvastatin plus niacin treatment are warranted.

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

    OpenAIRE

    Sarman Singh; Manoj Kumar; Pragati Singh

    2015-01-01

    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 ...

  1. The therapeutic role of niacin in dyslipidemia management.

    Science.gov (United States)

    Boden, William E; Sidhu, Mandeep S; Toth, Peter P

    2014-03-01

    There is abundant epidemiologic evidence to support the independent, inverse relationship between low levels of high-density lipoprotein cholesterol (HDL-C) and incident cardiovascular (CV) risk, the clinical importance of which is underscored by the high prevalence of low HDL-C in populations with coronary heart disease (CHD), with or without elevated levels of low-density lipoprotein cholesterol (LDL-C). The National Cholesterol Education Program recommended that optimal treatment for high-risk patients includes both lowering LDL-C and non-HDL-C to risk stratified levels and raising HDL-C when it is produces additive reductions in CHD morbidity and mortality and promotes regression of coronary atherosclerosis. Recently, 2 clinical outcome trials (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes [AIM-HIGH] and Second Heart Protection Study [HPS-2 THRIVE]) failed to show a reduction in CV events in patients treated to optimally low levels of LDL-C. Despite favorable effects on HDL-C and triglycerides, these studies did not demonstrate incremental clinical benefit with niacin when added to simvastatin, although notable limitations were identified in each of these trials. Thus, there is insufficient evidence from clinical trials to recommend HDL-targeted therapy for additional event reduction at the present time. However, niacin should continue to be used as an adjuvant therapy for reducing atherogenic lipoprotein burden in patients who have not reached their risk stratified LDL-C and non-HDL-C targets. PMID:24363242

  2. Effects of niacin on milk production and blood parameters in early lactation of dairy cows.

    Science.gov (United States)

    Ghorbani, Behnam; Vahdani, Narges; Zerehdaran, Saeed

    2008-06-15

    To investigate the effects of niacin supplementation in the diet of high producing cows at early lactation, 21 holstein dairy cows were used in this experiment. Animal were assigned in to three groups based on their milk yield and calving date soon after parturition. They were received a basal diet and 0 (group 1), 6 (group 2), 12 (group 3) g of supplementation niacin per day over a 10 weeks experimental period. Milk volume was recorded and milk samples were collected for each cow at two weeks interval for analysis of fat, protein, lactose and SNF (Solid-None Fat). Blood samples were also taken for the measurement of glucose, triglyceride, Beta-hydroxy butyrate and total protein at two weeks intervals. No significant difference were observed between milk yield, milk fat, protein, lactose and SNF content in cows received niacin compared to the control group (p > 0.05). Plasma glucose in groups 2 and 3 compared to the control were higher and this difference were statistically significant (p niacin supplementation. BHBA were lower in cows received niacin and this difference were significant (p Niacin has showed an increase in the level of plasma glucose and a notable decrease in the amount of blood triglyceride, beta-hydroxy butyrate and total protein, which may be due to the effect of this vitamin on the energy metabolism in cows.

  3. Hyperferritinaemia in the absence of iron overload

    OpenAIRE

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

    1997-01-01

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

  4. 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.

  5. Measuring flushing symptoms with extended-release niacin using the flushing symptom questionnaire©: results from a randomised placebo-controlled clinical trial

    OpenAIRE

    Paolini, J F; Mitchel, Y.B.; Reyes, R; Thompson-Bell, S; Yu, Q.; Lai, E; Watson, D J; Norquist, J M; McCrary Sisk, C; Bays, H E

    2008-01-01

    Introduction Niacin is underutilised because of flushing. Lack of a quantitative tool to assess niacin-induced flushing has precluded the objective evaluation of flushing associated with extended-release (ER) niacin formulations. We developed the Flushing Symptom Questionnaire© (FSQ), a quantitative tool to assess patient-reported flushing, and assessed its ability to characterise ER niacin-induced flushing. Methods This study focused on the responses to one question in the FSQ, the Global Fl...

  6. Niacin in pharmacological doses alters microRNA expression in skeletal muscle of obese Zucker rats.

    Directory of Open Access Journals (Sweden)

    Aline Couturier

    Full Text Available Administration of pharmacological niacin doses was recently reported to have pronounced effects on skeletal muscle gene expression and phenotype in obese Zucker rats, with the molecular mechanisms underlying the alteration of gene expression being completely unknown. Since miRNAs have been shown to play a critical role for gene expression through inducing miRNA-mRNA interactions which results in the degradation of specific mRNAs or the repression of protein translation, we herein aimed to investigate the influence of niacin at pharmacological doses on the miRNA expression profile in skeletal muscle of obese Zucker rats fed either a control diet with 30 mg supplemented niacin/kg diet or a high-niacin diet with 780 mg supplemented niacin/kg diet for 4 wk. miRNA microarray analysis revealed that 42 out of a total of 259 miRNAs were differentially expressed (adjusted P-value <0.05, 20 being down-regulated and 22 being up-regulated, between the niacin group and the control group. Using a biostatistics approach, we could demonstrate that the most strongly up-regulated (log2 ratio ≥0.5 and down-regulated (log2 ratio ≤-0.5 miRNAs target approximately 1,800 mRNAs. Gene-term enrichment analysis showed that many of the predicted target mRNAs from the most strongly regulated miRNAs were involved in molecular processes dealing with gene transcription such as DNA binding, transcription regulator activity, transcription factor binding and in important regulatory pathways such as Wnt signaling and MAPK signaling. In conclusion, the present study shows for the first time that pharmacological niacin doses alter the expression of miRNAs in skeletal muscle of obese Zucker rats and that the niacin-regulated miRNAs target a large set of genes and pathways which are involved in gene regulatory activity indicating that at least some of the recently reported effects of niacin on skeletal muscle gene expression and phenotype in obese Zucker rats are mediated through

  7. Combined use of extended-release niacin and atorvastatin: safety and effects on lipid modification

    Institute of Scientific and Technical Information of China (English)

    SANG Zhen-chi; WANG Fei; ZHOU Qing; LI Yue-hua; LI Yi-gang; WANG Hong-ping; CHEN Shu-yan

    2009-01-01

    Background Cholesterol-lowering therapy with statins has been reported to reduce the morbidity and mortality of cardiovascular diseases. This study aimed to investigate the effects of combined application of extended-release niacin and atorvastatin on lipid profile modification and the risks of adverse events in patients with coronary artery disease. Methods Consecutive 108 patients with coronary artery disease and serum total cholesterol (TC) ≥ 3.5 mmol/L were randomized into two groups: group A using atorvastatin and group B using extended-release niacin (niacin ER) and atorvastatin. Plasma lipid profile, glucose, and adverse events were assessed at the hospitalization, and 6 and 12 months after treatment. In addition, clinical cardiovascular events were evaluated after 12 months of treatment. Results The levels of TC, low density lipoprotein cholesterol (LDL-C) were significantly decreased (P0.05). Conclusions Combined use of extended-release niacin with atorvastatin was superior to atorvastatin monotherapyalone in lipid profile regulation. Combination therapy with niacin ER and atorvastatin was well tolerated and safe in patients with coronary artery disease.

  8. Combined effects of niacin and chromium treatment on heart of hyperlipidemic rats.

    Science.gov (United States)

    Döger, M Mutluhan; Sokmen, Bahar B; Yanardag, Refiye

    2011-10-01

    The present study was undertaken to investigate the effects of the combination of niacin and chromium(III)-chloride on heart glutathione (GSH), lipid peroxidation (LPO) levels, serum paraoxonase (PON), gamma-glutamyl transferase (GGT) activities and protein carbonyl contents (PCC) of hyperlipidemic rats. In this study, female Swiss albino rats were used. They were divided into four groups. The animals of the first group (group I) were fed with pellet chow. The rats (group II) were fed with a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 20% sunflower oil added to the pellet chow, and given 3% alcoholic water for 60 days. The rats (group III) were fed with the same lipogenic diet and treated by gavage technique with CrCl(3) 6H(2)O to a dose of 250 µg/kg and 100 mg/kg niacin for 45 days, 15 days after experimental animals were done hyperlipidemic. Group IV was fed with pellet chow and treated with 250 µg/kg CrCl(3) 6H(2)O and 100 mg/kg niacin for 45 days. On the 60th day, the heart tissue and blood samples were taken from animals. As a result, heart LPO, serum GGT activity and serum PCC were increased; serum PON activity and heart GSH levels were decreased in hyperlipidemic rats. Treatment with combined niacin and chromium reversed these effects. In conclusion, the combined treatment with niacin and chromium might induce a protective effect on heart tissue.

  9. Establishment of true niacin deficiency in quinolinic acid phosphoribosyltransferase knockout mice.

    Science.gov (United States)

    Terakata, Miki; Fukuwatari, Tsutomu; Sano, Mitsue; Nakao, Natsuki; Sasaki, Ryuzo; Fukuoka, Shin-Ichi; Shibata, Katsumi

    2012-12-01

    Pyridine nucleotide coenzymes are involved in >500 enzyme reactions and are biosynthesized from the amino acid L-tryptophan (L-Trp) as well as the vitamin niacin. Hence, "true" niacin-deficient animals cannot be "created" using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid (QA) phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected in qprt(-/-)mice. The qprt(+/+), qprt(+/-), or qprt(-/-) mice (8 wk old) were fed a complete diet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. When qprt(-/-)mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt(+/+) and qprt(+/-) mice. On the contrary, in the qprt(-/-) mice fed the NiA-free diet, food intake and body weight were reduced to 60% (P niacin, such as blood and liver NAD concentrations, were also lower in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice. Urinary excretion of QA was greater in the qprt(-/-) mice than in the qprt(+/+) and qprt(+/-) mice (P niacin-deficient mice.

  10. Effects of niacin combination therapy with statin or bile acid resin on lipoproteins and cardiovascular disease.

    Science.gov (United States)

    Zambon, Alberto; Zhao, Xue-Qiao; Brown, B Greg; Brunzell, John D

    2014-05-01

    Two large studies in populations selected for cardiovascular disease (CVD) demonstrated that raising high-density lipoprotein (HDL) cholesterol with niacin added to statin therapy did not decrease CVD. We examine the association of lipoprotein subfractions with niacin and changes in coronary stenosis and CVD event risk. One hundred and seven patients from 2 previous studies using niacin in combination with either statin or bile acid-binding resin were selected to evaluate changes in lipoproteins separated by density-gradient ultracentrifugation to progression of coronary artery disease as assessed by quantitative coronary angiography. Improvement in coronary stenosis was significantly associated with the decrease of cholesterol in the dense low-density lipoprotein (LDL) particles and across most of the intermediate density lipoprotein (IDL) and very low density lipoprotein particle density range, but, not with any of the HDL fraction or of the more buoyant LDL fractions. Event-free survival was significantly associated with the decrease of cholesterol in the dense LDL and IDL; there was no association with changes in cholesterol in the HDL and buoyant LDL fractions. Niacin combination therapy raises HDL cholesterol and decreases dense LDL and IDL cholesterol levels. Changes in LDL and IDL are related to improvement in CVD. Lipoprotein subfraction analysis should be performed in larger studies utilizing niacin in combination with statins.

  11. Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B

    NARCIS (Netherlands)

    Heemskerk, M.M.; Berg, S.A. van den; Pronk, A.C.M.; Klinken, J.B. van; Boon, M.R.; Havekes, L.M.; Rensen, P.C.N.; Willems van Dijk, K.; Harmelen, V. van

    2014-01-01

    The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA level

  12. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on Dietary Reference Values for niacin

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for niacin. Niacin is a generic term for nicotinic acid and nicotinamide. Niacin can be synthesised in the human body from the indispensable amino......) for adults of 1.3 mg NE/MJ (5.5 mg NE/1 000 kcal) adopted by the Scientific Committee for Food (1993), based on data on urinary excretion of niacin metabolites as an endpoint. The Population Reference Intake (PRI) of 1.6 mg NE/MJ (6.6 mg NE/1 000 kcal) is derived from the AR assuming a coefficient...... of variation of 10 %. For infants aged 7-11 months, children and adolescents, as well as for pregnant and lactating women, the Panel considers that there is no evidence that the relationship between niacin requirement and energy requirement differs from that of adults; therefore, the AR and PRI for adults...

  13. 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 

  14. Response of lactating cows to supplemental rumen protected methionine and Niacin

    Institute of Scientific and Technical Information of China (English)

    Yanxia GAO; Jianguo LI; Wenbin JIA; Qiufeng LI; Yufeng CAO

    2008-01-01

    Eight Chinese Holstein cows were used in a 4×4 Latin square design to determine the effects of rumen protected methionine (RPMet) and Niacin on milk yield and milk composition of lactating cows with 14 d adaptation and 6-d sampling periods. The cows were fed the control diet or the control diet plus RPMet tion in the diet increased 4% fat corrected milk (FCM) yield (P 0.05) and lactose percentage (P>0.05). Dietary niacin supplementation increased milk yield (P 0.05) and SNF (P>0.05). RPMet supplementation in the diet of lactating cows significantly decreased serum urea nitrogen (P0.05). Niacin supplementation influ-enced the contents of glucose and NEFA in serum, but had no effects on the urea nitrogen, total cholesterol and triglyceride (P>0.05).

  15. 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......) cholesterol level, but its clinical efficacy and safety are uncertain. METHODS: After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants' ability to take extended-release niacin without clinically significant adverse...... revascularization). RESULTS: During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower and an HDL cholesterol level...

  16. Synthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid.

    Science.gov (United States)

    Vu, Chi B; Bemis, Jean E; Benson, Ericka; Bista, Pradeep; Carney, David; Fahrner, Richard; Lee, Diana; Liu, Feng; Lonkar, Pallavi; Milne, Jill C; Nichols, Andrew J; Picarella, Dominic; Shoelson, Adam; Smith, Jesse; Ting, Amal; Wensley, Allison; Yeager, Maisy; Zimmer, Michael; Jirousek, Michael R

    2016-02-11

    This report describes the synthesis and preliminary biological characterization of novel fatty acid niacin conjugates and fatty acid salicylate conjugates. These molecular entities were created by covalently linking two bioactive molecules, either niacin or salicylic acid, to an omega-3 fatty acid. This methodology allows the simultaneous intracellular delivery of two bioactives in order to elicit a pharmacological response that could not be replicated by administering the bioactives individually or in combination. The fatty acid niacin conjugate 5 has been shown to be an inhibitor of the sterol regulatory element binding protein (SREBP), a key regulator of cholesterol metabolism proteins such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1. On the other hand, the fatty acid salicylate conjugate 11 has been shown to have a unique anti-inflammatory profile based on its ability to modulate the NF-κB pathway through the intracellular release of the two bioactives.

  17. Effects of niacin on nitric oxide synthase expression in rat lungs exposed to silica

    Institute of Scientific and Technical Information of China (English)

    WANG Shixin; DU Haike; ZHANG Xizhen; CAI Shaoxi; FAN Huaquan; WANG Chang'en

    2004-01-01

    The aim of this study was to evaluate the effects of niacin in diet on the expression of nitric oxide synthase (NOS) in rat lungs of the animal model of silicosis established by direct tracheal instillation of silica particles into rat lungs surgically. The niacin concentration in serum was analyzed by high performance liquid chromatography (HPLC). The expression of inducible nitric oxide synthase (iNOS) protein in paraffin-embedded lung sections was determined by streptavidin/peroxidase (SP) staining. Quantitative analysis by Image-Pro Plus was also performed on the expression of iNOS. The results showed that niacin concentration in serum of the niacin-treated rats was significantly higher than that in the control and silica-treated rats. After 7 days of silica instillation, iNOS integrated optical density (IOD) in rat lungs and total NOS and iNOS activities in bronchoalveolar lavage fluid (BALF) in silica-treated rats rose by 273420.75, 2.61 units/mL and 1.89 units/mL respectively, when compared with those in the control rats. Niacin treatment significantly reduced silica-induced iNOS IOD in rat lung tissues and total NOS and iNOS activities in BALF supernatant by 248292.35, 1.50 units/mL and 0.91 units/mL, respectively, as compared with those in silica-treated rats. Therefore, niacin can effectively attenuate the pathological expression of NOS in rat lung tissues induced by silica particles.

  18. Lipid profiles of rats fed with diets supplemented with vitamins niacin and pyridoxine

    Directory of Open Access Journals (Sweden)

    Magna da Glória Lameiro

    2012-04-01

    Full Text Available Hypercholesterolemia is a major risk factor for cardiovascular disease. Supplements containing the vitamins niacin (B3 and pyridoxine (B6 can promote the reduction of total cholesterol and an increase in HDL cholesterol. In this study, the effects of diets supplemented with niacin (B3 and pyridoxine (B6 on the hepatic and serum lipid profiles of Wistar rats were assessed. The diets were prepared with combinations of three concentrations of niacin (3, 4 and 5 g/kg and pyridoxine (6, 12 and 18 mg/kg and one with neither vitamin. The animals were divided into eleven experimental groups of six animals per group, and nine groups were fed on a standard diet with 7.5% fat and vitamin supplementation. Another group was fed with 7.5% fat without vitamin supplements. A control group received the standard diet (AIN-93M without modifications (4% fat. The weight gain, food intake, serum and hepatic total cholesterol, serum cholesterol fractions (HDL, LDL, and VLDL, serum and hepatic triacylglycerols and hepatic and fecal lipid contents were measured after 30 days. The diet with the highest concentration of niacin and lowest concentration of pyridoxine had the lowest level of total hepatic cholesterol. Hepatic triacylglycerols were reduced by the highest concentration of niacin (5 g/kg, and this reduction was enhanced by increasing the pyridoxine concentration. The diets supplemented with niacin and pyridoxine reduced the levels of serum total cholesterol, LDL, VLDL, triacylglycerols and hepatic lipids. These effects on the lipid profile varied with the concentrations of the two vitamins and the interactions between them.

  19. 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.

  20. The membrane proteins of the overloaded and senescent heart.

    Science.gov (United States)

    Chevalier, B; Charlemagne, D; Callens-el Amrani, F; Carre, F; Moalic, J M; Delcayre, C; Mansier, P; Swynghedauw, B

    1992-01-01

    Cardiac hypertrophy which occurs during chronic mechanical overload is one of the numerous examples of biological adaptation to environmental requirements. As such, it is obtained at random by trial and error, and adaptation represents the sum of various modifications in gene expression, including the shift in isoform of myosin or in iso Na+, K+ ATPase, the decrease in beta-adrenergic and muscarinic receptors, ryanodine channels or SR Ca2+ ATPase densities and the unchanged density in Ca2+ current. Some of these changes are beneficial at the cellular level, but are finally detrimental for the organism as a whole, as is the slowing of Vmax. It was suggested that the calcium homeostasis of the hypertrophied cardiocyte was fragile and that this modified cell was less able to buffer the changes in the intracellular calcium, thus providing a biological basis for the arrhythmogenicity of the hypertrophied heart. These various modifications may provide a new key for future pharmaceutical research. PMID:1323260

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

    Directory of Open Access Journals (Sweden)

    Paul C Adams

    2009-01-01

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

  2. 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.

  3. The biochemical pathways of central nervous system neural degeneration in niacin deifciency

    Institute of Scientific and Technical Information of China (English)

    Linshan Fu; Venkatesh Doreswamy; Ravi Prakash

    2014-01-01

    Neural degeneration is a very complicated process. In spite of all the advancements in the mo-lecular chemistry, there are many unknown aspects of the phenomena of neurodegeneration which need to be put together. It is a common sequela of the conditions of niacin deifciency. Neural degeneration in Pellagra manifests as chromatolysis mainly in pyramidal followed by other neurons and glial cells. However, there is a gross lack of understanding of biochemi-cal mechanisms of neurodegeneration in niacin deifciency states. Because of the necessity of niacin or its amide derivative NAD in a number of biochemical pathways, it is understandable that several of these pathways may be involved in the common outcome of neural degener-ation. Here, we highlight ifve pathways that could be involved in the neuraldegeneration for which evidence has accumulated through several studies. These pathways are:1) the trypto-phan-kyneurenic acid pathway, 2) the mitochondrial ATP generation related pathways, 3) the poly (ADP-ibose) polymerase (PARP) pathway, 4) the BDNF-TRKB Axis abnormalities, 5) the genetic inlfuences of niacin deifciency.

  4. 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.

  5. 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.

  6. Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

    Science.gov (United States)

    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.

  7. Critical appraisal of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia.

    Science.gov (United States)

    Hussein, Ayman A; Nicholls, Stephen J

    2010-04-15

    Niacin is a B-complex vitamin which has been used for decades for the management of mixed dyslipidemias and primary hypercholesterolemia. It decreases the risk of cardiovascular events either when used as a monotherapy or in combination with other lipid lowering medications. However, a major limitation to its use is niacin-induced flushing occurring even with the extended-release formulations. Laropiprant, a selective prostaglandin-2 receptor inhibitor, specifically targets the cascade of events causing the flushing. It has been recently used in combination with extended-release niacin. This article will review the early experience with this combination with focus on efficacy, safety, tolerability and current place in therapy. Early data are promising and suggest that more patients in clinical practice will benefit from niacin combined with laropiprant. Ongoing clinical trials will provide a better insight on the long-term safety of the drug and its efficacy for reducing cardiovascular events.

  8. CQ Switch Analysis under Traffic Overload

    Directory of Open Access Journals (Sweden)

    I. Maljević

    2011-06-01

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

  9. Minimally invasive aortic banding in mice: effects of altered cardiomyocyte insulin signaling during pressure overload.

    Science.gov (United States)

    Hu, Ping; Zhang, Dongfang; Swenson, LeAnne; Chakrabarti, Gopa; Abel, E Dale; Litwin, Sheldon E

    2003-09-01

    We developed a minimally invasive method for producing left ventricular (LV) pressure overload in mice. With the use of this technique, we quickly and reproducibly banded the transverse aorta with low surgical morbidity and mortality. Minimally invasive transverse aortic banding (MTAB) acutely and chronically increased LV systolic pressure, increased heart weight-to-body weight ratio, and induced myocardial fibrosis. We used this technique to determine whether reduced insulin signaling in the heart altered the cardiac response to pressure overload. Mice with cardiac myocyte-restricted knockout of the insulin receptor (CIRKO) have smaller hearts than wild-type (WT) controls. Four weeks after MTAB, WT and CIRKO mice had comparably increased LV systolic pressure, increased cardiac mass, and induction of mRNA for beta-myosin heavy chain and atrial natriuretic factor. However, CIRKO hearts were more dilated, had depressed LV systolic function by echocardiography, and had greater interstitial fibrosis than WT mice. Expression of connective tissue growth factor was increased in banded CIRKO hearts compared with WT hearts. Thus lack of insulin signaling in the heart accelerates the transition to a more decompensated state during cardiac pressure overload. The use of the MTAB approach should facilitate the study of the pathophysiology and treatment of pressure-overload hypertrophy. PMID:12738623

  10. Java Modular Extension for Operator Overloading

    OpenAIRE

    Melentyev, Artem

    2014-01-01

    The paper introduces a modular extension (plugin) for Java language compilers and Integrated Development Environments (IDE) which adds operator overloading feature to Java language while preserving backward compatibility. The extension use the idea of library-based language extensibility similar to SugarJ. But unlike most language extensions, it works directly inside the compiler and does not have any external preprocessors. This gives much faster compilation, better language compatibility an...

  11. Formulation of Controlled-Release Capsules of Biopharmaceutical Classification System I Drugs Using Niacin as a Model

    OpenAIRE

    Chuong, Monica C.; Palugan, Luca; Su, Tiffany M.; Busano, Claudelle; Lee, Ronald; Di Pretoro, Giustino; Shah, Anee

    2010-01-01

    Vitamin B3 is made up of niacin (nicotinic acid) and its amide, niacinamide. Both have equivalent vitamin activity, but only niacin (not niacinamide) is effective in lowering elevated low-density lipoprotein cholesterol and triglyceride levels in the blood. Administration of an extended-release (ER) oral tablet would frequently encounter food. If hydrogel is used to formulate the matrix of a biopharmaceutical classification system I drug (high solubility and high permeability), the dosage for...

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

    Directory of Open Access Journals (Sweden)

    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

  13. The Effects of Tetrahydro-iso-alpha Acids and Niacin on Monocyte-Edothelial Cell Interactions and Flow-mediated Vasodilation.

    Science.gov (United States)

    Lamb, Joseph J; Konda, Veera R; Desai, Anuradha; Bland, Jeffrey S; Tripp, Matthew L

    2012-09-01

    Niacin favorably modifies cardiovascular risk factors but is associated with flushing and shows limited benefit in improving endothelial function. We investigated whether combining anti-inflammatory tetrahydro-iso-alpha acids (THIAA) from hops with niacin would improve endothelial function. We hypothesized that the THIAA+niacin combination would demonstrate benefits not seen with niacin alone. In an in vitro model, a THIAA+niacin mixture inhibited several TNF-α-induced cytokines in human aortic endothelial cells and in human monocytic cells and was significantly more efficacious than niacin alone. Subsequently, the effect of 125 mg THIAA and 500 mg niacin on endothelial-regulated flow-mediated vasodilation (FMD) was explored in a pilot study of 11 dyslipidemic volunteers. The 12-week treatment (2 tablets/day) resulted in a clinically relevant FMD increase compared to a trend toward an FMD decrease with placebo; the between-arm difference was statistically significant. THIAA+niacin treatment also improved total cholesterol, low-density lipoprotein cholesterol, and uric acid. No significant improvement in these parameters was observed with placebo. High-sensitivity C-reactive protein was significantly increased only in the placebo arm. Nutritional support with a THIAA+niacin combination may provide benefits for endothelial function in those with dyslipidemia. PMID:24278836

  14. Targeting mulitple dyslipidemias with fixed combinations – focus on extended release niacin and simvastatin

    Directory of Open Access Journals (Sweden)

    Anbu Pandian

    2008-10-01

    Full Text Available Anbu Pandian1, Anjali Arora2, Laurence S Sperling1, Bobby V Khan11Emory University School of Medicine and Grady Memorial Hospital Vascular Research Atlanta, Georgia USA; 2Sir Ganga Ram Hospital, New Delhi, IndiaAbstract: Dyslipidemia is a major risk factor in the initiation and progression of cardiovascular diseases such as atherosclerosis. Several pharmacological agents have been developed over the past 50 years which target various lipid components such as low density lipoprotein (LDL cholesterol, triglyceride, and high density lipoprotein (HDL cholesterol. Similar to other risk factors such as hypertension and diabetes mellitus, the management of dyslipidemia can be complicated and may require combination therapy for effective treatment. This review discusses the biochemical mechanisms of action and clinical uses for simvastatin (the most widely available and commercially prescribed statin and niacin, and the combination of these agents in the management and treatment of dyslipidemia.Keywords: dyslipidemia, HDL cholesterol, triglyceride, statin, niacin

  15. 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 < median intake of whole grains (P = 0·03) and red and processed meat (P = 0·01): 0·69 (95 % CI 0·50, 0·96) and 1·56 (95 % CI 1·13, 2·16), respectively. Our data suggest that a high intake of niacin from 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.

  16. Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?

    Science.gov (United States)

    Mani, Preethi; Rohatgi, Anand

    2016-01-01

    High-density lipoprotein cholesterol (HDL-C) has been shown in epidemiologic studies to be associated with cardiovascular (CV) risk and thus significant efforts have been focused on HDL-C modulation. Multiple pharmaceutical agents have been developed with the goal of increasing HDL-C. Niacin, the most widely used medication to raise HDL-C, increases HDL-C by up to 25 % and was shown in multiple surrogate end point studies to reduce CV risk. However, two large randomized controlled trials of niacin, AIM-HIGH and HPS2-THRIVE, have shown that despite its effects on HDL-C, niacin does not decrease the incidence of CV events and may have significant adverse effects. Studies of other classes of agents such as cholesteryl ester transfer protein (CETP) inhibitors have also shown that even dramatic increases in HDL-C do not necessarily translate to reduction in clinical events. While these findings have cast doubt upon the importance of HDL-C modulation on CV risk, it is becoming increasingly clear that HDL function-related measures may be better targets for CV risk reduction. Increasing ApoA-I, the primary apolipoprotein associated with HDL, correlates with reduced risk of events, and HDL particle concentration (HDL-P) inversely associates with incident CV events adjusted for HDL-C and LDL particle measures. Cholesterol efflux, the mechanism by which macrophages in vessel walls secrete cholesterol outside cells, correlates with both surrogate end points and clinical events. The effects of niacin on these alternate measures of HDL have been conflicting. Further studies should determine if modulation of these HDL function markers translates to clinical benefits. Although the HDL cholesterol hypothesis may be defunct, the HDL function hypothesis is now poised to be rigorously tested. PMID:26048725

  17. 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.

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

    Science.gov (United States)

    Singh, Sarman; Kumar, Manoj; Singh, Pragati

    2015-01-01

    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. PMID:25694828

  19. A Comparative Study of SIP Overload Control Algorithms

    OpenAIRE

    Hong, Yang; Huang, Changcheng; Yan, James

    2012-01-01

    Recent collapses of SIP servers in the carrier networks indicates two potential problems of SIP: (1) the current SIP design does not easily scale up to large network sizes, and (2) the built-in SIP overload control mechanism cannot handle overload conditions effectively. In order to help carriers prevent widespread SIP network failure effectively, this chapter presents a systematic investigation of current state-of-the-art overload control algorithms. To achieve this goal, this chapter first ...

  20. Critical appraisal of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Ayman A Hussein

    2010-04-01

    Full Text Available Ayman A Hussein, Stephen J NichollsCardiovascular Medicine Department, Cleveland Clinic Foundation, Cleveland, OH, USAAbstract: Niacin is a B-complex vitamin which has been used for decades for the management of mixed dyslipidemias and primary hypercholesterolemia. It decreases the risk of cardiovascular events either when used as a monotherapy or in combination with other lipid lowering medications. However, a major limitation to its use is niacin-induced flushing occurring even with the extended-release formulations. Laropiprant, a selective prostaglandin-2 receptor inhibitor, specifically targets the cascade of events causing the flushing. It has been recently used in combination with extended-release niacin. This article will review the early experience with this combination with focus on efficacy, safety, tolerability and current place in therapy. Early data are promising and suggest that more patients in clinical practice will benefit from niacin combined with laropiprant. Ongoing clinical trials will provide a better insight on the long-term safety of the drug and its efficacy for reducing cardiovascular events.Keywords: niacin, laropiprant, dyslipidemias, hypercholesterolemia

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

    Science.gov (United States)

    Miller, Wayne L

    2016-08-01

    Volume regulation, assessment, and management remain basic issues in patients with heart failure. The discussion presented here is directed at opening a reassessment of the pathophysiology of congestion in congestive heart failure and the methods by which we determine volume overload status. Peer-reviewed historical and contemporary literatures are reviewed. Volume overload and fluid congestion remain primary issues for patients with chronic heart failure. The pathophysiology is complex, and the simple concept of intravascular fluid accumulation is not adequate. The dynamics of interstitial and intravascular fluid compartment interactions and fluid redistribution from venous splanchnic beds to central pulmonary circulation need to be taken into account in strategies of volume management. Clinical bedside evaluations and right heart hemodynamic assessments can alert clinicians of changes in volume status, but only the quantitative measurement of total blood volume can help identify the heterogeneity in plasma volume and red blood cell mass that are features of volume overload in patients with chronic heart failure and help guide individualized, appropriate therapy-not all volume overload is the same. PMID:27436837

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

    Science.gov (United States)

    Miller, Wayne L

    2016-08-01

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

  3. Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice

    NARCIS (Netherlands)

    Hoorn, J.W.A. van der; Haan, W. de; Berbée, J.P.P.; Havekes, L.M.; Jukema, J.W.; Rensen, P.C.; Princen, H.M.G.

    2008-01-01

    Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-11-01

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

  6. 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%海马神经元细胞内钙超载对慢性间歇低氧小鼠认知功能的损伤及盐酸美金刚的保护作用

    Institute of Scientific and Technical Information of China (English)

    明红; 陈锐; 王婧; 琚静美; 孙丽; 张国兴

    2014-01-01

    Objective 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.Methods 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.Results Compared with the UC group,CIH mice displayed markedly more locomotor activity (P < 0.05) in Open filed test,longer mean escape latency (P < 0.05),less number of times of crossing the platform (P <0.01) and less percentage of time in target quadrant (P <0.01).Furthermore,exposure to CIH enhanced [Ca2+]i (vs.UC mice,155 ±12 vs.92 ±8,P<0.01),and up-regulated the expression of cleaved caspase-3 (P < 0.01),but down-regulated the level of phospho-ERK1/2 (P < 0.05) in the hippocampus.Pre-treatment with memantine significantly decreased hyperlocomotion (P < 0.05),attenuated memory deficit (P < 0.05),mitigated [Ca2 +] i (vs.CIH mice,90 ± 8 vs.155 ± 12,P < 0.01),decrease the expression of cleaved caspase-3 (P < 0.01),but increased the level of phosphoERK1/2(P < 0.05) comparing to the CIH group.Conclusion The neurobehavioral impairments induced by CIH are mediated,at least in part,by intracellular calcium concentration overload,neuron apoptosis

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

    CERN Document Server

    Shen, Charles; Nahum, Erich

    2008-01-01

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

  8. Spatio-temporal propagation of cascading overload failures

    CERN Document Server

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

    2015-01-01

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

  9. Engineering and the problem of moral overload.

    Science.gov (United States)

    Van den Hoven, Jeroen; Lokhorst, Gert-Jan; Van de Poel, Ibo

    2012-03-01

    When thinking about ethics, technology is often only mentioned as the source of our problems, not as a potential solution to our moral dilemmas. When thinking about technology, ethics is often only mentioned as a constraint on developments, not as a source and spring of innovation. In this paper, we argue that ethics can be the source of technological development rather than just a constraint and technological progress can create moral progress rather than just moral problems. We show this by an analysis of how technology can contribute to the solution of so-called moral overload or moral dilemmas. Such dilemmas typically create a moral residue that is the basis of a second-order principle that tells us to reshape the world so that we can meet all our moral obligations. We can do so, among other things, through guided technological innovation. PMID:21533834

  10. Self-* overload control for distributed web systems

    CERN Document Server

    Bartolini, Novella; Silvestri, Simone

    2008-01-01

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

  11. Bioimpedance can solve problems of fluid overload.

    Science.gov (United States)

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

    2015-03-01

    Bioimpedance (BI) techniques for measuring normal hydration status (NHS) can be generally classified as (1) by frequency as single frequency at 50 kHz, BI analysis, and multifrequency BI spectroscopy and (2) by method as whole body (wrist to ankle) measurement and calf BI spectroscopy. The aim of this article was to review current BI methods for clinical practice in patients with end-stage of kidney disease. BI vector analysis using whole-body single-frequency BI at 50 kHz may be useful for population studies to indicate a range of degree of fluid loading and of nutritional status. Whole body multifrequency BI spectroscopy is used to estimate extracellular (ECV), intracellular fluid volume, and total body water in dialysis patients. The whole-body BI model is used in the body composition monitor (BCM). The whole-body BI model is established with ECV, intracellular fluid volume, and body weight based on parameters from regression analysis in healthy subjects to calculate fluid overload in dialysis patients. Calf BI methods have been developed to measure NHS by 2 ways: (1) continuous measurement of the intradialytic resistance curve until flattening occurs; (2) calf normalized resistivity in the range of healthy subjects (18.5 × 10(-2) Ω m(3)/kg in male and 19.1 × 10(-2) Ω m(3)/kg in female). In general, for population studies, BI vector analysis or ECV/total body water may be useful; BCM is a commercially available device that can certainly guide volume reduction safely over time. For more exact measure of fluid overload, calf BI methods appear to be most accurate, but these are at present research tools. BI techniques are not only useful in assessing NHS but also in the study of nutrition and body composition. PMID:25556307

  12. Urinary Excretion of Fatty Acid-Binding Protein Reflects Stress Overload on the Proximal Tubules

    OpenAIRE

    Kamijo, Atsuko; Sugaya, Takeshi; Hikawa, Akihisa; Okada, Mitsuhiro; Okumura, Fumikazu; Yamanouchi, Masaya; Honda, Akiko; Okabe, Masaru; Fujino, Tomoya; Hirata, Yasunobu; Omata, Masao; Kaneko, Ritsuko; Fujii, Hiroshi; Fukamizu, Akiyoshi; Kimura, Kenjiro

    2004-01-01

    Urinary excretion of human liver-type fatty acid-binding protein (hL-FABP), which is expressed in human proximal tubules and engaged in free fatty acid (FFA) metabolism, was reported to reflect the clinical prognosis of chronic kidney disease. Here we have investigated the pathophysiological significance of hL-FABP in a model of protein overload nephropathy. Because L-FABP is not expressed in the wild-type mice, we generated hL-FABP chromosomal gene transgenic (Tg) mice. Tg mice were intraper...

  13. Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?

    OpenAIRE

    Mani, Preethi; Rohatgi, Anand

    2015-01-01

    High-density lipoprotein cholesterol (HDL-C) has been shown in epidemiologic studies to be associated with cardiovascular (CV) risk and thus significant efforts have been focused on HDL-C modulation. Multiple pharmaceutical agents have been developed with the goal of increasing HDL-C. Niacin, the most widely used medication to raise HDL-C, increases HDL-C by up to 25 % and was shown in multiple surrogate end point studies to reduce CV risk. However, two large randomized controlled trials of n...

  14. DETERMINATION OF FERRITIN AND HEMOSIDERIN IRON IN PATIENTS WITH NORMAL IRON STORES AND IRON OVERLOAD BY SERUM FERRITIN KINETICS

    OpenAIRE

    Saito, Hiroshi; Tomita, Akihiro; Ohashi, Haruhiko; MAEDA, HIDEAKI; Hayashi, Hisao; Naoe, Tomoki

    2012-01-01

    ABSTRACT We attempted to clarify the storage iron metabolism from the change in the serum ferritin level. We assumed that the nonlinear decrease in serum ferritin was caused by serum ferritin increase in iron mobilization. Under this assumption, we determined both ferritin and hemosiderin iron levels by computer-assisted simulation of the row of decreasing assay-dots of serum ferritin in 11 patients with normal iron stores free of both iron deficiency and iron overload; chronic hepatitis C (C...

  15. Simultaneous determination of niacin, niacinamide and nicotinuric acid in human plasma.

    Science.gov (United States)

    Pfuhl, P; Kärcher, U; Häring, N; Baumeister, A; Tawab, Mona Abdel; Schubert-Zsilavecz, M

    2005-01-01

    A sensitive, specific, accurate, and reproducible HPLC/MS-method for the simultaneous quantitative determination of niacin (NA) and its main metabolites niacinamide (NAM) and nicotinuric acid (NUR) in human plasma using chinolin-3-carboxylic acid as an internal standard was developed and validated according to international guidelines for method validation. All analytes and the internal standard were separated from acidified plasma by solid phase extraction. Afterwards the extracted samples were analyzed by HPLC/MS in the positive electrospray ionization mode (ESI) and selected ion monitoring (SIM). The total run time was 7 min between injections. The assay had a lower limit of quantification of 50.0 ng/mL for each analyte using 1 mL of plasma. The calibration curves were linear in the measured range between 50.0 and 750 ng/mL plasma. The overall precision and accuracy for all concentrations of quality controls and standards was better than 15%. No indications were found for possible instabilities of niacin, niacinamide and nicotinuric acid in plasma at -20 degrees C, in the extraction solvent or after repeated thawing/freezing cycles. In stabilities were observed in whole blood and in plasma at room temperature. The recovery of the extraction method ranged from 86 to 89% for the three analytes.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. [Navigation aid through the information overload].

    Science.gov (United States)

    Günther, Judith; Schindler, Birgit; Suter, Katja

    2014-10-01

    We live in the modern information society. "To be informed" has a crucial impact on the personal, professional, economic and social development. The knowledge of things and their relationships is essential for acute decisions as well as for long-term planning. And at no time it was easier to get the information required within shorter time periods--no matter to whatsoever. The offer of information of the World Wide Web is inexhaustible. This also applies to information about all possible therapeutic and pharmaceutical issues. But is the information found reliable, too? And are easily accessible sources credible? Can we deal with the information overload at these days or do we actually risk paddling only on the surface of the "information-sea", without ever perceiving the actual information depth and width, less to use it? How can we protect being taken in by marketing strategies? The present article describes a structured proceed when seeking literature to find useful medical and pharmaceutical information in a time saving manner. PMID:25632609

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

    Science.gov (United States)

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

    2013-02-01

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

  19. Effect of Extended-Release Niacin/Laropiprant Combination on Plasma Adiponectin and Insulin Resistance in Chinese Patients with Dyslipidaemia

    Directory of Open Access Journals (Sweden)

    Miao Hu

    2015-01-01

    Full Text Available Objectives. This study examined whether the increase of adiponectin associated with extended-release (ER niacin/laropiprant combination attenuates the adverse effect of niacin on glucose and insulin resistance in Hong Kong Chinese patients with dyslipidaemia. Methods. Patients (N=121 were treated with ER niacin/laropiprant 1 g/20 mg for 4 weeks and then the dose was doubled for an additional 8 weeks. Measurements of fasting lipids, glucose, insulin, and adiponectin were performed at baseline and during the study. Results. There were significant (P<0.001 increases in glucose (9.4 ± 13.1%, insulin (70.2 ± 91.0%, HOMA-IR (87.8 ± 103.9%, and adiponectin (169.3 ± 111.6%. The increase in adiponectin was significantly associated with increase in glucose (r=0.221, P<0.05, insulin (r=0.184, P<0.05, and HOMA-IR (r=0.237, P<0.01 and the association remained significant after adjustment for changes in body weight or body fat mass. Conclusion. Treatment with ER niacin/laropiprant led to a significant increase in adiponectin levels but worsening of glucose levels and insulin resistance, and the increase in adiponectin and insulin resistance were correlated suggesting the increase in adiponectin did not ameliorate the deterioration in insulin resistance. Clinical trial is registered with number on WHO-ICTRP: ChiCTR-ONC-10001038.

  20. Effect of Extended-Release Niacin/Laropiprant Combination on Plasma Adiponectin and Insulin Resistance in Chinese Patients with Dyslipidaemia

    Science.gov (United States)

    Yang, Ya-Ling; Masuda, Daisaku; Yamashita, Shizuya; Tomlinson, Brian

    2015-01-01

    Objectives. This study examined whether the increase of adiponectin associated with extended-release (ER) niacin/laropiprant combination attenuates the adverse effect of niacin on glucose and insulin resistance in Hong Kong Chinese patients with dyslipidaemia. Methods. Patients (N = 121) were treated with ER niacin/laropiprant 1 g/20 mg for 4 weeks and then the dose was doubled for an additional 8 weeks. Measurements of fasting lipids, glucose, insulin, and adiponectin were performed at baseline and during the study. Results. There were significant (P < 0.001) increases in glucose (9.4 ± 13.1%), insulin (70.2 ± 91.0%), HOMA-IR (87.8 ± 103.9%), and adiponectin (169.3 ± 111.6%). The increase in adiponectin was significantly associated with increase in glucose (r = 0.221, P < 0.05), insulin (r = 0.184, P < 0.05), and HOMA-IR (r = 0.237, P < 0.01) and the association remained significant after adjustment for changes in body weight or body fat mass. Conclusion. Treatment with ER niacin/laropiprant led to a significant increase in adiponectin levels but worsening of glucose levels and insulin resistance, and the increase in adiponectin and insulin resistance were correlated suggesting the increase in adiponectin did not ameliorate the deterioration in insulin resistance. Clinical trial is registered with number on WHO-ICTRP: ChiCTR-ONC-10001038. PMID:26063948

  1. Risk factors and outcomes in transfusion-associated circulatory overload

    OpenAIRE

    Murphy, EL; Kwaan, N; Looney, MR; Gajic, O; Hubmayr, RD; Gropper, MA; Koenigsberg, M; Wilson, G.; Matthay, M; Bacchetti, P.; Toy, P

    2013-01-01

    Background: Transfusion-associated circulatory overload is characterized by new respiratory distress and hydrostatic pulmonary edema within 6 hours after blood transfusion, but its risk factors and outcomes are poorly characterized. Methods: Using a case control design, we enrolled 83 patients with severe transfusion-associated circulatory overload identified by active surveillance for hypoxemia and 163 transfused controls at the University of California, San Francisco (UCSF) and Mayo Clinic ...

  2. Application of Chaos Theory in Trucks' Overloading Enforcement

    Directory of Open Access Journals (Sweden)

    Abbas Mahmoudabadi

    2013-01-01

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

  3. Effects of encapsulated niacin on metabolism and production of periparturient dairy cows.

    Science.gov (United States)

    Morey, S D; Mamedova, L K; Anderson, D E; Armendariz, C K; Titgemeyer, E C; Bradford, B J

    2011-10-01

    Nicotinic acid (niacin) can suppress lipolysis, but responses to dietary niacin have been inconsistent in cattle. Our aim was to determine if 24 g/d of encapsulated niacin (EN; providing 9.6g/d of bioavailable nicotinic acid) alters lipid metabolism and productivity of transition cows. Beginning 21 d before expected calving, primiparous (n = 9) and multiparous (n = 13) cows (body condition score of 3.63 ± 0.08) were sequentially assigned within parity to EN (12 g provided with ration twice daily) or control through 21 d postpartum. Liver biopsies were collected on d -21, -4, 1, 7, and 21 relative to parturition. Blood samples were collected on d -21, -14, -7, -4, 1, 4, 7, 14, and 21 relative to parturition. On d 7 postpartum, a caffeine clearance test was performed to assess liver function, and on d 21 to 23 postpartum, blood samples were collected every 8h to monitor posttreatment nonesterified fatty acid (NEFA) responses. Data were analyzed using mixed models with repeated measures over time. A treatment × time × parity effect was observed on prepartum dry matter intake (DMI), which was caused by a 4 kg/d decrease in DMI of EN-treated multiparous cows compared with control multiparous cows during the final 4 d prepartum. A significant increase in plasma nicotinamide concentration occurred in EN-treated cows on d -7 and 21 relative to parturition. Prepartum glucose concentration decreased in treated animals, with no difference in plasma insulin concentration. Treatment × time × parity effects were detected for NEFA and β-hydroxybutyrate concentrations during the postpartum period. Plasma NEFA peaked at 1,467 ± 160 μM for control animals compared with 835 ± 154 μM for EN-treated animals. After treatments ended on d 21, no evidence was found for a plasma NEFA rebound in either parity group. A treatment × parity × time interaction was detected for liver triglyceride content, indicating a tendency for less liver triglyceride in EN-treated primiparous cows

  4. Fat overload syndrome after the rapid infusion of SMOFlipid emulsion.

    Science.gov (United States)

    Hojsak, Iva; Kolaček, Sanja

    2014-01-01

    Fat overload syndrome is a well-known complication of intravenous lipid emulsion therapy. It is characterized by headaches, fever, jaundice, hepatosplenomegaly, respiratory distress, and spontaneous hemorrhage. Other symptoms include anemia, leukopenia, thrombocytopenia, low fibrinogen levels, and coagulopathy. Several reports in the literature describe fat overload syndrome caused by rapid infusion of lipid emulsions, all with soybean-based lipid emulsions. We report fat overload syndrome in a 2-year-old girl with short bowel syndrome on home parenteral nutrition. Fat overload syndrome occurred as a result of accidental, very rapid infusion of a 20% soy oil, medium-chain triglyceride, olive and fish oil-based lipid emulsion (SMOFlipid) that showed the same complications seen with an earlier lipid emulsion (Intralipid). The patient was successfully treated with supportive care combining fluid infusion, transfusion of platelets, and substitution of serum albumin (0.5 g/kg/d) and fresh-frozen plasma (10 mL/kg). In the next couple of days, she received extra platelets, erythrocyte transfusion, and filgrastim (Neupogen; 5 µg/kg/d) due to a very low leukocyte count. To the best of our knowledge, this is the first case of fat overload syndrome caused by SMOFlipid emulsion described in the literature. PMID:23520135

  5. Niacin-a critical component to the management of atherosclerosis: contemporary management of dyslipidemia to prevent, reduce, or reverse atherosclerotic cardiovascular disease.

    Science.gov (United States)

    Mason, Carol M; Doneen, Amy L

    2012-01-01

    Niacin (nicotinic acid) is the most effective agent for raising high-density lipoprotein cholesterol levels and can improve the entire lipid panel in patients with dyslipidemia. Niacin-containing regimens are among the few treatments studied for dyslipidemia that have both elicited significant reductions in atherosclerotic progression (by angiography or imaging) and also significantly reduced (by approximately 90% vs control) the incidence of cardiovascular events in a single clinical trial. However, cutaneous flushing-an uncomfortable but typically transient adverse effect of niacin-often results in patient nonadherence with this potentially life-saving therapy. Effective counseling regarding the highly favorable benefit-risk ratio for niacin and management strategies such as careful dose escalation, follow-up monitoring, regimen adjustments, and the use of treatment adjuncts (eg, aspirin) can improve patient adherence with niacin therapy. Clinicians are uniquely positioned to provide such counseling to appropriate patients for niacin treatment and hence encourage wider use of this important and necessary cardioprotective medication.

  6. An overview of niacin on fat metabolism in ruminant%烟酸在反刍动物脂肪代谢中的研究进展

    Institute of Scientific and Technical Information of China (English)

    瞿明仁

    2012-01-01

    Niacin is the necessary vitamin to animal. It is also a direct precursor of NAD, NADP. Niacin has important influence on metabolism of carbohydrate, protein and lipid. In order to promote research of niacin on fat metabolism in ruminant, this paper describes the physicochemical properties of niacin and its role in fat metabolism, effect of niacin on VFA in rumen; regulation of niacin on fat metabolism in ruminant.%烟酸是动物机体的必需维生素,是合成机体需要的重要辅酶NAD和NADP的直接前体,对动物碳水化合物、蛋白质、脂类代谢有重要影响.文中阐述了烟酸的理化性质及其在脂肪代谢中的作用、烟酸对瘤胃中挥发性脂肪酸的影响及对反刍动物脂肪代谢的调控等,以期促进烟酸在反刍动物脂肪代谢中的研究.

  7. Eccentric Strengthening for Chronic Lateral Epicondylosis

    OpenAIRE

    Wen, Dennis Y.; Schultz, Brian J.; Schaal, Bob; Graham, Scott T.; Kim, Byung Sung

    2011-01-01

    Background: Effective treatments for chronic lateral epicondylosis have not been studied adequately. Eccentric overload exercises have been used with success for other chronic tendinopathy, mainly Achilles and patellar. Hypothesis/Purpose: To compare a wrist extensor eccentric strengthening exercise program with a wrist extensor stretching/modality program for the treatment of chronic lateral epicondylosis. The authors hypothesized that the eccentric strengthening program would produce more f...

  8. Salvaging transient data with overloads and zero offsets

    Energy Technology Data Exchange (ETDEWEB)

    Smallwood, D.O.; Cap, J.S. [Sandia National Labs., Albuquerque, NM (United States). Mechanical and Thermal Environments Dept.

    1997-10-21

    The authors are sometimes presented with data with serious flaws, like overloads, zero shifts, and impulse noise, including much of the available pyrotechnic data. Obviously, these data should not be used if at all possible. However, they are sometimes forced to use these data as the only data available. Methods to salvage these data are discussed. Using the methods requires judgment, and the results must be accepted with the understanding that the answers are credible, not necessarily correct. None of the methods will recover information lost due to overloads or non-linearities of the data system. The best that can be accomplished is the recovery of data, after the data system has recovered from the overload. Several correction methods are discussed: high pass filtering of the data, correction with two forms of an exponential function, and a correction with the form t exp({minus}{alpha}t). Examples showing the results of the methods will be given using flawed pyrotechnic data.

  9. Development of a chromatographic low pressure flow injection system using amperometric detection: Application to the analysis of niacin in coffee.

    Science.gov (United States)

    Santos, João Rodrigo; Rangel, António O S S

    2015-11-15

    In this work, an analytical flow system able to perform low pressure chromatography with amperometric detection is presented. As case study, the determination of niacin (vitamin B3) in coffee brewed samples was selected. The manifold comprised a 1.0 cm length monolithic column coated with didecyldimethylammonium bromide, a laboratory-made boron doped diamond electrode, and featured in-line ionic strength adjustment of the mobile phase. The figures of merit concerning the selected case study namely, detection limit, 7.90 × 10(-7) M, determination rate, ca. 10 samplesh(-1), mobile phase and ISA solution consumption, ca. 2.6 mL per analysis, and CV, below 5% for retention time and peak height, showed the competitiveness of this analytical strategy comparing to the described HPLC methods for niacin determination. The strategy displays a simple configuration, low cost, fast and easy assembling, foreseeing its use to general purpose applications.

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

    Science.gov (United States)

    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.

  11. Overload prevention in model supports for wind tunnel model testing

    Directory of Open Access Journals (Sweden)

    Anton IVANOVICI

    2015-09-01

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

  12. 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

  13. Neurotoxic effects of iron overload under high glucose concentration

    Institute of Scientific and Technical Information of China (English)

    Shi Zhao; Lin Zhang; Zihui Xu; Weiqun Chen

    2013-01-01

    Iron overload can lead to cytotoxicity, and it is a risk factor for diabetic peripheral neuropathy. However, the underlying mechanism remains unclear. We conjectured that iron overload-induced neurotoxicity might be associated with oxidative stress and the NF-E2-related factor 2 (Nrf2)/ARE signaling pathway. As an in vitro cellular model of diabetic peripheral neuropathy, PC12 cells ex-posed to high glucose concentration were used in this study. PC12 cells were cultured with ferric ammonium citrate at different concentrations to create iron overload. PC12 cells cultured in ferric ammonium citrate under high glucose concentration had significantly low cellviability, a high rate of apoptosis, and elevated reactive oxygen species and malondialdehyde levels. These changes were dependent on ferric ammonium citrate concentration. Nrf2 mRNA and protein expression in the fer-ric ammonium citrate groups were inhibited markedly in a dose-dependent manner. Al changes could be inhibited by addition of deferoxamine. These results indicate that iron overload aggravates oxidative stress injury in neural cells under high glucose concentration and that the Nrf2/ARE sig-naling pathway might play an important role in this process.

  14. Information Overload in Multi-Stage Selection Procedures

    NARCIS (Netherlands)

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

    2004-01-01

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

  15. 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.

  16. Functional hallux limitus and lesser-metatarsal overload.

    Science.gov (United States)

    Clough, James G

    2005-01-01

    The implications of functional hallux limitus for lesser-metatarsal overload are discussed. A new method of treating functional hallux limitus is proposed, and three case histories are reviewed showing adequate resolution of symptoms using the proposed method of treatment. A proposed mechanism for the development of functional hallux limitus is discussed, and different methods of identification are illustrated. PMID:16291854

  17. Effects of Information Overload on Brazilian E-Consumers

    Directory of Open Access Journals (Sweden)

    Rafael Lucian

    2009-01-01

    Full Text Available Problem statement: E-commerce is a reality; Companies must consider this media as an important trade channel without distances between products and consumers. A key issue of e-commerce is how companies are disclosing information to its customers. This study aims to measure if there is relationship between the information overload in the virtual environment and the response of satisfaction and confusion of consumers. Approach: Research had exploratory-experimental character and it was used a quasi-experiment. Due to the methodology adopted, two samples were obtained, the first of control with 114 respondents and the second of experiment with 178 cases reported. Data analysis was made though descriptive statistics (central tendency and dispersion, multivariate (factor analysis and non-parametric (Mann-Whitney U test. Results: A factorial matrix was built and it was found that information overload relates to the responses of satisfaction and confusion in the environment of e-commerce. There was a statistical significance level supporting these relationships. Conclusion/Recommendation: The main implication of information load was the feeling of not having done the best buy, generating a possible repentance. Related to the feeling of confusion generated by the large amount of information, the physical and virtual environment has the same properties. The performed analyses in this study indicated that there is a relationship between the e-commerce consumer satisfaction and the experience of information overload. Future studies might investigate the relationship between information overload and other responses.

  18. 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

  19. 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.

  20. Probe-based end-to-end overload control for networks of SIP servers

    OpenAIRE

    Wang, Jinzhu; Liao, Jianxin; Li, Tonghong; Jing WANG; Wang, Jingyu; Qi, Qi

    2013-01-01

    The Session Initiation Protocol (SIP) has been adopted by the IETF as the control protocol for creating, modifying and terminating multimedia sessions. Overload occurs in SIP networks when SIP servers have insufficient resources to handle received messages. Under overload, SIP networks may suffer from congestion collapse due to current ineffective SIP overload control mechanisms. This paper introduces a probe-based end-to-end overload control (PEOC) mechanism, which is deployed at the edge se...

  1. Iron deficiency and iron overload: effects of diet and genes.

    Science.gov (United States)

    Burke, W; Imperatore, G; Reyes, M

    2001-02-01

    Like most essential nutrients, Fe needs to be maintained in the body at a defined level for optimal health, with appropriate adaptation to varying Fe needs and supply. The primary mechanism for controlling Fe level is the regulation of Fe absorption. Several different proteins have been identified as contributors to the process. Despite a complex regulatory system, Fe disorders (both Fe deficiency and Fe overload) occur. Fe deficiency is a common problem worldwide, resulting from inadequate dietary Fe and blood loss. Complications include pre-term labour, developmental delay, and impaired work efficiency. No specific genetic syndromes causing isolated Fe deficiency have been described, but animal studies and clinical observations suggest that such a relationship may be a possibility. Conversely, the known causes of Fe overload are genetic. Fe overload is less common than Fe deficiency, but can result in serious medical complications, including cirrhosis, primary liver cancer, diabetes, cardiomyopathy and arthritis. The most common and best characterized syndrome of Fe overload is hereditary haemochromatosis (HHC), an autosomal recessive disorder. Mutations in the HFE protein cause HHC, but the clinical presentation is variable. Of particular interest is the factor that some FIFE genotypes appear to be associated with protection from Fe deficiency. Other genetic variants in the regulatory pathway may influence the likelihood of Fe deficiency and Fe overload. Studies of genetic variants in HFE and other regulatory proteins provide important tools for studying the biological processes in Fe regulation. This work is likely to lead to new insights into Fe disorders and potentially to new therapeutic approaches. It will not be complete, however, until coordinated study of both genetic and nutritional factors is undertaken. PMID:11310426

  2. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    Science.gov (United States)

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

    1997-01-01

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

  3. Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats

    Science.gov (United States)

    Guo, Yuanxin; Lei, Wenjuan; Wang, Jianfeng; Hu, Xinyue; Wei, Yuling; Ji, Chaonan; Yang, Junqing

    2016-01-01

    Although COX-2 inhibition in animal models of neurodegenerative diseases has shown neuroprotection, recent studies have revealed some serious side effects (ulcers, bleeding, fatal cerebrovascular diseases etc.) and the limited benefits of COX-2 inhibitors. A more focused approach is necessary to explore the therapeutic effect of the COX downstream signaling pathway in neurological research. The aim of this study was to explore the alterations of the PGES-PGE2-EP signal pathway and the effect of misoprostol on neurodegeneration by chronic aluminum-overload in rats. Adult rats were treated by intragastric administration of aluminum gluconate. The PGE2 content and expression of PGES and EPs in the hippocampi of rats were detected using ELISA, q-PCR and Western blot analysis, respectively. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the rat hippocampi were also detected. The misoprostol treatment dose-dependently improved spatial learning and memory function as well as healing after hippocampal neuron damage induced by chronic aluminum-overload in rats. Meanwhile, the administration of misoprostol resulted in a decrease in the PGE2 level and down-regulation of the mPGES-1, EP2 and EP4 expression levels, while there was a dose-dependent up-regulation of EP3 expression. These results suggest that misoprostol possesses a neuroprotective property, and the mechanism involves affecting the EP3 level and reducing the endogenous production of PGE2 through a negative feedback mechanism, increasing the EP3 expression level, decreasing the EP2 and EP4 expression levels, and rebuilding the mPGES-1-PGE2-EP1-4 signal pathway balance. In this way, misoprostol has a counteractive effect on oxidant stress and inflammation in the central nervous system. The PGES-PGE2-EPs signaling pathway is a potential therapeutic strategy for treating neurodegeneration in patients. PMID:27033056

  4. Design and Implementation on No-Parking Overloading Detection System%不停车超限检测系统的设计与实现

    Institute of Scientific and Technical Information of China (English)

    李聪; 李梦霆

    2014-01-01

    近年来,公路货运车辆超限超载运输问题日渐严重,已成为危害公路交通可持续发展的“痼疾”。治理超限超载运输,是一项重要的社会责任。根据《公路超限检测站管理办法》(中华人民共和国交通运输部令2011年第7号)规定,进行不停车超限检测系统高速动态预检系统与低速精检系统的设计与研究,主要实现对主线道路上正常行驶的车辆的不停车称重,引导超限车辆进站检测,对进站车辆进行精确称重检测,打印检测结果。%In recent years, overloading transportation problem of highway freight vehicle is becoming more and more serious, which has become a chronic hazard of sustainable development of highway transportation. Governing overloading transportation is an important social responsibility. According to the highway overload-ing inspection management approach (Ministry of Transport of the People′s Republic of China order No. sev-en in 2011) regulations, the article researches and designs high speed dynamic detection system and low speed precision detection system of the no parking overloading detection system, mainly to achieve non-stop weighing for the normal vehicles running on the main line of the road, guide the overloaded vehicles to be de-tected accurately in the station, and print the test results.

  5. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Science.gov (United States)

    2010-07-01

    ... Equipment-General § 75.518 Electric equipment and circuits; overload and short circuit protection. Automatic... electric equipment and circuits against short circuit and overloads. Three-phase motors on all electric... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload...

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

    Directory of Open Access Journals (Sweden)

    Wen Liang

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

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

    Science.gov (United States)

    McMurtry, Brandon M.; Turner, Andrew M.; Saito, Sean E. J.; Kaiser, Ralf I.

    2016-06-01

    The formation of pyridine carboxylic acids in interstellar ice grains was simulated by electron exposures of binary pyridine (C5H5N)-carbon dioxide (CO2) 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-C5H4NCOOH) along with 2,3-, 2,5-, 3,4-, and 3,5-pyridine dicarboxylic acid (C5H3N(COOH)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.

  8. Aceruloplasminaemia: a rare but important cause of iron overload.

    Science.gov (United States)

    Doyle, Adam; Rusli, Ferry; Bhathal, Prithi

    2015-01-01

    We present a case of a 20-year-old man referred to our service with iron overload and mildly deranged liver biochemistry. Although liver histopathology was consistent with haemochromatosis, iron studies were not consistent with this diagnosis. Serum ceruloplasmin levels were undetectable, leading to a diagnosis of aceruloplasminaemia. Unlike other iron overload disorders, neurological complications are a unique feature of this illness, and often irreversible, once established. The patient was treated with iron chelation prior to the onset of neurological injury, and experienced progressive normalisation of his ferritin and liver biochemistry. This is one of the youngest diagnosed cases in the published literature and, crucially, was a rare case of diagnosis and treatment prior to the onset of neurological sequelae. This is presented alongside a review of previously published cases of aceruloplasminaemia, including responses to iron chelation therapy. PMID:25976187

  9. Epidemiology and diagnostic testing for hemochromatosis and iron overload.

    Science.gov (United States)

    Adams, P C

    2015-05-01

    Hemochromatosis is the most common genetic disease in northern European populations. Body iron stores progressively increase in most patients, which can lead to cirrhosis of the liver, hepatocellular carcinoma, heart failure, arthritis, and pigmentation. Simple blood tests such as the serum ferritin and transferrin saturation are useful to suggest the diagnosis which can be confirmed in most cases with a simple genetic test for the C282Y mutation of the HFE gene. However, these blood tests are often misinterpreted and there are rare patients with iron overload without HFE mutations. A diagnostic approach is presented based on a large referral practice and a population-based study (HEIRS) which screened for iron overload in 101,168 participants.

  10. JOB SATISFACTION, ROLE OVERLOAD AND GENDER IN TURKEY

    OpenAIRE

    BOZKURT, Veysel; AYTAÇ, Serpil; Bondy, Jules; Emirgil, Faik

    2011-01-01

    ABSTRACTJob satisfaction is widely studied in academic literature but there are still limited studies about the relationship between job satisfaction with the role overload in Turkey, especially in the context of gender.Working women's lives in contemporary Turkey are divided between home and work.Women are faced with a wide range of competing demands like being in paid employment, familial duties as wives and mothers, and other gendered roles and tasks more broadly within the community.The i...

  11. Stress 2.0 : Social Media Overload among Swiss Teenagers

    OpenAIRE

    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 understudied, even more so when social network sites are concerned. Our study explores how feelings of overexposure and stress relate to the self-expressive needs of teenagers, made explicit through ...

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

    Directory of Open Access Journals (Sweden)

    I. Portioli

    2013-05-01

    Full Text Available BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years old with beta-thalassemia and transfusional emosiderosis randomized to once-daily oral 5, 10, 20, 30 mg/kg/day in comparison of subcutaneous deferoxamine 20-60 mg/mg/kg/day x 5/week. CONCLUSIONS Deferasirox 20-30 mg/kg/day produced reductions in liver iron concentration (LIC similar to those with deferoxamine. Adverse effect of deferasirox (increases of serum creatinine and aminotransferases, including the gastrointestinal ones, are similar but more frequent than those occurring with deferoxamine. Information is lacking on the effects of deferasirox on cardiac iron and cardiac dysfunction which is the most serious complication of transfusional iron overload.

  13. Formal Constraints on Memory Management for Composite Overloaded Operations

    Directory of Open Access Journals (Sweden)

    Damian W.I. Rouson

    2006-01-01

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

  14. Effects of Phenotypic and Genotypic Factors on the Lipid Responses to Niacin in Chinese Patients With Dyslipidemia

    Science.gov (United States)

    Hu, Miao; Yang, Ya-Ling; Ng, Chi-Fai; Lee, Chui-Ping; Lee, Vivian W.Y.; Hanada, Hiroyuki; Masuda, Daisaku; Yamashita, Shizuya; Tomlinson, Brian

    2015-01-01

    Abstract The acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2 catalyze the final step in triglycerides biosynthesis. This study examined the relationships of baseline phenotypes and the common polymorphisms in DGAT1 and DGAT2 with the lipid responses to niacin. Lipid responses in Chinese patients with dyslipidemia treated with the extended release (ER) niacin/laropiprant combination 1000/20 mg for 4 weeks and then 2000/40 mg for 8 weeks (n = 121, the primary study) or with ER niacin 1500 mg for at least 4 weeks (n = 68, the replication study) were analyzed according to genotypes of DGAT1 rs7003945 T>C and DGAT2 rs3060 T>C polymorphisms. Treatment with ER niacin improved all lipid parameters in both studies. Absolute and percentage changes in lipids were related to their baseline levels, particularly for low-density lipoprotein cholesterol (LDL-C). The DGAT2 rs3060 T>C polymorphism was associated with lower baseline LDL-C, apoB, high-density lipoprotein cholesterol (HDL-C), and apoAI in patients on statin therapy in the primary study. Subjects with the DGAT2 rs3060 T>C variant had less reduction in LDL-C in the primary study and smaller changes in triglyceride and HDL-C in the replication study but these associations became non-significant after adjusting for baseline lipid values. The DGAT1 rs7003945 T>C polymorphism was not related to lipid baseline values or changes in either study. Concomitant statin therapy and lower body weight were also associated with greater reduction in LDL-C. Baseline lipid levels were the main determinants of lipid responses especially for LDL-C. The DGAT2 rs3060 polymorphism might influence the lipid responses depending on baseline phenotype, but this association did not persist after adjustment for the baseline lipid levels. PMID:25997070

  15. Acute iron overload and oxidative stress in brain

    International Nuclear Information System (INIS)

    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 h

  16. Acute iron overload and oxidative stress in brain.

    Science.gov (United States)

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

    2013-12-01

    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, 6h 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 8h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21h 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 6h after Fe administration. CAT activity was significantly increased after 8h 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 6h of Fe overload

  17. Randomized, double-blind, placebo-controlled and active-controlled study to assess the relative abuse potential of oxycodone HCl-niacin tablets compared with oxycodone alone in nondependent, recreational opioid users

    Directory of Open Access Journals (Sweden)

    Webster LR

    2012-08-01

    Full Text Available Lynn R Webster,1 Robert L Rolleri,2,3 Glenn C Pixton,3 Kenneth W Sommerville31Lifetree Clinical Research, Salt Lake City, UT, USA; 2Salix Pharmaceuticals, Inc., Raleigh, NC, USA; 3Pfizer Inc, Cary, NC, USABackground: Abuse-deterrent formulations attempt to address public health and societal concerns regarding opioid abuse. Oxycodone HCl-niacin tablets combine oxycodone HCl with niacin and functional inactive excipients to create potential barriers to oral, intranasal, and intravenous abuse. This study compared the relative abuse potential of oral immediate-release oxycodone HCl-niacin with that of oral immediate-release oxycodone HCl and placebo in nondependent, recreational opioid users.Methods: Forty-nine participants received oxycodone HCl-niacin 40/240 mg and 80/480 mg, oxycodone 40 mg and 80 mg, and placebo in a randomized, double-blind, placebo-controlled and active-controlled, five-way crossover study. Primary endpoints based on a bipolar 100 mm visual analog scale for drug liking were area under effect curve (AUE0–1h, AUE0–2h, AUE0–3h, peak disliking, and effect at 0.5 hours post-dose (E0.5h. Other endpoints included take drug again assessment, overall drug liking, and pupillometry.Results: There were statistically significant differences between oxycodone HCl-niacin and oxycodone HCl doses for all primary endpoints (P < 0.0001, all comparisons, suggesting reduced abuse potential with oxycodone HCl-niacin. Take drug again and overall drug liking showed greater liking of oxycodone alone. Oxycodone HCl-niacin 80/480 mg had consistently lower liking assessments than oxycodone HCl-niacin 40/240 mg, suggesting a dose-response to the aversive effects of niacin. Opioid-related adverse events were similar for equivalent oxycodone doses. The treatment-emergent adverse events most specifically associated with oxycodone HCl-niacin (ie, skin-burning sensation, warmth, and flushing were consistent with the expected vasocutaneous effects of

  18. Distinct right ventricle remodeling in response to pressure overload in the rat.

    Science.gov (United States)

    Mendes-Ferreira, P; Santos-Ribeiro, D; Adão, R; Maia-Rocha, C; Mendes-Ferreira, M; Sousa-Mendes, C; Leite-Moreira, A F; Brás-Silva, C

    2016-07-01

    Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies. PMID:27199115

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

    CERN Document Server

    Shen, Charles

    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 can we make it work? We provide a comprehensive explanation of the default SIP-over-TCP overload behavior through server instrumentation. We also propose and implement novel but simple overload control algorithms without any kernel or protocol level modification. Experimental evaluation shows that with our mechanism the overload performance improves from its original zero throughput to nearly full capacity. Our work leads to the important general insight that the traditional notion of TCP flow control alone is incapable of...

  20. A Study on Improving the Overloaded Speech Waveform to Distinguish Alcohol Intoxication using Spectral Compensation

    Directory of Open Access Journals (Sweden)

    Won-Hee Lee

    2015-10-01

    Full Text Available In this study, speech characteristics from before and after alcohol intoxication has been comparatively analyzed through speech analysis to obtain the degree of intoxication along with its parameters. However, the overload of the input signal must be considered prior to anything else. When distinguishing intoxication under overload conditions, an error cannot be avoided. Therefore, distinguishing the level of intoxication must be conducted by using a method that is not significantly influenced by overload. Thus, reliability of distinguishing the degree of intoxication was enhanced by preprocessing the overload to compensate the spectrum. The SNR and intoxication distinguishment rate resulted comparatively better at about 2 and 5% overload clipping rate, however, resulted in an error and increase at 10% overload clipping rate.

  1. Effect of band-overload on fatigue crack growth rate of HSLA steel

    Science.gov (United States)

    Abhinay, S. V.; Tenduwe, Om Prakash; Kumar, Ajit; Dutta, K.; Verma, B. B.; Ray, P. K.

    2015-02-01

    Fatigue crack growth behavior is important parameter of structural materials. This parameters can be used to predict their life, service reliability and operational safety in different conditions. The material used in this investigation is an HSLA steel. In this investigation effect of single overload and band-overload on fatigue crack growth of same steel are studied using compact tension (CT) specimens under mode-I condition and R=0.3. It is observed that overload and band-overload applications resulted retardation on the fatigue crack growth rate in most of the cases. It is also noticed that maximum retardation took place on application of seven successive overload cycles. Application of ten and more overload cycles caused no crack growth retardation.

  2. Salt overload damages the glycocalyx sodium barrier of vascular endothelium

    OpenAIRE

    Oberleithner, Hans; Peters, Wladimir; Kusche-Vihrog, Kristina; Korte, Stefanie; Schillers, Hermann; Kliche, Katrin; Oberleithner, Kilian

    2011-01-01

    Sodium overload stiffens vascular endothelial cells in vitro and promotes arterial hypertension in vivo. The hypothesis was tested that the endothelial glycocalyx (eGC), a mesh of anionic biopolymers covering the surface of the endothelium, participates in the stiffening process. By using a mechanical nanosensor, mounted on an atomic force microscope, height (∼400 nm) and stiffness (∼0.25 pN/nm) of the eGC on the luminal endothelial surface of split-open human umbilical arteries were quantifi...

  3. Aeronautical Magnetic Torque Limiter for Passive Protection against Overloads

    Directory of Open Access Journals (Sweden)

    Cristian Cristache

    2016-09-01

    Full Text Available Actual aerospace and defense technologies present multiple limitations that need to be overcome in order to evolve to less contaminating and more efficient aircraft solutions. Contactless technologies come with essential advantages such as the absence of wear and friction. This work describes the design, prototype, and performance test according to RTCA-DO-160 of an aeronautical magnetic torque limiter. The results show correct continuous transmission operation (2250 rpm and 24 Nm from −50 °C to +90 °C. Moreover, overload protection has been demonstrated for more than 200 jamming events without damage or required maintenance to the device.

  4. Semicircular canals circumvent Brownian Motion overload of mechanoreceptor hair cells

    DEFF Research Database (Denmark)

    Muller, Mees; Heeck, Kier; Elemans, Coen P H

    2016-01-01

    Vertebrate semicircular canals (SCC) first appeared in the vertebrates (i.e. ancestral fish) over 600 million years ago. In SCC the principal mechanoreceptors are hair cells, which as compared to cochlear hair cells are distinctly longer (70 vs. 7 μm), 10 times more compliant to bending (44 vs. 500...... to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors...

  5. Quantum Overloading Cryptography Using Single-Photon Nonlocality

    Institute of Scientific and Technical Information of China (English)

    TAN Yong-Gang; CAI Qing-Yu; SHI Ting-Yun

    2007-01-01

    @@ Using the single-photon nonlocality, we propose a quantum novel overloading cryptography scheme, in which a single photon carries two bits information in one-way quantum channel. Two commutative modes of the single photon, the polarization mode and the spatial mode, are used to encode secret information. Strict time windows are set to detect the impersonation attack. The spatial mode which denotes the existence of photons is noncommutative with the phase of the photon, so that our scheme is secure against photon-number-splitting attack. Our protocol may be secure against individual attack.

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

    OpenAIRE

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

    2015-01-01

    Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and ...

  7. 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...

  8. Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

    OpenAIRE

    Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E.; Zhong, Ju-ming

    2015-01-01

    Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- a...

  9. EFFECT OF OVERLOAD ON CRACK GROWTH IN FIBER REINFORCED METAL LAMINATES

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    This paper is concerned with fatigue behavior of glass fiber reinforced aluminium laminates (GLARE) under overload fatigue loading. The effect of single overload on the crack growth rates in GLARE was investigated, and the mechanism of the retardation of crack growth determined. Crack growth retardation by overload was observed in GLARE, but much smaller than monolithic metals. The retardation of crack growth in GLARE is only controlled by the effective stress intensity factor experienced by the constituent metals at crack tips.

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

    OpenAIRE

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

    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 t...

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

    Science.gov (United States)

    2012-07-16

    Iron Overload; Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult

  12. Relationship between glycemic status and progression of carotid intima-media thickness during treatment with combined statin and extended-release niacin in ARBITER 2

    Directory of Open Access Journals (Sweden)

    Allen J Taylor

    2007-03-01

    Full Text Available Allen J Taylor, Daming Zhu, Lance E Sullenberger, Hyun J Lee, Jeannie K Lee, Karen A Grace Cardiology Service, Walter Reed Army Medical Center, Washington, DC, USA Background: We previously reported in a placebo-controlled study that extended-release niacin slowed the progression of carotid atherosclerosis when added to statin monotherapy. This analysis examines the relationship between glycemic status and the effects of niacin on common carotid intima-media thickness (CIMT and HDL cholesterol.Methods: Post-hoc, subgroup analysis of ARBITER 2, a randomized, placebo-controlled trial of once-daily extended-release niacin (1000 mg added to background statin therapy in 167 patients (mean age 67 years with known coronary heart disease. The primary analysis was a comparison of the primary endpoint, the change in CIMT, between participants with either normal glycemic status, diabetes mellitus (DM or the metabolic syndrome (MS.Results: Baseline cardiovascular risk variables were significantly worse in those with abnormal glycemic status, particularly among subjects with MS. Niacin increased HDL-C to a similar degree (~20% across normals, DM and MS. Placebo-treated patients had the greatest CIMT progression, regardless of glycemic status. The lowest progression rate was observed in niacin treated patients with normal glycemic status. Among all niacin treated subjects, there was a significant linear relationship between change in CIMT and change in HDL-C (r = –0.16; p = 0.05, which was of similar magnitude in subgroups with normal glycemic status (r = –0.23; p = 0.08 and DM (r = –0.22; p = 0.17. In those with MS, there was no relationship between changes in HDL and CIMT, (r = 0.11; p = 0.44, whereas blood glucose was positive correlated to change in CIMT (r = 0.30; p = 0.04. In multivariable linear models controlling for MS characteristics and blood glucose changes, only the change in HDL independently predicted change in CIMT.Conclusions: During

  13. Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains

    Directory of Open Access Journals (Sweden)

    Agarwal Anupam

    2005-12-01

    Full Text Available Abstract Background Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD, which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA. To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10 that were made to develop proteinuria by BSA overload. Methods Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy. Results Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta. Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria. Conclusion By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes.

  14. Ly6C(low and not Ly6C(high macrophages accumulate first in the heart in a model of murine pressure-overload.

    Directory of Open Access Journals (Sweden)

    Christina Weisheit

    Full Text Available Cardiac tissue remodeling in the course of chronic left ventricular hypertrophy requires phagocytes which degrade cellular debris, initiate and maintain tissue inflammation and reorganization. The dynamics of phagocytes in left ventricular hypertrophy have not been systematically studied. Here, we characterized the temporal accumulation of leukocytes in the cardiac immune response by flow cytometry and fluorescence microscopy at day 3, 6 and 21 following transverse aortic constriction (TAC. Cardiac hypertrophy due to chronic pressure overload causes cardiac immune response and inflammation represented by an increase of immune cells at all three time points among which neutrophils reached their maximum at day 3 and macrophages at day 6. The cardiac macrophage population consisted of both Ly6C(low and Ly6C(high macrophages. Ly6C(low macrophages were more abundant peaking at day 6 in response to pressure overload. During the development of cardiac hypertrophy the expression pattern of adhesion molecules was investigated by qRT-PCR and flow cytometry. CD11b, CX3CR1 and ICAM-1 determined by qRT-PCR in whole cardiac tissue were up-regulated in response to pressure overload at day 3 and 6. CD11b and CX3CR1 were significantly increased by TAC on the surface of Ly6C(low but not on Ly6C(high macrophages. Furthermore, ICAM-1 was up-regulated on cardiac endothelial cells. In fluorescence microscopy Ly6C(low macrophages could be observed attached to the intra- and extra-vascular vessel-wall. Taken together, TAC induced the expression of adhesion molecules, which may explain the accumulation of Ly6C(low macrophages in the cardiac tissue, where these cells might contribute to cardiac inflammation and remodeling in response to pressure overload.

  15. 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.

    Science.gov (United States)

    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.

  16. 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.

    Science.gov (United States)

    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. PMID:22924176

  17. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2016-01-01

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

  18. Iron Loading and Overloading due to Ineffective Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Toshihiko Tanno

    2010-01-01

    Full Text Available Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron molecules are incorporated into the hemoglobin contained within each erythrocyte. Thus, iron usage for the hemoglobin production is a primary regulator of plasma iron supply and demand. In many anemias, additional sources of iron from diet and tissue stores are needed to meet the erythroid demand. Among a subset of anemias that arise from ineffective erythropoiesis, iron absorption and accumulation in the tissues increases to levels that are in excess of erythropoiesis demand even in the absence of transfusion. The mechanisms responsible for iron overloading due to ineffective erythropoiesis are not fully understood. Based upon data that is currently available, it is proposed in this review that loading and overloading of iron can be regulated by distinct or combined mechanisms associated with erythropoiesis. The concept of erythroid regulation of iron is broadened to include both physiological and pathological hepcidin suppression in cases of ineffective erythropoiesis.

  19. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle.

    Science.gov (United States)

    Fujimaki, Shin; Machida, Masanao; Wakabayashi, Tamami; Asashima, Makoto; Takemasa, Tohru; Kuwabara, Tomoko

    2016-01-01

    Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise. PMID:26779264

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

    Science.gov (United States)

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

    2015-04-01

    The aim of this study was to evaluate the effect of overload training on the function of peritoneal macrophages in rats, and to test the hypothesis that glutamine in vivo supplementation would partly reverse the eventual functional alterations induced by overload training in these cells. Forty male Wistar rats were randomly divided into 5 groups: control group (C), overload training group (E1), overload training and restore one week group (E2), glutamine-supplementation group (EG1), and glutamine-supplementation and restore 1-week group (EG2). All rats, except those placed on sedentary control were subjected to 11 weeks of overload training protocol. Blood hemoglobin, serum testosterone, and corticosterone of rats were measured. Moreover, the functions (chemotaxis, phagocytosis, cytokines synthesis, reactive oxygen species generation) of peritoneal macrophages were determined. Data showed that blood hemoglobin, serum testosterone, corticosterone and body weight in the overload training group decreased significantly as compared with the control group. Meanwhile, the chemotaxis capacity (decreased by 31%, p = .003), the phagocytosis capacity (decreased by 27%, p = .005), the reactive oxygen species (ROS) generation (decreased by 35%, p = .003) and the cytokines response capability of macrophages were inhibited by overload training. However, the hindering of phagocytosis and the cytokines response capability of macrophages induced by overload training could be ameliorated and reversed respectively, by dietary glutamine supplementation. These results suggest that overload training impairs the function of peritoneal macrophages, which is essential for the microbicidal actions of macrophages. This may represent a novel mechanism of immunodepression induced by overload training. Nonetheless, dietary glutamine supplementation could partly reverse the impaired macrophage function resulting from overload training. PMID:25028814

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

    Science.gov (United States)

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

    2015-04-01

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

  2. 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

  3. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2015. Scientific opinion on niacin and contribution to normal energy-yielding metabolism: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    deliver an opinion on the scientific substantiation of a health claim related to niacin and contribution to normal energy-yielding metabolism. The Panel considers that niacin, the food constituent that is the subject of the health claim, is sufficiently characterised. Contribution to normal energy......-yielding metabolism applies to all ages, including infants and young children (from birth to three years). The Panel concludes that a cause and effect relationship has been established between the dietary intake of niacin and contribution to normal energy-yielding metabolism. The following wording reflects the...... scientific evidence: ‘Niacin contributes to normal energy-yielding metabolism.’ The target population is infants and young children up to three years of age....

  4. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  5. 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…

  6. 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…

  7. A combined LIFO-priority algorithm for overload control of SIP server

    OpenAIRE

    Kuzminykh, Ievgeniia

    2012-01-01

    In this paper a simulation model of message service procedure in SIP server in the normal conditions and in the congestion state is represented. The paper proposes local overload control for SIP server applied FIFO discipline in normal state and LIFO discipline with priority service model during overload.

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

    Directory of Open Access Journals (Sweden)

    Chen Wang

    2016-01-01

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

  9. 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. 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 PMID:27055182

  10. "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)…

  11. Information Overload in the New World of Work: Qualitative Study into the Reasons

    NARCIS (Netherlands)

    Heerdt, ter Jeroen; Bondarouk, Tanya; Bondarouk, Tanya; Ruel, Huub; 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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    Science.gov (United States)

    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.…

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

    Science.gov (United States)

    Rodriguez, Jacinto

    2013-01-01

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

  15. Aluminium overload after 5 years in skin biopsy following post-vaccination with subcutaneous pseudolymphoma.

    Science.gov (United States)

    Guillard, Olivier; Fauconneau, Bernard; Pineau, Alain; Marrauld, Annie; Bellocq, Jean-Pierre; Chenard, Marie-Pierre

    2012-10-01

    Aluminium hydroxide is used as an effective adjuvant in a wide range of vaccines for enhancing immune response to the antigen. The pathogenic role of aluminium hydroxide is now recognized by the presence of chronic fatigue syndrome, macrophagic myofasciitis and subcutaneous pseudolymphoma, linked to intramuscular injection of aluminium hydroxide-containing vaccines. The aim of this study is to verify if the subcutaneous pseudolymphoma observed in this patient in the site of vaccine injection is linked to an aluminium overload. Many years after vaccination, a subcutaneous nodule was discovered in a 45-year-old woman with subcutaneous pseudolymphoma. In skin biopsy at the injection site for vaccines, aluminium (Al) deposits are assessed by Morin stain and quantification of Al is performed by Zeeman Electrothermal Atomic Absorption Spectrophotometry. Morin stain shows Al deposits in the macrophages, and Al assays (in μg/g, dry weight) were 768.10±18 for the patient compared with the two control patients, 5.61±0.59 and 9.13±0.057. Given the pathology of this patient and the high Al concentration in skin biopsy, the authors wish to draw attention when using the Al salts known to be particularly effective as adjuvants in single or repeated vaccinations. The possible release of Al may induce other pathologies ascribed to the well-known toxicity of this metal.

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

    Directory of Open Access Journals (Sweden)

    Teng Ma

    2015-08-01

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

  17. Research on the overload protection reliability of moulded case circuit-breakers and its test device

    Institute of Scientific and Technical Information of China (English)

    LI Kui; LU Jian-guo; WU Yi; QIN Zhi-jun; YAO Dong-mei

    2007-01-01

    This paper analyzed the reliability and put forward the reliability index of overload protection for moulded case circuit breaker. The success rate was adopted as its reliability index of overload protection. Based on the reliability index and the reliability level, the reliability examination plan was analyzed and a test device for the overload protection of moulded case circuit-breaker was developed. In the reliability test of overload protection, two power sources were used, which reduced the time of conversion and regulation between two different test currents in the overload protection test, which made the characteristic test more accurate. The test device was designed on the base of a Windows system, which made its operation simple and friendly.

  18. Iron overload in the liver diagnostic and quantification

    Energy Technology Data Exchange (ETDEWEB)

    Alustiza, Jose M. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)]. E-mail: jmalustiza@osatek.es; Castiella, Agustin [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Juan, Maria D. de [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Emparanza, Jose I. [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Artetxe, Jose [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain); Uranga, Maite [Osatek SA, P Dr. Beguiristain 109, 20014, San Sebastian, Guipuzcoa (Spain)

    2007-03-15

    Hereditary Hemochromatosis is the most frequent modality of iron overload. Since 1996 genetic tests have facilitated significantly the non-invasive diagnosis of the disease. There are however many cases of negative genetic tests that require confirmation by hepatic iron quantification which is traditionally performed by hepatic biopsy. There are many studies that have demonstrated the possibility of performing hepatic iron quantification with Magnetic Resonance. However, a consensus has not been reached yet regarding the technique or the possibility to reproduce the same method of calculus in different machines. This article reviews the state of the art of the question and delineates possible future lines to standardise this non-invasive method of hepatic iron quantification.

  19. Biological tissue magnetism in the frame of iron overload diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lazaro, Francisco J. [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza 50018 (Spain) and Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Zaragoza 50009 (Spain)]. E-mail: osoro@unizar.es; Gutierrez, Lucia [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Zaragoza 50018 (Spain); Abadia, Ana R. [Departamento de Farmacologia y Fisiologia, Universidad de Zaragoza, Zaragoza 50013 (Spain); Romero, Maria S. [Departamento de Medicina y Psiquiatria, Universidad de Zaragoza, Zaragoza 50009 (Spain); Lopez, A. [CNAM-Salesianos Zaragoza, Zaragoza 50009 (Spain)

    2007-09-15

    The conspicuous magnetic properties of iron, paradoxically, rarely participate in the methods routinely employed in the clinical environment to detect iron containing species in tissues. In the organism iron is just a trace metal and it mostly occurs as part of haemoproteins or ferritin, which show paramagnetic, diamagnetic or antiferromagnetic behaviour, hence resulting in a very low contribution to the tissue susceptibility. Detailed magnetic measurements make it nowadays possible to identify such species in tissues that correspond to individuals with iron overload pathologies. Since, as alternatives to the conventional biopsy, magnetism-based noninvasive techniques to diagnose and manage such diseases are recently under development, the deep knowledge of the magnetic properties of the different forms of iron in tissues is of high applied interest.

  20. Biological tissue magnetism in the frame of iron overload diseases

    International Nuclear Information System (INIS)

    The conspicuous magnetic properties of iron, paradoxically, rarely participate in the methods routinely employed in the clinical environment to detect iron containing species in tissues. In the organism iron is just a trace metal and it mostly occurs as part of haemoproteins or ferritin, which show paramagnetic, diamagnetic or antiferromagnetic behaviour, hence resulting in a very low contribution to the tissue susceptibility. Detailed magnetic measurements make it nowadays possible to identify such species in tissues that correspond to individuals with iron overload pathologies. Since, as alternatives to the conventional biopsy, magnetism-based noninvasive techniques to diagnose and manage such diseases are recently under development, the deep knowledge of the magnetic properties of the different forms of iron in tissues is of high applied interest

  1. Iron excretion in iron dextran-overloaded mice

    Science.gov (United States)

    Musumeci, Marco; Maccari, Sonia; Massimi, Alessia; Stati, Tonino; Sestili, Paola; Corritore, Elisa; Pastorelli, Augusto; Stacchini, Paolo; Marano, Giuseppe; Catalano, Liviana

    2014-01-01

    Background Iron homeostasis in humans is tightly regulated by mechanisms aimed to conserve iron for reutilisation, with a negligible role played by excretory mechanisms. In a previous study we found that mice have an astonishing ability to tolerate very high doses of parenterally administered iron dextran. Whether this ability is linked to the existence of an excretory pathway remains to be ascertained. Materials and methods Iron overload was generated by intraperitoneal injections of iron dextran (1 g/kg) administered once a week for 8 weeks in two different mouse strains (C57bl/6 and B6D2F1). Urinary and faecal iron excretion was assessed by inductively coupling plasma-mass spectrometry, whereas cardiac and liver architecture was evaluated by echocardiography and histological methods. For both strains, 24-hour faeces and urine samples were collected and iron concentration was determined on days 0, 1 and 2 after iron administration. Results In iron-overloaded C57bl/6 mice, the faecal iron concentration increased by 218% and 157% on days 1 and 2, respectively (p<0.01). The iron excreted represented a loss of 14% of total iron administered. Similar but smaller changes was also found in B6D2F1 mice. Conversely, we found no significant changes in the concentration of iron in the urine in either of the strains of mice. In both strains, histological examination showed accumulation of iron in the liver and heart which tended to decrease over time. Conclusions This study indicates that mice have a mechanism for removal of excess body iron and provides insights into the possible mechanisms of excretion. PMID:24960657

  2. Mycobacterium avium Complex Infection in a Patient with Sickle Cell Disease and Severe Iron Overload

    Directory of Open Access Journals (Sweden)

    Kamal Shemisa

    2014-01-01

    Full Text Available A 34-year-old female with sickle cell anemia (hemoglobin SS disease and severe iron overload presented to our institution with the subacute presentation of recurrent pain crisis, fever of unknown origin, pancytopenia, and weight loss. A CT scan demonstrated both lung and liver nodules concerning for granulomatous disease. Subsequent biopsies of the liver and bone marrow confirmed the presence of noncaseating granulomas and blood cultures isolated Mycobacterium avium complex MAC. Disseminated MAC is considered an opportunistic infection typically diagnosed in the immunocompromised and rarely in immunocompetent patients. An appreciable number of mycobacterial infection cases have been reported in sickle cell disease patients without immune dysfunction. It has been reported that iron overload is known to increase the risk for mycobacterial infection in vitro and in vivo studies. While iron overload is primarily known to cause end organ dysfunction, the clinical relationship with sickle cell disease and disseminated MAC infection has not been reported. Clinical iron overload is a common condition diagnosed in the sub-Saharan African population. High dietary iron, genetic defects in iron trafficking, as well as hemoglobinopathy are believed to be the etiologies for iron overload in this region. Patients with iron overload in this region were 17-fold more likely to die from Mycobacterium tuberculosis. Both experimental and clinical evidence suggest a possible link to iron overload and mycobacterial infections; however larger observational studies are necessary to determine true causality.

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

    Science.gov (United States)

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

    2001-01-01

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

  4. Overload of families taking care of elderly people with Alzheimer's Disease: a comparative study

    Directory of Open Access Journals (Sweden)

    Ana Carla Borghi

    2013-07-01

    Full Text Available OBJECTIVE: to compare the overload of the main and secondary family carers of patients with Alzheimer's Disease, and identify which dimension generates most impact. METHOD: a comparative study conducted in the city of Maringá, State of Paraná, with 20 primary carers of elderly patients with Alzheimer's Disease and 20 secondary caregivers. The data was collected in May and June 2012, using the Scale for Assessment of Overload of Members of Psychiatric Patients' Families (FBIS-BR, and the results were analysed using the Mann-Whitney test and analysis of variance. RESULTS: the global objective overload, and also in each subscale, was significantly greater in the group of main caregivers; the subjective overload showed no difference between the groups. Comparing the subscales, the routine assistance provided to the patient had greater influence on objective overload in both groups, and the concern with the elderly patient was the dimension that had most influence on the subjective overload of main caregivers and also of secondary caregivers. CONCLUSION: the differences in overload between the different groups reinforces the need for planning of health care actions for each type of caregiver, seeking to reduce these differences.

  5. Efficacy and safety of a combination therapy of atorvastatin and krill oil versus atorvastatin and niacin in dyslipidemia: a randomized, open, and comparator study

    Directory of Open Access Journals (Sweden)

    Tom Devasia

    2014-02-01

    Conclusions: In our study the conventional combination therapy of statin and niacin is found to be more efficacious than the newer statin and krill oil combination in lowering LDL levels and increasing HDL levels in dyslipidemic patients. A further study with a higher sample size could confirm the findings of this study. [Int J Basic Clin Pharmacol 2014; 3(1.000: 201-205

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Effect of niacin supplementation on digestibility, nitrogen utilisation and milk and blood variables in lactating dairy cows fed a diet with a negative rumen nitrogen balance.

    Science.gov (United States)

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

    2012-06-01

    The aim of the present experiment was to determine if a niacin supplementation of 6 g/d to lactating dairy cow diets can compensate negative effects of a rumen nitrogen balance (RNB) deficit. A total of nine ruminally and duodenally fistulated lactating multiparous German Holstein cows were successively assigned to one of three diets consisting of 10 kg maize silage (dry matter [DM] basis) and 7 kg DM concentrate: Diet RNB- (n = 6) with energy and utilisable crude protein 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]); Diet RNB0 (n = 7) with energy, uCP and a RNB (0.08 g N/MJ ME) according to the average requirement of the animals and, finally, Diet NA (n = 5), which was the same diet as RNB-, but supplemented with 6 g niacin/d. Samples of milk were taken on two consecutive days, blood samples were taken on one day pre- and post-feeding and faeces and urine were collected completely over five consecutive days. The negative RNB reduced milk and blood urea content and apparent total tract digestibility of DM, organic matter (OM) and neutral detergent fibre (NDF). Also N excretion with urine, the total N excreted with urine and faeces and the N balance were reduced when the RNB was negative. Supplementation of niacin elevated plasma glucose concentration after feeding and the N balance increased. Supplementing the diet with a negative RNB with niacin led to a more efficient use of dietary N thereby avoiding the negative effects of the negative RNB on the digestibility of DM, OM and NDF.

  8. Effect of niacin supplementation on digestibility, nitrogen utilisation and milk and blood variables in lactating dairy cows fed a diet with a negative rumen nitrogen balance.

    Science.gov (United States)

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

    2012-06-01

    The aim of the present experiment was to determine if a niacin supplementation of 6 g/d to lactating dairy cow diets can compensate negative effects of a rumen nitrogen balance (RNB) deficit. A total of nine ruminally and duodenally fistulated lactating multiparous German Holstein cows were successively assigned to one of three diets consisting of 10 kg maize silage (dry matter [DM] basis) and 7 kg DM concentrate: Diet RNB- (n = 6) with energy and utilisable crude protein 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]); Diet RNB0 (n = 7) with energy, uCP and a RNB (0.08 g N/MJ ME) according to the average requirement of the animals and, finally, Diet NA (n = 5), which was the same diet as RNB-, but supplemented with 6 g niacin/d. Samples of milk were taken on two consecutive days, blood samples were taken on one day pre- and post-feeding and faeces and urine were collected completely over five consecutive days. The negative RNB reduced milk and blood urea content and apparent total tract digestibility of DM, organic matter (OM) and neutral detergent fibre (NDF). Also N excretion with urine, the total N excreted with urine and faeces and the N balance were reduced when the RNB was negative. Supplementation of niacin elevated plasma glucose concentration after feeding and the N balance increased. Supplementing the diet with a negative RNB with niacin led to a more efficient use of dietary N thereby avoiding the negative effects of the negative RNB on the digestibility of DM, OM and NDF. PMID:22724166

  9. Hypertrophy signaling pathways in experimental chronic aortic regurgitation

    DEFF Research Database (Denmark)

    Olsen, Niels Thue; Dimaano, Veronica L; Fritz-Hansen, Thomas;

    2013-01-01

    The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging on...... of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy....

  10. Chronic Diarrhea

    Science.gov (United States)

    ... infections that cause chronic diarrhea be prevented? Chronic Diarrhea What is chronic diarrhea? Diarrhea that lasts for more than 2-4 ... represent a life-threatening illness. What causes chronic diarrhea? Chronic diarrhea has many different causes; these causes ...

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

    Directory of Open Access Journals (Sweden)

    Tomoyuki Koya

    Full Text Available Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1, and up-regulate heat shock proteins (HSPs in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (p<0.05. Significant up-regulations of interleukin (IL-1β and tumor necrosis factor mRNAs were observed in HSF1-null, but not in wild-type, mice following 2 weeks of overloading. Overloading-related increases of IL-6 and AFT3 mRNA expressions seen after 2 weeks of overloading tended to decrease after 4 weeks in both types of mice. In HSF1-null mice, however, the significant overloading-related increase in the expression of IL-6, not ATF3, mRNA was noted even at 4th week. Inhibition of muscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.

  12. Revaluation of clinical and histological criteria for diagnosis of dysrnetabolic iron overload syndrome

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

    AIM: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical,biochemical and histopathological findings.METHODS: We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes.The metabolic syndrome (MS) was defined according to ATPⅢ criteria.Iron overload was assessed by liver biopsy.Liver histology was evaluated by Ishak's score and iron accumulation by Deugnier's score; steatosis was diagnosed when present in ≥ 5% of hepatocytes.RESULTS: According to transferrin saturation levels,we observed significant differences in the amount of hepatic iron overload and iron distribution,as well as the number of metabolic abnormalities.Using Receiving Operating Curve analysis,we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload (P < 0.0001).Patients with ≥ 2 metabolic alterations and steatosis had lower amount of hepatic iron,lower transferrin saturation and higher sinusoidal iron than patients with < 2 MS components and absence of steatosis.CONCLUSION: In our patients,the presence of ≥2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation,suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation.These patients may have the typical dysmetabolic iron overload syndrome.By contrast,patients with transferrin saturation ≥ 60% had more severe iron overload,few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.

  13. 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"--

  14. Study on abnormal iron metabolism and iron overload in patients with aplastic anemia

    Institute of Scientific and Technical Information of China (English)

    金朋

    2013-01-01

    Objective To investigate the abnormalities of iron metabolism,the prevalence and risk factors of iron overload and clinical characteristics of patients with aplastic anemia (AA) .Methods A cross-sectional study was conducted on 520 newly diagnosed AA patients.Results Iron overload was observed in 66 (13%) of 520 AA patients,in which a higher prevalence of iron overload was seen not only in patients with infections (19/86,22%) than those without infections (47/434,11%,P<0.01) ,but also in patients with hepatitis associated AA

  15. CTGF knockout does not affect cardiac hypertrophy and fibrosis formation upon chronic pressure overload

    NARCIS (Netherlands)

    Fontes, Magda S C; Kessler, Elise L; van Stuijvenberg, Leonie; Brans, Maike A; Falke, LL; Kok, Bart; Leask, Andrew; van Rijen, HVM; Vos, MA; Goldschmeding, Roel; van Veen, AAB

    2015-01-01

    BACKGROUND: One of the main contributors to maladaptive cardiac remodeling is fibrosis. Connective tissue growth factor (CTGF), a matricellular protein that is secreted into the cardiac extracellular matrix by both cardiomyocytes and fibroblasts, is often associated with development of fibrosis. How

  16. Overload and neovascularization of shoulder tendons in volleyball players

    Directory of Open Access Journals (Sweden)

    Notarnicola Angela

    2012-08-01

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

  17. Competing for Attention in Social Media under Information Overload Conditions

    CERN Document Server

    Feng, Ling; Li, Baowen; Stanley, H Eugene; Havlin, Shlomo; Braunstein, Lidia A

    2014-01-01

    Although the many forms of modern social media have become major channels for the dissemination of information, they are becoming overloaded because of the rapidly-expanding number of information feeds. We analyze the expanding user-generated content in Sina Weibo, the largest micro-blog site in China, and find evidence that popular messages often follow a mechanism that differs from that found in the spread of disease, in contrast to common believe. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that in contrast to epidemics, 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. Thus the greater the number of friends an individual has the greater the number of repeated contacts needed to spread the message, which is a result of competition for attention. We model this process using a fractional susceptible infected recove...

  18. Semicircular Canals Circumvent Brownian Motion Overload of Mechanoreceptor Hair Cells.

    Directory of Open Access Journals (Sweden)

    Mees Muller

    Full Text Available Vertebrate semicircular canals (SCC first appeared in the vertebrates (i.e. ancestral fish over 600 million years ago. In SCC the principal mechanoreceptors are hair cells, which as compared to cochlear hair cells are distinctly longer (70 vs. 7 μm, 10 times more compliant to bending (44 vs. 500 nN/m, and have a 100-fold higher tip displacement threshold (< 10 μm vs. <400 nm. We have developed biomechanical models of vertebrate hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (<10 Hz signals. We observe that very low frequency mechanoreception requires increased stimulus amplitude, and argue that this is adaptive to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors of the SCC.

  19. Performance Analysis of Novel Overload Control with Threshold Mechanism

    Directory of Open Access Journals (Sweden)

    Doo Il Choi

    2016-01-01

    Full Text Available We propose a novel overload control method with hysteresis property; that is, we analyze the M/G/1/K queueing system where the service and arrival rates are varied depending on the queue-length. We use two threshold values: L1(≤L2 and L2(≤K. When the queue-length increases by an amount between L1 and L2, we apply one of the following two strategies to reduce the queue-length, either we decrease the mean service time or we decrease the arrival rate. If the queue-length exceeds L2 with one strategy, we apply the other; thus, there are two models that depend on the method that was applied first. We derive the queue-length distribution at departure and at arbitrary epochs using the embedded Markov chain method and the supplementary variable method. We investigate performance measures including the loss probability and mean waiting time using various numerical examples.

  20. Semicircular Canals Circumvent Brownian Motion Overload of Mechanoreceptor Hair Cells.

    Science.gov (United States)

    Muller, Mees; Heeck, Kier; Elemans, Coen P H

    2016-01-01

    Vertebrate semicircular canals (SCC) first appeared in the vertebrates (i.e. ancestral fish) over 600 million years ago. In SCC the principal mechanoreceptors are hair cells, which as compared to cochlear hair cells are distinctly longer (70 vs. 7 μm), 10 times more compliant to bending (44 vs. 500 nN/m), and have a 100-fold higher tip displacement threshold (< 10 μm vs. <400 nm). We have developed biomechanical models of vertebrate hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (<10 Hz) signals. We observe that very low frequency mechanoreception requires increased stimulus amplitude, and argue that this is adaptive to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors of the SCC. PMID:27448330

  1. Reliability testing and reliability analysis of the over-load protective relay

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jing-ying; CHEN Hong-jian; LIU Guo-jin; ZHANG Yong; WU Pin-hua

    2007-01-01

    The over-load protective relay is widely used for motor protection. The reliability of the over-load protective relay directly affects the safe running of a motor. The reliability testing and reliability analysis of the over-load protective relay is an important way to improve the reliability of products. In this paper, the reliability test method of the over-load protective relay is studied, and the reliability tests of the typical products are carried out on a reliability tester developed by authors. In terms of the testing results, the reliability analysis is finished. The failure reasons are found and the measures are put forward to improve the reliability of the products.

  2. Bioimpedance Spectroscopy for the Detection of Fluid Overload in Chinese Peritoneal Dialysis Patients

    OpenAIRE

    Kwan, Bonnie Ching-Ha; Szeto, Cheuk-Chun; Chow, Kai-Ming; Law, Man-Ching; Cheng, Mei Shan; Leung, Chi-Bon; Pang, Wing-Fai; Kwong, Vickie Wai-Ki; Li, Philip Kam-tao

    2014-01-01

    ♦ Background: Fluid overload probably contributes to the cardiovascular risk of peritoneal dialysis (PD) patients. We studied the relationship between over-hydration as determined by bioimpedance spectroscopy and dialysis adequacy, nutritional status, and arterial stiffness in Chinese PD patients.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Iron Overload Assessment in Adult Thalassaemic Patients Using MRI T2

    Directory of Open Access Journals (Sweden)

    Azita Azarkeivan

    2009-01-01

    Full Text Available "nd anemia in our country. Blood transfusion is the continual treatment of this disease. But transfusion causes a serious side effect which is iron overload in vital organs such as the heart, liver and the endocrine system. Accumulated iron in these organs may cause high risk secondary problems which threaten the patients' life. Early assessment of the iron overload in vital organs and applying for early treatment can be beneficial for increasing life quality in these patients. Assessment of cardiac and hepatic iron overload using MRI T2 technique and comparing it with serum ferritin level was the goal of this study. "nMaterials and Methods: The referred thalassaemic patients to Zafar adult thalassaemia clinic were the population of this study. Serum ferritin test was carried out for all these patients. Cardiac and hepatic iron overload assessment of these patients was performed in Noor medical imaging center using MRI T2 technique. The iron overload results of all patients were classified as normal, mild, moderate and severe. We compared them with the patients’ clinical parameters, especially the serum ferritin level. Results were analyzed by SPSS software. "nResults: 700 adult patients with the mean age of 25.76 (SD±10.4 were studied in this research project. There were 360 males (51.4% and 340 (48.6% females enrolled in this study. Among them, there were 502 (71.7% major thalassaemia, 158 (22.6% intermediate thalassaemia, 7 alpha thalassaemia, 9 sickle cell anemia and 10 hemochromatosis patients. The mean of serum ferritin level was 2327.6 mg/dl (SD±2095.8. Classified results of cardiac iron overload assessment were normal in 366 (66.5% patients, mild in 44 (8% patients, moderate in 64 (11.6% patients, and severe in 76 (13.8%patients. The classified results of hepatic iron overload assessment were: normal in 122 (22.2% patients, mild in 137 (25% patients, moderate in 235 (42.8% patients and severe in 55 (10% patients. Iron overload

  6. The Dietary Niacin Requirement of Large GIFT Tilapia%吉富罗非鱼成鱼对烟酸的需要量

    Institute of Scientific and Technical Information of China (English)

    黄凤; 文华; 吴凡; 蒋明; 刘伟; 田娟; 邵辉

    2013-01-01

    Total 360 large GIFT tilapia, Oreochromis niloticus, with average initial body mass of (220. 16 ± 7. 66) g were randomly divided into 6 groups consisting of 3 replicates (20 fish per net). Each group was fed a diet that mass fractions of niacin were 11. 84 ( control group) , 37. 78 , 64. 70, 89. 44, 157. 15 , 335. 36 mg o kg-1 for 10 weeks. Growth, feed utilization, body composition, some serum biochemical indices and liver niacin concentration were measured to detect the suitable requirement of niacin in diet of large GIFT tilapia. The results showed that the addition of niacin to diets significantly improved fish mass gain rate(MGR, % ) and feed efficiency ( FE) ; the crude protein content in whole-body of fish in the 157. 15 and 335. 36 mg o kg-1 groups was significantly higher than that of other groups. The crude lipid content of fish in the 64. 70 mg o kg-1 group was the highest and significantly higher than that of the control group; there were no significant differences in carcase moisture and crude ash of the fish. The serum total cholesterol(T-CHO, mmol o L-1) , high density lipoprotein cholesterol( HDL-C, mmol o L-1) and total protein(TP, mmol o L-1 ) content first increased then decreased as the level of dietary niacin increased, and they reached the peak when feeding the fish mass fraction of niacin 157. 15 mg o kg-1 . The addition of niacin to diets significantly reduced serum triglyceride (TG, mmol o L-1 ) content. The niacin content in liver first increased then plateaued with increasing dietary niacin levels and it was significantly higher in the niacin added groups than that of the control group. Regression analysis showed that large GIFT tilapia were estimated to need mass fraction of niacin 63. 62, 158. 52 - 172. 41 mg o kg-1 respectively to maintain their maximum growth and normal physiological function.%选用初始体质量为(220.16±7.66)g的吉富罗非鱼Oreochromis niloticus 360尾,随机分成6组(每组3个重复,每重复20尾),分

  7. The Study on On-line Scheduling Algorithm of Imprecise Computation under Transient Overload

    Institute of Scientific and Technical Information of China (English)

    WEIZhenhua; HONGBingrong; QIAOYongqiang; CAIZesu; PENGJunjie

    2003-01-01

    Transient overload always occurs in realtime computer system. An on-line scheduling algorithm of imprecise computation is proposed in this paper to deal with it. This algorithm can be sure of getting acceptable computation result under the condition of overload, and at the same time it can improve the computation precision as much as possible. The system model of imprecise computation and the on-line imprecise computation algorithm are elaborated. And the algorithm is proved correct by simulation.

  8. 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...

  9. 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 ...

  10. Haemochromatosis genotype and iron overload: association with hypertension and left ventricular hypertrophy

    DEFF Research Database (Denmark)

    Ellervik, C; Tybjaerg-Hansen, A; Appleyard, M;

    2010-01-01

    We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH).......We hypothesized that there is an association between haemochromatosis genotype C282Y/C282Y and/or iron overload and risk of hypertension and/or left ventricular hypertrophy (LVH)....

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

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

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

  12. Quantitative evaluation of right ventricular overload in cor pulmonale using 201Tl myocardial SPECT

    International Nuclear Information System (INIS)

    To determine quantitatively the discriminant and characteristics of cor pulmonale, 201Tl myocardial perfusion SPECT was performed in 16 patients with chronic obstructive pulmonary disease (COPD) and 7 with restrictive pulmonary disease (RPD). One section of the short-axis SPECT image in which the right ventricle was most clearly visualized was selected. Tl-score was defined as the ratio of the sum of counts in the region of interest (ROI) at the anterior, mid, and posterior regions of the right ventricular free wall to the sum of counts in ROI at the posterior, lateral, and anterior walls of the left ventricle, and the anterior and posterior regions of the interventricular septum. In the group of COPD patients, Tl-score was positively correlated with mean pulmonary arterial pressure (mPAP), total pulmonary vascular resistance (TPR), and arterial carbon dioxide tension (PaCO2), while it was inversely correlated with arterial oxygen tension (PaO2). However, there was no significant correlation between Tl-score and mPAP, TPR, PaCO2, and PaO2 in the group of RPD patients. In assessing pulmonary hypertension as defined by mPAP over 20 mmHg, a Tl-score greater than 0.25 was useful with a sensitivity of 69% and a specificity of 90%. The occurrence of cor pulmonale is a major factor in determining the prognosis of COPD patients. It was concluded that 201Tl myocardial SPECT is useful for evaluating right ventricular overload quantitatively, as well as for assessing core pulmonale, especially in COPD patients, since the ratio of Tl counts in the right and left ventricles was significantly correlated with right cardiopulmonary hemodynamic parameters. (N.K.)

  13. Interactions of aging, overload, and creatine supplementation in rat plantaris muscle.

    Science.gov (United States)

    Schuenke, Mark D; Brooks, Naomi E; Hikida, Robert S

    2011-01-01

    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. PMID:21876808

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    2016-09-01

    Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with (89)Zr, a long half-life (78.4h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with (89)Zr directly at pH5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/μmol. The (89)Zr-MP was stable in human plasma and PBS for at least 48h. The half-life of (89)Zr-MP was about 15.70±1.74h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that (89)Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy. PMID:27359110

  16. Iron overload in non-transfusion-dependent thalassemia: association with genotype and clinical risk factors.

    Science.gov (United States)

    Tantiworawit, Adisak; Charoenkwan, Pimlak; Hantrakool, Sasinee; Choeyprasert, Worawut; Sivasomboon, Chate; Sanguansermsri, Torpong

    2016-06-01

    In the present study, we sought to determine the prevalence of iron overload in patients with non-transfusion-dependent thalassemia (NTDT) and its association with genotype and other clinical risk factors, and to evaluate the correlation between serum ferritin (SF) and liver iron concentration (LIC). Myocardial and liver iron concentration was measured by MRI using a T2* gradient multi-echo sequence in NTDT patients, aged 10-50 years. Of 91 patients, 54 (59 %) had hepatic iron overload. None had cardiac iron overload. The clinical risk factors for hepatic iron overload were age >20 years (adjusted OR 30.2, 95 % CI 4.5-203, p 10 units (adjusted OR 53.6, 95 % CI 3.2-884, p = 0.005). Beta-thalassemia genotype was associated with higher risk of iron overload by univariate analysis, but the association was not significant when adjusted for other clinical factors. The correlation coefficient between SF and LIC was 0.60 (p < 0.001). In conclusion, the prevalence of hepatic iron overload is high in NTDT. Older age, lower hemoglobin level, and higher cumulative RBC transfusion are significant risk factors. SF and LIC show a significant positive correlation. PMID:27052211

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

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

    Science.gov (United States)

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

    2005-01-01

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

  20. The thrower's elbow: arthroscopic treatment of valgus extension overload syndrome.

    Science.gov (United States)

    O'Holleran, James D; Altchek, David W

    2006-02-01

    Injury to the medial collateral ligament of the elbow (MCL) can be a career-threatening injury for an overhead athlete without appropriate diagnosis and treatment. It has been considered separately from other athletic injuries due to the unique constellation of pathology that results from repetitive overhead throwing. The past decade has witnessed tremendous gains in understanding of the complex interplay between the dynamic and static stabilizers of the athlete's elbow. Likewise, the necessity to treat these problems in a minimally invasive manner has driven the development of sophisticated techniques and instrumentation for elbow arthroscopy. MCL injuries, ulnar neuritis, valgus extension overload with osteophyte formation and posteromedial impingement, flexor pronator strain, medial epicondyle pathology, and osteochondritis dissecans (OCD) of the capitellum have all been described as sequelae of the overhead throwing motion. In addition, loose body formation, bony spur formation, and capsular contracture can all be present in conjunction with these problems or as isolated entities. Not all pathology in the thrower's elbow is amenable to arthroscopic treatment; however, the clinician must be familiar with all of these problems in order to form a comprehensive differential diagnosis for an athlete presenting with elbow pain, and he or she must be comfortable with the variety of open and arthroscopic treatments available to best serve the patient. An understanding of the anatomy and biomechanics of the thrower's elbow is critical to the care of this population. The preoperative evaluation should focus on a thorough history and physical examination, as well as on specific diagnostic imaging modalities. Arthroscopic setup, including anesthesia, patient positioning, and portal choices will be discussed. Operative techniques in the anterior and posterior compartments will be reviewed, as well as postoperative rehabilitation and surgical results. Lastly, complications

  1. IRON OVERLOAD AND GROWTH OF THALASSEMIC PATIENTS IN MARWAR REGION

    Directory of Open Access Journals (Sweden)

    Bhavana Singhal , Neha Shama* and Ranjana Mathur

    2012-07-01

    Full Text Available Growth disturbances are a major clinical feature of thalassemic patients. Regular blood transfusions and iron-chelation therapy greatly contribute to the quality and longevity of thalassemic patients. The main objective of present study was to compare the current growth of Thalassemia major patients, taking into accounts the iron overload, transfusion and iron chelation therapy, therefore we planned this study. The present study was conducted on 63 Thalassemic patients were enrolled in this study from June 2008 to October 2008. These subjects were categorised into two groups: 36 children (10 years. Enrolled subjects were examined for various anthropometric parameters as height, weight and body mass index. Venous blood samples were obtained for estimating serum ferritin. Family history (carrier status of father, mother or siblings, age of diagnosis, age of first blood transfusion, frequency of blood transfusion and details of chelation therapy were recorded during the study Serum Ferritin level was very significantly elevated in the adolescents when compared to children because the number of transfusion increases as age advance. Percentile curves (NCHS growth curves showed pronounced growth retardation in height and weight after 10 years of age in both sexes. A very significant difference (t=3.43, p<0.01was observed between the serum Ferritin value of total no. of thalassemic children (1496.59 ±74.05 ng/ML and the thalassemic adolescents (2397.97 ± 1199.57 ng/ML. Determination of serum ferritin and routine growth monitoring at regular intervals is necessary to detect any disturbance in growth and to establish an appropriate protocol for investigation and treatment.

  2. Glutathione synthesis inhibitor butathione sulfoximine regulates ceruloplasmin by dual but opposite mechanism: Implication in hepatic iron overload.

    Science.gov (United States)

    Tapryal, Nisha; Mukhopadhyay, Chaitali; Mishra, Manoj Kumar; Das, Dola; Biswas, Sudipta; Mukhopadhyay, Chinmay K

    2010-06-01

    Glutathione (GSH) depletion is often detected in chronic pathological conditions like hepatitis C infection, alcohol consumption or xenobiotic assault with simultaneous reactive oxygen species (ROS) generation and hepatic iron overload. However, relation between GSH depletion and regulators of iron homeostasis is not clear so far. To determine that hepatic HepG2 cells were treated with GSH synthesis inhibitor butathione sulfoximine (BSO) and a dual regulation of ceruloplasmin (Cp) that involves in hepatic iron release was detected unlike other iron homeostasis regulators. BSO treatment that caused marginal GSH deficiency increased Cp synthesis due to increased transcription mediated by activator protein (AP)-1-binding site. In higher GSH deficiency (> 40 %) with increased ROS generation, Cp expression was decreased due to promotion of Cp mRNA decay mediated by 3'untranslated region (3'UTR) as found by transfecting chimera of chloramphenicol acetyl transferase (CAT) gene with Cp 3'UTR. RNA gel shift assay showed significant reduction in 3'UTR binding protein complex in similar condition. Decreased CAT expression and RNA-protein complex binding are reversed by pretreatment with antioxidant N-acetyl cysteine suggesting 3'UTR binding protein complex is redox-sensitive. This unique and opposite regulation of Cp provides a mechanism of hepatic iron-deposition during glutathione deficiency detected in chronic pathological conditions.

  3. ASCERTAINMENT OF ADMISSIBLE SYSTEMATIC OVERLOADS IN THE DISTRIBUTIVE OIL-TRANSFORMERS

    Directory of Open Access Journals (Sweden)

    V. A. Anishchenko

    2015-01-01

    Full Text Available The capacity of power-distributive oil-transformers is selected on the basis of their operational mode cost-effectiveness and power-supply reliability of the electrical recipients on condition that the transformers duty should not lead to reduction of their normal life-in-service. Unconscionable and protracted overloads intrinsically decrease reliability and respectively service life of the transformers owing to increased wear of the winding insulation because of the excessive heat. The unaccounted previous loading history and possible changes of the risen overload in the course of its further development can lead to poor accuracy in the admissible overload time estimation. Therefore, that may lead to intolerable excessive heat in the winding insulation or underutilization of the potential overload capacity of the transformers. Which limits the potentiality of complete demand satisfaction of the electrical consumers. This is exactly why the acting GOST 14209–97 strongly recommends the consumers to make their own calculations of the load-carrying capacity based on the real load curves.The authors present a method for ascertainment of the admissible duration of the systematic non-emergency overload of a distributive oil-transformer. The ascertainment method accounts for the overload repetition-factor alteration on the time-interval of its occurrence and respectively the variation in the transformer thermal state. The employment of this method will allow improving accuracy in ascertainment of the admissible duration of the systematic non-emergency overloads and eventually the reliability of the transformer operation and the power-supply system in its entirety. The method realization is intended by means of the transformer-load monitoring as one of the tasks of the electric-energy automated control and accounting system.

  4. Biological responses to overload training in endurance sports.

    Science.gov (United States)

    Fry, R W; Morton, A R; Garcia-Webb, P; Crawford, G P; Keast, D

    1992-01-01

    Five subjects undertook 10 days of twice daily interval training sessions on a treadmill followed by 5 days of active recovery. On days 1, 6, 11, and 16 the subjects were required to undertake a test of submaximal and maximal work capacity on a treadmill combined with a performance test consisting of a run to exhaustion with the treadmill set at 18 km.h-1 and 1% gradient. Also on these days a pre-exercise blood sample was collected and analysed for a range of haematological, biochemical and immunological parameters. The subjects experienced a significant fall in performance on day 11 which had returned to pretraining levels on day 16. Serum ferritin concentrations were depressed significantly from pretraining concentrations at the conclusion of the recovery period while the expression of lymphocyte activation antigens (CD25+ and HLA-DR+) was increased both after the training phase and the recovery phase. The number of CD56+ cells in the peripheral circulation was depressed at the conclusion of the recovery period. Several parameters previously reported to change in association with overload training failing to reflect the decrease in performance experienced by subjects in this study, suggesting that overtraining may best be diagnosed through a multifactorial approach to the recognition of symptoms. The most important factor to consider may be a decrease in the level of performance following a regeneration period. The magnitude of this decreased performance necessary for the diagnosis of overtraining and the nature of an "appropriate" regeneration period are, however, difficult to define and may vary depending upon the training background of the subjects and the nature of the preceding training. It may or may not be associated with biochemical, haematological, physiological and immunological indicators. Individual cases may present a different range of symptoms and diagnosis of overtraining should not be excluded based on the failure of blood parameters to

  5. 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.

  6. Low Acceleration Overload Catapult Technique for Throwing the Small Scout Robot

    Directory of Open Access Journals (Sweden)

    Jianzhong Wang

    2016-09-01

    Full Text Available The small scout robot is generally thrown into the war zone by soldier. The short thrown distance and the danger of soldier exposed to the enemy limit the application of the small scout robot. So this paper presents a type of low acceleration overload catapult device of no flash, no smoke and no sound. It can throw the small scout robot covertly to long distances with low acceleration overload, and avoid the danger that soldier be exposed to the enemy when artificial throwing. The high and low pressure chambers of the catapult device achieve the low acceleration overload launching, and eliminate the risk of robot damaged by huge acceleration overload. The covert launching of no flash, no smoke and no sound is achieved by the piston to seal the gun propellant gas in barrel. Based on the interior ballistic model, the interior ballistic performance is calculated. The experiment for measuring the acceleration overload of the projectile is achieved by using the catapult device prototype and the measurement system developed by authors. The simulation and test results show that this catapult device can meet the requirement to throw the small scout robot into the war zone.

  7. 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.

  8. 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.

  9. 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.

  10. Shape-memory alloy overload protection device for osseointegrated transfemoral implant prosthetic limb attachment system

    Science.gov (United States)

    Xu, Wei; Shao, Fei; Hughes, Steven

    2002-11-01

    The osseointegrated trans-femoral implant system provides a direct anchoring technique to attach prosthetic limb. This technique was first introduced PI Brenmark in Sweden. The UK had the first clinical trial in 1997 and currently has 6 active limb wearers. The success of this procedure has the potential for improved gait function and mobility, increased employability and significant long-term improvements in the quality of life for above knee amputees. However, the significant load involved in the trans-femoral implant system has caused permanent deformation and/or fractures of the implant abutment in several occasions. To protect the implant system, the implant abutment in particularly, an overloading protection device was introduced. The device uses mechanical mechanism to release torsion overload on the abutment. However, the bending overload protection remains unsolved. To solve the problem, a new overload protection device was developed. This device uses SMA component for bending overload protection. In this paper, the results of non-linear finite element modelling of the SMA and steel (AISI 1040) components were presented. Experiments were also carried out using steel components to assess the design which is based on the non-linear property of the materials.

  11. Effects of extended-release niacin/laropiprant, simvastatin, and the combination on correlations between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients with dyslipidemia

    OpenAIRE

    Farnier M; Chen E; Johnson-Levonas AO; McCrary Sisk C; Mitchel YB

    2014-01-01

    Michel Farnier,1 Erluo Chen,2 Amy O Johnson-Levonas,2 Christine McCrary Sisk,2 Yale B Mitchel21Point Médical, Dijon, France; 2Merck and Co, Inc., Whitehouse Station, NJ, USABackground: Statins modify correlations between apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C) and apoB and non-high-density lipoprotein cholesterol (non-HDL-C); however, it is not known whether niacin-based therapies have similar effects.Objective: To evaluate the effects of extended-re...

  12. Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control

    Directory of Open Access Journals (Sweden)

    Bays HE

    2015-02-01

    Full Text Available Harold E Bays,1 Eliot A Brinton,2 Joseph Triscari,3 Erluo Chen,3 Darbie Maccubbin,3 Alexandra A MacLean,3 Kendra L Gibson,3 Rae Ann Ruck,3 Amy O Johnson-Levonas,3 Edward A O’Neill,3 Yale B Mitchel3 1Louisville Metabolic & Atherosclerosis Research Center (L-MARC, Louisville, KY, USA; 2Utah Foundation for Biomedical Research, Salt Lake City, UT, USA; 3Merck & Co, Inc., Whitehouse Station, NJ, USA Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM may alter lipid levels and may alter the efficacy of lipid-modifying agents. Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT in subgroups of patients with T2DM with better or poorer glycemic control. Methods: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796, examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. Results: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C, non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a, compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. Conclusion: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758. Keywords: lipid-modifying agents, hyperglycemia, LDL, HDL, triglycerides

  13. 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.)

  14. 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.

  15. Dynamic Strain Evolution around a Crack Tip under Steady- and Overloaded-Fatigue Conditions

    Directory of Open Access Journals (Sweden)

    Soo Yeol Lee

    2015-11-01

    Full Text Available We investigated the evolution of the strain fields around a fatigued crack tip between the steady- and overloaded-fatigue conditions using a nondestructive neutron diffraction technique. The two fatigued compact-tension specimens, with a different fatigue history but an identical applied stress intensity factor range, were used for the direct comparison of the crack tip stress/strain distributions during in situ loading. While strains behind the crack tip in the steady-fatigued specimen are irrelevant to increasing applied load, the strains behind the crack tip in the overloaded-fatigued specimen evolve significantly under loading, leading to a lower driving force of fatigue crack growth. The results reveal the overload retardation mechanism and the correlation between crack tip stress distribution and fatigue crack growth rate.

  16. 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.

  17. 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...

  18. Calcium overload injury of rats' enterocyte IEC-6 by heat stress in vitro

    OpenAIRE

    Geng, Yan; Liu, Ya-Nan; Fu, Wei; Na PENG; Zhi-guo PAN; Yu-mei LEI; Su, Lei

    2013-01-01

    Objective To investigate the effect of gradient heat stress on calcium overload of rats' enterocyte IEC-6 and calcium overload-related cell injury in vitro. Methods Thermal gradient was set in culturing IEC-6 cells in vitro. After thermal stimulation, Fluo-3Am probe with fluorescence microscope or flow cytometry was used to detect the change in intracellular Ca2+ concentration of IEC-6 cells. Phase contrast microscope was used to observe the morphological change in IEC-6. Coomassie blue dying...

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

    OpenAIRE

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

    2011-01-01

    Insulin resistance (IR) and systemic hypertension are independently associated with heart failure. We reported previously that nitric oxide synthase 3 (NOS3) has a beneficial effect on left ventricular (LV) remodeling and function after pressure-overload in mice. The aim of our study was to investigate the interaction of IR and NOS3 in pressure-overload-induced LV remodeling and dysfunction. Wild-type (WT) and NOS3-deficient (NOS3−/−) mice were fed either a standard diet (SD) or a high-fat di...

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

    Science.gov (United States)

    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.

  1. PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells

    International Nuclear Information System (INIS)

    Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. Conclusion: Altogether, our in vitro data on steatotic HepaRG cells treated with PPAR agonists correlated well with clinical investigations, bringing a proof of concept that drug-induced reversal of steatosis in human can be evaluated in in vitro before conducting long-term and costly in vivo studies in animals and patients. - Highlights: • There is no pharmacological agent approved for the treatment of NAFLD. • This study demonstrates that PPAR agonists can reduce fatty acid-induced steatosis. • Some nuclear receptors appear to be potent actors in the control

  2. PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells

    Energy Technology Data Exchange (ETDEWEB)

    Rogue, Alexandra [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France); Biologie Servier, Gidy (France); Anthérieu, Sébastien; Vluggens, Aurore [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France); Umbdenstock, Thierry [Technologie Servier, Orléans (France); Claude, Nancy [Institut de Recherches Servier, Courbevoie (France); Moureyre-Spire, Catherine de la; Weaver, Richard J. [Biologie Servier, Gidy (France); Guillouzo, André, E-mail: Andre.Guillouzo@univ-rennes1.fr [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France)

    2014-04-01

    Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. Conclusion: Altogether, our in vitro data on steatotic HepaRG cells treated with PPAR agonists correlated well with clinical investigations, bringing a proof of concept that drug-induced reversal of steatosis in human can be evaluated in in vitro before conducting long-term and costly in vivo studies in animals and patients. - Highlights: • There is no pharmacological agent approved for the treatment of NAFLD. • This study demonstrates that PPAR agonists can reduce fatty acid-induced steatosis. • Some nuclear receptors appear to be potent actors in the control

  3. Distribution of costameric proteins in the diaphragm of patients with chronic obstructive pulmonary disease.

    NARCIS (Netherlands)

    Wijnhoven, J.H.; Hafmans, T.G.M.; Dekhuijzen, P.N.R.

    2006-01-01

    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an increased load on the diaphragm. Increased (eccentric) loading has been shown to result in disturbances in the cytoskeleton. OBJECTIVES: We hypothesized that due to a continuous overload of the diaphragm in COPD patients,

  4. The Effects of Extended Release Niacin in Combination with Omega 3 Fatty Acid Supplements in the Treatment of Elevated Lipoprotein (a

    Directory of Open Access Journals (Sweden)

    Alan F. Helmbold

    2010-01-01

    Full Text Available Objective. To assess the effectiveness of niacin/fish oil combination therapy in reducing Lipoprotein (a [Lp(a] levels after twelve weeks of therapy. Background. Lipoprotein (a accumulates in atherosclerotic lesions and promotes smooth muscle cell growth and is both atherogenic and thrombogenic. A clinical trials of combination therapy for the reduction of Lp(a has not been previously reported. Methods. The study was an observational study following subjects with an elevated Lp(a (>70 nmol/L to assess impact of 12 weeks of combination Omega 3FA, niacin, and the Mediterranean diet on Lp(a. Results. Twenty three patients were enrolled with 7 patients lost to follow up and 2 patients stopped due to adverse events. The average Lp(a reduction in the remaining 14 subjects after 12 weeks of combination therapy was 23%± 17% [=.003] with a significant association of the reduction of Lp(a with increasing baseline levels of Lp(a [R2=0.633, =.001]. Conclusions. There was a significant reduction in Lp(a levels with combination therapy. A more pronounced effect was noted in patients with higher baseline levels of Lp(a.

  5. 30 CFR 75.518-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short circuit protection; minimum requirements. 75.518-1 Section 75.518-1 Mineral Resources MINE SAFETY...-UNDERGROUND COAL MINES Electrical Equipment-General § 75.518-1 Electric equipment and circuits; overload...

  6. 30 CFR 77.506-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Science.gov (United States)

    2010-07-01

    ...-1 Electric equipment and circuits; overload and short circuit protection; minimum requirements... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short circuit protection; minimum requirements. 77.506-1 Section 77.506-1 Mineral Resources MINE...

  7. Steroidal and Nonsteroidal Mineralocorticoid Receptor Antagonists Cause Differential Cardiac Gene Expression in Pressure Overload-induced Cardiac Hypertrophy.

    Science.gov (United States)

    Grune, Jana; Benz, Verena; Brix, Sarah; Salatzki, Janek; Blumrich, Annelie; Höft, Beata; Klopfleisch, Robert; Foryst-Ludwig, Anna; Kolkhof, Peter; Kintscher, Ulrich

    2016-05-01

    Pharmacological blockade of mineralocorticoid receptors (MR) is known as an efficacious therapy in chronic heart failure. Therapy with steroidal MR antagonists such as spironolactone or eplerenone (EPL) is often limited because of side effects. Recently, a new highly selective and potent, nonsteroidal MR antagonist, finerenone (FIN), has been developed. To investigate the effects of FIN on pressure-induced cardiac hypertrophy, the transverse aortic constriction (TAC) model was used in C57BL/6 mice treated with FIN (10 mg·kg·d), EPL (200 mg·kg·d) or vehicle (VEH). First, we analyzed cardiac gene expression 4 weeks after TAC using a pathway-focused quantitative polymerase chain reaction array. FIN caused a distinct cardiac gene expression profile compared to VEH and EPL, including differential expression of BNP (brain natriuretic peptide) and Tnnt2 (troponin T type 2). FIN treatment led to a significant reduction of TAC-induced left ventricular (LV) wall thickening assessed by echocardiography. In accordance, FIN-treated mice showed a significant lower increase of calculated left ventricular mass compared with VEH- and EPL-treated mice (FIN: 28.4 ± 3.7 mg; EPL: 38.4 ± 4.3 mg; VEH: 39.3 ± 3.1 mg; P < 0.05). These data show beneficial effects of nonsteroidal MR antagonism by FIN on left ventricular mass development in pressure overload associated with a distinct cardiac gene expression profile. PMID:26859196

  8. Transformation rate between ferritin and hemosiderin assayed by serum ferritin kinetics in patients with normal iron stores and iron overload.

    Science.gov (United States)

    Saito, Hiroshi; Hayashi, Hisao

    2015-11-01

    Ferritin iron, hemosiderin iron, total iron stores and transformation rate were determined by serum ferritin kinetics. The transformation rate between ferritin and hemosiderin is motivated by the potential difference between them. The transformer determines transformation rate according to the potential difference in iron mobilization and deposition. The correlations between transformation rate and iron stores were studied in 11 patients with chronic hepatitis C (CHC), 1 patent with treated iron deficiency anemia (TIDA), 9 patients with hereditary hemochromatosis (HH) and 4 patients with transfusion-dependent anemia (TD). The power regression curve of approximation showed an inverse correlation between transformation rate and ferritin iron, hemosiderin iron in part and total iron stores in HH. Such an inverse correlation between transformation rate and iron stores implies that the larger the amount of iron stores, the smaller the transformation of iron stores. On the other hand, a minimal inverse correlation between transformation rate and ferritin iron and no correlation between transformation rate and hemosiderin iron or total iron stores in CHC indicate the derangement of storage iron metabolism in the cells with CHC. Radio-iron fixation on the iron storing tissue in iron overload was larger than that in normal subjects by ferrokinetics. This is consistent with the inverse correlation between transformation rate and total iron stores in HH. The characteristics of iron turnover between ferritin and hemosiderin were disclosed from the correlation between transformation rate and ferritin iron, hemosiderin iron or total iron stores. PMID:26663936

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

    Science.gov (United States)

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

    2015-01-01

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

  10. 30 CFR 77.506 - Electric equipment and circuits; overload and short-circuit protection.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short-circuit protection. 77.506 Section 77.506 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... WORK AREAS OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.506 Electric equipment...

  11. [Non-transferrin-bound iron: a promising biomarker in iron overload disorders].

    NARCIS (Netherlands)

    Maas, R.P.P.W.M.; Voets, P.J.; Swart, L. de; Swinkels, D.W.

    2013-01-01

    - Iron overload disorders are common and, if left untreated, severe systemic diseases that can have both genetic and acquired causes.- Hereditary haemochromatosis, beta-thalassaemia, myelodysplastic syndromes and sickle cell disease are among the most important examples.- Iron that is not bound to t

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

    NARCIS (Netherlands)

    Liang, Wen

    2015-01-01

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

  13. 'Sorting the Wheat from the Chaff': Investigating Overload in Educational Discussion Systems

    Science.gov (United States)

    Kear, Karen; Heap, N.W.

    2007-01-01

    This paper reports on research to investigate design features of asynchronous discussion systems for higher education. The research aims to identify features that increase the benefits of discussion systems and reduce the problems. The paper focuses on a major theme that emerged from interviews with learners and teachers: information overload.…

  14. Variation and significance of microtubules in rat volume overload cardiac hypertrophy

    Institute of Scientific and Technical Information of China (English)

    刘华胜; 马爱群; 王春梅; 刘勇; 田红燕; 白玲

    2003-01-01

    Objective To investigate the function of microtubules in volume overload cardiac hypertrophy of rat. Methods The structure of microtubules was observed using an immunofluorescent microscope, while the pixel intensity and distribution of microtubule imaging was estimated from laser scanning confocal images of left ventricular cardiocytes immuno-labeled with an antibody to β-tubulin. Results The pixels of the microtubule image taken just after volume overload were not evenly distributed. At 6 hours after overload, the pixel intensity of the microtubule image was decreased to less than 150 (arbitrary units), which was the same as the pixel intensity and distribution of the colchicine depolymerized microtubule image. The changes were partially recovered to 200 (arbitrary units) after 4 more days. The pixel intensity of the control microtubule image was 250 (arbitrary units) and had an even distribution. The structuring of the microtubules was more disordered as volume overload hypertrophy developed. Conclusions There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in the hypertrophic myocardium and microtubule is one of the members of the signal transduction pathways governing the hypertrophic response of cardiomyocytes in the hypertrophic myocardium. The disordered microtubule array may be targeted during heart failure treatment.

  15. Logarithmic quantitation model using serum ferritin to estimate iron overload in secondary haemochromatosis.

    OpenAIRE

    Güngör, T; Rohrbach, E.; Solem, E; Kaltwasser, J P; Kornhuber, B

    1996-01-01

    Nineteen children and adolescents receiving repeated transfusions and subcutaneous desferrioxamine treatment were investigated in an attempt to quantitate iron overload non-invasively. Before patients were started on desferrioxamine individual relationships were correlated for 12 to 36 months between transfused iron, absorbed iron estimated gastrointestinally, and increasing serum ferritin concentrations. Patients with inflammation, increased liver enzymes, or haemolysis were excluded from an...

  16. 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

  17. 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...

  18. 77 FR 11598 - Thermal Overload Protection for Electric Motors on Motor-Operated Valves

    Science.gov (United States)

    2012-02-27

    ... function. II. Further Information DG-1264, was published in the Federal Register on May 02, 2011 (76 FR... COMMISSION Thermal Overload Protection for Electric Motors on Motor-Operated Valves AGENCY: Nuclear... for Electric Motors on Motor-Operated Valves.'' This regulatory guide describes a method acceptable...

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

    International Nuclear Information System (INIS)

    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

  20. Fatigue crack growth due to overloads in plain concrete using scaling laws

    Indian Academy of Sciences (India)

    Sonalisa Ray; J M Chandra Kishen

    2012-02-01

    Scaling laws are represented in power law form and can be utilized to extract the characteristic properties of a new phenomenon with the help of self-similar solutions. In this work, an attempt has been made to propose a scaling law analytically, for plain concrete when subjected to variable amplitude loading. Due to the application of overload on concrete structures, acceleration in the crack growth process takes place. A closed form expression has been developed to capture the acceleration in crack growth rate in conjunction with the principles of dimensional analysis and self-similarity. The proposed model accounts for parameters such as, the tensile strength, fracture toughness, overload effect and the structural size. Knowing the governed and the governing parameters of the physical problem and by using the concepts of self-similarity, a relationship is obtained between the different parameters involved. The predicted results are compared with experimental crack growth data for variable amplitude loading and are found to capture the overload effect with sufficient accuracy. Through a sensitivity analysis, fracture toughness is found to be the most dominant parameter in accelerating the crack length due to application of overload.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Alejandra Rodriguez

    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.

  3. Scientific Opinion on the safety and efficacy of niacin (nicotinic acid and nicotinamide as a feed additive for all animal species based on a dossier submitted by Vertellus Specialties Belgium BV

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Additives and Products or Substances used in Animal Feed

    2012-07-01

    Full Text Available

    The term ‘niacin’ is used as a generic description of nicotinic acid and nicotinamide with pyridine as the basic structure. Nicotinic acid and nicotinamide function mainly as precursors of the co-enzymes NAD and NADP. Thus, nicotinamide has physiologically critical roles in mitochondrial respiration and in the metabolism of carbohydrates, lipids, and amino acids. Niacin is safe for the target animals with a margin of safety that is at least ten times the requirements and use levels. The FEEDAP Panel assumes that exposure figures for a population already include the contribution of edible tissues and products of animals fed niacin-supplemented diets. Information on niacin metabolism and the limited data available on retention in edible tissues and products indicate that supplemental levels in feeds even far higher than the requirements (1–35 mg/kg feed are highly unlikely to lead the tolerable upper intake level being exceeded. The FEEDAP Panel considers that the use of niacin in animal nutrition is not of safety concern for consumers. Nicotinic acid and nicotinamide are not irritant to skin, but can cause irritancy to eyes and mucous membranes. They are unlikely to cause skin sensitisation. Workers might be exposed to a respirable dust when handling nicotinic acid and nicotinamide, which should be regarded as being potentially harmful to their health. The use of nicotinic acid and nicotinamide in animal nutrition does not pose a risk to the environment. Nicotinic acid and nicotinamide are regarded as effective sources of niacin in animal nutrition.

  4. Scientific Opinion on the safety and efficacy of niacin (nicotinic acid and nicotinamide as a feed additive for all animal species based on a dossier submitted by Lonza Benelux BV

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Additives and Products or Substances used in Animal Feed

    2012-07-01

    Full Text Available

    The term ‘niacin’ is used as a generic description of nicotinic acid and nicotinamide with pyridine as the basic structure. Nicotinic acid and nicotinamide function mainly as precursors of the co-enzymes NAD and NADP. Thus, nicotinamide has physiologically critical roles in mitochondrial respiration and in the metabolism of carbohydrates, lipids, and amino acids. Oral administration routes of nicotinic acid and nicotinamide via feed or water for drinking were considered bioequivalent. Niacin is safe for the target animals with a margin of safety that is at least ten times the requirements and use levels. The FEEDAP Panel assumes that exposure figures for a population already include the contribution of edible tissues and products of animals fed niacin-supplemented diets. Information on niacin metabolism and the limited data available on retention in edible tissues and products indicate that supplemental levels in feeds even far higher than the requirements (1–35 mg/kg feed are highly unlikely to lead the tolerable upper intake level being exceeded. The FEEDAP Panel considers that the use of niacin in animal nutrition is not of safety concern for consumers. Nicotinic acid and nicotinamide are not irritant to skin, but can cause irritancy to eyes and mucous membranes. They are unlikely to cause skin sensitisation. Workers might be exposed to a respirable dust when handling nicotinic acid, which should be regarded as being potentially harmful to their health. Nicotinamide is considered to be of no concern for inhalation exposure. The use of nicotinic acid and nicotinamide in animal nutrition does not pose a risk to the environment. Nicotinic acid and nicotinamide are regarded as effective sources of niacin in animal nutrition.

  5. 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

  6. Ultrasound Changes in Achilles Tendon and Gastrocnemius Medialis Muscle on Squat Eccentric Overload and Running Performance.

    Science.gov (United States)

    Sanz-López, Fernando; Berzosa Sánchez, César; Hita-Contreras, Fidel; Cruz-Diaz, David; Martínez-Amat, Antonio

    2016-07-01

    Sanz-López, F, Berzosa Sánchez, C, Hita-Contreras, F, Cruz-Diaz, D, and Martínez-Amat, A. Ultrasound changes in Achilles tendon and gastrocnemius medialis muscle on squat eccentric overload and running performance. J Strength Cond Res XX(X): 000-000, 2015-Previous studies have proven the adaptation to load in the Achilles tendon and gastrocnemius muscle after different types of exercise, such as running, heel drop training, and a variety of sports. These findings have been applied to improve performance and in the treatment and prevention of overuse injuries. However, the effects that squat performance may have on the Achilles tendon and gastrocnemius muscle are still unknown. Squats are a widely used training exercise that involves calf-muscle activation. Similarly, no reports have been published regarding the adaptation to load of trained and untrained subjects during several consecutive days of running. The purpose of this study was to analyze changes in the Achilles tendon and in the pennation angles of the gastrocnemius medialis after eccentric overload training and within 3 days of running. Twenty healthy males who volunteered for this study were divided into 2 groups. Subjects in the eccentric overload training (ECC) group performed 6 weeks of eccentric overload training (twice weekly, 4 sets of 7 repetitions in a Yoyo squat device) before the running intervention. All participants, ECC and control (CONT) groups, ran on 3 consecutive days. After the eccentric training, an increase in the cross-sectional area of the Achilles tendon and in the pennation angle was observed. As for the running intervention, the behavior of tissues in both groups was similar. These results suggest that eccentric overload training with squats promotes changes in the Achilles tendon and in the pennation angle of the gastrocnemius medialis muscle. Nevertheless, significant changes in the tissue do not appear between the running performance of trained and untrained subjects. PMID

  7. Effects of iron and copper overload on the human liver: an ultrastructural study.

    Science.gov (United States)

    Fanni, D; Fanos, V; Gerosa, C; Piras, M; Dessi, A; Atzei, A; Van, Eyken P; Gibo, Y; Faa, G

    2014-01-01

    Iron and copper ions play important roles in many physiological functions of our body, even though the exact mechanisms regulating their absorption, distribution and excretion are not fully understood. Metal-related human pathology may be observed in two different clinical settings: deficiency or overload. The overload in liver cells of both trace elements leads to multiple cellular lesions. Here we report the main pathological changes observed at transmission electron microscopy in the liver of subjects affected by Beta-thalassemia and by Wilson's disease. The hepatic iron overload in beta-thalassemia patients is associated with haemosiderin storage both in Kupffer cells and in the cytoplasm of hepatocytes. Haemosiderin granules are grouped inside voluminous lysosomes, also called siderosomes. Other ultrastructural changes are fat droplets, proliferation of the smooth endoplasmic reticulum and fibrosis. Apoptosis of hepatocytes and infiltration of sinusoids by polymorphonucleates is also detected in beta-thalassemia. Ultrastructural changes in liver biopsies from Wilson's disease patients are characterized by severe mitochondrial changes, associated with an increased number of perossisomes, cytoplasmic lipid droplets and the presence of lipolysosomes, characteristic cytoplasmic bodies formed by lipid vacuoles surrounded by electron-dense lysosomes. In patients affected by Wilson's disease, nuclei are frequently involved, with disorganization of the nucleoplasm and with glycogen inclusions. On the contrary, no significant changes are detected in Kupffer cells. Our data show that iron and copper, even though are both transition metals, are responsible of different pathological changes at ultrastructural level. In particular, copper overload is associated with mitochondrial damage, whereas iron overload only rarely may cause severe mitochondrial changes. These differences underlay the need for further studies in which biochemical analyses should be associated with

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

    Science.gov (United States)

    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

  9. Calcium overload injury of rats' enterocyte IEC-6 by heat stress in vitro

    Directory of Open Access Journals (Sweden)

    Yan GENG

    2013-07-01

    Full Text Available Objective To investigate the effect of gradient heat stress on calcium overload of rats' enterocyte IEC-6 and calcium overload-related cell injury in vitro. Methods Thermal gradient was set in culturing IEC-6 cells in vitro. After thermal stimulation, Fluo-3Am probe with fluorescence microscope or flow cytometry was used to detect the change in intracellular Ca2+ concentration of IEC-6 cells. Phase contrast microscope was used to observe the morphological change in IEC-6. Coomassie blue dying method was employed to test the change in IEC-6 cytoskeleton. CCK-8 assay was used to assess cellular viability. Adhesion assay was applied to test the change in basilar membrane adhesiveness of IEC-6 cells. Results Compared with normal control group, cells of heat stress groups showed a thermal-dependent increase in intracellular Ca2+ concentration (P<0.01. Cells of heat stress groups were rounded in shape, the pseudopod was shorter, and cell space was enlarged. These phenomena were more obvious in 45℃ culture than in that of 43℃. Coomassie blue dying showed that the cytoskeleton of cells in heat stress groups became thickened and disordered, and stress fibers appeared. These phenomena were also more obvious in 45℃ culture than in that of 43℃. A thermal-dependant decline of cell viability in heat stress groups was observed via CCK-8 assay (P<0.01, and a thermal-dependant decline of basilar membrane adhesiveness in heat stress groups was observed via adhesion assay (P<0.01. Conclusion Heat stress may cause calcium overload of IEC-6 cells, and thus resulting in a series of calcium overload-related cell injury. Further investigation of the effect and mechanism of heat stress on calcium overload of intestinal mucosa endothelial cells may help further understand the mechanism of the pathogenesis of heat stroke.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Hepatic iron overload and fibrosis in patients with beta thalassemia major after hematopoietic stem cell transplantation: A pilot study.

    Science.gov (United States)

    Ghavamzadeh, Ardeshir; Mirzania, Mehrzad; Kamalian, Naser; Sedighi, Nahid; Azimi, Parisima

    2015-04-01

    Currently, hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with beta-thalassemia major, but liver iron overload in these patients will not decrease and hepatic fibrosis may still progress despite successful HSCT. Liver biopsy samples were taken from 14 patients (Out of 25 patients) who underwent HSCT. All patients met three criteria: negative HCV antibody, liver fibrosis in samples before HSCT and lack of regular treatment for iron overload after HSCT (Because patients did not consent to phlebotomy or they had not regular follow-up). We evaluated liver fibrosis and liver iron overload by a semi quantitative method, Perls' Prussian blue staining, before and after HSCT. HSCT was successful in all the patients. Liver iron overload did not change after transplant (P=0.61), but hepatic fibrosis progressed after transplant (P=0.01). In patients with beta thalassemia major who previously had some degree of liver fibrosis, HSCT alone cannot reduce liver iron overload and liver fibrosis will increase. We recommend that regardless of the amount of iron overload in patients with beta thalassemia major that have shown some degree of fibrosis in their liver biopsy before transplantation, appropriate steps should be taken to reduce iron overload as soon as possible after successful transplantation.

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

    Directory of Open Access Journals (Sweden)

    Christopher L Dearth

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

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

    Science.gov (United States)

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

    2001-01-01

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

  14. Metal Ion Imbalance-Related Oxidative Stress Is Involved in the Mechanisms of Liver Injury in a Rat Model of Chronic Aluminum Exposure.

    Science.gov (United States)

    Yang, Yang; Wang, Hong; Guo, Yuanxin; Lei, Wenjuan; Wang, Jianfeng; Hu, Xinyue; Yang, Junqing; He, Qin

    2016-09-01

    The objective of the study is to investigate the effects of chronic aluminum overload on rat liver function and its induction of pathological changes in metal ion levels and oxidative stress in hepatic tissues. Wistar rats were intragastrically administered aluminum gluconate (200 mg Al(3+)/Kg) once a day, 5 days a week, for 20 weeks. HE staining was used to visualize pathological changes in rat liver tissue. A biochemical method was adopted to detect ALT, AST, ALP, and GGT levels, as well as liver SOD activity and blood plasma MDA content. A plasma atomic emission spectrophotometer was used to detect Al, Mn, Fe, Zn, and Cu ion contents in liver tissue. Our results showed obvious vacuolar degeneration, granular degeneration, and spotty necrosis in chronic Al-overload rat hepatocytes. The levels of ALT, AST, ALP, and GGT were significantly increased. Liver SOD activity was significantly decreased, and MDA content was significantly increased. In Al-overload rat liver, Al, Mn, Fe, and Cu contents were significantly increased, and in Al-overload rat serum, Mn, Fe, Zn, and Cu contents were significantly decreased. However, the Al level in Al-overload rat serum was not significantly different from that in control rat serum. These results suggest that chronic aluminum overload causes obvious damage to rat liver and causes imbalances in Al, Mn, Fe, Zn, and Cu levels in rat liver and serum. Metal ion imbalance-related oxidative stress may be involved in the mechanism of chronic liver injury caused by aluminum overload. PMID:26811106

  15. Fluid overload is associated with increases in length of stay and hospital costs: pooled analysis of data from more than 600 US hospitals

    Directory of Open Access Journals (Sweden)

    Magee G

    2013-06-01

    Full Text Available Glenn Magee,1 Art Zbrozek21Premier Research Services, Charlotte, NC, USA; 2CSL Behring, King of Prussia, PA, USABackground: Fluid overload, including transfusion-associated circulatory overload (TACO, is a serious complication of fresh frozen plasma (FFP transfusion. The incidence of fluid overload is underreported and its economic impact is unknown. An evaluation of fluid overload cases in US hospitals was performed to assess the impact of fluid overload on length and cost of hospital stay.Study design and methods: Retrospective analysis was performed using a clinical and economic database covering >600 US hospitals. Data were collected for all inpatients discharged during 2010 who received ≥1 unit FFP during hospitalization. Incidence of fluid overload was determined through International Classification of Diagnosis (ICD-9 codes. Multivariate regression analysis was performed for primary outcome measures: hospital length of stay (LOS and total hospital costs.Results: Data were analyzed for 129,839 FFP-transfused patients, of whom 4,138 (3.2% experienced fluid overload (including TACO. Multivariate analysis, adjusting for baseline characteristics, found that increased LOS and hospital costs were independently associated with fluid overload. Patients diagnosed with fluid overload had longer mean LOS (12.9 days versus 10.0 days; P < 0.001 and higher mean hospital cost per visit ($46,644 versus $32,582; P < 0.001 compared with patients without fluid overload.Conclusion: For a population of US inpatients who received FFP during hospitalization, fluid overload was associated with a 29% increase in LOS and a $14,062 increase in hospital costs per visit. These findings suggest that the incidence of fluid overload in the general population is greater than historically reported. A substantial economic burden may be associated with fluid overload in the US.Keywords: fresh frozen plasma, fluid overload, hospital costs, hypervolemia, length of stay

  16. Age morphofunctional features of organs and systems of organism under different gravitational overload influence and different methods of their correction

    Directory of Open Access Journals (Sweden)

    Pikalyk V.S.

    2009-01-01

    Full Text Available Age features of a structure and function of separate organs and systems of an organism were investigated under effect of gravitational overloads, and also efficiency of protection methods of various nature. Age features of a morphgenesis of bone system, lungs, stomach, myocardium, thymus gland, spleen, suprarenal glands, cellular and biochemical composition of blood are established under effect of gravitational overloads in experiment. Morphological proofs of effectiveness of methods of stability augmentation to gravitational overloads, namely physical, pharmacological (application of domestic medicines Glutarginum and Lipoflavon and their combinations are received.

  17. 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.

  18. [Point of note in the treatment of osteoporotic patients complicated with chronic kidney disease].

    Science.gov (United States)

    Inaba, Masaaki

    2016-09-01

    Chronic kidney disease causes secondary hyperparathyroidism due to an accumulation of phosphate in the circulation, resulting in the development of CKD-mineral bone disease(MBD), which increases the risk of cardiovascular disease and fracture. Increase of bone fracture in CKD might be explained by phosphate overload, increased oxidative stress, malnutrition, and the increased risk of fall due to sarcopenia. It is recently emphasized that the overtreatment of osteoporosis might induce the development of adynamic bone disease by calcium overload and/or oversuppression of bone turnover, which might stimulate ectopic calcification including vessel wall. Considering for the high prevalence of CKD in elderly osteoporotic women, we should be careful to avoid the induction of calcium/phosphate overload and over-suppression of bone turnover when we treat osteoporosis for such patients. PMID:27561342

  19. Fe Analysis of Effect of Tyre Overload and Inflation Pressure on Rolling Loss in Cars

    Directory of Open Access Journals (Sweden)

    Gyadari Ramesh

    2015-08-01

    Full Text Available Rolling loss or rolling resistance is an ever important property for the tyre and automotive industries because of its practical implication. Fuel consumption and tyre rolling loss in all types of automobiles have become increasingly important because of adverse environmental effects (air pollution and global warming and economic costs (high petroleum price. In this thesis, the effect of rolling resistance and overload on fuel consumption of automobile car tyres is discussed. The investigations are made on two tyre models of automobile cars Skoda Rapid and Ford Classic. Theoretical calculations are also done to determine the rolling resistance due to inflation pressure. The default weight is considered for 5 persons and also the tyre overload is considered by taking 6 and 7 people’s weight.

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

    Directory of Open Access Journals (Sweden)

    Xian-hui Dong

    2015-01-01

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

  1. Information Overload in Group Communication: From Conversation to Cacophony in the Twitch Chat

    CERN Document Server

    Nematzadeh, Azadeh; Ahn, Yong-Yeol; Flammini, Alessandro

    2016-01-01

    Online communication channels, especially social web platforms, are rapidly replacing traditional ones. Online platforms allow users to overcome physical barriers, enabling worldwide participation. However, the power of online communication bears an important negative consequence --- we are exposed to too much information to process. Too many participants, for example, can turn online public spaces into noisy, overcrowded fora where no meaningful conversation can be held. Here we analyze a large dataset of public chat logs from Twitch, a popular video streaming platform, in order to examine how information overload affects online group communication. We measure structural and textual features of conversations such as user output, interaction, and information content per message across a wide range of information loads. Our analysis reveals the existence of a transition from a conversational state to a cacophony --- a state of overload with lower user participation, more copy-pasted messages, and less informat...

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  3. A review on synchronous CDMA systems: optimum overloaded codes, channel capacity, and power control

    Directory of Open Access Journals (Sweden)

    Hosseini Seyed Amirhossein

    2011-01-01

    Full Text Available Abstract This paper is a tutorial review on important issues related to code-division multiple-access (CDMA systems such as channel capacity, power control, and optimum codes; specifically, we consider optimum overloaded codes that achieve errorless transmission in the absence of noise for the binary and nonbinary cases. A survey of lower and upper bounds for the sum channel capacity of such systems is given in the presence and absence of channel noise. The asymptotic results for the channel capacity are also investigated. The channel capacity, errorless transmission codes, and power estimation for near-far effects are also explored. The emphasis of this tutorial review is on the overloaded CDMA systems.

  4. Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload.

    Science.gov (United States)

    Wehman, Brody; Sharma, Sudhish; Pietris, Nicholas; Mishra, Rachana; Siddiqui, Osama T; Bigham, Grace; Li, Tieluo; Aiello, Emily; Murthi, Sarah; Pittenger, Mark; Griffith, Bartley; Kaushal, Sunjay

    2016-06-01

    Limited therapies exist for patients with congenital heart disease (CHD) who develop right ventricular (RV) dysfunction. Bone marrow-derived mesenchymal stem cells (MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n = 5) or placebo (n = 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P lesions. PMID:27106046

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

    Directory of Open Access Journals (Sweden)

    J Pienaar

    2007-02-01

    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.

  6. MCT8 is Downregulated by Short Time Iodine Overload in the Thyroid Gland of Rats.

    Science.gov (United States)

    de Souza, E C L; Dias, G R M; Cardoso, R C; Lima, L P; Fortunato, R S; Visser, T J; Vaisman, M; Ferreira, A C F; Carvalho, D P

    2015-11-01

    Wolff-Chaikoff effect is characterized by the blockade of thyroid hormone synthesis and secretion due to iodine overload. However, the regulation of monocarboxylate transporter 8 during Wolff-Chaikoff effect and its possible role in the rapid reduction of T4 secretion by the thyroid gland remains unclear. Patients with monocarboxylate transporter 8 gene loss-of-function mutations and monocarboxylate transporter 8 knockout mice were shown to have decreased serum T4 levels, indicating that monocarboxylate transporter 8 could be involved in the secretion of thyroid hormones from the thyroid gland. Herein, we aimed to evaluate the regulation of monocarboxylate transporter 8 during the Wolff-Chaikoff effect and the escape from iodine overload, besides the importance of iodine organification for this regulation. Monocarboxylate transporter 8 mRNA and protein levels significantly decreased after 1 day of NaI administration to rats, together with decreased serum T4; while no alteration was observed in LAT2 expression. Moreover, both monocarboxylate transporter 8 expression and serum T4 was restored after 6 days of NaI. The inhibition of thyroperoxidase activity by methimazole prevented the inhibitory effect of NaI on thyroid monocarboxylate transporter 8 expression, suggesting that an active thyroperoxidase is necessary for MCT8 downregulation by iodine overload, similarly to other thyroid markers, such as sodium iodide symporter. Therefore, we conclude that thyroid monocarboxylate transporter 8 expression is downregulated during iodine overload and that the normalization of its expression parallels the escape phenomenon. These data suggest a possible role for monocarboxylate transporter 8 in the changes of thyroid hormones secretion during the Wolff-Chaikoff effect and escape.

  7. Erythrocyte ferritin content in idiopathic haemochromatosis and alcoholic liver disease with iron overload.

    OpenAIRE

    Van der Weyden, M B; Fong, H; Salem, H. H.; Batey, R G; Dudley, F J

    1983-01-01

    The erythrocyte ferritin content was measured in patients with either idiopathic haemochromatosis or alcoholic liver disease and iron overload to define its value as a marker for an excess of tissue iron. The mean erythrocyte ferritin content in patients with untreated idiopathic haemochromatosis was increased 60-fold and fell with phlebotomy. After phlebotomy many patients had an increased red cell ferritin content despite normal serum ferritin concentrations. That this reflected persistent ...

  8. The relationship between non transferrin bound iron and iron overload in thalassaemia and sickle syndromes.

    OpenAIRE

    Shah, F. T.

    2007-01-01

    Iron overload is a major cause of morbidity and subsequent mortality in patients with thalassaemia major, its effects in thalassaemia intermedia and sickle cell anaemia are however less well known. The presence of non transferrin bound iron is well described in adult thalassaemia patients but it is unclear as to when NTBI appears and what relationship it has to ineffective erythropoiesis and end organ damage. Data is presented on children with thalassaemia from a five-year prospective study s...

  9. Masking of Pressure Overload in a Patient with Pulmonary Thromboembolism Accompanied by Atrial Septal Aneurysm

    OpenAIRE

    Yu, Tae Kyung; Kim, Woo Shik; Kim, Weon

    2011-01-01

    A pulmonary thromboembolism (PTE) causes a dramatic pressure overload to the right heart. Previous case reports have shown that elevated right atrial pressure secondary to a PTE can cause right-to-left shunting in the presence of an atrial septal aneurysm (ASA). A 57-year-old female with diabetes, hypertension, and an old cerebral infarction was admitted to our hospital with acute PTE. Initial transthoracic echocardiography (TTE) showed an ASA swing from the right side to the left side, and r...

  10. Fe Analysis of Effect of Tyre Overload and Inflation Pressure on Rolling Loss in Cars

    OpenAIRE

    Gyadari Ramesh; Malloji Mallesham

    2015-01-01

    Rolling loss or rolling resistance is an ever important property for the tyre and automotive industries because of its practical implication. Fuel consumption and tyre rolling loss in all types of automobiles have become increasingly important because of adverse environmental effects (air pollution and global warming) and economic costs (high petroleum price). In this thesis, the effect of rolling resistance and overload on fuel consumption of automobile car tyres is discussed. ...

  11. Overload: Regulating the Sources of Information about Attention-Deficit/Hyperactivity Disorder

    OpenAIRE

    Shaitelman, Kenneth

    2005-01-01

    Information relating to attention-deficit/hyperactivity disorder (AD/HD) has flooded the consumer and medical markets in recent years. Information “overload†is often problematic, but it is especially the case with AD/HD. Those afflicted with the disorder are uniquely unsuited to make sense of the mass of information that is presented to them. The purpose of this article, therefore, is to examine whether any legal controls exist to regulate the flow of informati...

  12. High fat diet subverts hepatocellular iron uptake determining dysmetabolic iron overload

    OpenAIRE

    Paola Dongiovanni; Claudia Lanti; Stefano Gatti; Raffaela Rametta; Stefania Recalcati; Marco Maggioni; Anna Ludovica Fracanzani; Patrizia Riso; Gaetano Cairo; Silvia Fargion; Luca Valenti

    2015-01-01

    Increased serum ferritin associated with mild hepatic iron accumulation, despite preserved upregulation of the iron hormone hepcidin, is frequently observed in patients with dysmetabolic overload syndrome (DIOS). Genetic factors and Western diet represent predisposing conditions, but the mechanisms favoring iron accumulation in DIOS are still unclear. Aims of this study were to assess the effect a high-fat diet (HFD) on hepatic iron metabolism in an experimental model in rats, to further char...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kapadia, A J; Tourassi, G D; Sharma, A C [Department of Radiology, Duke Advanced Imaging Laboratories, Durham, NC 27705 (United States); Crowell, A S; Kiser, M R; Howell, C R [Department of Physics, Duke University, Durham, NC 27706 (United States)], E-mail: anuj.kapadia@duke.edu

    2008-05-21

    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{sup -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.

  14. Global Transcriptional Response to Hfe Deficiency and Dietary Iron Overload in Mouse Liver and Duodenum

    OpenAIRE

    Alejandra Rodriguez; Tiina Luukkaala; Fleming, Robert E.; Britton, Robert S.; Bacon, Bruce R.; Seppo Parkkila

    2009-01-01

    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...

  15. Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with iron overload and progressive liver disease.

    Science.gov (United States)

    Schaefer, Benedikt; Haschka, David; Finkenstedt, Armin; Petersen, Britt-Sabina; Theurl, Igor; Henninger, Benjamin; Janecke, Andreas R; Wang, Chia-Yu; Lin, Herbert Y; Veits, Lothar; Vogel, Wolfgang; Weiss, Günter; Franke, Andre; Zoller, Heinz

    2015-11-01

    Liver disease due to alpha-1-antitrypsin deficiency (A1ATD) is associated with hepatic iron overload in a subgroup of patients. The underlying cause for this association is unknown. The aim of the present study was to define the genetics of this correlation and the effect of alpha-1-antitrypsin (A1AT) on the expression of the iron hormone hepcidin. Full exome and candidate gene sequencing were carried out in a family with A1ATD and hepatic iron overload. Regulation of hepcidin expression by A1AT was studied in primary murine hepatocytes. Cells co-transfected with hemojuvelin (HJV) and matriptase-2 (MT-2) were used as a model to investigate the molecular mechanism of this regulation. Observed familial clustering of hepatic iron overload with A1ATD suggests a genetic cause, but genotypes known to be associated with hemochromatosis were absent. Individuals homozygous for the A1AT Z-allele with environmental or genetic risk factors such as steatosis or heterozygosity for the HAMP non-sense mutation p.Arg59* presented with severe hepatic siderosis. In hepatocytes, A1AT induced hepcidin mRNA expression in a dose-dependent manner. Experiments in overexpressing cells show that A1AT reduces cleavage of the hepcidin inducing bone morphogenetic protein co-receptor HJV via inhibition of the membrane-bound serine protease MT-2. The acute-phase protein A1AT is an inducer of hepcidin expression. Through this mechanism, A1ATD could be a trigger of hepatic iron overload in genetically predisposed individuals or patients with environmental risk factors for hepatic siderosis. PMID:26310624

  16. Marital Quality in Dual-Career Couples: Impact of Role Overload and Coping Resources

    OpenAIRE

    Schnurman-Crook, Abrina M.

    2001-01-01

    An explanatory model of stress and coping among dual-career partners examined the influence of role overload on individual coping strategies and relational coping resources as mediators, using marital quality as the measured outcome. Individual coping strategies included problem-focused and emotion-focused coping. Relational coping resources included maintenance behaviors, cooperative negotiation, and coercive negotiation. Data from a sample of 226 married, dual-career partners were subjected...

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

    OpenAIRE

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

    2015-01-01

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

  18. Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes

    OpenAIRE

    Zhao, Mingming; Fajardo, Giovanni; Urashima, Takashi; Spin, Joshua M; Poorfarahani, Sara; Rajagopalan, Viswanathan; Huynh, Diem; Connolly, Andrew; Quertermous, Thomas; Bernstein, Daniel

    2011-01-01

    In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α1-adrenergic receptors (ARs) and not β-ARs. However, mice with deletions of both major cardiac α1-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of β-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of β-AR antagonists and the likelihood that patients treated with these agents could develop conditions of furth...

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

    OpenAIRE

    Pienaar, J.; C F Sieberhagen; K Mostert

    2007-01-01

    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)...

  20. Pulmonary Function in Patients with End-Stage Renal Disease: Effects of Hemodialysis and Fluid Overload.

    Science.gov (United States)

    Yılmaz, Süreyya; Yildirim, Yasar; Yilmaz, Zülfükar; Kara, Ali Veysel; Taylan, Mahsuk; Demir, Melike; Coskunsel, Mehmet; Kadiroglu, Ali Kemal; Yilmaz, Mehmet Emin

    2016-01-01

    BACKGROUND Respiratory system disorders are one of the most prevalent complications in end-stage renal disease patients on hemodialysis. However, the pathogenesis of impaired pulmonary functions has not been completely elucidated in these patients. We designed a study to investigate acute effects of hemodialysis treatment on spirometry parameters, focusing on the relationship between pulmonary function and fluid status in hemodialysis patients. MATERIAL AND METHODS We enrolled 54 hemodialysis patients in this study. Multifrequency bioimpedance analysis (BIA) was used to assess fluid status before and 30 min after the midweek of hemodialysis (HD). Overhydration (OH)/extracellular water (ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined as OH/ECW ≥7%. Spirometry was performed before and after hemodialysis. RESULTS Forced vital capacity (FVC), FVC%, and forced expiratory volume in the first second (FEV1) levels were significantly increased after hemodialysis. FVC, FVC%, FEV1, FEV1%, mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75), FEF25-75%, peak expiratory flow rate (PEFR), and PEFR% were significantly lower in patients with fluid overload than in those without. OH/ECW ratio was negatively correlated with FVC, FVC%, FEV1, FEV1%, FEF25-75, FEF25-75%, PEFR, and PEFR%. Stepwise multiple regression analysis revealed that male sex and increased ultrafiltration volume were independently associated with higher FVC, whereas increased age and OH/ECW ratio were independently associated with lower FVC. CONCLUSIONS Fluid overload is closely associated with restrictive and obstructive respiratory abnormalities in HD patients. In addition, hemodialysis has a beneficial effect on pulmonary function tests, which may be due to reduction of volume overload. PMID:27497672

  1. Hepatic iron overload in thalassemic patients: proposal and validation of an MRI method of assessment

    Energy Technology Data Exchange (ETDEWEB)

    Bonetti, M.G. [Servicio di Radiologia e Diagnostica per Immagini, Ancona (Italy)]|[IRCCS, San Giovanni Rotondo (Italy). Dipt. di Diagnostica per Immagini; Castriota-Scanderberg, A. [IRCCS, San Giovanni Rotondo (Italy). Dipt. di Diagnostica per Immagini; Criconia, G.M. [IRCCS, San Giovanni Rotondo (Italy). Reparto di Cardiologia; Mazza, P. [Servizio di Ematologia, Ospedale SS. Annunziata., Taranto (Italy); Sacco, M. [IRCCS, San Giovanni Rotondo (Italy). Reparto di Pediatria; Amurri, B. [Servizio di Ematologia, Ospedale SS. Annunziata., Taranto (Italy); Masi, C. [Servizio di Ematologia, Ospedale SS. Annunziata., Taranto (Italy)

    1996-09-01

    Background. A simple, accurate reproducible and noninvasive method of body iorn overload assessment whoul be of great clinical use. Objective. The purpose of the study was the implementation of a 0.5-T MRI method for liver iron overload measurement. Materials and methods. Thirty paptients with thalassemia major took part in the study. Liver and paraspinal muscle signal intensity (SI) measurements were performed on T1-weighted images and normalized on a standard phantom, and a subjective hemochromatosis grading scale was made on both T1- and T2-weighted images. Serum ferritin levels and tissue iron from liver biopsy specimes were determined for comparison. Results. A close correlation was found between biotopic liver iron and both the liver-to-phantom SI ratio (r=-0.88) and the subjective grading scale (rho=0.89). Serum ferritin correlated poorly with liver iron deposition, whether assesssed by biopsy (r=0.62) of MRI (r=-0.69). Conclusions. Both the subjective and the quantitative MRI methods proposed here are clinicaly valuable, with the former being adequate for a gross, the latter for an accurate estimation of tissue iron overload.

  2. Hepatic iron overload in thalassemic patients: proposal and validation of an MRI method of assessment

    International Nuclear Information System (INIS)

    Background. A simple, accurate reproducible and noninvasive method of body iorn overload assessment whoul be of great clinical use. Objective. The purpose of the study was the implementation of a 0.5-T MRI method for liver iron overload measurement. Materials and methods. Thirty paptients with thalassemia major took part in the study. Liver and paraspinal muscle signal intensity (SI) measurements were performed on T1-weighted images and normalized on a standard phantom, and a subjective hemochromatosis grading scale was made on both T1-and T2-weighted images. Serum ferritin levels and tissue iron from liver biopsy specimes were determined for comparison. Results. A close correlation was found between biotopic liver iron and both the liver-to-phantom SI ratio (r=-0.88) and the subjective grading scale (rho=0.89). Serum ferritin correlated poorly with liver iron deposition, whether assesssed by biopsy (r=0.62) of MRI (r=-0.69). Conclusions. Both the subjective and the quantitative MRI methods proposed here are clinicaly valuable, with the former being adequate for a gross, the latter for an accurate estimation of tissue iron overload

  3. 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.

  4. Effect of mild iron overload on liver and kidney lipid peroxidation.

    Science.gov (United States)

    Galleano, M; Puntarulo, S

    1994-10-01

    1. Hepatotoxicity is the most common finding in patients with iron overload since the liver is the major recipient of iron excess, even though the kidney could be a target of iron toxicity. The effect of iron overload was studied in the early stages after iron-dextran injection in rats, as a model for secondary hemocromatosis. 2. Total hepatic and kidney iron content was markedly elevated over control values 20 h after the iron administration. Plasma GOT, GPT and LDH activities were not affected, suggesting that liver cell permeability was not affected by necrosis. 3. Spontaneous liver chemiluminescence was measured as an indicator of oxidative stress and lipid peroxidation. Light emission was increased four-fold 6 h after iron supplementation. 4. Increases in the generation of thiobarbituric acid reactive substances (TBARS in liver and kidney homogenates were detected after iron administration. 5. The activities of catalase, SOD and glutathione peroxidase were determined. Enzymatic activities declined in liver homogenates by 25, 36 and 32%, respectively, 20 h after iron injection. These activities were not affected in kidney as compared to control values, except for SOD activity that was decreased by 26%. 6. The content of alpha-tocopherol was decreased by 31% in whole kidney homogenates and by 40% in plasma. 7. Our data indicate that lipid peroxidation occurs after mild iron overload both in liver and kidney. Enzymatic antioxidants are consumed significantly in liver and alpha-tocopherol content decreases in kidney, suggesting an organ-specific antioxidant effect.

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

    Institute of Scientific and Technical Information of China (English)

    刘华胜; 马爱群; 王一理; 刘勇; 李恒力; 田红燕

    2002-01-01

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

  6. Cellular growth defects triggered by an overload of protein localization processes.

    Science.gov (United States)

    Kintaka, Reiko; Makanae, Koji; Moriya, Hisao

    2016-01-01

    High-level expression of a protein localized to an intracellular compartment is expected to cause cellular defects because it overloads localization processes. However, overloads of localization processes have never been studied systematically. Here, we show that the expression levels of green fluorescent proteins (GFPs) with localization signals were limited to the same degree as a toxic misfolded GFP in budding yeast cells, and that their high-level expression caused cellular defects associated with localization processes. We further show that limitation of the exportin Crm1 determined the expression limit of GFP with a nuclear export signal. Although misfolding of GFP with a vesicle-mediated transport signal triggered endoplasmic reticulum stress, it was not the primary determinant of its expression limit. The precursor of GFP with a mitochondrial targeting signal caused a cellular defect. Finally, we estimated the residual capacities of localization processes. High-level expression of a localized protein thus causes cellular defects by overloading the capacities of localization processes. PMID:27538565

  7. 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.

  8. Effect of pumping chamber on performance of non-overload centrifugal pump

    Institute of Scientific and Technical Information of China (English)

    谷云庆; 吴登昊; 牟介刚; 蒋兰芳; 代东顺; 施瀚昱; 郑水华

    2015-01-01

    In order to specify the characteristics of un-overloaded centrifugal pumps, the IH100-65-200 pump was chosen as the model pump. Different calculation models for centrifugal pumps were established under different pumping chamber sectional parameters. In the numerical simulation of the centrifugal pumps flow field, the shaft power, head, efficiency, and the changes of the internal flow field under different sectional areas and sectional shapes were studied with the RNGk−εturbulence model, and the influence of the pumping chamber section characteristics of the non-overloaded centrifugal pumps were analyzed. The results show that sectional areas have a significant impact on the non-overload characteristics of centrifugal pumps. The shaft power and head of centrifugal pump are increasing with a lager sectional area, by which the gradient of head curves decreases. The efficiency is improved under a large flow rate condition, but the head and the efficiency are reduced at a small flow rate. It is also observed that the sectional shapes have less influence on the shaft power, the hydraulic performance and flow field characteristics of a centrifugal pump.

  9. An ODE for an overloaded X model involving a stochastic averaging principle

    Directory of Open Access Journals (Sweden)

    Ward Whitt

    2011-01-01

    Full Text Available We study an ordinary differential equation (ODE arising as the many-server heavy-traffic fluid limit of a sequence of overloaded Markovian queueing models with two customer classes and two service pools. The system, known as the X model in the call-center literature, operates under the fixed-queue-ratio-with-thresholds (FQR-T control, which we proposed in a recent paper as a way for one service system to help another in face of an unanticipated overload. Each pool serves only its own class until a threshold is exceeded; then one-way sharing is activated with all customer-server assignments then driving the two queues toward a fixed ratio. For large systems, that fixed ratio is achieved approximately. The ODE describes system performance during an overload. The control is driven by a queue-difference stochastic process, which operates in a faster time scale than the queueing processes themselves, thus achieving a time-dependent steady state instantaneously in the limit. As a result, for the ODE, the driving process is replaced by its long-run average behavior at each instant of time; i.e., the ODE involves a heavy-traffic averaging principle (AP.

  10. Signaling pathway-focused gene expression profiling in pressure overloaded hearts

    Directory of Open Access Journals (Sweden)

    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.

  11. Design of overload vehicle monitoring and response system based on DSP

    Science.gov (United States)

    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.

  12. The Design and Optimization of a Highly Sensitive and Overload-Resistant Piezoresistive Pressure Sensor

    Directory of Open Access Journals (Sweden)

    Xiawei Meng

    2016-03-01

    Full Text Available A piezoresistive pressure sensor with a beam-membrane-dual-island structure is developed for micro-pressure monitoring in the field of aviation, which requires great sensitivity and overload resistance capacity. The design, fabrication, and test of the sensor are presented in this paper. By analyzing the stress distribution of sensitive elements using the finite element method, a novel structure incorporating sensitive beams with a traditional bossed diaphragm is built up. The proposed structure proved to be advantageous in terms of high sensitivity and high overload resistance compared with the conventional bossed diaphragm and flat diaphragm structures. Curve fittings of surface stress and deflection based on ANSYS simulation results are performed to establish the sensor equations. Fabricated on an n-type single crystal silicon wafer, the sensor chips are wire-bonded to a printed circuit board (PCB and packaged for experiments. The static and dynamic characteristics are tested and discussed. Experimental results show that the sensor has a sensitivity as high as 17.339 μV/V/Pa in the range of 500 Pa at room temperature, and a high overload resistance of 200 times overpressure. Due to the excellent performance, the sensor can be applied in measuring micro-pressure lower than 500 Pa.

  13. The Design and Optimization of a Highly Sensitive and Overload-Resistant Piezoresistive Pressure Sensor.

    Science.gov (United States)

    Meng, Xiawei; Zhao, Yulong

    2016-03-09

    A piezoresistive pressure sensor with a beam-membrane-dual-island structure is developed for micro-pressure monitoring in the field of aviation, which requires great sensitivity and overload resistance capacity. The design, fabrication, and test of the sensor are presented in this paper. By analyzing the stress distribution of sensitive elements using the finite element method, a novel structure incorporating sensitive beams with a traditional bossed diaphragm is built up. The proposed structure proved to be advantageous in terms of high sensitivity and high overload resistance compared with the conventional bossed diaphragm and flat diaphragm structures. Curve fittings of surface stress and deflection based on ANSYS simulation results are performed to establish the sensor equations. Fabricated on an n-type single crystal silicon wafer, the sensor chips are wire-bonded to a printed circuit board (PCB) and packaged for experiments. The static and dynamic characteristics are tested and discussed. Experimental results show that the sensor has a sensitivity as high as 17.339 μV/V/Pa in the range of 500 Pa at room temperature, and a high overload resistance of 200 times overpressure. Due to the excellent performance, the sensor can be applied in measuring micro-pressure lower than 500 Pa.

  14. Estimating User Influence in Online Social Networks Subject to Information Overload

    Science.gov (United States)

    Li, Pei; Sun, Yunchuan; Chen, Yingwen; Tian, Zhi

    2014-11-01

    Online social networks have attracted remarkable attention since they provide various approaches for hundreds of millions of people to stay connected with their friends. Due to the existence of information overload, the research on diffusion dynamics in epidemiology cannot be adopted directly to that in online social networks. In this paper, we consider diffusion dynamics in online social networks subject to information overload, and model the information-processing process of a user by a queue with a batch arrival and a finite buffer. We use the average number of times a message is processed after it is generated by a given user to characterize the user influence, which is then estimated through theoretical analysis for a given network. We validate the accuracy of our estimation by simulations, and apply the results to study the impacts of different factors on the user influence. Among the observations, we find that the impact of network size on the user influence is marginal while the user influence decreases with assortativity due to information overload, which is particularly interesting.

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

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

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

  16. Heterozygous Mutations in BMP6 Pro-peptide Lead to Inappropriate Hepcidin Synthesis and Moderate Iron Overload in Humans

    OpenAIRE

    Daher, Raed; Kannengiesser, Caroline; Houamel, Dounia; Lefebvre, Thibaud; Bardou-Jacquet, Edouard; Ducrot, Nicolas; Kerguenec, Caroline,; Jouanolle, Anne-Marie; Robreau, Anne-Marie; Oudin, Claire; Le Gac, Gerald; Moulouel, Boualem; Loustaud-Ratti, Véronique; Bedossa, Pierre; Valla, Dominique

    2015-01-01

    Background & Aims Hereditary hemochromatosis is a heterogeneous group of genetic disorders characterized by parenchymal iron overload. It is caused by defective expression of liver hepcidin, the main regulator of iron homeostasis. Iron stimulates the gene encoding (HAMP) hepcidin via the BMP6 signaling to SMAD. Although several genetic factors have been found to cause late-onset hemochromatosis, many patients have unexplained signs of iron overload. We investigated BMP6 function in these indi...

  17. Comparison of the Prophylactic Effect of Silymarin and Deferoxamine on Iron Overload-Induced Hepatotoxicity in Rat

    OpenAIRE

    Najafzadeh, Hossein; Razi Jalali, Mohammad; Morovvati, Hassan; Taravati, Farnaz

    2010-01-01

    In pathologic conditions or poisoning states, iron overload can affect different tissues including liver. In this study, the prophylactic effect of deferoxamine and silymarin was compared in decreasing experimental iron-overload-induced hepatotoxicity in rats. The study was done in six groups of rats, which received drugs q2 days for 2 weeks. The rats in groups 1 to 6 received drugs, respectively: normal saline, iron dextran, iron dextran + deferoxamine (intraperitoneally), iron dextran + sil...

  18. Neurohumoral fluid regulation in chronic liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    1998-01-01

    Impaired homeostasis of the blood volume, with increased fluid and sodium retention, is a prevailing element in the deranged systemic and splanchnic haemodynamics in patients with liver disease. In this review, some basic elements of the circulatory changes that take place and of neurohumoral fluid...... regulation are outlined in order to provide an update of recent investigations on the neuroendocrine compensation of circulatory and volume dysfunction in chronic liver disease. The underlying pathophysiology is a systemic vasodilatation in which newly described potent vasoactive substances such as nitric...... 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...

  19. Work-Family Conflict among Junior Physicians: Its Mediating Role in the Relationship between Role Overload and Emotional Exhaustion

    Directory of Open Access Journals (Sweden)

    Aminah Ahmad

    2010-01-01

    Full Text Available Problem statement: The use of a mediation model for understanding the mediating impact of work-family conflict on the relationship between role overload and emotional exhaustion has not been given much attention. Approach: This study tested a mediation model consisting of emotional exhaustion as the dependent variable and role overload as the independent variable, with work-family conflict as its mediator. Data were gathered from a sample of 220 female junior physicians aged 40 years and below, having at least one child as well as working full-time in 14 public hospitals in Malaysia, using self-administered questionnaires. The data were analyzed using correlation and multiple regression analyses. Results: Results of correlation analyses revealed that role overload was significantly related to work-family conflict and emotional exhaustion and work-family conflict was significantly related to emotional exhaustion. Results of a series of multiple regression analyzed indicated that work-family conflict partially mediated the relationship between role overload and emotional exhaustion. Conclusion/Recommendations: Junior physicians who experience role overload seem to be more emotionally drained and seem to experience greater conflict between work and family roles. There is a need to reduce the role overload that physicians experience by reviewing the ratio between physicians and patients and re-assessing the number of work hours and the weekly frequency of on-calls. Limiting on-call frequency and hours may be more likely to reduce work-family conflict as well as emotional exhaustion.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  1. Scientific Opinion on the safety and efficacy of niacin (nicotinic acid and nicotinamide) as a feed additive for all animal species based on a dossier submitted by Vertellus Specialties Belgium BV

    OpenAIRE

    EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP)

    2012-01-01

    The term ‘niacin’ is used as a generic description of nicotinic acid and nicotinamide with pyridine as the basic structure. Nicotinic acid and nicotinamide function mainly as precursors of the co-enzymes NAD and NADP. Thus, nicotinamide has physiologically critical roles in mitochondrial respiration and in the metabolism of carbohydrates, lipids, and amino acids. Niacin is safe for the target animals with a margin of safety that is at least ten times the requirements and use levels. ...

  2. Blog Overload

    Science.gov (United States)

    Dawson, Kara M.

    2007-01-01

    The most effective blogs provide important and cutting-edge information (e.g., Tech Crunch), communicate deeply personal experiences through narrative (e.g., the Cancer Blog), or write to a specific audience (e.g., chemistry teachers). Most people with successful blogs are deeply committed to posting, for personal reasons, such as a passion for…

  3. 烟酸对高脂血症兔脂肪组织Caveolin-1mRNA表达的影响%Effect of niacin on Caveolin-1 expression in adipose tissue of hypercholesterolemic rabbits

    Institute of Scientific and Technical Information of China (English)

    李志乐; 徐戈; 雷敏; 欧婷; 王利兵

    2012-01-01

    Objective To investigate the effect of niacin on caveolin-lexpression in adipose tissue from hypercholesterolemic rabbits. Methods 16 New Zealand white rabbits were fed with high-fat diet for 8 weeks , and then randomly divided into two groups : hyperlipidemia group maintained on high fat diet for 6 weeks ; niacin treatment group:the same fat diet plus niacin [200 mg/(kg-d)] for 6 weeks. Control group was fed with normal diet for 14 weeks. All rabbits were detected the blood lipid and caveolin-1 expression of adipose tissue from groin by FQ-PCR. Results Niacin treatment group showed less serum levels of TC、TG and LDL-C , more level of LDL-C and caveolin-lexpression comparing with hyperlipidemia group. Conclusion Niacin can significantly improve the lipid profile and up-regulate caveolin-lexpression in adipose tissue.%目的:探讨烟酸对高脂血症兔脂肪组织caveolin-1表达的影响.方法:16只健康雄性新西兰大白兔给予高脂饮食8周,随机分为高脂组(继续饲以高脂饲料6周)与烟酸组[在高脂饮食基础上给予烟酸200 mg/(kg·d)6周],另选8只兔予普通饮食14周为正常对照组.实验前后测血脂及采用实时荧光定量PCR检测各组兔腹股沟皮下脂肪组织caveolin-1 mRNA的表达.结果:与高脂组比较,烟酸组TC、TG和LDL-C明显降低,而HDL-C水平明显升高,脂肪组织caveolin-1 mRNA的表达显著升高.结论:烟酸可明显改善血脂谱及上调高脂血症脂肪组织caveolin-1的表达水平.

  4. Effects of extended-release niacin/laropiprant, simvastatin, and the combination on correlations between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients with dyslipidemia

    Science.gov (United States)

    Farnier, Michel; Chen, Erluo; Johnson-Levonas, Amy O; McCrary Sisk, Christine; Mitchel, Yale B

    2014-01-01

    Background Statins modify correlations between apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C) and apoB and non-high-density lipoprotein cholesterol (non-HDL-C); however, it is not known whether niacin-based therapies have similar effects. Objective To evaluate the effects of extended-release niacin (ERN)/laropiprant (LRPT), simvastatin (SIMVA), and ERN/LRPT + SIMVA (pooled ERN/LRPT + SIMVA) on apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients. Methods This post-hoc analysis of a 12-week study evaluated the apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients randomized equally to double-blind ERN/LRPT 1 g/20 mg, SIMVA 10, 20, or 40 mg, or ERN/LRPT 1 g/20 mg + SIMVA (10, 20, or 40 mg) once daily for 4 weeks. At week 5, doses were doubled in all groups except SIMVA 40 mg (unchanged) and ERN/LRPT 1 g/20 mg + SIMVA 40 mg (switched to ERN/LRPT 2 g/40 mg + SIMVA 40 mg). Simple linear regression analyses were used to calculate LDL-C and non-HDL-C levels corresponding to known apoB baseline values (ie, in untreated patients) and following treatment. Results The apoB:LDL-C and apoB:non-HDL-C correlations were higher and the predicted LDL-C and non-HDL-C levels for a known apoB value were considerably lower following treatment with ERN/LRPT, SIMVA and ERN/LRPT + SIMVA compared with untreated patients at baseline. Conclusion Greater dissociation of apoB, LDL-C, and non-HDL-C targets occur following treatment with ERN/LRPT, SIMVA, and ERN/LRPT + SIMVA in patients with dyslipidemia. The achievement of more aggressive LDL-C and non-HDL-C goals in patients receiving lipid-modifying therapy may further reduce coronary risk by normalizing apoB-containing atherogenic lipoproteins. PMID:24855368

  5. Effects of extended-release niacin/laropiprant, simvastatin, and the combination on correlations between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients with dyslipidemia

    Directory of Open Access Journals (Sweden)

    Farnier M

    2014-05-01

    Full Text Available Michel Farnier,1 Erluo Chen,2 Amy O Johnson-Levonas,2 Christine McCrary Sisk,2 Yale B Mitchel21Point Médical, Dijon, France; 2Merck and Co, Inc., Whitehouse Station, NJ, USABackground: Statins modify correlations between apolipoprotein B (apoB and low-density lipoprotein cholesterol (LDL-C and apoB and non-high-density lipoprotein cholesterol (non-HDL-C; however, it is not known whether niacin-based therapies have similar effects.Objective: To evaluate the effects of extended-release niacin (ERN/laropiprant (LRPT, simvastatin (SIMVA, and ERN/LRPT + SIMVA (pooled ERN/LRPT + SIMVA on apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients.Methods: This post-hoc analysis of a 12-week study evaluated the apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients randomized equally to double-blind ERN/LRPT 1 g/20 mg, SIMVA 10, 20, or 40 mg, or ERN/LRPT 1 g/20 mg + SIMVA (10, 20, or 40 mg once daily for 4 weeks. At week 5, doses were doubled in all groups except SIMVA 40 mg (unchanged and ERN/LRPT 1 g/20 mg + SIMVA 40 mg (switched to ERN/LRPT 2 g/40 mg + SIMVA 40 mg. Simple linear regression analyses were used to calculate LDL-C and non-HDL-C levels corresponding to known apoB baseline values (ie, in untreated patients and following treatment.Results: The apoB:LDL-C and apoB:non-HDL-C correlations were higher and the predicted LDL-C and non-HDL-C levels for a known apoB value were considerably lower following treatment with ERN/LRPT, SIMVA and ERN/LRPT + SIMVA compared with untreated patients at baseline.Conclusion: Greater dissociation of apoB, LDL-C, and non-HDL-C targets occur following treatment with ERN/LRPT, SIMVA, and ERN/LRPT + SIMVA in patients with dyslipidemia. The achievement of more aggressive LDL-C and non-HDL-C goals in patients receiving lipid-modifying therapy may further reduce coronary risk by normalizing apoB-containing atherogenic lipoproteins.Keywords: apoB, LDL-C, non-HDL-C

  6. 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.

  7. Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Christina Westphal

    Full Text Available The aim of this study was to investigate the effects of 17β-estradiol (E2, the selective ERα agonist 16α-LE2, and the selective estrogen receptor modulator (SERM raloxifene on remodeling processes during the development of myocardial hypertrophy (MH in a mouse model of pressure overload. Myocardial hypertrophy in ovariectomized female C57Bl/6J mice was induced by transverse aortic constriction (TAC. Two weeks after TAC, placebo treated mice developed left ventricular hypertrophy and mild systolic dysfunction. Estrogen treatment, but not 16α-LE2 or raloxifene reduced TAC induced MH compared to placebo. E2, 16α-LE2 and raloxifene supported maintenance of cardiac function in comparison with placebo. Nine weeks after induction of pressure overload, MH was present in all TAC groups, most pronounced in the raloxifene treated group. Ejection fraction (EF was decreased in all animals. However, 16α-LE2 treated animals showed a smaller reduction of EF than animals treated with placebo. E2 and 16α-LE2, but not raloxifene diminished the development of fibrosis and reduced the TGFβ and CTGF gene expression. Treatment with E2 or 16α-LE2 but not with raloxifene reduced survival rate after TAC significantly in comparison with placebo treatment. In conclusion, E2 and 16α-LE2 slowed down the progression of MH and reduced systolic dysfunction after nine weeks of pressure overload. Raloxifene did not reduce MH but improved cardiac function two weeks after TAC. However, raloxifene was not able to maintain EF in the long term period.

  8. C-Myc regulates substrate oxidation patterns during early pressure-overload hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R. [Seattle Children' s Research Inst., Seattle, WA (United States); Smith, Lincoln [Seattle Children' s Hospital, Seattle, WA (United States); Kajimoto, Masaki [Seattle Children' s Research Inst., Seattle, WA (United States); Bruce, Margaret [Seattle Children' s Research Inst., Seattle, WA (United States); Isern, Nancy G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL); Xu, Chun [Seattle Children' s Research Inst., Seattle, WA (United States); Portman, Michael A. [Seattle Children' s Research Inst., Seattle, WA (United States); Olson, Aaron [Seattle Children' s Research Inst., Seattle, WA (United States)

    2013-11-26

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of glycolytic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin. Western blots were used to evaluate metabolic enzymes. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (presumably glucose) contribution. Myc inactivation (MycKO-TAC) inhibited these metabolic changes. Hypertrophy in general increased protein levels of PKM2; however this change was not linked to Myc status. Protein post-translation modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. In conclusion, Myc regulates substrate utilization during early pressure overload hypertrophy. Our results show that the metabolic switch during hypertrophy is not necessary to maintain cardiac function, but it may be important mechanism to promote cardiomyocyte growth. Myc also regulates protein O-GlcNAcylation during hypertrophy.

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

    Directory of Open Access Journals (Sweden)

    Fan Yang

    2016-09-01

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

  10. Metabolic response to subacute and subchronic iron overload in a rat model.

    Science.gov (United States)

    Adham, Khadiga G; Farhood, Manal H; Daghestani, Maha H; Aleisa, Nadia A; Alkhalifa, Ahlam A; El Amin, Maha H; Virk, Promy; Al-Obeid, Mai A; Al-Humaidhi, Eman M H

    2015-12-01

    One of the common causes of iron overload is excessive iron intake in cases of iron-poor anemia, where iron saccharate complex (ISC) is routinely used to optimize erythropoiesis. However, non-standardized ISC administration could entail the risk of iron overload. To induce iron overload, Wistar rats were intraperitoneally injected with subacute (0.2 mg kg⁻¹) and subchronic (0.1 mg kg⁻¹) overdoses of ISC for 2 and 4 weeks, respectively. Iron status was displayed by an increase in transferrin saturation (up to 332%) and serum and liver iron burden (up to 19.3 μmol L⁻¹ and 13.2 μmol g⁻¹ wet tissue, respectively) together with a drop in total and unsaturated iron binding capacities "TIBC, UIBC" as surrogate markers of transferrin activity. Iron-induced leukocytosis (up to 140%), along with the decline in serum transferrin markers (up to 43%), respectively, mark positive and negative acute phase reactions. Chemical stress was demonstrated by a significant rise (p > 0.05) in indices of the hemogram (erythrocytes, hemoglobin, hematocrit, leukocytes) and stress metabolites [corticosterone (CORT) and lactate]. Yet, potential causes of the unexpected decline in serum activities of ALT, AST and LDH (p > 0.05) might include decreased hepatocellular enzyme production and/or inhibition or reduction of the enzyme activities. The current findings highlight the toxic role of elevated serum and liver iron in initiating erythropoiesis and acute phase reactions, modifying iron status and animal organ function, changing energy metabolism and bringing about accelerated glycolysis and impaired lactate clearance supposedly by decreasing anaerobic threshold and causing premature entering to the anaerobic system. PMID:26616369

  11. Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells

    International Nuclear Information System (INIS)

    Highlights: •We investigate free calcium as a central signalling element in endothelial cells. •Inhibition of glycolysis with 2-deoxy-D-glucose reduces cellular ATP. •This manoeuvre leads to a biphasic increase and overload of free calcium. •Pre-treatment with lithium for 24 h abolishes both phases of the calcium increase. •This provides a new strategy to protect endothelial calcium homeostasis and barrier function. -- Abstract: Cytosolic free calcium concentration ([Ca2+]i) is a central signalling element for the maintenance of endothelial barrier function. Under physiological conditions, it is controlled within narrow limits. Metabolic inhibition during ischemia/reperfusion, however, induces [Ca2+]i overload, which results in barrier failure. In a model of cultured porcine aortic endothelial monolayers (EC), we addressed the question of whether [Ca2+]i overload can be prevented by lithium treatment. [Ca2+]i and ATP were analysed using Fura-2 and HPLC, respectively. The combined inhibition of glycolytic and mitochondrial ATP synthesis by 2-desoxy-D-glucose (5 mM; 2-DG) plus sodium cyanide (5 mM; NaCN) caused a significant decrease in cellular ATP content (14 ± 1 nmol/mg protein vs. 18 ± 1 nmol/mg protein in the control, n = 6 culture dishes, P 2+]i (278 ± 24 nM vs. 71 ± 2 nM in the control, n = 60 cells, P 2+]i response of EC was biphasic with a peak after 1 min (183 ± 6 nM vs. 71 ± 1 nM, n = 60 cells, P 2+]i. A 24-h pre-treatment with 10 mM of lithium chloride before the inhibition of ATP synthesis abolished both phases of the 2-DG-induced [Ca2+]i increase. This effect was not observed when lithium chloride was added simultaneously with 2-DG. We conclude that lithium chloride abolishes the injurious [Ca2+]i overload in EC and that this most likely occurs by preventing inositol 3-phosphate-sensitive Ca2+-release from the endoplasmic reticulum. Though further research is needed, these findings provide a novel option for therapeutic strategies to

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

    Directory of Open Access Journals (Sweden)

    Porter John B

    2010-04-01

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

  13. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload

    OpenAIRE

    Porto, G.; CARDOSO, C.S.; Gordeuk, V; Cruz, E.; Fraga, J.; Areias, J; Oliveira, J. C.; Bravo, F. (Federico); GANGAIDZO, I.T.; MACPHAIL, A.P.; GOMO, Z.A.; MOYO, V.M.; Melo, G.; Silva, C.; JUSTICA, B.

    2001-01-01

    Eur J Haematol. 2001 Aug;67(2):110-8. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload. Porto G, Cardoso CS, Gordeuk V, Cruz E, Fraga J, Areias J, Oliveira JC, Bravo F, Gangaidzo IT, MacPhail AP, Gomo ZA, Moyo VM, Melo G, Silva C, Justiça B, de Sousa M. Haematology, Santo António General Hospital, Porto, Portugal. Abstract To identify a new marker of expression of diseas...

  14. Morphological transformations in rat thymus under influence of multiplegravitational overloads and after pharmaceutical correction

    Directory of Open Access Journals (Sweden)

    Moroz G.A.

    2012-01-01

    Full Text Available Using light and transmission electron microscopy techniques morphological features of mature male Wistar rats, which were exposed to hypergravity (9 g, 10 minutes, daily, 45times, were investigated. It was revealed, that reaction of thymus on multiple hypergravity resulted in haemodynamic changes and involution of lymphoid tissue according to the adaptive and compensatory reaction of the organ under repeated stress action. Administration of glutargin as an adaptogen under systematic hypergravity overloads provides certain corrective effect. Hypergravity-induced involution changes neither progress, nor totally arrest.

  15. Monitoring system for overload vehicles%汽车超载监测系统

    Institute of Scientific and Technical Information of China (English)

    江诗明; 徐伟; 吴智量; 林树雄

    2014-01-01

    This system based on the open source computer vision library(OpenCV)is used to execute the real-time iden-tification of overloading vehicles with different vehicle models. A vehicle model classifier is established according to the vehicle photo library,and then the vehicles entering the monitored area are recorded by a digital camera. The vehicle models are identi-fied in video recognition by the classifier. The rated load of a vehicle model is obtained by querying the database,and then the actual load of the vehicle running across the monitoring area is measured by the dynamic weighing technology for judging if the vehicle is overloaded immediately. This approach can avoid the demerit of the previous one that uses the unified weight to esti-mate whether vehicles with different models are overloaded or not. In addition,it can also avoid the coil measurement of speed. Testing results show that the system can quickly and accurately identify a vehicle model,and can promptly determine whether the vehicle is overloaded by means of dynamic weighing system. It has considerable practical value for road maintenance and road traffic safety.%为了实时识别各种车型的超载车辆,该系统基于开源计算机视觉库(OpenCV),先根据车辆照片库建立车型分类器,然后使用数字摄像机拍摄进入监控区域的车辆,在视频中使用分类器识别车型,根据所识别得到的车型去查询数据库获得该车型的核载,再通过动态称重技术获得车辆的实际载重,及时判别车辆是否超载。此方法可避免过去使用统一重量衡量不同车型是否超载的弊端,并可同时免线圈测量车速。测试结果表明系统能快速准确地识别出车型。配合动态称重系统,就能实时得出所通过的车辆是否超载,对公路养护和道路交通安全有相当大的实用意义。

  16. Viscoelastic properties of pressure overload hypertrophied myocardium: effect of serine protease treatment

    Science.gov (United States)

    Stroud, Jason D.; Baicu, Catalin F.; Barnes, Mary A.; Spinale, Francis G.; Zile, Michael R.

    2002-01-01

    To determine whether and to what extent one component of the extracellular matrix, fibrillar collagen, contributes causally to abnormalities in viscoelasticity, collagen was acutely degraded by activation of endogenous matrix metalloproteinases (MMPs) with the serine protease plasmin. Papillary muscles were isolated from normal cats and cats with right ventricular pressure overload hypertrophy (POH) induced by pulmonary artery banding. Plasmin treatment caused MMP activation, collagen degradation, decreased the elastic stiffness constant, and decreased the viscosity constant in both normal and POH muscles. Thus, whereas many mechanisms may contribute to the abnormalities in myocardial viscoelasticity in the POH myocardium, changes in fibrillar collagen appear to play a predominant role.

  17. [Chronicity, chronicization, systematization of delusions].

    Science.gov (United States)

    Trapet, P; Fernandez, C; Galtier, M C; Gisselmann, A

    1984-05-01

    Chronicity in psychopathology is indicative of a term, a decay. Chronicization only leads the way to this term. Here, chronicization is taken literally as an inscription in the time course of delusions. The mechanism of systematization seems to be a central mark in the approach to chronic delusions. It is not an alienation or an irreversible closing but an attempted accommodation with reality in the life of psychotic subjects, irrespective of the delusional structure. The role of therapy and drug treatment as a follow-up may in that case assume another meaning.

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

    Science.gov (United States)

    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).

  19. 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 < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

  20. Quantification of Niacin and Its Metabolite Nicotinuric Acid in Human Plasma by LC-MS/MS: Application to a Clinical Trial of a Fixed Dose Combination Tablet of Niacin Extended-Release/Simvastatin (500 mg/10 mg in Healthy Chinese Volunteers

    Directory of Open Access Journals (Sweden)

    Pingping Zhang

    2015-01-01

    Full Text Available Our paper aimed to develop rapid, sensitive, and specific LC-MS/MS method for the quantification of niacin (NA and its metabolite nicotinuric acid (NUA in human plasma. Following protein precipitation with acetonitrile, the NA, NUA, and internal standard (5-fluorouracil were separated on a Zorbax 300SB-C8 column (250 mm × 4.6 mm, 5 μm with a mobile phase consisting of methanol-2 mM ammonium acetate (3 : 97, v/v at a flow rate of 1 mL/min (split 1 : 1. A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in negative ion mode. The linear concentration ranges of the calibration curves were 5–800 ng/mL for NA and NUA. The intra-assay RSD for quality control (QC samples were from 5.0% to 8.7% for NA, and 5.5% to 7.6% for NUA. The interassay RSD for QC samples were from 2.8% to 9.4% for NA, and 3.7% to 5.8% for NUA. The relative errors for QC samples were from −2.2% to 2.3% for NA, and −0.6% to 3.2% for NUA. The method was successfully applied to the investigation of the pharmacokinetic profiles of NA, NUA in human after single dose administration of Niacin extended-release/Simvastatin tablet (500 mg/10 mg.

  1. Porphyria cutanea tarda as a complication of therapy for chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    James Azim; Heather McCurdy; Richard H Moseley

    2008-01-01

    There is a strong association between porphyria cutanea tarda (PCT) and chronic viral hepatitis C. Therapy for chronic viral hepatitis C may improve PCT. However, there are only a few reports of the de novo development of PCT during therapy for chronic viral hepatitis C. We describe the development of PCT in a 56-year-old patient with chronic viral hepatitis C after 12 wk of peginterferon/ribavirin therapy. In addition, the patient was homozygous for the H63D hereditary hemochromatosis gene (HFE) mutation. The association of PCT with chronic viral hepatitis C and the possible role of hepatic iron overload and ribavirin-induced hemolytic anemia in the development of PCT during therapy for chronic viral hepatitis C are discussed.

  2. Clinical and research status of niacin deficiency%烟酸缺乏症的临床及研究现状

    Institute of Scientific and Technical Information of China (English)

    李若虹; 吕景晶; 白彦萍

    2012-01-01

    Deficiency of niacin is the etiology of pellagra, which can be caused by many factors such as malnutrition, alcoholism, drugs, infections and tumors. For the patient of pellagra, many systems could be involved. Brain, gut and skin are the three most often involved systems. Pellagra is associated with a classic triad: dermatitis, diarrhea, and dementia, which is well known by the mnemonic "the 3DY\\ Hovever, it is more common for a patient of Pellagra to present with one or two clinical symptoms, and diverse manifestations could be presented. It is not easy to diagnose when early symptoms arc subtle or non-specific.%烟酸缺乏症是由烟酸缺乏引起的一组临床症候群,与营养不良、酗酒、药物、感染及肿瘤等多种因素有关.可累及皮肤、胃肠道及脑.典型临床表现为皮疹、腹泻和痴呆,但大部分患者只表现其中一种或两种,且临床表现多样.早期症状轻微,可能只出现非特异症状,容易漏诊和误诊.

  3. [Non-transferrin-bound iron: a promising biomarker in iron overload disorders].

    Science.gov (United States)

    Maas, Roderick P P W M; Voets, Philip J G M; de Swart, Louise; Swinkels, Dorine W

    2013-01-01

    Iron overload disorders are common and, if left untreated, severe systemic diseases that can have both genetic and acquired causes. Hereditary haemochromatosis, β-thalassaemia, myelodysplastic syndromes and sickle cell disease are among the most important examples. Iron that is not bound to transferrin, haem or ferritin (non-transferrin-bound iron, NTBI) seems to play a key role in the pathophysiology of these disorders. NTBI is a heterogeneous group of potentially toxic iron complexes in plasma which are generated almost exclusively under pathological conditions. Cellular uptake of NTBI contributes to its toxicity and is mediated by several organ-specific transporters and receptors. NTBI-induced toxicity is the result of oxidative damage to various macromolecules by reactive oxygen species (ROS). In the near future, we hypothesize that NTBI will have important implications for both diagnosis and treatment of iron overload disorders. However, before NTBI can be applied to patient care, the currently available assays need further clinical and analytical validation. PMID:24299624

  4. Heat Transfer Simulation to Liquid Nitrogen from HTS Tapes at the Overload Currents

    Science.gov (United States)

    Zubko, V. V.; Ryabov, S. M.; Fetisov, S. S.; Vysotsky, V. S.

    Knowledge of HTS materials behavior at overload currents is important to design fault current limiters or fault protection systems of electro-technical devices. There are sharp voltage peaks and voltage oscillations during rectangular current pulses (DC current) on HTS tapes cooled by liquid nitrogen. It is common knowledge that a homogeneous liquid can withstand certain amount of overheating before switching to the boiling phase. In the liquid nitrogen during the increase of the heat flux there is superheating (temperature overshoot) and boiling hysteresis takes place. We explain voltage peaks and voltage oscillations by the hysteresis phenomenon in boiling nitrogen during the increase and decrease of the heat flux in the nitrogen which is a result of current redistribution in the HTS tapes. Based on the measurements of voltage and temperature of the HTS tapes during current overload and numerical analysis of the process we estimated the heat-transfer characteristics from the HTS tapes to liquid nitrogen. We also obtained the information about limiting superheating of the liquid nitrogen. The influence of covers of the HTS tapes on superheating of the nitrogen is also discussed.

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

    Directory of Open Access Journals (Sweden)

    Rita Jermyn

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  7. Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study.

    Science.gov (United States)

    McLaren, Gordon D; Gordeuk, Victor R

    2009-01-01

    Hemochromatosis comprises a group of inherited disorders resulting from mutations of genes involved in regulating iron metabolism. The multicenter, multi-ethnic Hemochromatosis and Iron Overload Screening (HEIRS) Study screened approximately 100,000 participants in the US and Canada, testing for HFE mutations, serum ferritin and transferrin saturation. As in other studies, HFE C282Y homozygosity was common in Caucasians but rare in other ethnic groups, and there was a marked heterogeneity of disease expression in C282Y homozygotes. Nevertheless, this genotype was often associated with elevations of serum ferritin and transferrin saturation and with iron stores of more than four grams in men but not in women. If liver biopsy was performed, in some cases because of evidence of hepatic dysfunction, fibrosis or cirrhosis was often found. Combined elevations of serum ferritin and transferrin saturation were observed in non-C282Y homozygotes of all ethnic groups, most prominently Asians, but not often with iron stores of more than four grams. Future studies to discover modifier genes that affect phenotypic expression in C282Y hemochromatosis should help identify patients who are at greatest risk of developing iron overload and who may benefit from continued monitoring of iron status to detect progressive iron loading.

  8. First passage times in M2[X ]|G |1 |R queue with hysteretic overload control policy

    Science.gov (United States)

    Pechinkin, Alexander V.; Razumchik, Rostislav R.; Zaryadov, Ivan S.

    2016-06-01

    One of the reported approaches towards the solution of overload problem in networks of SIP servers is the implementation of multi-level hysteretic control of arrivals in SIP servers. Each level, being the parameter of the policy, specifies operation mode of SIP server i.e. it implicitly indicates what SIP server must do with the arriving packets. The choice of parameters' values is not guided by standards and is usually left for the network owner. In general, all operation modes of the considered policy can be grouped into two groups: normal mode (when all arriving packets are accepted) and congested mode (when part or all arriving packets are being dropped). Such grouping may serve as the criteria for choosing parameters' values of the policy: pick those values which minimize SIP server sojourn time in congested mode. In this short note we propose some analytical results which facilitate the solution of stated minimization problem. The considered mathematical model of SIP server is the queueing system M2[X ]|G |1 |R with batch arrivals and bi-level hysteretic control policy, which specifies three operation modes: normal (customers both flows are accepted), overload (only customers from one flow are accepted), discard (customers from both flows are blocked/lost)). The switching between modes can occur only on service completions. Analytical method allowing computation of stationary sojourn times in different operation modes (as well as first passage times between modes) is presented in brief. Numerical example is given.

  9. Correlates of Cancer Information Overload: Focusing on Individual Ability and Motivation.

    Science.gov (United States)

    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. PMID:26512760

  10. Fuzzy ranking based non-dominated sorting genetic algorithm-II for network overload alleviation

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Qifeng Zhou

    2015-01-01

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

  12. Writing, Reading, and Listening Differentially Overload Working Memory Performance Across the Serial Position Curve.

    Science.gov (United States)

    Tindle, Richard; Longstaff, Mitchell G

    2015-01-01

    Previous research has assumed that writing is a cognitively complex task, but has not determined if writing overloads Working Memory more than reading and listening. To investigate this, participants completed three recall tasks. These were reading lists of words before recalling them, hearing lists of words before recalling them, and hearing lists of words and writing them as they heard them, then recalling them. The experiment involved serial recall of lists of 6 words. The hypothesis that fewer words would be recalled overall when writing was supported. Post-hoc analysis revealed the same pattern of results at individual serial positions (1 to 3). However, there was no difference between the three conditions at serial position 4, or between listening and writing at positions 5 and 6 which were both greater than recall in the reading condition. This suggests writing overloads working memory more than reading and listening, particularly in the early serial positions. The results show that writing interferes with working memory processes and so is not recommended when the goal is to immediately recall information.

  13. Exercise ameliorates chronic kidney disease–induced defects in muscle protein metabolism and progenitor cell function

    OpenAIRE

    Wang, Xiaonan H.; Du, Jie; Klein, Janet D.; Bailey, James L; Mitch, William E.

    2009-01-01

    Chronic kidney disease (CKD) impairs muscle protein metabolism leading to muscle atrophy, and exercise can counteract this muscle wasting. Here we evaluated how resistance exercise (muscle overload) and endurance training (treadmill running) affect CKD-induced abnormalities in muscle protein metabolism and progenitor cell function using mouse plantaris muscle. Both exercise models blunted the increase in disease-induced muscle proteolysis and improved phosphorylation of Akt and the forkhead t...

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

    Directory of Open Access Journals (Sweden)

    Leilismara Sousa

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

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

    Science.gov (United States)

    Zhang, Ying; Zhao, Xin; Chang, Yanzhong; Zhang, Yuanyuan; Chu, Xi; Zhang, Xuan; Liu, Zhenyi; Guo, Hui; Wang, Na; Gao, Yonggang; Zhang, Jianping; Chu, Li

    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. PMID:27095094

  16. 1~14日龄北京鸭烟酸与色氨酸互作关系的研究%Interrelationship between Tryptophan and Niacin of Pekin Ducks Aged from 1 to 14 Days

    Institute of Scientific and Technical Information of China (English)

    谢明; 韩旭峰; 侯水生; 黄苇; 喻俊英

    2012-01-01

    本试验旨在研究1 ~14日龄北京鸭烟酸与色氨酸的互作关系.试验采用4×5二因子完全随机试验设计,设4个饲粮烟酸水平(35、75、115和155 mg/kg),5个饲粮色氨酸水平(0.132%、0.167%、0.202%、0.237%和0.272%).将840只1日龄健康雄性北京鸭随机分为20个组,每组6个重复,每个重复7只鸭.试验期14d.结果表明:1)饲粮中单独补充色氨酸可缓解饲粮烟酸缺乏导致的北京鸭生长抑制(P<0.05),而饲粮中单独补充烟酸不能缓解饲粮色氨酸缺乏导致的北京鸭生长抑制(P>0.05).2)依据折线模型,以平均日增重为评价指标,1~14日龄北京鸭烟酸需要量为81 mg/kg.3)依据折线模型,以平均日增重为评价指标,当饲粮烟酸水平分别为35、75、115和155 mg/kg时,1~14日龄北京鸭色氨酸需要量分别为0.254%、0.169%、0.170%和0.172%.t检验分析表明,饲粮烟酸水平为35mg/kg时色氨酸需要量极显著高于其他3个饲粮烟酸水平下色氨酸需要量(P<0.01).综合以上试验结果得出,北京鸭饲粮中烟酸与色氨酸之间的互作关系表现在饲粮烟酸水平对色氨酸需要量产生显著影响.当饲粮烟酸缺乏时,1~14日龄北京鸭色氨酸需要量显著升高.%This experiment was conducted to study the interrelationship between tryptophan and niacin of Pekin ducks aged 1 to 14 days. A 4 × 5 tow factorial experiment design which contained four dietary niacin levels (35, 75, 115 and 155 mg/kg) and five dietary tryptophan levels (0. 132% , 0. 167% , 0. 202% , 0. 237% and 0. 272% ) was used. Eight hundred and forty one-day-old male Pekin ducks were divided into 20 groups with 6 replicates per group and 7 ducks per replicate, and the experiment period lasted for 14 days. The results showed as follows: 1) the supplementation of tryptophan in diets could alleviate the growth depression caused by niacin deficiency (P 0. 05). 2) According to the broken-line regression analysis of

  17. Chronic cholecystitis

    Science.gov (United States)

    ... foods may relieve symptoms in people. However, the benefit of a low-fat diet has not been proven. Alternative Names Cholecystitis - chronic Images Cholecystitis, CT scan Cholecystitis, cholangiogram Cholecystolithiasis Gallstones, cholangiogram Cholecystogram References Wang ...

  18. Chronic Meningitis

    Science.gov (United States)

    ... School Lunch Lines FDA Cracks Down on Antibacterial Soaps Health Tip: Schedule a Back-to-School Dental ... the Professional Version Meningitis Introduction to Meningitis Acute Bacterial Meningitis Viral Meningitis Noninfectious Meningitis Recurrent Meningitis Chronic ...

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

    Science.gov (United States)

    Max, S. R.; Rance, N.

    1983-01-01

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

  20. Niacin and statin combination therapy for atherosclerosis regression and prevention of cardiovascular disease events: reconciling the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial with previous surrogate endpoint trials.

    Science.gov (United States)

    Michos, Erin D; Sibley, Christopher T; Baer, Jefferson T; Blaha, Michael J; Blumenthal, Roger S

    2012-06-01

    Despite substantial risk reductions targeting low-density lipoprotein cholesterol with statins, there remains significant residual risk as evidenced by incident and recurrent cardiovascular disease (CVD) events among statin-treated patients. Observational studies have shown that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased CVD risk. It remains unclear whether strategies aimed at increasing HDL-C in addition to background statin therapy will further reduce risk. The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial, which compared combined niacin/simvastatin with simvastatin alone, failed to demonstrate an incremental benefit of niacin among patients with atherosclerotic CVD and on-treatment low-density lipoprotein cholesterol values equivalents, or atherosclerosis. This viewpoint summarizes these imaging trials studying niacin and places them in the context of the failure of AIM-HIGH to support the HDL-C-increasing hypothesis.

  1. 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

  2. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    International Nuclear Information System (INIS)

    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

  3. Scientific Opinion on the safety and efficacy of niacin (nicotinamide as a feed additive for all animal species based on a dossier submitted by EUROPE-ASIA Import Export GmbH

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Additives and Products or Substances used in Animal Feed

    2012-07-01

    Full Text Available

    The term ‘niacin’ is used as a generic description of nicotinic acid and nicotinamide with pyridine as the basic structure. Nicotinic acid and nicotinamide function mainly as precursors of the co-enzymes NAD and NADP. Thus, nicotinamide has physiologically critical roles in mitochondrial respiration and in the metabolism of carbohydrates, lipids, and amino acids. Oral administration routes of nicotinamide via feed or water for drinking are considered bioequivalent. Nicotinamide is safe for the target animals with a margin of safety that is at least ten times the requirements and use levels. The FEEDAP Panel assumes that exposure figures for a population already include the contribution of edible tissues and products of animals fed niacin-supplemented diets. Information on niacin metabolism and the limited data available on retention in edible tissues and products indicate that supplemental levels in feeds even far higher than the requirements (1–35 mg/kg feed are highly unlikely to lead the tolerable upper intake level being exceeded. The FEEDAP Panel considers that the use of nicotinamide in animal nutrition is not of safety concern for consumers. Nicotinamide is not irritant to skin, but can cause irritancy to eyes and mucous membranes. It is unlikely to cause skin sensitisation. Workers might be exposed to a respirable dust when handling nicotinamide, which should be regarded as being potentially harmful to their health. The use of nicotinamide in animal nutrition does not pose a risk to the environment. Nicotinamide is regarded as an effective source of niacin in animal nutrition.

  4. 烟酸对人脐内皮细胞损伤的保护作用%Protective Effect of Niacin on Human Umbilical Vein Endothelial Cells Injury Induced by Cholesterol in Vitro

    Institute of Scientific and Technical Information of China (English)

    罗舜菁; 汪志宇; 刘成梅; 陈臣; 王文飞; 姚景宇; 高江宇

    2011-01-01

    To investigate protective effect of niacin on human umbilical vein endothelial cells ( HUVECs) , which injury treated by cholesterol. Use inverted microscope observation cells form, the growth rate of cells was detected by MTT (3-(4,5-dimethylthiazo l-2-yl)-2,5-diphenylte trazolium bromide) methods. With the increase of cholesterol concentration, the value of MTT was significantly reduced (P <0.05). Niacin significantly improved the growth of cells with dose dependent (P <0. 05). Cholesterol could induce injury for HUVECS, while niacin may prevent HUVECS from the injury.%研究了烟酸对胆固醇处理的人脐静脉内皮细胞(HUVECs)损伤的保护作用.使用倒置显微镜观察细胞形态,四甲基偶氮唑蓝(MTT)比色法测定HUVECs存活率.结果表明:随着胆固醇浓度的增加,用MTT比色法测得的吸光度逐渐降低,HUVECs存活率显著降低(P<0.05).烟酸呈剂量依赖性的显著改善胆固醇诱导所致下降的HUVECs存活率(P<0.05).胆固醇可以诱导内皮细胞损伤,烟酸对胆固醇诱导的人脐静脉内皮细胞损伤具有保护作用.

  5. A waveguide overloaded cavity kicker for the HLS II longitudinal feedback system

    CERN Document Server

    Li, Wubin; Sun, Baogen; Wu, Fangfang; Xu, Wei; Lu, Ping; Yang, Yongliang

    2013-01-01

    In the upgrade project of Hefei Light Source (HLS II), a new digital longitudinal bunch-by-bunch feedback system will be developed to suppress the coupled bunch instabilities in the storage ring effectively. We design a new waveguide overloaded cavity longitudinal feedback kicker as the feedback actuator. The beam pipe of the kicker is racetrack shape so as to avoid a transition part to the octagonal vacuum chamber. The central frequency and the bandwidth of the kicker have been simulated and optimized to achieve design goals by the HFSS code. The higher shunt impedance can be obtained by using a nose cone to reduce the feedback power requirement. Before the kicker cavity was installed in the storage ring, a variety of measurements were carried out to check its performance. All these results of simulation and measurement are presented.

  6. EFFECT OF STRESS AND PSYCHOLOGICAL OVERLOAD AT WORK ON PERFORMANCE OF EMPLOYEES

    Directory of Open Access Journals (Sweden)

    MAREK ŠOLC

    2009-12-01

    Full Text Available The workload represents a factor which acts burdensome on human organism and, depending on its level affects well-being, or leads to disease or injury. As a result, there is a distortion in optimal working relationship in the system man – machine – environment, which may be reflected in the reduction of productivity and efficiency throughout the system. The contribution deals with the issue of the effects of stress and psychological overload at work, which affects significantly the performance of employees. The article describes the basic legislation regarding the workload in conditions of the Slovak Republic, it describes the types of loads, different causes, manifestations and consequences of load. According to theoretical knowledge about stress and loads, the questionnaire method was applied for assessment of mental workload in terms of working conditions level in the unnamed service organization.

  7. Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Bosche, Bert, E-mail: bert.bosche@uk-essen.de [Department of Neurology, University of Duisburg-Essen (Germany); Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Schäfer, Matthias, E-mail: matthias.schaefer@sanofi.com [Institute of Physiology, Justus-Liebig-University Giessen (Germany); Graf, Rudolf, E-mail: rudolf.graf@nf.mpg.de [Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne (Germany); Härtel, Frauke V., E-mail: frauke.haertel@tu-dresden.de [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany); Schäfer, Ute, E-mail: ute.schaefer@medunigraz.at [Research Unit for Experimental Neurotraumatology, Medical University of Graz (Austria); Noll, Thomas, E-mail: thomas.noll@tu-dresden.de [Institute of Physiology, Medical Faculty Carl Gustav Carus, Technical University Dresden (Germany)

    2013-05-03

    Highlights: •We investigate free calcium as a central signalling element in endothelial cells. •Inhibition of glycolysis with 2-deoxy-D-glucose reduces cellular ATP. •This manoeuvre leads to a biphasic increase and overload of free calcium. •Pre-treatment with lithium for 24 h abolishes both phases of the calcium increase. •This provides a new strategy to protect endothelial calcium homeostasis and barrier function. -- Abstract: Cytosolic free calcium concentration ([Ca{sup 2+}]{sub i}) is a central signalling element for the maintenance of endothelial barrier function. Under physiological conditions, it is controlled within narrow limits. Metabolic inhibition during ischemia/reperfusion, however, induces [Ca{sup 2+}]{sub i} overload, which results in barrier failure. In a model of cultured porcine aortic endothelial monolayers (EC), we addressed the question of whether [Ca{sup 2+}]{sub i} overload can be prevented by lithium treatment. [Ca{sup 2+}]{sub i} and ATP were analysed using Fura-2 and HPLC, respectively. The combined inhibition of glycolytic and mitochondrial ATP synthesis by 2-desoxy-D-glucose (5 mM; 2-DG) plus sodium cyanide (5 mM; NaCN) caused a significant decrease in cellular ATP content (14 ± 1 nmol/mg protein vs. 18 ± 1 nmol/mg protein in the control, n = 6 culture dishes, P < 0.05), an increase in [Ca{sup 2+}]{sub i} (278 ± 24 nM vs. 71 ± 2 nM in the control, n = 60 cells, P < 0.05), and the formation of gaps between adjacent EC. These observations indicate that there is impaired barrier function at an early state of metabolic inhibition. Glycolytic inhibition alone by 10 mM 2-DG led to a similar decrease in ATP content (14 ± 2 nmol/mg vs. 18 ± 1 nmol/mg in the control, P < 0.05) with a delay of 5 min. The [Ca{sup 2+}]{sub i} response of EC was biphasic with a peak after 1 min (183 ± 6 nM vs. 71 ± 1 nM, n = 60 cells, P < 0.05) followed by a sustained increase in [Ca{sup 2+}]{sub i}. A 24-h pre-treatment with 10 mM of lithium

  8. Overloading of Landing Based on the Deformation of the Lunar Lander

    Institute of Scientific and Technical Information of China (English)

    Chen Jinbao; Nie Hong

    2008-01-01

    Along with the progress of sciences and technologies, a lot of explorations are taken in many countries or organizations in succession. Lunar, the natural satellite of the earth, become a focus of the space discovery again recently because of its abundant resource and high value in use, Lunar exploration is also one of the most important projects in China, A primary objective of the probe in lunar is to soft-land a manned spacecraft on the lunar surface. The soft-landing system is the key composition of the lunar lander. In the overall design of lunar lender, the analysis of touchdown dynamics during landing stage is an important work. The rigid-flexible coupling dyuamics of a system with flexible cantilevers attached to the main landex is analyzed. The equations arc derived from the subsystem method. Results show that the deformations of cantilevers have considerable effect on the overloading of the lunar lander system.

  9. MR marrow signs of iron overload in transfusion-dependent patients with sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Sheth, S.S. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Hurlet, A. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Comerci, S.C. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Ruzal-Shapiro, C. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States); Piomelli, S. [Department of Pediatrics, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, 3959 Broadway, New York, NY 10032 (United States); Berdon, W.E. [Department of Pediatric Radiology, Babies and Children`s Hospital, Columbia-Presbyterian Medical Center, New York, NY (United States)

    1995-11-01

    Magnetic resonance (MR) marrow signal in the axial and appendicular skeleton of 13 transfusion-dependent and chelated pediatric patients with sickle cell anemia (SSD) was compared with marrow signal in six non-transfusion-dependent patients with SSD. Hepatic, pancreatic, and renal MR signal were also evaluated. Indication for hypertransfusion therapy was primarily prior history of stroke. Transfusion-dependent patients had evidence of iron deposition throughout the imaged marrow and the liver, despite deferoxamine chelation therapy. Non-transfusion-dependent patients did not demonstrate grossly apparent signs of iron overload. Red marrow restoration was present in the spine, pelvis, and long bones and, in some patients, within the epiphyses. Marrow edema secondary to vaso-occlusive crises was evident in the metaphyses and diaphyses of long bones in areas of both red and fatty marrow and was best seen using fat-saturated T2-weighted imaging techniques. (orig.). With 4 figs., 2 tabs.

  10. Securing OFDM over Wireless Time-Varying Channels Using Subcarrier Overloading with Joint Signal Constellations

    Directory of Open Access Journals (Sweden)

    Gill R. Tsouri

    2009-01-01

    Full Text Available A method of overloading subcarriers by multiple transmitters to secure OFDM in wireless time-varying channels is proposed and analyzed. The method is based on reverse piloting, superposition modulation, and joint decoding. It makes use of channel randomness, reciprocity, and fast decorrelation in space to secure OFDM with low overheads on encryption, decryption, and key distribution. These properties make it a good alternative to traditional software-based information security algorithms in systems where the costs associated with such algorithms are an implementation obstacle. A necessary and sufficient condition for achieving information theoretic security in accordance with channel and system parameters is derived. Security by complexity is assessed for cases where the condition for information theoretic security is not satisfied. In addition, practical means for implementing the method are derived including generating robust joint constellations, decoding data with low complexity, and mitigating the effects of imperfections due to mobility, power control errors, and synchronization errors.

  11. A New Decoding Scheme for Errorless Codes for Overloaded CDMA with Active User Detection

    CERN Document Server

    Mousavi, Ali; Marvasti, Farokh

    2010-01-01

    Recently, a new class of binary codes for overloaded CDMA systems are proposed that not only has the ability of errorless communication but also suitable for detecting active users. These codes are called COWDA [1]. In [1], a Maximum Likelihood (ML) decoder is proposed for this class of codes. Although the proposed scheme of coding/decoding show impressive performance, the decoder can be improved. In this paper by assuming more practical conditions for the traffic in the system, we suggest an algorithm that increases the performance of the decoder several orders of magnitude (the Bit-Error-Rate (BER) is divided by a factor of 400 in some Eb/N0's The algorithm supposes the Poison distribution for the time of activation/deactivation of the users.

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

    Science.gov (United States)

    Zhou, Qifeng; Kesteven, Scott; Wu, Jianxin; Aidery, Parwez; Gawaz, Meinrad; Gramlich, Michael; Feneley, Michael P; Harvey, Richard P

    2015-01-01

    Mutations in the giant sarcomeric protein titin (TTN) are a major cause for inherited forms of dilated cardiomyopathy (DCM). We have previously developed a mouse model that imitates a TTN truncation mutation we found in a large pedigree with DCM. While heterozygous Ttn knock-in mice do not display signs of heart failure under sedentary conditions, they recapitulate the human phenotype when exposed to the pharmacological stressor angiotensin II or isoproterenol. In this study we investigated the effects of pressure overload by transverse aortic constriction (TAC) in heterozygous (Het) Ttn knock-in mice. Two weeks after TAC, Het mice developed marked impairment of left ventricular ejection fraction (p arsenal of cardiac disease models, adding a valuable tool to understand cardiac pathophysiological remodeling processes and to develop therapeutic approaches to combat heart failure. PMID:26504781

  13. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways

    Directory of Open Access Journals (Sweden)

    Dan Bao

    2015-08-01

    Full Text Available Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnTR92Q transgenic mice and thoracic aorta constriction (TAC-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.

  14. Effect of iron overload and iron deficiency on liver hemojuvelin protein.

    Directory of Open Access Journals (Sweden)

    Jan Krijt

    Full Text Available INTRODUCTION: Hemojuvelin (Hjv is a key component of the signaling cascade that regulates liver hepcidin (Hamp expression. The purpose of this study was to determine Hjv protein levels in mice and rats subjected to iron overload and iron deficiency. METHODS: C57BL/6 mice were injected with iron (200 mg/kg; iron deficiency was induced by feeding of an iron-deficient diet, or by repeated phlebotomies. Erythropoietin (EPO-treated mice were administered recombinant EPO at 50 U/mouse. Wistar rats were injected with iron (1200 mg/kg, or fed an iron-deficient diet. Hjv protein was determined by immunoblotting, liver samples from Hjv-/- mice were used as negative controls. Mouse plasma Hjv content was determined by a commercial ELISA kit. RESULTS: Liver crude membrane fraction from both mice and rats displayed a major Hjv-specific band at 35 kDa, and a weaker band of 20 kDa. In mice, the intensity of these bands was not changed following iron injection, repeated bleeding, low iron diet or EPO administration. No change in liver crude membrane Hjv protein was observed in iron-treated or iron-deficient rats. ELISA assay for mouse plasma Hjv did not show significant difference between Hjv+/+ and Hjv-/- mice. Liver Hamp mRNA, Bmp6 mRNA and Id1 mRNA displayed the expected response to iron overload and iron deficiency. EPO treatment decreased Id1 mRNA, suggesting possible participation of the bone morphogenetic protein pathway in EPO-mediated downregulation of Hamp mRNA. DISCUSSION: Since no differences between Hjv protein levels were found following various experimental manipulations of body iron status, the results indicate that, in vivo, substantial changes in Hamp mRNA can occur without noticeable changes of membrane hemojuvelin content. Therefore, modulation of hemojuvelin protein content apparently does not represent the limiting step in the control of Hamp gene expression.

  15. MicroRNAs and liver cancer associated with iron overload: therapeutic targets unravelled.

    Science.gov (United States)

    Greene, Catherine M; Varley, Robert B; Lawless, Matthew W

    2013-08-28

    Primary liver cancer is a global disease that is on the increase. Hepatocellular carcinoma (HCC) accounts for most primary liver cancers and has a notably low survival rate, largely attributable to late diagnosis, resistance to treatment, tumour recurrence and metastasis. MicroRNAs (miRNAs/miRs) are regulatory RNAs that modulate protein synthesis. miRNAs are involved in several biological and pathological processes including the development and progression of HCC. Given the poor outcomes with current HCC treatments, miRNAs represent an important new target for therapeutic intervention. Several studies have demonstrated their role in HCC development and progression. While many risk factors underlie the development of HCC, one process commonly altered is iron homeostasis. Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised. Aberrant miRNA expression in hepatic fibrosis and injury response have been reported, as have dysregulated miRNA expression patterns affecting cell cycle progression, evasion of apoptosis, invasion and metastasis. In 2009, miR-26a delivery was shown to prevent HCC progression, highlighting its therapeutic potential. Several studies have since investigated the clinical potential of other miRNAs with one drug, Miravirsen, currently in phase II clinical trials. miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy. Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years, yielding improved HCC survival rates and patient outcomes.

  16. Nicotinamide overload may play a role in the development of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Shi-Sheng Zhou; Li-Bin Zhang; Ning Luo; Fu-Ning Bian; Wei Zou; Lai-Bin Dong; Zhi-Gang Zhao; Sheng-Fan Li; Xiao-Jie Gong; Zeng-Guo Yu; Chang-Bin Sun; Da Li; Cong-Long Zheng; Dong-Ju Jiang; Zheng-Ning Li; Wu-Ping Sun; Ming Guo; Yong-Zhi Lun; Yi-Ming Zhou; Fu-Cheng Xiao; Li-Xin Jing; Shen-Xia Sun

    2009-01-01

    AIM: To investigate whether nicotinamide overload plays a role in type 2 diabetes.METHODS: Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N~1-methylnicotinamide on glucose metabolism, plasma H_2O_2 levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively.RESULTS: Diabetic subjects had significantly higher plasma N~1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P< 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N~1-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N~1-methylnicotinamide. Moreover, cumulative exposure to N~1-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H_2O_2 levels. Decrease in NAD/NADH ratio and increase in H_2O_2 generation were also observed in human erythrocytes after exposure to N~1-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N~1-methylnicotinamide clearance.CONCLUSION: These findings suggest that nicotinamide overload, which induced an increase in plasma N~1-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

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

    Science.gov (United States)

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

    1996-01-01

    This study was designed to explore the daily lived experiences of a group of employed, low-income Mexican women in their maternal and spousal roles. The participants were 41 auxiliary nurses recruited from two large urban hospitals in Mexico. Data were collected through the Women's Roles Interview Protocol (WRIP), which solicited the participants' perceptions of the satisfaction and stresses they experienced in their roles as mothers and spouses, and their descriptions of the coping strategies and the resources they used to deal with stressful life experiences related to these roles. Data analysis consisted of a qualitative thematic analysis of the narrative responses to open-ended questions in the WRIP. Satisfying aspects of the maternal and spousal roles, as identified by the participants, included giving to and receiving from their children and being valued and supported by their partners. Spousal approval of their work was also satisfying. These employed mothers, however, experienced many stressful aspects of functioning in multiple roles, including lack of resources, being absent from their children, self-doubt about their maternal role functioning, role overload and spousal absences. The women coped by juggling priorities and utilizing family resources. From the data analysis, the investigators developed a conceptual framework for understanding these women's experiences with parenting and marriage. The centrality of the family, a sense of value and empowerment as women in maternal and spousal roles, and the reality of role overload are discussed within the Mexican culture context of machismo, its female counterpart hembrismo, and family life. Implications for women's health are framed within a context of family and work. PMID:8708228

  18. Self-Control, Self-Efficacy, Role Overload, and Stress Responses among Siblings of Children with Cancer

    Science.gov (United States)

    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,…

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

    Science.gov (United States)

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

  20. Xiaoyaosan-containing serum inhibits corticosterone-induced apoptosis in PC12 cells by downregulating[Ca2+]i overload

    Institute of Scientific and Technical Information of China (English)

    Lin Li; Xuanhong Zhang; Tingting Yan; Qian Li; Shukao Liu; Lili Wu; Can Yan; Hongmei Tan

    2010-01-01

    Apoptosis in hippocampal neurons is an important contributor to depression.[Ca2+]i of hippocampal neurons may raise rapidly with increased cortioosterone concentrations,leading to apoptosis.The anti-depressant effects of Xiaoyaosan(Free and Easy Wanderer's Powder)may inhibit apoptosis by down regulating the[Ca2+]i overload.PC12 cells were containing with corticosterone to simulate neuronal injury,dosed with Xiaoyaosan-containing serum,and the following parameters were measured: apoptosis,[Ca2+]i overload,and changes in mitochondrial membrane potential(Δψm)and bioenergetics.High-dose Xiaoyaosan-containing serum(the dose of intragastric administration was 2.633 g herb/mL)not only inhibited morphological injury and cell apoptosis,but also suppressed[Ca2+]i overload induced by corticosterone.Xiaoyaosan also blocked the decrease in mitochondrial membrane potential and adenosine triphosphate levels induced by corticosterone.Xiaoyaosan dose-dependently suppresses corticosterone-induced apoptosis,potentially via inhibiting[Ca2+]i overload,and prevents impaired mitochondrial bioenergetics by maintaining mitochondrial membrane potential and adenosine triphosphate production,providing a putative mechanism for its antidepressant effects.

  1. Volume Overload Cleanup: An Approach for On-line SPE-GC, GPC-GC and GPC-SPE-GC

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. The influence of domestic overload on the association between job strain and ambulatory blood pressure among female nursing workers.

    Science.gov (United States)

    Portela, Luciana Fernandes; Rotenberg, Lucia; Almeida, Ana Luiza Pereira; Landsbergis, Paul; Griep, Rosane Harter

    2013-11-27

    Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP) alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers.

  5. Numerical simulation of fatigue crack growth rate and crack retardation due to an overload using a cohesive zone model

    NARCIS (Netherlands)

    Silitonga, S.; Maljaars, J.; Soetens, F.; Snijder, H.H.

    2014-01-01

    In this work, a numerical method is pursued based on a cohesive zone model (CZM). The method is aimed at simulating fatigue crack growth as well as crack growth retardation due to an overload. In this cohesive zone model, the degradation of the material strength is represented by a variation of the

  6. The Effect and Mechanism of Forsinopril on Ventricular Hypertrophy of SHR and Left Ventricular Pressure overloading Rat

    Institute of Scientific and Technical Information of China (English)

    黄恺; 戴闺柱

    2002-01-01

    The effects and mechanism of long-term angiotensin converting enzyme inhibitor (ACEI)Forsinopril on left ventricular hypertrophy of spontaneous hypertension rat (SHR) and left ventricular pressure overloading rat were studied. The left ventricular index (left ventricle weight/body weight) was used to evaluate left ventricular hypertrophy and the in situ hybridization to investigate the TGF-β1 gene expression in left ventricle. The results showed that Forsinopril significantly decreased the left ventricular index of both SHR and left ventricle pressure overloading rat. Forsinopril reduced the integral photic density of TGF-β1 gene statement from 2. 836± 0. 314 to 1.91 ± 0. 217(P<0.01, n=8 ) of SHR rat and from 3. 071±0. 456 to 2. 37640. 379 (P<0.01, n=8) of left ventricular pressure overloading rat respectively. It was concluded that Forsinopril could prevent the occurrence of left ventricular hypertrophy and reduce the TGF-β1 gene expression in left ventricle of both SHR and left ventricular pressure overloading rat significantly.

  7. 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.

  8. 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.

  9. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  10. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  11. Eccentric Strengthening for Chronic Lateral Epicondylosis

    Science.gov (United States)

    Wen, Dennis Y.; Schultz, Brian J.; Schaal, Bob; Graham, Scott T.; Kim, Byung Sung

    2011-01-01

    Background: Effective treatments for chronic lateral epicondylosis have not been studied adequately. Eccentric overload exercises have been used with success for other chronic tendinopathy, mainly Achilles and patellar. Hypothesis/Purpose: To compare a wrist extensor eccentric strengthening exercise program with a wrist extensor stretching/modality program for the treatment of chronic lateral epicondylosis. The authors hypothesized that the eccentric strengthening program would produce more favorable results than a stretching/modality program. Study Design: Prospective randomized controlled trial. Methods: Twenty-eight adults with lateral epicondylosis of greater than 4 weeks’ duration were randomized to an eccentric strengthening group or a stretching group. Exercises were taught by a physical therapist, and participants performed most of the exercises on their own at home. Pain scores with visual analog scale from 0 to 100 were obtained at baseline and then at 4, 8, 12, 16, and 20 weeks after the start of the exercise program. Results: Both groups improved their pain scores from baseline to the 4-week time point, followed by nonsignificant further decreases in pain scores thereafter. No statistically significant differences were found between the eccentric strengthening group and stretching groups at any follow-up time point. Conclusions: Despite previous reports documenting favorable results with eccentric exercises for other tendinopathy, the authors were unable to show any statistical advantage to eccentric exercises for lateral epicondylosis during these periods compared with local modalities and stretching exercises. PMID:23016049

  12. Chronic pain - resources

    Science.gov (United States)

    Pain - resources; Resources - chronic pain ... The following organizations are good resources for information on chronic pain: American Chronic Pain Association -- www.theacpa.org National Fibromyalgia and Chronic Pain Association -- www.fmcpaware.org ...

  13. Low back pain - chronic

    Science.gov (United States)

    Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause ...

  14. Chronic motor tic disorder

    Science.gov (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  15. Chronic Pelvic Pain

    Science.gov (United States)

    ... Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  16. Employees with Chronic Pain

    Science.gov (United States)

    ... Home | Accommodation and Compliance Series: Employees with Chronic Pain By Beth Loy, Ph.D. Preface Introduction Information ... at http://AskJAN.org/soar. Information about Chronic Pain How prevalent is chronic pain? Chronic pain has ...

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

    International Nuclear Information System (INIS)

    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 Ca2+ in aconitine poisoning. In this study, we explored the importance of pathological Ca2+ signaling in aconitine poisoning in vitro and in vivo. We found that Ca2+ 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 Ca2+ handling proteins demonstrated that aconitine promoted Ca2+ overload through the expression regulation of Ca2+ 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 Ca2+ overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca2+ overload causes arrhythmia in rats.

  18. Effects of Ligustrazine on Myocardial Fibrosis in Rats with Pressure Overload

    Institute of Scientific and Technical Information of China (English)

    任海玲; 江时森; 谢渡江; 汪春辉; 杭涛

    2004-01-01

    Objective: To investigate the effects of ligustrazine (Li) on myocardial fibrosis in rats with pressure overload. Methods: Pressure overload rat models were established by constricting the abdominal aorta. Sixty-three SD rats were divided into 3 groups: Sham operated group (SOG, n=21), operated group (OG, n=21) and operated combined with ligustrazine group (OG+Li, n=21). Each group was randomly assigned to seven time points: The 1st, 2nd, 4th, 7th, 14th, 21st and 30th day after operation. Three rats were included in each time point. Serial sections of cardiac tissues were examined and the morphological or morphometric analysis of the SOG, OG and OG+Li done by histopathological and computer image analyzer technique. Results: (1) It showed that there were reactive fibrosis (from the 4th day on after operation) and reparative fibrosis (from the 21st day on after operation) in the OG, while myocardial fibrosis in the OG+Li was alleviated. Though reactive fibrosis (from the 21st day on after operation) was shown, reparative fibrosis wasn′t seen. (2) Perivascular collagen area (PVCA) in the OG (2. 09±0. 45) was significantly higher than SOG (0.83±0.06) from the 1st day on after operation and then steadily increased, while in the OG+Li (1. 16±0.06), it was significantly lower than OG at the same time; collagen volume fraction (CVF) in the OG (3. 08±0.56) significantly increased compared with the SOG (2. 78±0.64) from the 2nd day on after operation and showed a trend of rapid ascending from the 21st day on after operation; and in the OG+Li (4. 69±0.85), it was significantly decreased compared with the OG (7. 56±0.88) from the 21st day on after operation, with all P<0. 05. Conclusion: Ligustrazine could alleviate and postpone the accumulation of myocardial collagen and has protective effects on the heart.

  19. Treating thalassemia major-related iron overload: the role of deferiprone

    Directory of Open Access Journals (Sweden)

    Berdoukas V

    2012-10-01

    Full Text Available Vasilios Berdoukas,1 Kallistheni Farmaki,2 Susan Carson,1 John Wood,3 Thomas Coates11Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, CA, USA; 2Thalassemia Unit, General Hospital of Corinth, Corinth, Greece; 3Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, CA, USAAbstract: Over the last 20 years, management for thalassemia major has improved to the point where we predict that patients' life expectancy will approach that of the normal population. These outcomes result from safer blood transfusions, the availability of three iron chelators, new imaging techniques that allow specific organ assessment of the degree of iron overload, and improvement in the treatment of hepatitis. In October 2011, the Food and Drug Administration licensed deferiprone, further increasing the available choices for iron chelation in the US. The ability to prescribe any of the three chelators as well as their combinations has led to more effective reduction of total body iron. The ability to determine the amount of iron in the liver and heart by magnetic resonance imaging allows the prescription of the most appropriate chelation regime for patients and to reconsider what our aims with respect to total body iron should be. Recent evidence from Europe has shown that by normalizing iron stores not only are new morbidities prevented but also reversal of many complications such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance, and type 2 diabetes can occur, improving survival and patients' quality of life. The most effective way to achieve normal iron stores seems to be with the combination of deferoxamine and deferiprone. Furthermore, outcomes should continue to improve in the future. Starting relative intensive chelation in younger children may prevent short stature and abnormal pubertal maturation as well as other iron-related morbidities. Also, further information should become available on the

  20. Adiponectin is required for cardiac MEF2 activation during pressure overload induced hypertrophy.

    Science.gov (United States)

    Dadson, Keith; Turdi, Subat; Hashemi, Sarah; Zhao, Jianzhong; Polidovitch, Nazar; Beca, Sanja; Backx, Peter H; McDermott, John C; Sweeney, Gary

    2015-09-01

    Cardiomyocyte (CM) hypertrophy and increased heart mass in response to pressure overload are associated with hyper-activation of the myocyte enhancer factor-2 (MEF2) family of transcriptional regulators, and concomitant initiation of the fetal gene program. Adiponectin, an adipokine that is reduced in individuals with obesity and diabetes, has been characterized both as a negative regulator or permissive factor in cardiac hypertrophy. We therefore sought to analyze temporal regulation of MEF2 activity in response to pressure overload (PO) and changes in adiponectin status. To address this we crossed a well characterized transgenic MEF2 "sensor" mouse (MEF2-lacZ) with adiponectin null mice (Ad-KO) to create compound MEF2 lacZ/Ad-KO mice. Initially, we established that transverse aortic banding induced PO in wild-type (WT) mice increased heart mass and CM hypertrophy from 1 to 4weeks following surgery, indicated by increased CM diameter and heart weight/tibia length ratio. This was associated with cardiac dysfunction determined by echocardiography. Hypertrophic changes and dysfunction were observed in Ad-KO mice 4weeks following surgery. MEF2 lacZ activity and endogenous ANF mRNA levels, used as indicators of hypertrophic gene activation, were both robustly increased in WT mice after MTAB but attenuated in the Ad-KO background. Furthermore, activation of the pro-hypertrophic molecule p38 was increased following MTAB surgery in WT mice, but not in Ad-KO animals, and treatment of primary isolated CM with recombinant adiponectin induced p38 phosphorylation in a time dependent manner. Adiponectin also increased MEF2 activation in primary cardiomyocytes, an effect attenuated by p38 MAPK inhibition. In conclusion, our data indicate that robust hypertrophic MEF2 activation in the heart in vivo requires a background of adiponectin signaling and that adiponectin signaling in primary isolated CM directly enhances MEF2 activity through activation of p38 MAPK. We conclude that

  1. Chronic coughing

    International Nuclear Information System (INIS)

    Chronic coughing was acknowledged to result from pathological state of the respiratory organs. Cardiac diseases could be accompanied by coughing as well. It was recommended to perform x-ray examinations, including biomedical radiography of the chest, computerized tomography, scintiscanning with 67Ga-citrate, bronchi examination in order to exclude heart disease. The complex examination permitted to detect localization and type of the changes in the lungs and mediastinum, to distinguish benign tumor from malignant one

  2. Effect of Combined versus Monotherapy with Deferoxamine and Deferiprone in Iron Overloaded Thalassemia Patients: a Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Sasan Hejazi

    2016-06-01

    Full Text Available Background: Patients with transfusional iron overload have depended on iron chelation therapy and improving chelation regimens have been of the highest priority. The aim of this study was to compare effect of combined versus monotherapy with Deferoxamine (DFO and Deferiprone (DFP in iron overloaded beta thalassemia (BT major patients Materials and Methods We studied 36 BT major patients (mean age 7.6±4.6; range 3–16 years attending the Ormieh Motahari hospital for regular transfusional support. Patients were randomly allocated to receive one of the following two treatments: DFO in combination with DFP (n=12, DFO alone (n=12 and DFP alone (n=12. Serum ferritin level, liver enzymes, blood urea nitrogen, and creatinine and side effects were monitored over a 12 months period. Results: After one year, serum ferritin decreased more significantly in patients on DFO+DFP therapy compared to patients who only received DFO or DFP alone (P

  3. Analysis on overloading vehicles to bridge damages%超载车辆对桥梁损伤的分析

    Institute of Scientific and Technical Information of China (English)

    赵云鹏

    2015-01-01

    分析了超载车辆对各种构造的桥梁造成损伤的表现形式及原因,并提出了避免超载车辆对桥梁结构造成损伤的预防措施,同时探讨了对桥梁进行维修加固的方法,以延长公路桥梁的使用寿命,消除交通安全隐患。%This paper analyzed the forms and causes of overloading vehicles to bridge damages with various structures,and proposed the preven-tion measures avoid overloading vehicle caused damages to bridge structure,at the same time,discussed the method made maintenance and rein-forcement to bridge,so as to prolong the service life of road bridges,eliminated the traffic safety hidden dangers.

  4. Influence of lead on repetitive behavior and dopamine metabolism in a mouse model of iron overload.

    Science.gov (United States)

    Chang, JuOae; Kueon, Chojin; Kim, Jonghan

    2014-12-01

    Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity. PMID:25584146

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

    Science.gov (United States)

    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J.; Marin, Jose J. G.; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U.; Bucio, Leticia; Montalvo-Jave, Eduardo E.; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen

    2016-01-01

    Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress. PMID:27635189

  6. Low-overhead interference mitigation scheme for collaborative channel assignment in overloaded multiantenna femtocells

    KAUST Repository

    Radaydeh, Redha Mahmoud Mesleh

    2012-09-01

    This paper proposes a collaborative-based scheme for a transmit antenna channel assignment in overloaded multiantenna femtocells, with the aim of reducing the overhead load. It is assumed that multiple femtocell access points (FAPs) are deployed to sequentially allocate the available resources to scheduled users while reducing the interference experienced by each active user. The FAPs operate concurrently and each of them is allocated an orthogonal channel and employs a transmit array of arbitrary size. The suitable FAP and its associated transmit channel are then identified based on the noncoherently predicted interference power levels on available channels when feedback links are capacity limited. The effect of possible FAP failure or infeasibility to collaborate is characterized for different operating conditions. The applicability of the proposed scheme for specific cases, such as the use of directional antennas in each FAP or shared channels among different FAPs, is also discussed. For arbitrary statistical models of interference power levels on different channels, the average numbers of collaboration requests and examined transmit antenna channels are quantified. Moreover, the statistics of the resulting interference power are derived, which are then used to study various system performance measures. The effect of the interference threshold on the aforementioned measures for processing load and achieved performance is investigated. Numerical and simulations results are presented to support the analytical development and to clarify the tradeoff between the achieved performance enhancement using the proposed scheme and the required processing load for different operating scenarios. © 1967-2012 IEEE.

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

    Science.gov (United States)

    Zhang, Ji; Qiao, Congzhen; Chang, Lin; Guo, Yanhong; Fan, Yanbo; Villacorta, Luis; Chen, Y Eugene; Zhang, Jifeng

    2016-01-01

    Fatty acid binding protein 4 (FABP4) is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG) mice using α myosin-heavy chain (α-MHC) promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC) procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway. PMID:27294862

  8. Fluid limits for overloaded multiclass FIFO single-server queues with general abandonment

    Directory of Open Access Journals (Sweden)

    Amber L. Puha

    2013-01-01

    Full Text Available We consider an overloaded multiclass nonidling first-in-first-outsingle-server queue with abandonment. The interarrival times, servicetimes, and deadline times are sequences of independent and identically,but generally distributed random variables. In prior work, Jennings andReed studied the workload process associated with this queue. Undermild conditions, they establish both a functional law of large numbersand a functional central limit theorem for this process. We build on thatwork here. For this, we consider a more detailed description of thesystem state given by K finite, nonnegative Borel measures on thenonnegative quadrant, one for each job class. For each time and jobclass, the associated measure has a unit atom associated with each jobof that class in the system at the coordinates determined by what arereferred to as the residual virtual sojourn time and residual patiencetime of that job. Under mild conditions, we prove a functional law oflarge numbers for this measure-valued state descriptor. This yieldsapproximations for related processes such as the queue lengths andabandoning queue lengths. An interesting characteristic of theseapproximations is that they depend on the deadline distributions intheir entirety.

  9. Nearly periodic behavior in the overloaded G/D/s+GI queue

    Directory of Open Access Journals (Sweden)

    Ward Whitt

    2011-01-01

    Full Text Available Under general conditions, the number of customers in a GI/D/s+GI many-server queue at time t converges to a unique stationary distribution as t → ∞. However, simulations show that the sample paths routinely exhibit nearly periodic behavior over long time intervals when the system is overloaded and s is large, provided that the system does not start in steady state. Moreover, the precise periodic behavior observed depends critically on the initial conditions. We provide insight into the transient behavior by studying the deterministic fluid model, which arises as the many-server heavy-traffic limit. The limiting fluid model also has a unique stationary point, but that stationary point is not approached from any other initial state as t → ∞. Instead, the fluid model performance approaches one of its uncountably many periodic steady states, depending on the initial conditions. Simulation experiments confirm that the time-dependent performance of the stochastic queueing model is well approximated by the fluid model. Like the fluid model, the behavior of the queueing system is highly sensitive to the initial conditions over long intervals of time.

  10. Effect of co-inheritance of β-thalassemia and hemochromatosis mutations on iron overload.

    Science.gov (United States)

    López-Escribano, Herminio; Ferragut, Joana F; Parera, Maria M; Guix, Pilar; Castro, José A; Ramon, M Misericòrdia; Picornell, Antònia

    2012-01-01

    Co-inheritance of mutations in the HFE gene underlying hereditary hemocromatosis (HH) may play a role in the variability of iron status in patients with β-thalassemia (β-thal) minor. Different studies have yielded conflicting results: some suggest iron overload might arise from the interaction of the β-thal trait with homozygosity or even heterozygosity for HFE mutations and others that it was unrelated to the HFE genotype. Because of the high frequency of HFE mutations in the Balearic Islands, where the β-thal trait is also moderately common, it is of interest to evaluate the effect of the co-inheritance of mutations in both genes on the severity of iron loading. A retrospective analysis of 142 individuals heterozygous for β-thal was performed to investigate the effect of HFE mutations on iron status of these patients. No significant differences were detected between β-thal carriers with and without HFE mutations. These results suggest that in the Balearic population the β-thal trait does not tend to be aggravated by the co-inheritance of HFE mutations.

  11. Interference mitigation enhancement of switched-based scheme in over-loaded femtocells

    KAUST Repository

    Gaaloul, Fakhreddine

    2012-06-01

    This paper proposes adequate methods to improve the interference mitigation capability of a recently investigated switched-based interference reduction scheme in short-range open-access and over-loaded femtocells. It is assumed that the available orthogonal channels for the femtocell network are distributed among operating access points in close vicinity, where each of which knows its allocated channels a priori. For the case when the feedback links are capacity-limited and the available channels can be universally shared and simultaneously used, the paper presents enhanced schemes to identify a channel to serve the desired scheduled user by maintaining the interference power level within a tolerable range. They attempt to either complement the switched-based scheme by minimum interference channel selection or adopt different interference thresholds on available channels, while aiming to reduce the channels examination load. The performance of the proposed schemes is quantified and then compared with those of the single-threshold switched-based scheme via numerical and simulation results. © 2012 IEEE.

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

    Science.gov (United States)

    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J; Marin, Jose J G; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U; Bucio, Leticia; Montalvo-Jave, Eduardo E; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen; Fernández-Checa, José C; Gomez-Quiroz, Luis Enrique

    2016-01-01

    Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress. PMID:27635189

  13. Sulfite triggers sustained calcium overload in cultured cortical neurons via a redox-dependent mechanism.

    Science.gov (United States)

    Wang, Xiao; Cao, Hui; Guan, Xin-Lei; Long, Li-Hong; Hu, Zhuang-Li; Ni, Lan; Wang, Fang; Chen, Jian-Guo; Wu, Peng-Fei

    2016-09-01

    Sulfite is a compound commonly used as preservative in foods and pharmaceuticals. Many studies have examined the neurotoxicity of sulfite, but its effect on neuronal calcium homeostasis has not yet been reported. Here, we observed the effect of sulfite on the cytosolic free calcium concentration ([Ca(2+)]i) in cultured cortical neurons using Fura-2/AM based calcium imaging technique. Sulfite (250-1000μM) caused a sustained increase in [Ca(2+)]i in the neurons via a dose-dependent manner. In Ca(2+)-free solution, sulfite failed to increase [Ca(2+)]i. After the depletion of the intracellular calcium store, the effect of sulfite on the [Ca(2+)]i was largely abolished. Pharmacological inhibition of phospholipase C (PLC)-inositol 1,4,5-triphosphate (IP3) signaling pathway blocked sulfite-induced increase of [Ca(2+)]i. Interestingly, antioxidants such as trolox and dithiothreitol, abolished the increase of [Ca(2+)]i induced by sulfite. Exposure to sulfite triggered generation of sulfur- and oxygen-centered free radicals in neurons and increased oxidative stress both in the cultured cortical neurons and the prefrontal cortex of rats. Furthemore, sulfite decreased cell viability in cultured cortical neurons via a calcium-dependent manner. Thus, our current study suggests that the redox-dependent calcium overload triggered by sulfite in cortical neuronsmay be involved in its neurotoxicity. PMID:27313092

  14. Effects of moderate heart failure and functional overload on rat plantaris muscle

    Science.gov (United States)

    Spangenburg, Espen E.; Lees, Simon J.; Otis, Jeff S.; Musch, Timothy I.; Talmadge, Robert J.; Williams, Jay H.

    2002-01-01

    It is thought that changes in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca(2+) uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca(2+) uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca(2+) uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca(2+) handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.

  15. Hyperferritinemia without iron overload in patients with bilateral cataracts: a case series

    Directory of Open Access Journals (Sweden)

    Mumford Andrew

    2011-09-01

    Full Text Available Abstract Introduction Hepatologists and internists often encounter patients with unexplained high serum ferritin concentration. After exclusion of hereditary hemochromatosis and hemosiderosis, rare disorders like hereditary hyperferritinemia cataract syndrome should be considered in the differential diagnosis. This autosomal dominant syndrome, that typically presents with juvenile bilateral cataracts, was first described in 1995 and has an increasing number of recognized molecular defects within a regulatory region of the L-ferritin gene (FTL. Case presentation Two patients (32 and 49-year-old Caucasian men from our ambulatory clinic were suspected as having this syndrome and a genetic analysis was performed. In both patients, sequencing of the FTL 5' region showed previously described mutations within the iron responsive element (FTL c.33 C > A and FTL c.32G > C. Conclusion Hereditary hyperferritinemia cataract syndrome should be considered in all patients with unexplained hyperferritinemia without signs of iron overload, particularly those with juvenile bilateral cataracts. Liver biopsy and phlebotomy should be avoided in this disorder.

  16. Business continuity strategies for cyber defence: battling time and information overload.

    Science.gov (United States)

    Streufert, John

    2010-11-01

    Can the same numbers and letters which are the life blood of modern business and government computer systems be harnessed to protect computers from attack against known information security risks? For the past seven years, Foreign Service officers and technicians of the US Government have sought to maintain diplomatic operations in the face of rising cyber attacks and test the hypothesis that an ounce of prevention is worth a pound of cure. As eight out of ten attacks leverage known computer security vulnerabilities or configuration setting weaknesses, a pound of cure would seem to be easy to come by. Yet modern security tools present an unusually consequential threat to business continuity - too much rather than too little information on cyber problems is presented, harking back to a phenomenon cited by social scientists in the 1960s called 'information overload'. Experience indicates that the longer the most serious cyber problems go untreated, the wider the attack surface adversaries can find. One technique used at the Department of State, called 'risk scoring', resulted in an 89 per cent overall reduction in measured risk over 12 months for the Department of State's servers and personal computers. Later refinements of risk scoring enabled technicians to correct unique security threats with unprecedented speed. This paper explores how the use of metrics, special care in presenting information to technicians and executives alike, as well as tactical use of organisational incentives can result in stronger cyber defences protecting modern organisations.

  17. Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis.

    Science.gov (United States)

    Nicolas, Gaël; Viatte, Lydie; Lou, Dan-Qing; Bennoun, Myriam; Beaumont, Carole; Kahn, Axel; Andrews, Nancy C; Vaulont, Sophie

    2003-05-01

    Hereditary hemochromatosis is a prevalent genetic disorder of iron hyperabsorption leading to hyperferremia, tissue iron deposition and complications including cirrhosis, hepatocarcinoma, cardiomyopathy and diabetes. Most individuals affected with hereditary hemochromatosis are homozygous with respect to a missense mutation that disrupts the conformation of HFE, an atypical HLA class I molecule (ref. 1; OMIM 235200). Mice lacking Hfe or producing a C282Y mutant Hfe protein develop hyperferremia and have high hepatic iron levels. In both humans and mice, hereditary hemochromatosis is associated with a paucity of iron in reticuloendothelial cells. It has been suggested that HFE modulates uptake of transferrin-bound iron by undifferentiated intestinal crypt cells, thereby programming the absorptive capacity of enterocytes derived from these cells; however, this model is unproven and controversial. Hepcidin, a peptide hormone (HAMP; OMIM 606464), seems to act in the same regulatory pathway as HFE. Although expression of mouse Hamp is normally greater during iron overload, Hfe-/- mice have inappropriately low expression of Hamp. We crossed Hfe-/- mice with transgenic mice overexpressing Hamp and found that Hamp inhibited the iron accumulation normally observed in the Hfe-/- mice. This argues against the crypt programming model and suggests that failure of Hamp induction contributes to the pathogenesis of hemochromatosis, providing a rationale for the use of HAMP in the treatment of this disease. PMID:12704388

  18. Heart and liver T2* assessment for iron overload using different software programs

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Juliano L. [University of Campinas, Unicamp, Campinas (Brazil); Radiologia Clinica de Campinas, Campinas (Brazil); Cardiology, Department of Internal Medicine, Campinas, SP (Brazil); Sampaio, Erika Fontana; Coelho, Otavio R. [University of Campinas, Unicamp, Campinas (Brazil); Verissimo, Monica; Pereira, Fabricio B. [Centro Infantil Boldrini, Campinas (Brazil); Silva, Jose Alvaro da; Figueiredo, Gabriel S. de; Kalaf, Jose M. [Radiologia Clinica de Campinas, Campinas (Brazil)

    2011-12-15

    To assess the level of agreement and interchangeability among different software programs for calculation of T2* values for iron overload. T2* images were analysed in 60 patients with thalassaemia major using the truncation method in three software programs. Levels of agreement were assessed using Pearson correlation and Bland-Altman plots. Categorical classification for levels of iron concentration by each software program was also compared. For the heart, all correlation coefficients were significant among the software programs (P < 0.001 for all coefficients). The mean differences and 95% limits of agreement were 0.2 (-4.73 to 5.0); 0.1 (-4.0 to 3.9); and -0.1 (-4.3 to 4.8). For the liver all correlations were also significant with P < 0.001. Bland-Altman plots showed differences of -0.02 (-0.7 to 0.6); 0.01 (-0.4 to 0.4); and -0.02 (-0.6 to 0.6). There were no significant differences in clinical classification among the software programs. All tools used in this study provided very good agreement among heart and liver T2* values. The results indicate that interpretation of T2* data is interchangeable with any of the software programs tested. (orig.)

  19. Inhibitory effect of MgSO4 on calcium overload after radiation-induced brain injuries

    International Nuclear Information System (INIS)

    Objective: To explore the neuroprotective effect of magnesium sulfate (MgSO4 ) on radiation-induced acute brain injuries. Methods: A total of 60 mature Sprague-Dawley rats were randomly divided into 3 groups: blank control group, experimental control group and experimental therapy group. The whole brain of SD rats of experimental control group and experimental therapy group was irradiated to a dose of 20 Gy using 6 MeV electrons. Magnesium sulfate was injected intraperitoneally into the rats of experimental therapy group before and after irradiation for five times. At different time points (24 h, 7 days, 14 days, 30 days after irradiation), the brain tissue was taken. Plasma direct reading spectrography was used to measure the contents of Ca2+, Mg2+ in brain tissue, and the percentage of brain water content was calculated with the wet-dry weight formula. Results: Compared with the blank control group, the percentage of brain water and content of Ca2+ in brain of the experimental control group increased markedly (P2+ decreased significantly (P2+ in brain of the experimental therapy group were significantly lower than those of the experimental control group (P<0.05). Conclusion: Magnesium sulfate used in the early stage after irradiation can inhibit the calcium overload in rat brain , and attenuate brain edema and injuries. (authors)

  20. Study on real working performance and overload safety factor of high arch dam

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Considering the fact that high arch dams have problems such as complicated stress,high cost,and hazards after being damaged,this paper intends to study the effects of load,material strength,and safety analysis method on dam safety and working performance of arch dams.In this article,the effects of temperature,self weight exaction way and water loading on structure response are first discussed,and a more reasonable way of considering is then put forward.By taking into consideration the mechanical property of materials and comparing the effects of different yield criteria on overloading safety of high arch dams,this paper concludes that brittle characteristics of concrete should be fully considered when conducting safety assessment for high arch dams to avoid overestimating the bearing capacity of the dams.By comparing several typical projects,this paper works out a safety assessment system of multiple safety and relevant engineering analogical analysis methods,which is closer to the actual situation,and thus is able to assess the response of high arch dam structure in a more comprehensive way,elicit the safety coefficients in different situations,and provide a new way of considering the safety assessment of high arch dams.

  1. MICU1 Serves as a Molecular Gatekeeper to Prevent In Vivo Mitochondrial Calcium Overload

    Directory of Open Access Journals (Sweden)

    Julia C. Liu

    2016-08-01

    Full Text Available MICU1 is a component of the mitochondrial calcium uniporter, a multiprotein complex that also includes MICU2, MCU, and EMRE. Here, we describe a mouse model of MICU1 deficiency. MICU1−/− mitochondria demonstrate altered calcium uptake, and deletion of MICU1 results in significant, but not complete, perinatal mortality. Similar to afflicted patients, viable MICU1−/− mice manifest marked ataxia and muscle weakness. Early in life, these animals display a range of biochemical abnormalities, including increased resting mitochondrial calcium levels, altered mitochondrial morphology, and reduced ATP. Older MICU1−/− mice show marked, spontaneous improvement coincident with improved mitochondrial calcium handling and an age-dependent reduction in EMRE expression. Remarkably, deleting one allele of EMRE helps normalize calcium uptake while simultaneously rescuing the high perinatal mortality observed in young MICU1−/− mice. Together, these results demonstrate that MICU1 serves as a molecular gatekeeper preventing calcium overload and suggests that modulating the calcium uniporter could have widespread therapeutic benefits.

  2. Research on energy conversion mechanism of rotodynamic pump and design of non-overload centrifugal pump

    Science.gov (United States)

    Zhang, X. L.; Hu, S. B.; Shen, Z. Z.; Wu, S. P.; Li, K.

    2016-05-01

    In this paper, an attempt has been made for the calculation of an expression for the intrinsic law of input power which has not yet been given by current theory of Rotodynamic pump. By adequate recognition of the characteristics of non-inertial system within the rotating impeller, it is concluded that the input power consists of two power components, the first power component, whose magnitude increases with the increase of the flow rate, corresponds to radial velocity component, and the second power component, whose magnitude decreases with the increase of the flow rate, corresponds to tangential velocity component, therefore, the law of rise, basic levelness and drop of input power curves of centrifugal pump, mixed-flow pump and axial-flow pump can be explained reasonably. Through further analysis, the main ways for realizing non-overload of centrifugal pump are obtained, and its equivalent design factor is found out, the factor correlates with the outlet angle of leading face and back face of the blade, wrap angle, number of blades, outlet width, area ratio, and the ratio of operating flow rate to specified flow rate and so on. These are verified with actual example.

  3. Age and individual differences in visual working memory deficit induced by overload.

    Science.gov (United States)

    Matsuyoshi, Daisuke; Osaka, Mariko; Osaka, Naoyuki

    2014-01-01

    Many studies on working memory have assumed that one can determine an individual's fixed memory capacity. In the current study, we took an individual differences approach to investigate whether visual working memory (VWM) capacity was stable irrespective of the number of to-be-remembered objects and participant age. Younger and older adults performed a change detection task using several objects defined by color. Results showed wide variability in VWM capacity across memory set sizes, age, and individuals. A marked decrease in the number of objects held in VWM was observed in both younger and older adults with low memory capacity, but not among high-capacity individuals, when set size went well beyond the limits of VWM capacity. In addition, a decrease in the number of objects held in VWM was alleviated among low-capacity younger adults by increasing VWM encoding time; however, increasing encoding time did not benefit low-capacity older adults. These findings suggest that low-capacity individuals are likely to show decreases in VWM capacity induced by overload, and aging exacerbates this deficit such that it cannot be recovered by simply increasing encoding time. Overall, our findings challenge the prevailing assumption that VWM capacity is fixed and stable, encouraging a revision to the strict view that VWM capacity is constrained by a fixed number of distinct "slots" in which high-resolution object representations are stored. PMID:24847293

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

    Directory of Open Access Journals (Sweden)

    Ji Zhang

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

  5. Myostatin dysfunction is associated with reduction in overload induced hypertrophy of soleus muscle in mice.

    Science.gov (United States)

    Minderis, P; Kilikevicius, A; Baltusnikas, J; Alhindi, Y; Venckunas, T; Bunger, L; Lionikas, A; Ratkevicius, A

    2016-08-01

    The aim of the study was to investigate if myostatin dysfunction would promote the gain in muscle mass and peak isometric force (P0 ) of soleus muscle (SOL) in response to functional overloading (FO) after ablation of the gastrocnemius muscle. Fifteen male Berlin high (BEH) mice homozygous for the compact mutation causing dysfunction of myostatin and 17 mice with the corresponding wild-type allele (BEH+/+) were subjected to FO of SOL for 28 days at the age of 14 weeks. Compared with BEH+/+ mice, SOL of BEH was heavier (mean ± SD, 13.5 ± 1.5 vs 21.4 ± 1.8 mg, respectively, P muscle length. Specific P0 became even more depressed in BEH compared with BEH+/+ strain (8.4 ± 1.4 vs 10.8 ± 1.3 N/g, respectively, P muscle to high functional demands. PMID:26304113

  6. Decitabine treatment could ameliorate primary iron-overload in myelodysplastic syndrome patients.

    Science.gov (United States)

    Shucheng, Gu; Chunkang, Chang; Youshan, Zhao; Juan, Guo; Chengming, Fei; Xi, Zhang; Chao, Xiao; Xiao, Li

    2015-04-01

    In order to research how does hypomethylating agents ameliorate iron metabolism in myelodysplastic syndrome (MDS), we performed methylation-specific, polymerase chain reaction (MSP), bisulfate genomic sequencing polymerase chain reaction (BSP), quantitative real-time PCR and western blot of hemojuvelin (HJV) and ELISA assay for hepcidin before and after demethylating therapy (decitabine) to determine whether the change of HJV methylation status would have an influence on hepcidin expression. Eleven of 22 MDS patients achieved CR or PR according to IWG criteria (50%). HJV mRNA was induced in decitabine responders (p = .006 comparing pre/post decitabine treatment) but not in non-responders (p = .121). Similarly, hepcidin serum expression increased from 320.77 ± 34.8 μg/L to 366.77 ± 21.90 μg/L (p = .012) in responders but did not significantly change in non-responders (p = .058), while no difference of adjusted serum ferritin (ASF) was found. In conclusion, hypermethylation of HJV promoter region could silence the gene expression and demethylating therapy might ameliorate iron-overload through HJV demethylation.

  7. Purchasing for someone else in a B2B context: joint effects of accountability and choice overload

    OpenAIRE

    Schaffrath, Kathrin

    2015-01-01

    A considerable volume of research has investigated the positive, as well as negative, effects of large assortments from a consumer perspective. Despite Business-to-Business suppliers typically offering very large assortments though, similar inquiries have yet to be made in the context of professional purchase decisions. Thus, it is unclear if professional buyers suffer from the same negative effects (particularly choice overload), as consumers do, for example, reduced satisfaction when having...

  8. Energetics of acute pressure overload of the porcine right ventricle. In vivo 31P nuclear magnetic resonance.

    OpenAIRE

    Schwartz, G G; Steinman, S; Garcia, J.; Greyson, C; Massie, B; Weiner, M W

    1992-01-01

    In vivo 31P nuclear magnetic resonance (NMR) spectroscopy of the right ventricular (RV) free wall was employed to determine (a) whether phosphorus energy metabolites vary reciprocally with workload in the RV and (b) the mechanisms that limit RV contractile function in acute pressure overload. In 20 open-chest pigs, phosphocreatine (PCr)/ATP ratio (an index of energy metabolism inversely related to free ADP concentration), myocardial blood flow (microspheres), and segment shortening (sonomicro...

  9. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.

    OpenAIRE

    Nicolas, Gaël; Bennoun, Myriam; Devaux, Isabelle; Beaumont, Carole; Grandchamp, Bernard; Kahn, Axel; Vaulont, Sophie

    2001-01-01

    We previously reported the disruption of the murine gene encoding the transcription factor USF2 and its consequences on glucose-dependent gene regulation in the liver. We report here a peculiar phenotype of Usf2(-/-) mice that progressively develop multivisceral iron overload; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart. In contrast, the splenic iron content is strikingly lower in knockout animal...

  10. Metal Dealing at the Origin of the Chordata Phylum: The Metallothionein System and Metal Overload Response in Amphioxus

    OpenAIRE

    Maria Guirola; Sílvia Pérez-Rafael; Mercè Capdevila; Oscar Palacios; Sílvia Atrian

    2012-01-01

    Non-vertebrate chordates, specifically amphioxus, are considered of the utmost interest for gaining insight into the evolutionary trends, i.e. differentiation and specialization, of gene/protein systems. In this work, MTs (metallothioneins), the most important metal binding proteins, are characterized for the first time in the cephalochordate subphylum at both gene and protein level, together with the main features defining the amphioxus response to cadmium and copper overload. Two MT genes (...

  11. Cross-Culture Management: An Examination on Task, Relationship and Work Overload Stress Orientations of Dutch and Vietnamese

    OpenAIRE

    Lam D. Nguyen; Kuo-Hao Lee; Mujtaba, Bahaudin G.; Alexander Ruijs

    2013-01-01

    Human capital plays an important role and acts as a strategic resource that helps firms achieve strategic competitiveness. In the global business context, understanding the expectations and behaviors of employees in different cultures is paramount for international and multicultural organizations to succeed. This paper examines the task and relationship orientations as well as the work overload stress perception of people in the low-context culture of the Netherlands and in the high-context c...

  12. Result of the impact of multicomponent intervention in knowledge acquired, support social (AS and overload of carers immigrants (SCI.

    Directory of Open Access Journals (Sweden)

    Remedios Rojano-Pérez

    2013-03-01

    Full Text Available General Objectives: determine the acquisition of knowledge of a program aimed at inmigrant caregivers multicomponent intervention and the influence of group intervention in the immigrant, caregiver burden and perception of social support.Specific objectives: profile and socio-labour situation of immigrant caregivers.MethodologyDesign: cross-transverse descriptive study.Intervention multicomponent in seminar-workshop with pre/post test, delivery of support materials. Four sessions of 1 h 30. Study population: 50 IC of the intervention group.Variables: Level of knowledge (variable result, socio-demographic variables, the scales as Duke-UNC, SCI of Zarit.Analysis: To achieve a 90% power to detect differences in the contrast of the null hypothesis H0:p1 = p2 through a bilateral chi-squared test for two independent samples, taking into account the level of significance is 5%, it will be necessary to include 50 CI of the intervention group.Results: The 41.3% (n 20, presented social support, caregiver 38% (n 19 overload, with sufficient care 30% (15 n knowledge, prior to intervention. Differences after the intervention, were found in the level of knowledge of the 90.4% (n 43. Significant difference was not found in the overload of the carers immigrants, or in social support.Discussion and conclusions: educational workshops have improved levels of knowledge of CI. Different studies show caregivers overload is more "resistant" to this type of intervention. You can influence the lack of significance of the overload of immigrant caregivers and social support, the little sample of participants.

  13. Evidence for angiotensin II type 2 receptor–mediated cardiac myocyte enlargement during in vivo pressure overload

    OpenAIRE

    Senbonmatsu, Takaaki; Ichihara, Sahoko; Price, Edward; Gaffney, F.Andrew; Inagami, Tadashi

    2000-01-01

    The pathophysiological roles of the angiotensin II type 2 receptor (AT2) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT2 we were able to prevent the left ventricular hypertrophy resulting from pressure overload, while cardiac contractile functions remained normal. This implies that AT2 is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT2 deletion were independent of activation of embryonic genes for cardiac hypertrophy. ...

  14. A framework for information overload research in organizations: insights from organization science, accounting, marketing, MIS, and related disciplines

    OpenAIRE

    Eppler, Martin J.; Mengis, Jeanne

    2005-01-01

    Based on literature from the domains of organization science, marketing, accounting, and management information systems, this review article examines the theoretical basis of the information overload discourse and presents an overview of the main definitions, situations, causes, effects, and countermeasures. It analyses the contributions from the last thirty years to consolidate the existing research in a conceptual framework, to identify future research directions, and to highlight implicati...

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

    Science.gov (United States)

    Qiao, Yang; He, Huan; Zhang, Zeyu; Liao, Zhangping; Yin, Dong; Liu, Dan; Yi, Bo; He, Ming

    2016-01-01

    Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU). We determined the protective role of SF against liver injury by examining liver-to-body ratio (%), transaminase and hepatocyte apoptosis in rats supplied with 10% dextrose intraperitoneal injection. In addition, antioxidative enzymes activities, ROS formation, mitochondrial swelling, and mitochondrial membrane potential (MMP) were all evaluated to clarify the mechanism of protective effect of SF associated with oxidative stress. After 15 weeks of SF treatment, we found a significant reduction in liver-to-body weight radio and elevation in both transaminase and hepatocyte apoptosis associated with iron-injected to levels comparable to those achieved with TAU. Both SF and TAU significantly attenuated the impaired liver function associated with iron-overloaded in mice, whereas neither showed any significant effect on the iron uptake. Furthermore, treatment with either SF or TAU in iron-overloaded mice attenuated oxidative stress, associated with elevated oxidant enzymes activities, decreased ROS production, prevented mitochondrial swelling and dissipation of MMP and then inhibited hepatic apoptosis. Taken together, the current study shows that, SF alleviated oxidative stress and liver damage associated with iron-overload conditions compared to the standard ROS scavenger (TAU), and potentially could encourage higher consumption and utilization as healthy and sustainable ingredients by the food and drink. PMID:27649133

  16. Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

    Science.gov (United States)

    Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

    2013-02-01

    In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload. PMID:23923610

  17. The MRI marker gene MagA attenuates the oxidative damage induced by iron overload in transgenic mice.

    Science.gov (United States)

    Guan, Xiaoying; Jiang, Xinhua; Yang, Chuan; Tian, Xiumei; Li, Li

    2016-06-01

    We aimed to create transgenic (Tg) mice engineered for magnetic resonance imaging (MRI). To ascertain if MagA expression contributes to oxidative stress and iron metabolism, we report the generation of Tg mice in which ubiquitous expression of MagA can be detected by MRI in vivo. Expression of MagA in diverse tissues of Tg mice was assessed, and iron accumulation and deposition of nanoparticles in tissues were analyzed. Levels of antioxidant enzymes, lipid peroxidation and cytokine production were determined, and iron metabolism-related proteins were also detected. MagA Tg showed no apparent pathologic symptoms and no histologic changes compared with wild-type (WT) mice. Overexpression of MagA resulted in specific alterations of the transverse relaxation rate (R2) of water. Transgene-dependent changes in R2 were detectable by MRI in iron-overloaded mice. We also evaluated antioxidant abilities between WT and Tg groups or two iron-overloaded groups. Together with the data of cytokines and iron metabolism-related proteins, we inferred that MagA could regulate nanoparticle production and thus attenuate the oxidative damage induced by iron overload. The novel MagA Tg mouse, which expresses an MRI reporter in many tissues, would be a valuable model of MagA molecular imaging in which to study diseases related to iron metabolism. PMID:26488480

  18. Combined Iron Chelator and Antioxidant Exerted Greater Efficacy on Cardioprotection Than Monotherapy in Iron-Overloaded Rats

    Science.gov (United States)

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Sripetchwandee, Jirapas; Srichairatanakool, Somdet; Fucharoen, Suthat; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2016-01-01

    Background Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX)) or an antioxidant (N-acetyl cysteine (NAC)) with a combined DFP and NAC treatments on left ventricular (LV) function with iron overload has not been investigated. Methods and Findings Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group) for 4 months. After 2 months, the HFe-fed rats were divided into 6 groups to receive either: a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day) or the combined DFP and NAC for 2 months. Our results demonstrated that HFe rats had increased plasma non-transferrin bound iron (NTBI), malondialdehyde (MDA), cardiac iron and MDA levels and cardiac mitochondrial dysfunction, leading to LV dysfunction. Although DFO, DFP, DFX or NAC improved these parameters, leading to improved LV function, the combined DFP and NAC therapy caused greater improvement, leading to more extensively improved LV function. Conclusions The combined DFP and NAC treatment had greater efficacy than monotherapy in cardioprotection through the reduction of cardiac iron deposition and improved cardiac mitochondrial function in iron-overloaded rats. PMID:27428732

  19. Study on Design Parameters of Overload Pavement%超载路面设计参数的研究

    Institute of Scientific and Technical Information of China (English)

    姚家鑫; 陶波

    2011-01-01

    Overload transportation is serious in Tianjin-Weichang Highway in urban area of Tianjin.Standard axle load 100 kN specified in design specification for pavement verification cannot satisfy the current situation of overload transportation and heavy traffic.Through analysis of early failure of Tianjin-Weichang Highway,based on the observation result with axle load testing equipment, the influence of vehicle overload on pavement design is analyzed and the design parameters applicable for heavy traffic are educed.These design parameters are applied in Tianjin-Weichang pavement design, which has achieved better effect.%天津市区津围公路超载运输现象较严重,按规范中的标准轴载100 kN进行路面结构检算,不能满足超载运输和大交通量的现状.通过对津围公路早期破坏现象的分析,利用轴载检测仪器的观测结果,分析车辆超载对路面设计的影响,导出适用于重载交通的设计参数,并应用于津围路面设计,取得了较好效果.

  20. Big Semi-Girder Overload Assembly Robot%大伸臂重载装配机器人

    Institute of Scientific and Technical Information of China (English)

    许家忠; 王东野; 蔡浩田; 褚纪伦

    2012-01-01

    面向航天、飞机、码头等领域的重载装配作业,提出了一种具有装配和操作功能的伸缩式重载装配机器人,以期避免人们对重载货柜直接操作导致的操作风险.给出机器人的一种5自由度造型,介绍了其机械结构及其软硬件的构成.给出了三种伸缩臂的加减速方案设计,并通过计算,比较确定了伸缩臂加减速的方案,为解决伸缩臂在加减速过程中发生震颤提供了强有力的依据.%For overloaded and assembly operation of aerospace, aircraft, pier and other kinds of domain, presents a flexible overloaded and assembly robot which possesses assemble and operative characteristics to avoid the operational risk resulted from people's direct operation to overloaded container. Giving a 5 degrees of freedom robot. Introduced mechanical structure and soft & hard ware formation are introduced. Giving three layouts of accelerate and decelerate proposal for flexible arm, the proposal of acceleration and deceleration in the way of calculation is identified. It provides a strength and convinced evidence to solve tremor in process of acceleration and deceleration.

  1. Effects of Niacin on Ruminal Fermentation Indexes and Microflora of Water Buffaloes%烟酸对水牛瘤胃发酵指标及微生物区系的影响

    Institute of Scientific and Technical Information of China (English)

    林波; 梁辛; 韦升菊; 李丽莉; 梁贤威; 李萍; 邹彩霞

    2015-01-01

    本试验旨在研究饲粮添加烟酸对水牛瘤胃发酵指标及微生物区系的影响。试验选用36头健康状况良好,体重接近的杂交泌乳水牛,随机分为4个组,分别在基础饲粮中添加0(对照)、4、8、12 g/d烟酸,烟酸与精料混合饲喂,进行预试期14 d,正试期42 d的饲养试验。试验结束后,胃管采集瘤胃液测定瘤胃发酵指标,并采用Illumina Miseq PE250高通量测序平台分别测序瘤胃细菌和甲烷菌16S rRNA基因以确定二者区系组成。结果表明:1)与对照组相比,添加12 g/d烟酸提高了水牛日均采食量(P0.05),烟酸各组均显著降低了瘤胃液总挥发性脂肪(TVFA)浓度(P0.05)。2)水牛瘤胃内细菌在门水平上主要以拟杆菌门和厚壁菌门为主,科水平上为普雷沃氏菌科和黄杆菌科;甲烷菌以甲烷短杆菌属为主,占90%以上,其次为甲烷球菌属和热原体属,水牛瘤胃微生物区系总体上与奶牛等其他利用植物纤维的反刍动物相似。3)与对照组相比,饲粮添加烟酸显著降低了瘤胃内厚壁菌门的比例( P0.05)。饲粮添加烟酸改变了水牛瘤胃发酵指标和微生物区系组成,瘤胃发酵指标的变化除了与烟酸对水牛热应激的缓解和消化吸收的影响有关,还与烟酸添加对瘤胃细菌区系的影响有关。%This study was conducted to study the effects of dietary addition of niacin on ruminal fermentation indexes and microflora of water buffaloes. Thirty-six healthy hybrid water buffaloes with similar body weight were selected and divided into four groups randomly. The four groups were fed the same basal diet but added with 0 ( control) , 4, 8 and 12 g/d, respectively. Niacin was mixed in concentrate to feed. The advanced ex-periment feeding period was 14 days and the formal experimental period was 42 days. At the end of experi-ment, rumen fluid samples were taken from rumen by stomach tube to test the ruminal fermentation indexes, 16S rRNA genes of

  2. 烟酸对水牛瘤胃发酵指标及微生物区系的影响%Effects of Niacin on Ruminal Fermentation Indexes and Microflora of Water Buffaloes

    Institute of Scientific and Technical Information of China (English)

    林波; 梁辛; 韦升菊; 李丽莉; 梁贤威; 李萍; 邹彩霞

    2015-01-01

    This study was conducted to study the effects of dietary addition of niacin on ruminal fermentation indexes and microflora of water buffaloes. Thirty-six healthy hybrid water buffaloes with similar body weight were selected and divided into four groups randomly. The four groups were fed the same basal diet but added with 0 ( control) , 4, 8 and 12 g/d, respectively. Niacin was mixed in concentrate to feed. The advanced ex-periment feeding period was 14 days and the formal experimental period was 42 days. At the end of experi-ment, rumen fluid samples were taken from rumen by stomach tube to test the ruminal fermentation indexes, 16S rRNA genes of ruminal bacteria and methanogen were tested to determine microbial community by Illumi-na Miseq PE250 high-throughput sequencing. The results showed as follows:1) compared with control group, the addition of 12 g/d of niacin increased average daily feed intake ( P0.05) , niacin groups significantly decreased rumen fluid total volatile fatty acid ( TVFA) con-centration (P0.05). 2) Water buffalo ruminal bacterial community was dominated by Bacteroidetes and Firmicutes at phyla level, Prevotellaceae and Fibrobacteraceae at family level, while ruminal methanogen community was dominated by Methanobrevibacter ( over 90%) at genus level, followed by Methanosphaera and Thermoplasma. Water buffalo ruminal bacteria and methanogen community composition was generally similar with other ruminants which could utilize plant fi-ber. 3) Compared with control group, the addition of niacin significantly decreased ruminal Firmicutes the pro-portion ( P0.05) . In conclusion, the addition of niacin changes ruminal fer-mentation indexes and microflora of water buffaloes, the changes of ruminal fermentation indexes on one hand are related with release on heat stress and improvement on digestion of niacin, on another hand are related with the change of ruminal microflora.%本试验旨在研究饲粮添加烟酸对水牛瘤胃发酵指标及微生

  3. Chronic Insomnia

    OpenAIRE

    Buysse, Daniel J.

    2008-01-01

    Ms. F, a 42-year-old divorced woman, presents for evaluation of chronic insomnia. She complains of difficulty falling asleep, often 30 minutes or longer, and difficulty maintaining sleep during the night, with frequent awakenings that often last 30 minutes or longer. These symptoms occur nearly every night, with only one or two “good” nights per month. She typically goes to bed around 10:00 p.m. to give herself adequate time for sleep, and she gets out of bed around 7:00 a.m. on work days and...

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

    Directory of Open Access Journals (Sweden)

    Craig Bolte

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

  5. 铁超载与肝细胞癌关系的研究进展%Recent progress in relationship between iron overload and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    赵睿

    2011-01-01

    Hepatocellular carcinoma (HCC) is associated with many specific etiologies. Some epidemiological investigations has shown that dietary iron overload is associated with HCC in Africans. And subsequent studies found that many iron-loading diseases, such as hereditary hemochromatosis, chronic hepatitis C, nonalcoholic fatty liver disease etc, appeared to increase the risk of HCC with the development of these diseases. The carcinogenic potential of these iron-loading diseases is probably mainly associated with genetic mutation, abnormal expression of iron metabolism related proteins, oxidative stress reaction, immune disorder and so on. We summarized the recent findings concerning the correlation between iron-loading diseases and HCC.%肝细胞癌(HCC)的发生与多种因素有关.早期的流行病学研究显示非洲人群饮食中铁过量与HCC发生相关,继而研究发现许多与铁沉积相关的疾病如遗传性血色素沉积症(HH)、丙型病毒性肝炎、非酒精性脂肪性肝病(NAFLD)等在发展过程中均有发生HCC的可能性,提示铁超载可能在其中发挥着直接或间接的作用.现认为铁超载的发生与基因突变、铁代谢相关基因蛋白的异常表达、氧化应激反应、免疫紊乱、促进癌细胞生长等因素有关.本文就铁超载与HCC的相关研究现状作一综述.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  8. Significance of iron reduction for the therapy of chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    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.

  9. Study on Detection of the Lovastatin Dissolution of Sustain-Release Tablet of Niacin and Lovastatin%洛伐他汀烟酸缓释片中洛伐他汀释放度检测研究

    Institute of Scientific and Technical Information of China (English)

    蒋艳霞; 吕治红; 秦晶晶

    2012-01-01

    The detection of the lovastatin dissolution of sustain-release tablet of niacin and lovastatin was established. According to the detection method of the lovastatin dissolution in Chinese Pharmacopoeia,the sustain-release tablet of niacin and lovastatin was stripped by 0. 5% sodium dodecyl sulfate phosphate buffer with rotation speed of 100 r · Min-1, and the lovastain dissolution was measured by HPLC. The chromatographic conditipns were as follows:silica gel octadecylsilanized was the filler,acetonitrile-O. 5% phosphoric acid solution (4:1) was the mobile phase, detectio'n wavelength was 238 nm, injected sample was 20 μL. The results showed,the lovastatin concentration had good linear relation with peak area in the range of 0. 59—40. 18 μg · mL-1 The recovery was 99. 0%~101. 0%. The relative standard deviation(RSD) was 0. 71%. This method is suitable for the detection of the lovastatin dissolution of sustain-release tablet of niacin and lovastatin with good repetition and stability.%建立了洛伐他汀烟酸缓释片中洛伐他汀释放度检测方法.取洛伐他汀烟酸缓释片按照《中国药典》洛伐他汀溶出度测定法进行溶出,以0.5%十二烷基硫酸钠磷酸盐缓冲溶液为溶剂,转速为100 r·min-1,于45 min取样,采用高效液相色谱法测定释放度.色谱条件:以十八烷基硅烷键合硅胶为填充剂,以乙腈—0.5%磷酸溶液(4∶1)为流动相,检测波长238 nm,进样量20μL.洛伐他汀浓度在0.59~40.18μg·mL-1范围内与峰面积线性关系良好;回收率在99.0%~101.0%之间,相对标准偏差(RSD)为0.71%.该方法重复性好、稳定性高,适合洛伐他汀烟酸缓释片中洛伐他汀释放度的测定.

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

    Directory of Open Access Journals (Sweden)

    Nathalia O Amaral

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

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

    Science.gov (United States)

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

    2016-07-01

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

  12. Treating thalassemia major-related iron overload: the role of deferiprone.

    Science.gov (United States)

    Berdoukas, Vasilios; Farmaki, Kallistheni; Carson, Susan; Wood, John; Coates, Thomas

    2012-01-01

    Over the last 20 years, management for thalassemia major has improved to the point where we predict that patients' life expectancy will approach that of the normal population. These outcomes result from safer blood transfusions, the availability of three iron chelators, new imaging techniques that allow specific organ assessment of the degree of iron overload, and improvement in the treatment of hepatitis. In October 2011, the Food and Drug Administration licensed deferiprone, further increasing the available choices for iron chelation in the US. The ability to prescribe any of the three chelators as well as their combinations has led to more effective reduction of total body iron. The ability to determine the amount of iron in the liver and heart by magnetic resonance imaging allows the prescription of the most appropriate chelation regime for patients and to reconsider what our aims with respect to total body iron should be. Recent evidence from Europe has shown that by normalizing iron stores not only are new morbidities prevented but also reversal of many complications such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance, and type 2 diabetes can occur, improving survival and patients' quality of life. The most effective way to achieve normal iron stores seems to be with the combination of deferoxamine and deferiprone. Furthermore, outcomes should continue to improve in the future. Starting relative intensive chelation in younger children may prevent short stature and abnormal pubertal maturation as well as other iron-related morbidities. Also, further information should become available on the use of other combinations in chelation treatment, some of which have been used only in a very limited fashion to date. All these advances in management require absolute cooperation and understanding of parents, children, and, subsequently, the patients themselves. Only with such cooperation can normal long-term survival be achieved, as

  13. Nonalcoholic steatohepatitis in Asian Indians is neither associated with iron overload nor with HFE gene mutations

    Institute of Scientific and Technical Information of China (English)

    Ajay Duseja; Reena Das; Mohit Nanda; Ashim Das; Gurjeewan Garewal; Yogesh Chawla

    2005-01-01

    AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH.METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Peris' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined.RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients.On histology, 71% of the patients had negative iron staining,21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P = 0.55) and fibrosis stage (P = 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation.CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.

  14. Age and individual differences in visual working memory deficit induced by overload

    Directory of Open Access Journals (Sweden)

    Daisuke eMatsuyoshi

    2014-05-01

    Full Text Available It has been assumed that one can determine the particular, fixed memory capacity for each person in many working memory literatures. In the study reported here, we investigated whether visual working memory (VWM capacity was stable irrespective of the number of to-be-remembered objects and ages using an individual-differences approach. Younger and older adult participants performed a change detection task using many objects defined by color. We found wide variability in the VWM capacity estimated by the change detection task, across memory set sizes, ages, and individuals. A marked drop in the number of objects held in VWM was observed in both younger and older adults with low memory capacity, but was not in high-capacity individuals, when set size went well beyond the limits of VWM capacity. In addition, a drop in the number of objects held in VWM was prevented in low-capacity younger adults by increasing time for VWM encoding, whereas a drop was still observed in low-capacity older adults. These findings suggest that low-capacity individuals are subject to a drop in VWM capacity induced by overload, and that aging exacerbates this deficit such that it cannot be recovered by simply increasing the encoding time for objects. Overall, our findings challenge the prevailing assumption that VWM capacity is fixed and stable, and call for a revision of the strict view that VWM capacity is constrained by a fixed number of distinct slots in which high-resolution object representations are stored.

  15. Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    Full Text Available BACKGROUND: Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3 is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload. METHODS AND RESULTS: PTX3 systemic knockout (PTX3-KO mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG, and the respective wild-type (WT littermate mice were subjected to transverse aortic constriction (TAC or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2 in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice. CONCLUSION: The local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload.

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

    Science.gov (United States)

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

    2016-07-01

    Introduction Blood volume changes and vascular refilling during hemodialysis (HD) and ultrafiltration (UF) have been assumed to depend on volume overload (Vo ). It was the aim to study the magnitude of vascular refilling in stable HD patients with moderate volume expansion in everyday dialysis using novel technical approaches. Methods Patients were studied during routine dialysis and UF based on clinical dry weight assessment. Pre-dialysis Vo was independently measured by bioimpedance spectroscopy. Vascular refilling volume (Vref ) was calculated as: Vref  = Vuf  - ΔV, where ΔV is the absolute blood volume change determined by on-line dialysate dilution using a commercial on-line hemodiafiltration machine incorporating a relative blood volume monitor, and where Vuf is the prescribed UF volume. Findings Thirty patients (dry weight: 81.0 ± 17.8 kg) were studied. Pre-dialysis Vo was 2.46 ± 1.45 L. Vuf was 2.27 ± 0.71 L, specific UF rate was 6.45 ± 2.43 mL/kg/h, and since ΔV was 0.66 ± 0.31 L, Vref was determined as 1.61 ± 0.58 L, corresponding to a constant refilling fraction (Fref ) of 70.6 ± 10.6%. Vref strongly correlated with Vuf (r(2)  = 0.82) but was independent of Vo and other volumes. Fref was also independent of Vo and other volumes normalized for various measures of body size. Discussion While vascular refilling and Fref is independent of Vo in treatments with moderate UF requirements, intravascular volume depletion increases with increasing UF requirements. The relationship between blood volume and Vo needs to be more closely examined in further studies to optimize volume control in everyday dialysis. PMID:27061224

  17. Chronic kidney disease

    Science.gov (United States)

    Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... 2012_CKD_GL.pdf . McCullough PA. Interface between renal disease ... patients with kidney failure. N Engl J Med . 2010;362(14):1312- ...

  18. Atypical Chronic Myelogenous Leukemia

    Science.gov (United States)

    ... myeloproliferative neoplasms, leukemia , and other conditions . Chronic Myelomonocytic Leukemia Key Points Chronic myelomonocytic leukemia is a disease ... chance of recovery) and treatment options. Chronic myelomonocytic leukemia is a disease in which too many myelocytes ...

  19. Chronic mucus hypersecretion

    DEFF Research Database (Denmark)

    Harmsen, L; Thomsen, S F; Sylvan Ingebrigtsen, Truls;

    2010-01-01

    Chronic mucus hypersecretion (CMH) is a common condition in patients with chronic respiratory diseases. Little is known about the incidence, prevalence and determinants of CMH in younger individuals....

  20. Production of amines in equine cecal contents in an in vitro model of carbohydrate overload.

    Science.gov (United States)

    Bailey, S R; Rycroft, A; Elliott, J

    2002-10-01

    Acute laminitis can be induced experimentally in horses by the administration of carbohydrate, resulting in fermentation within the cecum and ischemia-reperfusion of the digits. The products of fermentation that trigger acute laminitis are as yet unknown; however, compounds such as amines might play a role due to their potential vasoactive properties. The objectives of this study were to quantify the amines present in equine cecal contents and to use a model of carbohydrate overload in vitro to test the hypothesis that carbohydrate fermentation is associated with increased amine production. Cecal contents from each horse were divided into aliquots and incubated anaerobically with either cornstarch or inulin (a form of fructan carbohydrate; both 1 g/100 mL). The pH was measured and samples were taken at the same time for amine measurement by HPLC at 2-h intervals over a 24-h period. In a second set of experiments, the effects of the antibiotic virginiamycin (1 mg/100 mL), calcium (CaPO4; 0.3 g/100 mL), and plant steroidal saponin (Yucca schidigera extract; 0.1 g/100 mL) were examined on pH and amine concentrations in cecal contents incubated with starch or inulin. Both starch and inulin caused significant time-dependent falls in pH, from 6.7 +/- 0.1 at 0 h to 5.2 +/- 0.1 (starch) and 5.0 +/- 0.1 (inulin) at 24 h. Fermentation of carbohydrate was also associated with increased production of phenylethylamine and isoamylamine (two- to threefold increases) as well as putrescine and cadaverine (1.5- to twofold increases). Virginiamycin inhibited the fall in pH and increases in production of phenylethylamine and isoamylamine, while calcium phosphate moderated the changes in pH only. Yucca schidigera extract was without effect. These data show that fermentation of carbohydrate by equine cecal microbiota may lead to increased production of amines. PMID:12413088