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Sample records for acute volume overload

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

    PubMed Central

    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

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

    PubMed Central

    Barkoudah, Ebrahim; Kodali, Sindhura; Okoroh, Juliet; Sethi, Rosh; Hulten, Edward; Suemoto, Claudia; Bittencourt, Marcio Sommer

    2015-01-01

    Introduction Although diuretics are mainly used for the treatment of acute decompensated heart failure (ADHF), inadequate responses and complications have led to the use of extracorporeal ultrafiltration (UF) as an alternative strategy for reducing volume overloads in patients with ADHF. Objective The aim of our study is to perform meta-analysis of the results obtained from studies on extracorporeal venous ultrafiltration and compare them with those of standard diuretic treatment for overload volume reduction in acute decompensated heart failure. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched using a pre‑specified criterion. Pooled estimates of outcomes after 48 h (weight change, serum creatinine level, and all-cause mortality) were computed using random effect models. Pooled weighted mean differences were calculated for weight loss and change in creatinine level, whereas a pooled risk ratio was used for the analysis of binary all-cause mortality outcome. Results A total of nine studies, involving 613 patients, met the eligibility criteria. The mean weight loss in patients who underwent UF therapy was 1.78 kg [95% Confidence Interval (CI): −2.65 to −0.91 kg; p < 0.001) more than those who received standard diuretic therapy. The post-intervention creatinine level, however, was not significantly different (mean change = −0.25 mg/dL; 95% CI: −0.56 to 0.06 mg/dL; p = 0.112). The risk of all-cause mortality persisted in patients treated with UF compared with patients treated with standard diuretics (Pooled RR = 1.00; 95% CI: 0.64–1.56; p = 0.993). Conclusion Compared with standard diuretic therapy, UF treatment for overload volume reduction in individuals suffering from ADHF, resulted in significant reduction of body weight within 48 h. However, no significant decrease of serum creatinine level or reduction of all-cause mortality was observed. PMID:25626761

  3. Novel Insights Into Interactions Between Mitochondria and Xanthine Oxidase in Acute Cardiac Volume Overload

    PubMed Central

    Gladden, James D; Zelickson, Blake R; Wei, Chih-Chang; Ulasova, Elena; Zheng, Junying; Ahmed, Mustafa I.; Chen, Yuanwen; Bamman, Marcas; Ballinger, Scott; Darley-Usmar, Victor; Dell’Italia, Louis J

    2012-01-01

    Xanthine oxidoreductase (XOR) is increased in the left ventricle (LV) of humans with volume overload (VO) and mitochondrial inhibition of the respiratory chain occurs in animal models of VO. Since mitochondria are both a source and target of reactive oxygen and nitrogen species, we hypothesized that activation of XOR and mitochondrial dysfunction are interdependent. To test this we used the aortocaval fistula (ACF) rat model of VO and a simulation of the stretch response in isolated adult cardiomyocytes with and without the inhibitor of XOR, allopurinol, or the mitochondrially targeted antioxidant MitoQ. XO activity was increased in cardiomyocytes from ACF vs. sham rats (24h) without an increase in XO protein. A two-fold increase in LV end-diastolic pressure/wall stress and a decrease in LV systolic elastance with ACF were improved with allopurinol (100 mg/kg) started at ACF induction. Subsarcolemmal state 3 mitochondrial respiration was significantly decreased in ACF and normalized by allopurinol. Cardiomyocytes subjected to 3 hour cyclical stretch resulted in an increase in XO activity and mitochondrial swelling, which was prevented by allopurinol or MitoQ pretreatment. These studies establish an early interplay between cardiomyocyte XO activation and bioenergetic dysfunction that may provide a new target that prevents progression to heart failure in VO. PMID:21925594

  4. Acute renal failure and volume overload syndrome secondary to a femorofemoral arteriovenous fistula angioplasty in a kidney transplant recipient.

    PubMed

    Bertrand, Dominique; Desbuissons, Geoffroy; Pallet, Nicolas; Sartorius, Albane; Legendre, Christophe; Mamzer, Marie-France; Sberro Soussan, Rebecca

    2013-01-01

    Experimental and clinical studies analyzing the impact of AVF on cardiovascular and renal parameters, as well as outcomes, in kidney transplant recipients are lacking. On the other hand, it is not known whether AVF ligation after transplantation modifies hemodynamic parameters and kidney function. We report a case of a renal transplant recipient who developed an acute congestive heart failure accompanied by renal failure, which were triggered by femorofemoral AVF angioplasty. Prompt AVF ligation rapidly reversed clinical symptoms and normalized cardiac and renal functions. This paper illustrates the potential deleterious consequences of high-output AVF after kidney transplantation and raises considerations regarding the impact of the fistula on cardiac status and kidney function after kidney transplantation and, consequently, the management AVF after transplantation. PMID:23533921

  5. The MR appearance of volume overload in the lower extremities

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed

    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. Mechanisms of cardiac hypertrophy in canine volume overload

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  9. Response of various conduit arteries in tachycardia- and volume overload-induced heart failure.

    PubMed

    Lu, Xiao; Zhang, Zhen-Du; Guo, Xiaomei; Choy, Jenny Susana; Yang, Junrong; Svendsen, Mark; Kassab, Ghassan

    2014-01-01

    Although hemodynamics changes occur in heart failure (HF) and generally influence vascular function, it is not clear whether various HF models will affect the conduit vessels differentially or whether local hemodynamic forces or systemic factors are more important determinants of vascular response in HF. Here, we studied the hemodynamic changes in tachycardia or volume-overload HF swine model (created by either high rate pacing or distal abdominal aortic-vena cava fistula, respectively) on carotid, femoral, and renal arteries function and molecular expression. The ejection fraction was reduced by 50% or 30% in tachycardia or volume-overload model in four weeks, respectively. The LV end diastolic volume was increased from 65 ± 22 to 115 ± 78 ml in tachycardia and 67 ± 19 to 148 ± 68 ml in volume-overload model. Flow reversal was observed in diastolic phase in carotid artery of both models and femoral artery in volume-overload model. The endothelial function was also significantly impaired in carotid and renal arteries of tachycardia and volume-overload animals. The endothelial dysfunction was observed in femoral artery of volume-overload animals but not tachycardia animals. The adrenergic receptor-dependent contractility decreased in carotid and femoral arteries of tachycardia animals. The protein expressions of NADPH oxidase subunits increased in the three arteries and both animal models while expression of MnSOD decreased in carotid artery of tachycardia and volume-overload model. In conclusion, different HF models lead to variable arterial hemodynamic changes but similar vascular and molecular expression changes that reflect the role of both local hemodynamics as well as systemic changes in HF.

  10. Acute hypoproteinemic fluid overload: its determinants, distribution, and treatment with concentrated albumin and diuretics.

    PubMed

    Pappova, E; Bachmeier, W; Crevoisier, J L; Kollar, J; Kollar, M; Tobler, P; Zahler, H W; Zaugg, D; Lundsgaard-Hansen, P

    1977-01-01

    We simulated the use of massive volumes of crystalloid fluids as a treatment of acute plasma loss in a standardized experimental model and studied the factors determining the retention or excretion of the resulting acute hypoproteinemic fluid overload, its distribution within the body, and its treatment with concentrated albumin and diuretics. In accordance with the classic Starling concept, the serum protein level, i.e. the serum colloid osmotic pressure, determined the excretion/retention ratio of a given water and sodium load. Of the total fluid retention, fat and muscle each accommodated 25%, whereas the skin, which contributes only 7% to the total body weight, accounted for 37% and increased its volume by roughly one third. Concentrated albumin promoted fluid excretion in direct proportion to the achieved increment of the serum protein level and abolished the edema of fat, muscle and skin. Furosemide was virtually ineffective. The implications of these results for the 'adult respiratory distress syndrome' and disturbed wound healing are discussed and related to the concept of a critical threshold of the serum protein level. PMID:919420

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

    PubMed

    Miller, Wayne L

    2016-08-01

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

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

    PubMed

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

    1976-08-01

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

  13. Acute iron overload leads to hypothalamic-pituitary-gonadal axis abnormalities in female rats.

    PubMed

    Rossi, Emilly M; Marques, Vinicius B; Nunes, Dieli de O; Carneiro, Maria T W D; Podratz, Priscila L; Merlo, Eduardo; dos Santos, Leonardo; Graceli, Jones B

    2016-01-01

    Iron plays a critical role in a mammal's physiological processes. However, iron tissue deposits have been shown to act as endocrine disrupters. Studies that evaluate the effect of acute iron overload on hypothalamic-pituitary-gonadal (HPG) axis health are particularly sparse. This study demonstrates that acute iron overload leads to HPG axis abnormalities, including iron accumulation and impairment in reproductive tract morphology. Female rats were treated with iron-dextran (Fe rats) to assess their HPG morphophysiology. The increasing serum iron levels due to iron-dextran treatment were positively correlated with higher iron accumulation in the HPG axis and uterus of Fe rats than in control rats. An increase in the production of superoxide anions was observed in the pituitary, uterus and ovary of Fe rats. Morphophysiological reproductive tract abnormalities, such as abnormal ovarian follicular development and the reduction of serum estrogen levels, were observed in Fe rats. In addition, a significant negative correlation was obtained between ovary superoxide anion and serum estrogen levels. Together, these data provide in vivo evidence that acute iron overload is toxic for the HPG axis, a finding that may be associated with the subsequent development of the risk of reproductive dysfunction.

  14. Dietary Omega-3 Polyunsaturated Fatty Acids Suppress NHE-1 Upregulation in a Rabbit Model of Volume- and Pressure-Overload

    PubMed Central

    van Borren, Marcel M. G. J.; den Ruijter, Hester M.; Baartscheer, Antonius; Ravesloot, Jan H.; Coronel, Ruben; Verkerk, Arie O.

    2012-01-01

    Background: Increased consumption of omega-3 polyunsaturated fatty acids (ω3-PUFAs) from fish oil (FO) may have cardioprotective effects during ischemia/reperfusion, hypertrophy, and heart failure (HF). The cardiac Na+/H+-exchanger (NHE-1) is a key mediator for these detrimental cardiac conditions. Consequently, chronic NHE-1 inhibition appears to be a promising pharmacological tool for prevention and treatment. Acute application of the FO ω3-PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit the NHE-1 in isolated cardiomyocytes. We studied the effects of a diet enriched with ω3-PUFAs on the NHE-1 activity in healthy rabbits and in a rabbit model of HF induced by volume- and pressure-overload. Methods: Rabbits were allocated to four groups. The first two groups consisted of healthy rabbits, which were fed either a diet containing 1.25% (w/w) FO (ω3-PUFAs), or 1.25% high-oleic sunflower oil (ω9-MUFAs) as control. The second two groups were also allocated to either a diet containing ω3-PUFAs or ω9-MUFAs, but underwent volume- and pressure-overload to induce HF. Ventricular myocytes were isolated by enzymatic dissociation and used for intracellular pH (pHi) and patch-clamp measurements. NHE-1 activity was measured in HEPES-buffered conditions as recovery rate from acidosis due to ammonium prepulses. Results: In healthy rabbits, NHE-1 activity in ω9-MUFAs and ω3-PUFAs myocytes was not significantly different. Volume- and pressure-overload in rabbits increased the NHE-1 activity in ω9-MUFAs myocytes, but not in ω3-PUFAs myocytes, resulting in a significantly lower NHE-1 activity in myocytes of ω3-PUFA fed HF rabbits. The susceptibility to induced delayed afterdepolarizations (DADs), a cellular mechanism of arrhythmias, was lower in myocytes of HF animals fed ω3-PUFAs compared to myocytes of HF animals fed ω9-MUFAs. In our rabbit HF model, the degree of hypertrophy was similar in the ω3-PUFAs group compared to the ω9-MUFAs group

  15. Mechanical support of the pressure overloaded right ventricle: an acute feasibility study comparing low and high flow support.

    PubMed

    Verbelen, Tom; Verhoeven, Jelle; Goda, Motohiko; Burkhoff, Daniel; Delcroix, Marion; Rega, Filip; Meyns, Bart

    2015-08-15

    The objectives of this study were to assess the feasibility of low flow right ventricular support and to describe the hemodynamic effects of low versus high flow support in an animal model of acute right ventricular pressure overload. A Synergy Pocket Micro-pump (HeartWare International, Framingham, MA) was implanted in seven sheep. Blood was withdrawn from the right atrium to the pulmonary artery. Hemodynamics and pressure-volume loops were recorded in baseline conditions, after banding the pulmonary artery, and after ligating the right coronary artery in these banded sheep. End-organ perfusion (reflected by total cardiac output and arterial blood pressure) improved in all conditions. Intrinsic right ventricular contractility was not significantly impacted by support. Diastolic unloading of the pressure overloaded right ventricle (reflected by decreases in central venous pressure, end-diastolic pressure and volume, and ventricular capacitance) was successful, but with a concomitant and flow-dependent increase of the systolic afterload. This unloading diminished with right ventricular ischemia. Right ventricular mechanical support improves arterial blood pressure and cardiac output. It provides diastolic unloading of the right ventricle, but with a concomitant and right ventricular assist device flow-dependent increase of systolic afterload. These effects are most distinct in the pressure overloaded right ventricle without profound ischemic damage. We advocate the low flow strategy, which is potentially beneficial for the afterload sensitive right ventricle and has the advantage of avoiding excessive increases in pulmonary artery pressure when pulmonary hypertension exists. This might protect against the development of pulmonary edema and hemorrhage.

  16. Featured Article: Cardioprotective effects of lysyl oxidase inhibition against volume overload-induced extracellular matrix remodeling

    PubMed Central

    El Hajj, Elia C; El Hajj, Milad C; Ninh, Van K

    2015-01-01

    A hallmark of heart failure (HF) is adverse extracellular matrix (ECM) remodeling, which is regulated by the collagen cross-linking enzyme, lysyl oxidase (LOX). In this study, we evaluate the efficacy of LOX inhibition to prevent adverse left ventricular (LV) remodeling and dysfunction using an experimental model of HF. Sprague–Dawley rats were subjected to surgically induced volume overload (VO) by creation of aortocaval fistula (ACF). A LOX inhibitor, beta-aminopropionitrile (BAPN; 100 mg/kg/day), was administered to rats with ACF or sham surgery at eight weeks postsurgery. Echocardiography was used to assess progressive alterations in cardiac ventricular structure and function. Left ventricular (LV) catheterization was used to assess alterations in contractility, stiffness, LV pressure and volume, and other indices of cardiac function. The LV ECM alterations were assessed by: (a) histological staining of collagen, (b) protein expression of collagen types I and III, (c) hydroxyproline assay, and (d) cross-linking assay. LOX inhibition attenuated VO-induced increases in cardiac stress, and attenuated increases in interstitial myocardial collagen, total collagen, and protein levels of collagens I and III. Both echocardiography and catheterization measurements indicated improved cardiac function post-VO in BAPN treated rats vs. untreated. Inhibition of LOX attenuated VO-induced decreases in LV stiffness and cardiac function. Overall, our data indicate that LOX inhibition was cardioprotective in the volume overloaded heart. PMID:26582054

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

    PubMed

    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.

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

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

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

    PubMed

    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 P<0.001) during the first 2 trimesters of pregnancy and increased thereafter. Stroke volume index and cardiac index showed the opposite trend compared with mean arterial pressure and total vascular resistance index (both P<0.05). Myocardial and ventricular function were significantly enhanced in the first 2 trimesters but progressively declined thereafter. By the end of pregnancy, significant chamber diastolic dysfunction and impaired myocardial relaxation was evident in 17.9% and 28.4% of women, respectively, whereas myocardial contractility was preserved. There was full recovery of cardiac function at 1 year postpartum. Cardiovascular changes during pregnancy are thought to represent a physiological adaptation to volume overload. The findings of a drop in stroke volume index, impaired myocardial relaxation with diastolic dysfunction, and a tendency toward eccentric remodeling in a significant proportion of cases at term are suggestive of cardiovascular maladaptation to the volume-overloaded state in some apparently normal pregnancies. These unexpected cardiovascular findings have important implications for the management of both normal and pathological pregnancy states.

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

    PubMed

    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 P<0.001) during the first 2 trimesters of pregnancy and increased thereafter. Stroke volume index and cardiac index showed the opposite trend compared with mean arterial pressure and total vascular resistance index (both P<0.05). Myocardial and ventricular function were significantly enhanced in the first 2 trimesters but progressively declined thereafter. By the end of pregnancy, significant chamber diastolic dysfunction and impaired myocardial relaxation was evident in 17.9% and 28.4% of women, respectively, whereas myocardial contractility was preserved. There was full recovery of cardiac function at 1 year postpartum. Cardiovascular changes during pregnancy are thought to represent a physiological adaptation to volume overload. The findings of a drop in stroke volume index, impaired myocardial relaxation with diastolic dysfunction, and a tendency toward eccentric remodeling in a significant proportion of cases at term are suggestive of cardiovascular maladaptation to the volume-overloaded state in some apparently normal pregnancies. These unexpected cardiovascular findings have important implications for the management of both normal and pathological pregnancy states. PMID:26962206

  1. Molecular and structural transition mechanisms in long‐term volume overload

    PubMed Central

    Mohamed, Belal A.; Schnelle, Moritz; Khadjeh, Sara; Lbik, Dawid; Herwig, Melissa; Linke, Wolfgang A.; Toischer, Karl

    2015-01-01

    Abstract Aim We have previously reported that early phase (1 week) of experimental volume overload (VO) has an adaptive phenotype while wall stress‐matched pressure overload (PO) is maladaptive. Here we investigate the transition from adaptation to heart failure (HF) in long‐term VO. Methods and results FVB/N wild‐type mice were subjected to VO induced by aortocaval shunt, and were followed by serial echocardiography until in vivo left ventricular ejection fraction was below <50% (135 ± 35 days). Heart failure was evident from increased lung and liver weight and increased mortality compared with sham. Maladaptive remodelling resulted in significantly reduced sarcomeric titin phosphorylation (causing increased sarcomeric stiffness), whereas interstitial fibrosis was not increased. This was paralleled by re‐expression of the fetal gene program, activation of calcium/calmodulin‐dependent protein kinase II (CaMKII), decreased protein kinase B (Akt) phosphorylation, high oxidative stress, and increased apoptosis. Consistently, development of HF and mortality were significantly aggravated in Akt‐deficient mice. Conclusion Transition to HF in VO is associated with decreased Akt and increased CaMKII signalling pathways together with increased oxidative stress and apoptosis. Lack of interstitial fibrosis together with sarcomeric titin hypophosphorylation indicates an increased stiffness at the sarcomeric but not matrix level in VO‐induced HF (in contrast to PO). Transition to HF may result from myocyte loss and myocyte dysfunction owing to increased stiffness. PMID:26694078

  2. Left ventricular cellular hypertrophy in pressure- and volume-overload valvular heart disease.

    PubMed

    Schoen, F J; Lawrie, G M; Titus, J L

    1984-09-01

    To determine the dependence of myocyte hypertrophy in chronic valvular heart disease on the site and type of lesion, the myocardium was studied from 11 patients with either pressure-overload hypertrophy (PO; four patients with aortic stenosis and two with mixed aortic stenosis/insufficiency) or pure volume-overload hypertrophy (VO; two patients with mitral regurgitation and three with aortic insufficiency). These patients, all without coronary artery disease, died zero to 34 days after valve replacement surgery. Diameters of 25 longitudinally oriented myocytes in the circular midwall myocardium were measured with a calibrated light microscope eyepiece reticle on each of five transmural, transverse, histologic sections from the apical, anterolateral, posterolateral, anteroseptal, and posteroseptal left ventricle. Statistical analysis by modified two-way analysis of variance (ANOVA) demonstrated that mean myocyte size (based on 125 measurements) varied widely among cases but was not statistically different among sites. The myocyte diameter for PO lesions (25.9 +/- 1.1 micron, mean +/- SEM) was significantly greater (P less than 0.05) than that for pure VO lesions (20.4 +/- 0.7 micron), despite equal relative heart weights (measured/predicted from body weight: 2.5 +/- 0.2 [mean +/- SD] versus 2.5 +/- 0.5). This study suggests that 1) cellular hypertrophy in valvular heart disease occurs uniformly throughout the left ventricular myocardium; and 2) mean myocyte diameters are greater in PO than in VO hypertrophy for equivalent cardiac enlargement. PMID:6236142

  3. Physiologic and molecular characterization of a murine model of right ventricular volume overload

    PubMed Central

    Zhao, Mingming; Hu, Dong-Qing; Fajardo, Giovanni; Katznelson, Ethan; Punn, Rajesh; Spin, Joshua M.; Chan, Frandics P.; Bernstein, Daniel

    2013-01-01

    Pulmonary insufficiency (PI) is a common long-term sequel after repair of tetralogy of Fallot, causing progressive right ventricular (RV) dilation and failure. We describe the physiologic and molecular characteristics of the first murine model of RV volume overload. PI was created by entrapping the pulmonary valve leaflets with sutures. Imaging, catheterization, and exercise testing were performed at 1, 3, and 6 mo and compared with sham controls. RNA from the RV free wall was hybridized to Agilent whole genome oligonucleotide microarrays. Volume overload resulted in RV enlargement, decreased RV outflow tract shortening fraction at 1 mo followed by normalization at 3 and 6 mo (39 ± 2, 44 ± 2, and 41 ± 2 vs. 46 ± 3% in sham), early reversal of early and late diastolic filling velocities (E/A ratio) followed by pseudonormalization (0.87 ± 0.08, 0.82 ± 0.08, and 0.96 ± 0.08 vs. 1.04 ± 0.03; P < 0.05), elevated end-diastolic pressure (7.6 ± 0.7, 6.9 ± 0.8, and 7 ± 0.5 vs. 2.7 ± 0.2 mmHg; P < 0.05), and decreased exercise duration (26 ± 0.4, 26 ± 1, and 22 ± 1.3 vs. 30 ± 1.1 min; P < 0.05). Subendocardial RV fibrosis was evident by 1 mo. At 1 mo, 372 genes were significantly downregulated. Mitochondrial pathways and G protein-coupled receptor signaling were the most represented categories. At 3 mo, 434 genes were upregulated and 307 downregulated. While many of the same pathways continued to be downregulated, TNF-α, transforming growth factor-β1 (TGF-β1), p53-signaling, and extracellular matrix (ECM) remodeling transitioned from down- to upregulated. We describe a novel murine model of chronic RV volume overload recapitulating aspects of the clinical disease with gene expression changes suggesting early mitochondrial bioenergetic dysfunction, enhanced TGF-β signaling, ECM remodeling, and apoptosis. PMID:23504182

  4. Diastolic right ventricular filling vortex in normal and volume overload states.

    PubMed

    Pasipoularides, Ares; Shu, Ming; Shah, Ashish; Womack, Michael S; Glower, Donald D

    2003-04-01

    Functional imaging computational fluid dynamics simulations of right ventricular (RV) inflow fields were obtained by comprehensive software using individual animal-specific dynamic imaging data input from three-dimensional (3-D) real-time echocardiography (RT3D) on a CRAY T-90 supercomputer. Chronically instrumented, lightly sedated awake dogs (n = 7) with normal wall motion (NWM) at control and normal or diastolic paradoxical septal motion (PSM) during RV volume overload were investigated. Up to the E-wave peak, instantaneous inflow streamlines extended from the tricuspid orifice to the RV endocardial surface in an expanding fanlike pattern. During the descending limb of the E-wave, large-scale (macroscopic or global) vortical motions ensued within the filling RV chamber. Both at control and during RV volume overload (with or without PSM), blood streams rolled up from regions near the walls toward the base. The extent and strength of the ring vortex surrounding the main stream were reduced with chamber dilatation. A hypothesis is proposed for a facilitatory role of the diastolic vortex for ventricular filling. The filling vortex supports filling by shunting inflow kinetic energy, which would otherwise contribute to an inflow-impeding convective pressure rise between inflow orifice and the large endocardial surface of the expanding chamber, into the rotational kinetic energy of the vortical motion that is destined to be dissipated as heat. The basic information presented should improve application and interpretation of noninvasive (Doppler color flow mapping, velocity-encoded cine magnetic resonance imaging, etc.) diastolic diagnostic studies and lead to improved understanding and recognition of subtle, flow-associated abnormalities in ventricular dilatation and remodeling. PMID:12666664

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

    PubMed Central

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

    2010-01-01

    To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 ± 2 wk (means ± SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 ± 0.030; P < 0.05), whereas the apical site did not [P = not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 ± 0.003 at 2 wk and 0.054 ± 0.021 at final; both P < 0.05), which contributed to a significant increase in wall thickness at the final study (0.181 ± 0.047; P < 0.05), whereas the apical site did not (P = NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture. PMID:15242833

  6. Post-traumatic overload or acute syndrome of the os trigonum: a possible cause of posterior ankle impingement.

    PubMed

    Mouhsine, E; Crevoisier, X; Leyvraz, P F; Akiki, A; Dutoit, M; Garofalo, R

    2004-05-01

    The purpose of this paper is to discuss the post-traumatic overload syndrome of the os trigonum as a possible cause of posterior ankle impingement and hindfoot pain. We have reviewed 19 athletes who were referred to our foot unit between 1995 and 2001 because of posterior ankle pain, and in whom a post-traumatic overload syndrome of os trigonum was diagnosed. All these patients were followed up over a period of 2 years. In 11 cases a chronic repetitive movements in forced plantar flexion was found. In the other eight cases the pain appeared to persist after a standard treatment of an ankle sprain in inversion plantar flexion. The diagnosis was based on clinical history, physical examination and X-rays that revealed a non-fused os trigonum. The confirmation of diagnosis was carried-out injecting local anaesthetic under fluoroscopic control. In all cases a corticosteroid injection as first line treatment was performed. In 6 cases a second injection was necessary to alleviate pain because incomplete recovery with the first injection. Three cases (16%) were recalcitrant to this treatment and in these three cases a surgical excision of the os trigonum was carried out. Our conclusion is that after some chronic athletic activity or an acute ankle sprain the os trigonum, if present, may undergo mechanical overload, remain undisrupted and become painful. Treatment by corticosteroid injection often resolves the problem.

  7. Effect of Progressive Volume-Based Overload During Plyometric Training on Explosive and Endurance Performance in Young Soccer Players.

    PubMed

    Ramírez-Campillo, Rodrigo; Henríquez-Olguín, Carlos; Burgos, Carlos; Andrade, David C; Zapata, Daniel; Martínez, Cristian; Álvarez, Cristian; Baez, Eduardo I; Castro-Sepúlveda, Mauricio; Peñailillo, Luis; Izquierdo, Mikel

    2015-07-01

    The purpose of the study was to compare the effects of progressive volume-based overload with constant volume-based overload on muscle explosive and endurance performance adaptations during a biweekly short-term (i.e., 6 weeks) plyometric training intervention in young soccer players. Three groups of young soccer players (age 13.0 ± 2.3 years) were divided into: control (CG; n = 8) and plyometric training with (PPT; n = 8) and without (NPPT; n = 8) a progressive increase in volume (i.e., 16 jumps per leg per week, with an initial volume of 80 jumps per leg each session). Bilateral and unilateral horizontal and vertical countermovement jump with arms (CMJA), 20-cm drop jump reactive strength index (RSI20), maximal kicking velocity (MKV), 10-m sprint, change of direction speed (CODS), and Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1) were measured. Although both experimental groups significantly increased CMJA, RSI20, CODS, and endurance performance, only PPT showed a significant improvement in MKV and 10-m sprint time. In addition, only PPT showed a significantly higher performance improvement in jumping, MKV, and Yo-Yo IR1 compared with CG. Also, PPT showed higher meaningful improvement compared with NPPT in all (except 1) jump performance measures. Furthermore, although PPT involved a higher total volume compared with NPPT, training efficiency (i.e., percentage change in performance/total jump volume) was similar between groups. Our results show that PPT and NPPT ensured significant improvement in muscle explosive and endurance performance measures. However, a progressive increase in plyometric training volume seems more advantageous to induce soccer-specific performance improvements.

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

    PubMed Central

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

    2016-01-01

    Background: Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality. Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI, and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization. The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI. Methods: Septic rat models were established by cecal ligation and puncture (CLP). Rats were divided into the sham group, the CLP group, and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group. Nicotinamide adenine dinucleotide (NAD+), cADPR, CD38, and intracellular Ca2+ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor (TNF)-α, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities were measured. Results: NAD+, cADPR, CD38, and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca2+ levels (P = 0.007), attenuated lung histological injury (P = 0.023), reduced TNF-α and MDA levels (P < 0.001 and P = 0.002, respectively) and recovered SOD activity (P = 0.031) in the lungs of septic rats. Conclusions: The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI. PMID:27411462

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

    PubMed

    Sedmera, David; Neckar, Jan; Benes, Jiri; Pospisilova, Jana; Petrak, Jiri; Sedlacek, Kamil; Melenovsky, Vojtech

    2016-01-01

    Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio. ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group. Optical mapping showed a prolongation of action potential duration in the hypertrophied hearts. Minimal conduction velocity (CV) showed a bell-shaped curve, with a significant increase in the mild cases and there was a negative correlation of both minimal and maximal CV with heart to body weight ratio. Since the CV is influenced by gap junctional coupling as well as the autonomic nervous system, we measured the amounts of tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) as a proxy for sympathetic and parasympathetic innervation, respectively. At the protein level, we confirmed a significant decrease in total and phosphorylated connexin43 that was proportional to the level of hypertrophy, and similarly decreased levels of TH and ChAT. Even at a single time-point, severity of morphological phenotype correlates with progression of molecular and electrophysiological changes, with the most hypertrophied hearts showing the most severe changes that might be related to arrhythmogenesis. PMID:27610087

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

    PubMed Central

    Sedmera, David; Neckar, Jan; Benes, Jiri; Pospisilova, Jana; Petrak, Jiri; Sedlacek, Kamil; Melenovsky, Vojtech

    2016-01-01

    Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio. ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group. Optical mapping showed a prolongation of action potential duration in the hypertrophied hearts. Minimal conduction velocity (CV) showed a bell-shaped curve, with a significant increase in the mild cases and there was a negative correlation of both minimal and maximal CV with heart to body weight ratio. Since the CV is influenced by gap junctional coupling as well as the autonomic nervous system, we measured the amounts of tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) as a proxy for sympathetic and parasympathetic innervation, respectively. At the protein level, we confirmed a significant decrease in total and phosphorylated connexin43 that was proportional to the level of hypertrophy, and similarly decreased levels of TH and ChAT. Even at a single time-point, severity of morphological phenotype correlates with progression of molecular and electrophysiological changes, with the most hypertrophied hearts showing the most severe changes that might be related to arrhythmogenesis. PMID:27610087

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

    PubMed Central

    Sedmera, David; Neckar, Jan; Benes, Jiri; Pospisilova, Jana; Petrak, Jiri; Sedlacek, Kamil; Melenovsky, Vojtech

    2016-01-01

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

  12. Postoperative Fluid Overload is a Useful Predictor of the Short-Term Outcome of Renal Replacement Therapy for Acute Kidney Injury After Cardiac Surgery.

    PubMed

    Xu, Jiarui; Shen, Bo; Fang, Yi; Liu, Zhonghua; Zou, Jianzhou; Liu, Lan; Wang, Chunsheng; Ding, Xiaoqiang; Teng, Jie

    2015-08-01

    To analyze the predictive value of postoperative percent fluid overload (PFO) of renal replacement therapy (RRT) for acute kidney injury (AKI) patients after cardiac surgery.Data from 280 cardiac surgery patients between 2005 January and 2012 April were collected for retrospective analyses. A receiver operating characteristic (ROC) curve was used to compare the predictive values of cumulative PFO at different times after surgery for 90-day mortality.The cumulative PFO before RRT initiation was 7.9% ± 7.1% and the median PFO 6.1%. The cumulative PFO before and after RRT initiation in intensive care unit (ICU) was higher in the death group than in the survival group (8.8% ± 7.6% vs 6.1% ± 5.6%, P = 0.001; -0.5[-5.6, 5.1]% vs 6.9[2.2, 14.6]%, P < 0.001). The cumulative PFO during the whole ICU stay was 14.3% ± 15.8% and the median PFO was 10.7%. The areas under the ROC curves to predict the 90-day mortality by PFO at 24 hours, cumulative PFO before and after RRT initiation, and PFO during the whole ICU stay postoperatively were 0.625, 0.627, 0.731, and 0.752. PFO during the whole ICU stay ≥7.2% was determined as the cut-off point for 90-day mortality prediction with a sensitivity of 77% and a specificity of 64%. Kaplan-Meier survival estimates showed a significant difference in survival among patients with cumulative PFO ≥ 7.2% and PFO < 7.2% after cardiac surgery (log-rank P < 0.001).Postoperative cumulative PFO during the whole ICU stay ≥7.2% would have an adverse effect on 90-day short-term outcome, which may provide a strategy for the volume control of AKI-RRT patients after cardiac surgery.

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

    PubMed

    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

  14. Abnormal cerebellar volume in acute and remitted major depression.

    PubMed

    Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Hirjak, Dusan; Thomann, Philipp A; Wolf, Robert C

    2016-11-01

    Abnormal cortical volume is well-documented in patients with major depressive disorder (MDD), but cerebellar findings have been heterogeneous. It is unclear whether abnormal cerebellar structure relates to disease state or medication. In this study, using structural MRI, we investigated cerebellar volume in clinically acute (with and without psychotropic treatment) and remitted MDD patients. High-resolution structural MRI data at 3T were obtained from acute medicated (n=29), acute unmedicated (n=14) and remitted patients (n=16). Data from 29 healthy controls were used for comparison purposes. Cerebellar volume was investigated using cerebellum-optimized voxel-based analysis methods. Patients with an acute MDD episode showed increased volume of left cerebellar area IX, and this was true for both medicated and unmedicated individuals (p<0.05 cluster-corrected). Remitted patients exhibited bilaterally increased area IX volume. In remitted, but not in acutely ill patients, area IX volume was significantly associated with measures of depression severity, as assessed by the Hamilton Depression Rating Scale (HAMD). In addition, area IX volume in remitted patients was significantly related to the duration of antidepressant treatment. In acutely ill patients, no significant relationships were established using clinical variables, such as HAMD, illness or treatment duration and number of depressive episodes. The data suggest that cerebellar area IX, a non-motor region that belongs to a large-scale brain functional network with known relevance to core depressive symptom expression, exhibits abnormal volume in patients independent of clinical severity or medication. Thus, the data imply a possible trait marker of the disorder. However, given bilaterality and an association with clinical scores at least in remitted patients, the current findings raise the possibility that cerebellar volume may be reflective of successful treatment as well.

  15. Accuracy and Reproducibility of Right Ventricular Quantification in Patients with Pressure and Volume Overload Using Single-Beat Three-Dimensional Echocardiography

    PubMed Central

    Knight, Daniel S.; Grasso, Agata E.; Quail, Michael A.; Muthurangu, Vivek; Taylor, Andrew M.; Toumpanakis, Christos; Caplin, Martyn E.; Coghlan, J. Gerry; Davar, Joseph

    2015-01-01

    Background The right ventricle is a complex structure that is challenging to quantify by two-dimensional (2D) echocardiography. Unlike disk summation three-dimensional (3D) echocardiography (3DE), single-beat 3DE can acquire large volumes at high volume rates in one cardiac cycle, avoiding stitching artifacts or long breath-holds. The aim of this study was to assess the accuracy and test-retest reproducibility of single-beat 3DE for quantifying right ventricular (RV) volumes in adult populations of acquired RV pressure or volume overload, namely, pulmonary hypertension (PH) and carcinoid heart disease, respectively. Three-dimensional and 2D echocardiographic indices were also compared for identifying RV dysfunction in PH. Methods A prospective cross-sectional study was performed in 100 individuals who underwent 2D echocardiography, 3DE, and cardiac magnetic resonance imaging: 49 patients with PH, 20 with carcinoid heart disease, 11 with metastatic carcinoid tumors without cardiac involvement, and 20 healthy volunteers. Two operators performed test-retest acquisition and postprocessing for inter- and intraobserver reproducibility in 20 subjects. Results: RV single-beat 3DE was attainable in 96% of cases, with mean volume rates of 32 to 45 volumes/sec. Bland-Altman analysis of all subjects (presented as mean bias ± 95% limits of agreement) revealed good agreement for end-diastolic volume (−2.3 ± 27.4 mL) and end-systolic volume (5.2 ± 19.0 mL) measured by 3DE and cardiac magnetic resonance imaging, with a tendency to underestimate stroke volume (−7.5 ± 23.6 mL) and ejection fraction (−4.6 ± 13.8%) by 3DE. Subgroup analysis demonstrated a greater bias for volumetric underestimation, particularly in healthy volunteers (end-diastolic volume, −11.9 ± 18.0 mL; stroke volume, −11.2 ± 20.2 mL). Receiver operating characteristic curve analysis showed that 3DE-derived ejection fraction was significantly superior to 2D echocardiographic

  16. Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides.

    PubMed

    Zhang, Xiaowei; Nakajima, Takero; Kamijo, Yuji; Li, Gang; Hu, Rui; Kannagi, Reiji; Kyogashima, Mamoru; Aoyama, Toshifumi; Hara, Atsushi

    2009-12-25

    Sulfatides, possible antithrombotic factors belonging to sphingoglycolipids, are widely distributed in mammalian tissues and serum. We recently found that the level of serum sulfatides was significantly lower in hemodialysis patients than that in normal subjects, and that the serum level closely correlated to the incidence of cardiovascular disease. These findings suggest a relationship between the level of serum sulfatides and kidney function; however, the molecular mechanism underlying this relationship remains unclear. In the present study, the influence of kidney dysfunction on the metabolism of sulfatides was examined using an established murine model of acute kidney injury, protein-overload nephropathy in mice. Protein-overload treatment caused severe proximal tubular injuries within 4days, and this treatment obviously decreased both serum and hepatic sulfatide levels. The sphingoid composition of serum sulfatides was very similar to that of hepatic ones at each time point, suggesting that the serum sulfatide level is dependent on the hepatic secretory ability of sulfatides. The treatment also decreased hepatic expression of cerebroside sulfotransferase (CST), a key enzyme in sulfatide metabolism, while it scarcely influenced the expression of the other sulfatide-metabolizing enzymes, including arylsulfatase A, ceramide galactosyltransferase, and galactosylceramidase. Pro-inflammatory responses were not detected in the liver of these mice; however, potential oxidative stress was increased. These results suggest that down-regulation of hepatic CST expression, probably affected by oxidative stress from kidney injury, causes reduction in liver and serum sulfatide levels. This novel mechanism, indicating the crosstalk between kidney injury and specific liver function, may prove useful for helping to understand the situation where human hemodialysis patients have low levels of serum sulfatides.

  17. Fluid intake and changes in limb volumes in male ultra-marathoners: does fluid overload lead to peripheral oedema?

    PubMed

    Bracher, Alexia; Knechtle, Beat; Gnädinger, Markus; Bürge, Jolanda; Rüst, Christoph Alexander; Knechtle, Patrizia; Rosemann, Thomas

    2012-03-01

    An increase in body mass due to oedema has been previously described. The aim of this study was to investigate a potential association between both fluid and electrolyte intake and the formation of peripheral oedemas. Fluid and electrolyte intakes and the changes in limb volumes in 50 male 100-km ultra-marathoners were measured. Pre- and post-race serum sodium concentration ([Na(+)]), serum aldosterone concentration, serum copeptin concentration, serum and urine osmolality and body mass were determined. Fluid intake, renal function parameters and urinary output, as well as the changes of volume in the extremities, were measured. The changes of volume in the limbs were measured using plethysmography. Serum [Na(+)] increased by 1.6%; body mass decreased by 1.9 kg. Serum copeptin and aldosterone concentrations were increased. The change in serum copeptin concentration and the change in serum [Na(+)] correlated positively; the change in serum [Na(+)] and body mass correlated negatively. A mean fluid intake of 0.58 L/h was positively related to running speed and negatively to post-race serum [Na(+)]. Total fluid intake was positively related to the changes in both arm and lower leg volumes. Running speed was positively associated with the changes in arm and lower leg volumes; race time was related to the changes in serum copeptin or aldosterone concentrations. To conclude, fluid intake was related to the changes in limb volumes, where athletes with an increased fluid intake developed an increase in limb volumes. PMID:21720884

  18. Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid

    PubMed Central

    Pesakhov, Stella; Nachliely, Matan; Barvish, Zeev; Aqaqe, Nasma; Schwartzman, Bar; Voronov, Elena; Sharoni, Yoav; Studzinski, George P.; Fishman, Daniel; Danilenko, Michael

    2016-01-01

    Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by extremely heterogeneous molecular and biologic abnormalities that hamper the development of effective targeted treatment modalities. While AML cells are highly sensitive to cytotoxic Ca2+ overload, the feasibility of Ca2+- targeted therapy of this disease remains unclear. Here, we show that apoptotic response of AML cells to the synergistically acting polyphenols curcumin (CUR) and carnosic acid (CA), combined at low, non-cytotoxic doses of each compound was mediated solely by disruption of cellular Ca2+ homeostasis. Specifically, activation of caspase cascade in CUR+CA-treated AML cells resulted from sustained elevation of cytosolic Ca2+ (Ca2+cyt) and was not preceded by endoplasmic reticulum stress or mitochondrial damage. The CUR+CA-induced Ca2+cyt rise did not involve excessive influx of extracellular Ca2+ but, rather, occurred due to massive Ca2+ release from intracellular stores concomitant with inhibition of Ca2+cyt extrusion through the plasma membrane. Notably, the CUR+CA combination did not alter Ca2+ homeostasis and viability in non-neoplastic hematopoietic cells, suggesting its cancer-selective action. Most importantly, co-administration of CUR and CA to AML-bearing mice markedly attenuated disease progression in two animal models. Collectively, our results provide the mechanistic and translational basis for further characterization of this combination as a prototype of novel Ca2+-targeted pharmacological tools for the treatment of AML. PMID:26870993

  19. Combination of Urinary Sodium/Creatinine Ratio and Plasma Brain Natriuretic Peptide Level Predicts Successful Tolvaptan Therapy in Patients With Heart Failure and Volume Overload.

    PubMed

    Sato, Yuichi; Dohi, Kaoru; Watanabe, Kiyotaka; Tanimura, Muneyoshi; Takeuchi, Tetsushiro; Sugiura, Emiyo; Sugimoto, Tadafumi; Kumagai, Naoto; Ogura, Toru; Nakamori, Shiro; Fujimoto, Naoki; Yamada, Norikazu; Ito, Masaaki

    2016-01-01

    To evaluate the short-term clinical and hemodynamic effects of tolvaptan therapy and to identify predictors of the therapeutic outcomes, we retrospectively recruited 60 consecutive hospitalized heart failure (HF) patients (70 ± 11 years) with volume overload. The subjects were divided into two groups on the basis of the changes in HF symptom scores and hemodynamic status assessed by right heart catheterization after tolvaptan therapy (median: 7 days). The majority of patients were successfully treated (group 1). However, 22% of patients (group 2) were unsuccessfully treated, in whom 1) the HF symptom score worsened or 2) there was a stationary HF symptom score ≥ 6 points, and mean PCWP > 18 mmHg and mean RAP > 10 mmHg, after tolvaptan therapy. HF symptom scores, hemodynamic parameters, and plasma brain natriuretic peptide (BNP) level improved in group 1, but all of these parameters remained unchanged in group 2. Lower urine sodium/creatinine ratio (UNa/UCr) and higher BNP level at baseline were independently associated with unsuccessful tolvaptan therapy, and UNa/UCr best predicts unsuccessful tolvaptan therapy with a cut-off value of 46.5 mEq/g·Cr (AUC 0.847, 95% CI: 0.718-0.976, sensitivity 77%, specificity 81%, P < 0.01). Double-positive results of UNa/UCr < 46.5 mEq/g·Cr and plasma BNP level > 778 pg/mL predicted unsuccessful tolvaptan therapy with high diagnostic accuracy (sensitivity 54%, specificity 100%, positive predictive value 100%, negative predictive value 89%, and accuracy 90%). In summary, short-term tolvaptan therapy ameliorated HF symptoms and provided hemodynamic improvement in the majority of patients, and UNa/UCr and BNP level strongly predicted the therapeutic outcomes. PMID:26973271

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

    PubMed

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

    2015-10-01

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

  1. Death by information overload.

    PubMed

    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.

  2. Baroreflex Responses to Acute Changes in Blood Volume in Humans

    NASA Technical Reports Server (NTRS)

    Thompson, Cynthia A.; Tatro, Dana L.; Ludwig, David A.; Convertino, Victor A.

    1990-01-01

    To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro- reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationships of the cardiopulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venotis Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). Altered vascular volume had no effect on response relations of the carotid-cardiac baroreflex but did alter the gain of the cardiopulmonary baroreflex (-7.93 q 1.71, -4.36 q 1.38, and -2.56 q 1.59 peripheral resistance units/mmHg for hypovolemic, normovolemic, and hypervolemic, respectively) independent of shifts in baseline FVR and PVP. These results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulnionary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

  3. Iron overload in hematopoietic cell transplantation.

    PubMed

    Majhail, N S; Lazarus, H M; Burns, L J

    2008-06-01

    Iron overload, primarily related to RBC transfusions, is a relatively common complication in hematopoietic cell transplant (HCT) recipients. Iron overload increases the risk of infections, veno-occlusive disease and hepatic dysfunction post transplant. Elevated pretransplant ferritin levels have been reported to increase the risk of nonrelapse mortality following HCT and might influence the risk of acute and chronic GVHD. Serum ferritin is sensitive but not specific for iron overload and is a poor predictor of body iron burden. Estimation of hepatic iron content with a liver biopsy or magnetic resonance imaging should be considered prior to initiating therapy for post transplant iron overload. A subgroup of transplant survivors with mild iron overload and no end-organ damage may not need therapy. Phlebotomy is the treatment of choice with iron-chelation therapy reserved for patients not eligible for phlebotomy. Natural history, evolution and treatment of iron overload in transplant survivors have not been adequately investigated and more studies are needed to determine its impact on short-term and long-term morbidity and mortality. PMID:18438425

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

    PubMed

    Červenka, L; Melenovský, V; Husková, Z; Sporková, A; Bürgelová, M; Škaroupková, P; Hwang, S H; Hammock, B D; Imig, J D; Sadowski, J

    2015-01-01

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

  5. Signs of Overload

    MedlinePlus

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

  6. Baroreflex Responses to Acute Changes in Blood Volume in Humans

    NASA Technical Reports Server (NTRS)

    Thompson, Cynthia A.; Tatro, Dana L.; Ludwig, David A.; Convertino, Victor A.

    1990-01-01

    To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro-reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationship, of the cardio-pulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venous Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). The results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

  7. Mean platelet volume and cardiovascular outcomes in acute myocardial infarction

    PubMed Central

    Ranjith, Mangalachulli Pottammal; DivyaRaj, Rajendran; Mathew, Dolly; George, Biju; Krishnan, Mangalath Narayanan

    2016-01-01

    Objective High levels of mean platelet volume (MPV) may be associated with adverse outcomes in patients with myocardial infarction (MI). We examined the association between MPV and the risk of death and adverse cardiovascular outcomes in patients with MI. Methods We studied consecutive patients with MI admitted to a tertiary-care hospital during a period of 1 year. MPV was measured at admission and at third month. Patients were followed up for 1-year primary composite outcome of cardiovascular death, stroke, fatal or non-fatal MI and cardiac failure. Patients were classified according to tertile of baseline MPV. Results A total of 1206 patients with MI, including 934 men (77.4%) and 272 women (22.6%) were studied. The mean age of the study population was 56 years. At 1-year follow-up, 292 (28.57%) primary outcome occurred: cardiovascular mortality 78 (7.6%), fatal or non-fatal MI 153 (15.0%), stroke 30 (2.9%) and cardiac failure 128 (12.52%). Patients with the highest tertile MPV had higher primary outcome as compared with those with MPV in the lowest tertile (adjusted OR=2.31; 95% CI 1.60 to 3.35; p<0.001). Total mortality was also more in high-MPV group (adjusted OR 2.62; 95% CI 1.47 to 4.70; p<0.001). There were no significant changes in mean MPV values at admission from those at third month interval (9.15, (SD 0.99) vs 9.19 (SD 0.94); p=0.2). Conclusions Elevated MPV was associated with worse outcome in patients with acute MI. Elevated MPV in these patients may be due to inherently large platelets. Trial registration number http://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=5485&EncHid=98036.61144&modid=1&compid=19; CTRI/2012/12/003222. PMID:27326224

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

    PubMed Central

    2011-01-01

    Background Chronic hemodynamic overloading leads to heart failure (HF) due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF) and sham-operated rats harvested at the advanced, decompensated stage of HF. Methods We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip. Results In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs. Conclusions The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy. PMID:22078724

  9. Liver toxicity of thioacetamide is increased by hepatocellular iron overload.

    PubMed

    Ackerman, Zvi; Pappo, Orit; Link, Gabriela; Glazer, Maya; Grozovski, Maria

    2015-02-01

    An increase in hepatic iron concentration might exacerbate liver injury. However, it is unknown whether hepatic iron overload may exacerbate acute liver injury from various toxins. Therefore, we evaluated how manipulations to increase hepatic iron concentration affected the extent of acute liver injury from thioacetamide. In this study, we used rats with either "normal" or increased hepatic iron concentration. Iron overload was induced by either providing excess iron in the diet or by injecting iron subcutaneously. Both routes of providing excess iron induced an increase in hepatic iron overload. Meanwhile, the subcutaneous route induced both hepatocellular and sinusoidal cell iron deposition; the oral route induced lesser degree of hepatic iron concentration and only hepatocellular iron overload. Thioacetamide administration to the rats with "normal" hepatic iron concentration induced hepatic cell necrosis and apoptosis associated with a remarkable increase in serum aminotransaminases and depletion of hepatic glutathione and other antioxidative indices. Thioacetamide administration to the iron-overloaded rats exacerbated the extent of liver injury only in the rats orally induced with iron overload. In the rats subcutaneously induced with iron overload, the extent of liver injury from thioacetamide was not different from that observed in the rats with "normal" iron overload. It was concluded that the outcome of thioacetamide-induced acute liver injury may depend on both the level of hepatic iron concentration and on the cellular distribution of iron. While isolated hepatocellular iron overload may exacerbate thioacetamide-induced acute liver injury, a combined hepatocellular and sinusoidal cell iron deposition, even at high hepatic iron concentration, had no such an effect. PMID:25161090

  10. Overloading the Competent Reader.

    ERIC Educational Resources Information Center

    Smith, Frank

    Two sources of information are involved in reading; the visual information picked up by the eyes from the printed page and the nonvisual information, or prior knowledge, that the reader possesses. An overreliance on visual information leads to an overloading of the cognitive process involved in reading and loss in comprehension. Overreliance on…

  11. Interdisciplinary Research and Information Overload.

    ERIC Educational Resources Information Center

    Wilson, Patrick

    1996-01-01

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

  12. Cardioprotective effects of sarcolemmal and mitochondrial K-ATP channel openers in an experimental model of autoimmune myocarditis. Role of the reduction in calcium overload during acute heart failure.

    PubMed

    Niwano, Shinichi; Hirasawa, Shoji; Niwano, Hiroe; Sasaki, Sae; Masuda, Ray; Sato, Kiyotaka; Masuda, Takashi; Izumi, Tohru

    2012-01-01

    It has been reported that K-ATP channel openers have a cardioprotective effect in acute ischemia as a pharmacological preconditioning effect. In the present study, the chronic effects of clinical K-ATP channel openers, ie, nicorandil (Nic) and mexiletine (Mex), on cardiac function were evaluated in a rat model of experimental autoimmune myocarditis (EAM). Nicorandil (3 or 10 mg/kg/day) or Mex (10 or 25 mg/kg/day) was administered to the EAM rats, and the effects were compared with those in untreated EAM rats (control EAM) and sham rats without EAM on day 21 (acute phase) or day 60 (chronic phase). In the acute phase, the control EAM rats exhibited a reduced left ventricular ejection fraction (LVEF) and prolonged monophasic action potential duration (MAPD). Neither drug had an affect on the LVEF or degree of myocarditis, but Mex 25 mg suppressed the MAPD prolongation. In the chronic phase, EAM+Nic and EAM+Mex 25 mg exhibited a higher LVEF than the control EAM. Although the control EAM exhibited sustained MAPD prolongation, the other groups showed recovery of the MAPD in the chronic phase. The mitochondorial redox state was lower in the control EAM than in the sham, and EAM+Nic exhibited a similar level of the redox state as the sham in the chronic phase. Nicorandil exhibited a cardioprotective effect through the protection of mitochondrial function. Mexiletine exhibited a cardioprotective effect possibly through a reduction in the calcium overload by shortening the MAPD in the acute phase. PMID:22688320

  13. Kinetics of drug action in disease states. XXXVII. Effects of acute fluid overload and water deprivation on the hypnotic activity of phenobarbital and the neurotoxicity of theophylline in rats.

    PubMed

    Zhi, J G; Levy, G

    1989-12-01

    Fluid overload and dehydration are potentially serious physiologic perturbations. Their effects on the pharmacodynamics of drugs are essentially unknown. This investigation was designed to determine the effects of acute fluid overload or water deprivation on the hypnotic activity of phenobarbital and on the neurotoxicity of theophylline in male Lewis rats. In the first experiment, 5% dextrose in water (D5W) was infused i.v. in an amount equal to 5 or 10% of body weight and phenobarbital was infused immediately thereafter until the onset of loss of righting reflex (LRR). The total infused dose and the serum and cerebrospinal fluid (CSF) concentrations of phenobarbital at that time were significantly lower than in control animals. When phenobarbital was infused about 2.5 hr after D5W, the infused dose and the serum and CSF concentrations of phenobarbital at LRR were normal. When the rats received D5W and an injection of vasopressin, 25 I.U./kg, or vasopressin only, the infused dose and the serum and CSF concentrations of phenobarbital at LRR were significantly lower than in controls despite the 2.5-hr interval between the respective pretreatments and the phenobarbital infusion. Water deprivation for 24 or 48 hr had no significant effect on phenobarbital dose and concentrations at LRR. Intravenous infusion of D5W to 10% of body weight immediately or 2.5 hr before theophylline infusion had no significant effect on the total infused dose and the serum and CSF concentrations of theophylline at onset of maximal seizures. This lack of effect occurred despite appreciable hyponatremia and hypomagnesemia immediately after D5W infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

    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

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

    PubMed Central

    Yilmaz, 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/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

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

    PubMed Central

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

    2015-01-01

    On-column focusing is essential for satisfactory performance using capillary scale columns. On-column focusing results from generating transient conditions at the head of the column that lead to high solute retention. Solvent-based on-column focusing is a well-known approach to achieve this. Temperature-assisted on-column focusing (TASF) can also be effective. TASF improves focusing by cooling a short segment of the column inlet to a temperature that is lower than the column temperature during the injection and then rapidly heating the focusing segment to the match the column temperature. A troublesome feature of an earlier implementation of TASF was the need to leave the capillary column unpacked in that portion of the column inside the fitting connecting it to the injection valve. We have overcome that problem in this work by packing the head of the column with solid silica spheres. In addition, technical improvements to the TASF instrumentation include: selection of a more powerful thermo-electric cooler to create faster temperature changes and electronic control for easy incorporation into conventional capillary instruments. Used in conjunction with solvent-based focusing and with isocratic elution, volumes of paraben samples (esters of p-hydroxybenzoic acid) up to 4.5-times the column liquid volume can be injected without significant bandspreading due to volume overload. Interestingly, the shapes of the peaks from the lowest volume injections that we can make, 30 nL, are improved when using TASF. TASF is very effective at reducing the detrimental effects of precolumn dispersion using isocratic elution. Finally, we show that TASF can be used to focus the neuropeptide galanin in a sample solvent with elution strength stronger than the mobile phase. Here, the stronger solvent is necessitated by the need to prevent peptide adsorption prior to and during analysis. PMID:26091787

  17. Preliminary Assessment of Tricuspid Valve Annular Velocity Parameters by Cardiac Magnetic Resonance Imaging in Adults with a Volume-Overloaded Right Ventricle: Comparison of Unrepaired Atrial Septal Defect and Repaired Tetralogy of Fallot.

    PubMed

    Ito, Seiji; McElhinney, Doff B; Adams, Robert; Bhatla, Puneet; Chung, Sohae; Axel, Leon

    2015-08-01

    The aim is to compare tricuspid valve (TV) atrioventricular junction (AVJ) annular motion parameters in unrepaired atrial septal defect (ASD) and repaired Tetralogy of Fallot (TOF) by cardiac magnetic resonance (CMR) imaging. We retrospectively reviewed CMR studies performed between November 2007 and November 2013 in patients 16-45 years of age with unrepaired ASD (with or without partial anomalous pulmonary venous return) and with repaired TOF, who had previous infundibulotomy, but have not undergone pulmonary valve replacement. Longitudinal motion of lateral TV in four-chamber view cine image was tracked through the cardiac cycle with custom software. Twenty TOF patients and 12 ASD patients were included, and values were compared with 80 controls. Right ventricular end-diastolic volume index and right ventricular end-systolic volume index were similar in the ASD and TOF groups and were significantly higher in both groups than in controls. Maximum displacement of the TV in systole, velocity at half-maximal displacement during systole, and velocity at half-maximal displacement during early diastole were all significantly lower in the TOF group than the ASD group [1.39 ± 0.47 vs. 2.21 ± 0.46 (cm, p < 0.01), 5.9 ± 2.1 vs. 10.1 ± 2.3 (cm/s, p < 0.01), and 7.7 ± 2.6 vs. 10.9 ± 3.1 (cm/s, p < 0.05)]. TOF patients have diminished early diastolic TV AVJ velocity compared to patients with an unrepaired ASD, despite similar RV volumes. This observation could suggest diastolic dysfunction or cardiac mechanics unique to the postoperative, volume-overloaded right ventricle in patients with repaired TOF.

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

    PubMed

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

    2015-07-31

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

  19. The Effect of Pulsatility Index on Infarct Volume in Acute Lacunar Stroke

    PubMed Central

    Kim, Yoon; Lee, Hanbin; An, Se-A; Yim, Byeongsoo; Kim, Jonguk; Kim, Ok Joon; Kim, Won Chan; Kim, Hyun Sook; Oh, Seung Hun

    2016-01-01

    Purpose Lacunar stroke, in the context of small vessel disease, is a type of cerebral infarction caused by occlusion of a penetrating artery. Pulsatility index (PI) is an easily measurable parameter in Transcranial Doppler ultrasound (TCD) study. PI reflects distal cerebral vascular resistance and has been interpreted as a surrogate marker of small vessel disease. We hypothesized that an increased PI, a marker of small vessel disease, might be associated with a larger infarct volume in acute lacunar stroke. Materials and Methods This study included 64 patients with acute lacunar stroke who underwent TCD and brain MRI. We evaluated the association between the mean PI value of bilateral middle cerebral arteries and infarct volume on diffusion-weighted MRI using univariate and multivariate linear regression. Results The mean infarct volume and PI were 482.18±406.40 mm3 and 0.86±0.18, respectively. On univariate linear regression, there was a significant positive association between PI and infarct volume (p=0.001). In the multivariate model, a single standard deviation increase of PI (per 0.18) was associated with an increase of 139.05 mm3 in infarct volume (95% confidence interval, 21.25 to 256.85; p=0.022). Conclusion We demonstrated that PI was an independent determinant of infarct volume in acute lacunar stroke. The PI value measured in acute stroke may be a surrogate marker of the extent of ischemic injury. PMID:27189290

  20. How to Avoid Fluid Overload

    PubMed Central

    Ogbu, Ogbonna C.; Murphy, David J.; Martin, Greg S.

    2015-01-01

    Purpose of the review This review highlights recent evidence describing the outcomes associated with fluid overload in critically ill patients and provides an overview of fluid management strategies aimed at preventing fluid overload during the resuscitation of patients with shock. Recent findings Fluid overload is a common complication of fluid resuscitation and is associated with increased hospital costs, morbidity and mortality. Summary Fluid management goals differ during the resuscitation, optimization, stabilization and evacuation phases of fluid resuscitation. To prevent fluid overload, strategies that reduce excessive fluid infusions and emphasize the removal of accumulated fluids should be implemented. PMID:26103147

  1. Change in plasma volume and prognosis in acute decompensated heart failure: an observational cohort study

    PubMed Central

    Hudson, Sarah R; Chan, Daniel

    2016-01-01

    Objectives This study aimed to develop an inexpensive, readily available prognostic indicator in acute decompensated heart failure patients to guide management and improve outcome. Prognostic biomarkers for heart failure exist but are expensive and not routinely performed. Increasing plasma volume has been associated with worse outcomes. Setting UK University Teaching Hospital. Design Observational Cohort study. Participants 967 patients with acute decompensated heart failure. Methods Haemoglobin and haematocrit were measured at admission and discharge and were used to calculate the plasma volume change using the Strauss-Davis-Rosenbaum formula. Main outcome measures Endpoints were death and the composite of death and/or heart failure hospitalisation. Change in plasma volume was added to ADHERE scoring to determine predictive value. Results During follow-up, 536 died and 626 died or were hospitalised with heart failure. Multivariable Cox models showed change in plasma volume was an independent predictor of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.150 [1.031–1.283], p = 0.012) and death or heart failure hospitalisation (HR: 1.138 [1.029–1.259], p = 0.012). Kaplan–Meier analysis of change in plasma volume tertiles for outcome measures showed significant difference for the top tertile compared to the lower two. Multivariable analysis of change in plasma volume with ADHERE scoring showed change in plasma volume change remained an independent predictor of death (HR: 1.138 [1.026–1.261], p = 0.015) and death or heart failure hospitalisation (HR: 1.129 [1.025–1.243], p = 0.014). Conclusions Change in plasma volume over an admission can be used for prognostication and adds value to the ADHERE score. Change in plasma volume can be easily and inexpensively calculated from routine blood tests. Clinically, this may facilitate targeted treatment of acute decompensated heart failure patients at greatest risk. PMID:27609799

  2. Exercise training improves renal excretory responses to acute volume expansion in rats with heart failure.

    PubMed

    Zheng, Hong; Li, Yi-Fan; Zucker, Irving H; Patel, Kaushik P

    2006-12-01

    Experiments were performed to test the postulate that exercise training (ExT) improves the blunted renal excretory response to acute volume expansion (VE), in part, by normalizing the neural component of the volume reflex typically observed in chronic heart failure (HF). Diuretic and natriuretic responses to acute VE were examined in sedentary and ExT groups of rats with either HF or sham-operated controls. Experiments were performed in anesthetized (Inactin) rats 6 wk after coronary ligation surgery. Histological data indicated that there was a 34.9 +/- 3.0% outer and 42.5 +/- 3.2% inner infarct of the myocardium in the HF group. Sham rats had no observable damage to the myocardium. In sedentary rats with HF, VE produced a blunted diuresis (46% of sham) and natriuresis (35% of sham) compared with sham-operated control rats. However, acute VE-induced diuresis and natriuresis in ExT rats with HF were comparable to sham rats and significantly higher than sedentary HF rats. Renal denervation abolished the salutary effects of ExT on renal excretory response to acute VE in HF. Since glomerular filtration rates were not significantly different between the groups, renal hemodynamic changes may not account for the blunted renal responses in rats with HF. Additional experiments confirmed that renal sympathetic nerve activity responses to acute VE were blunted in sedentary HF rats; however, ExT normalized the renal sympathoinhibition in HF rats. These results confirm an impairment of neurally mediated excretory responses to acute VE in rats with HF. ExT restored the blunted excretory responses as well as the renal sympathoinhibitory response to acute VE in HF rats. Thus the beneficial effects of ExT on cardiovascular regulation in HF may be partly due to improvement of the neural component of volume reflex.

  3. The Mythology of Information Overload.

    ERIC Educational Resources Information Center

    Tidline, Tonyia J.

    1999-01-01

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

  4. Iron overload and hematologic malignancies.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2004-01-01

    Although iron is essential for cell replication and survival, an increase of body iron stores has been implicated in the development of cancer. However, while the association between iron overload and hepatocellular carcinoma is well documented, the relationship with nonhepatocellular malignancies remains ill-defined. In this review, we briefly report the present knowledge regarding the association between iron overload and hematologic malignancies.

  5. The Utility of 3D Left Atrial Volume and Mitral Flow Velocities as Guides for Acute Volume Resuscitation.

    PubMed

    Santosa, Claudia M; Rose, David D; Fleming, Neal W

    2015-01-01

    Left ventricular end-diastolic pressure (LVEDP) is the foundation of cardiac function assessment. Because of difficulties and risks associated with its direct measurement, correlates of LVEDP derived by pulmonary artery (PA) catheterization or transesophageal echocardiography (TEE) are commonly adopted. TEE has the advantage of being less invasive; however TEE-based estimation of LVEDP using correlates such as left ventricular end-diastolic volume (LVEDV) has technical difficulties that limit its clinical usefulness. Using intraoperative acute normovolemic hemodilution (ANH) as a controlled hemorrhagic model, we examined various mitral flow parameters and three-dimensional reconstructions of left atrial volume as surrogates of LVEDP. Our results demonstrate that peak E wave velocity and left atrial end-diastolic volume (LAEDV) correlated with known changes in intravascular volume associated with ANH. Although left atrial volumetric analysis was done offline in our study, recent advances in echocardiographic software may allow for continuous display and real-time calculation of LAEDV. Along with the ease and reproducibility of acquiring Doppler images of flow across the mitral valve, these two correlates of LVEDP may justify a more widespread use of TEE to optimize intraoperative fluid management. The clinical applicability of peak E wave velocity and LAEDV still needs to be validated during uncontrolled resuscitation.

  6. 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.

    PubMed

    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.

  7. Hormonal and electrolyte responses to acute isohemic volume expansion in unanesthetized rats

    NASA Technical Reports Server (NTRS)

    Chenault, V. M.; Morris, M.; Lynch, C. D.; Maultsby, S. J.; Hutchins, P. M.

    1993-01-01

    This study was undertaken to explore the time course of the metabolic response to isohemic blood volume expansion (30%) in normotensive, unanesthetized Sprague-Dawley rats. Whole blood, drawn from a femoral artery catheter of conscious donor rats, was infused into the jugular vein of recipient rats. Blood samples were drawn from a carotid artery of recipient rats at time points beginning immediately post-volume expansion (IPVE) up through 5 days post-volume expansion (PVE). To characterize the attendant compensatory mechanisms, the plasma concentrations of electrolytes and fluid regulatory hormones were determined. Hematocrit began to raise IPVE and was significantly elevated above control IPVE 20, 30, 40, 60, and 90 min, and 2, 4, 6, 8, 12, and 24 hr PVE. Consistent with our current understanding of the hormonal response to excess volume, atrial natriuretic factor was significantly increased above the prevolume expansion (control) values 0-30 min PVE. Surprisingly, plasma aldosterone levels were significantly increased above control at 20 and 30 min and 6 hr PVE, whereas plasma renin activity was significantly decreased 30-40 min PVE. Plasma sodium was not changed from control values except for a significant increase at 6 hr post-volume expansion. Plasma potassium, osmolality, and arginine vasopressin levels were not altered by the volume expansion. These studies delineate the physiologic time scheme operative in the regulation of fluid volume during acute ischemic volume expansion.

  8. Diagnostic importance of admission platelet volume indices in patients with acute chest pain suggesting acute coronary syndrome

    PubMed Central

    Dehghani, Mohammad Reza; Taghipour-Sani, Leila; Rezaei, Yousef; Rostami, Rahim

    2014-01-01

    Objective Acute coronary syndrome (ACS) is a challenging issue in cardiovascular medicine. Given platelet role in atherothrombosis, we sought to determine whether platelet indices can be used as diagnostic tests for patients who suffered from an acute chest discomfort. Methods We prospectively enrolled 862 patients with an acute chest pain and 184 healthy matched controls. They were divided into four groups: 184 controls, 249 of non-ACS, 421 of unstable angina (UA), and 192 of myocardial infarction (MI) cases. Blood samples were collected at admission to the emergency department for routine hematologic tests. Results The mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR) were significantly greater in patients with MI compared with those of non-ACS or control subjects. Negative and significant correlations existed between MPV, PDW, and P-LCR values and platelet count (P < 0.001). Receiver operating characteristic (ROC) curves showed that the MPV, PDW, and P-LCR with cut-off values of 9.15 fL, 11.35 fL, and 20.25% and with area under the curves of 0.563, 0.557, and 0.560, respectively, detected MI patients among those who had chest discomfort. The sensitivities and specificities were found to be 72% and 40%, 73% and 37%, and 68% and 44% for MPV, PDW, and P-LCR, respectively. Conclusion An elevated admission MPV, PDW, and P-LCR may be of benefit to detect chest pain resulting in MI from that of non-cardiac one, and also for risk stratification of patients who suffered from an acute chest discomfort. PMID:25634396

  9. Calculation of the Residual Blood Volume after Acute, Non-Ongoing Hemorrhage Using Serial Hematocrit Measurements and the Volume of Isotonic Fluid Infused: Theoretical Hypothesis Generating Study.

    PubMed

    Oh, Won Sup; Chon, Sung-Bin

    2016-05-01

    Fluid resuscitation, hemostasis, and transfusion is essential in care of hemorrhagic shock. Although estimation of the residual blood volume is crucial, the standard measuring methods are impractical or unsafe. Vital signs, central venous or pulmonary artery pressures are inaccurate. We hypothesized that the residual blood volume for acute, non-ongoing hemorrhage was calculable using serial hematocrit measurements and the volume of isotonic solution infused. Blood volume is the sum of volumes of red blood cells and plasma. For acute, non-ongoing hemorrhage, red blood cell volume would not change. A certain portion of the isotonic fluid would increase plasma volume. Mathematically, we suggest that the residual blood volume after acute, non-ongoing hemorrhage might be calculated as 0·25N/[(Hct1/Hct2)-1], where Hct1 and Hct2 are the initial and subsequent hematocrits, respectively, and N is the volume of isotonic solution infused. In vivo validation and modification is needed before clinical application of this model.

  10. Calculation of the Residual Blood Volume after Acute, Non-Ongoing Hemorrhage Using Serial Hematocrit Measurements and the Volume of Isotonic Fluid Infused: Theoretical Hypothesis Generating Study

    PubMed Central

    2016-01-01

    Fluid resuscitation, hemostasis, and transfusion is essential in care of hemorrhagic shock. Although estimation of the residual blood volume is crucial, the standard measuring methods are impractical or unsafe. Vital signs, central venous or pulmonary artery pressures are inaccurate. We hypothesized that the residual blood volume for acute, non-ongoing hemorrhage was calculable using serial hematocrit measurements and the volume of isotonic solution infused. Blood volume is the sum of volumes of red blood cells and plasma. For acute, non-ongoing hemorrhage, red blood cell volume would not change. A certain portion of the isotonic fluid would increase plasma volume. Mathematically, we suggest that the residual blood volume after acute, non-ongoing hemorrhage might be calculated as 0·25N/[(Hct1/Hct2)–1], where Hct1 and Hct2 are the initial and subsequent hematocrits, respectively, and N is the volume of isotonic solution infused. In vivo validation and modification is needed before clinical application of this model. PMID:27134507

  11. Does Preinterventional Flat-Panel Computer Tomography Pooled Blood Volume Mapping Predict Final Infarct Volume After Mechanical Thrombectomy in Acute Cerebral Artery Occlusion?

    SciTech Connect

    Wagner, Marlies; Kyriakou, Yiannis; Mesnil de Rochemont, Richard du; Singer, Oliver C.; Berkefeld, Joachim

    2013-08-01

    PurposeDecreased cerebral blood volume is known to be a predictor for final infarct volume in acute cerebral artery occlusion. To evaluate the predictability of final infarct volume in patients with acute occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA) and successful endovascular recanalization, pooled blood volume (PBV) was measured using flat-panel detector computed tomography (FPD CT).Materials and MethodsTwenty patients with acute unilateral occlusion of the MCA or distal ACI without demarcated infarction, as proven by CT at admission, and successful Thrombolysis in cerebral infarction score (TICI 2b or 3) endovascular thrombectomy were included. Cerebral PBV maps were acquired from each patient immediately before endovascular thrombectomy. Twenty-four hours after recanalization, each patient underwent multislice CT to visualize final infarct volume. Extent of the areas of decreased PBV was compared with the final infarct volume proven by follow-up CT the next day.ResultsIn 15 of 20 patients, areas of distinct PBV decrease corresponded to final infarct volume. In 5 patients, areas of decreased PBV overestimated final extension of ischemia probably due to inappropriate timing of data acquisition and misery perfusion.ConclusionPBV mapping using FPD CT is a promising tool to predict areas of irrecoverable brain parenchyma in acute thromboembolic stroke. Further validation is necessary before routine use for decision making for interventional thrombectomy.

  12. Limited Reliability of CT perfusion acute infarct volume measurements compared to DWI in anterior circulation stroke

    PubMed Central

    Schaefer, Pamela W.; Souza, Leticia; Kamalian, Shervin; Hirsch, Joshua A.; Yoo, Albert J.; Kamalian, Shahmir; Gonzalez, R. Gilberto; Lev, Michael H.

    2015-01-01

    Background and Purpose DWI can reliably identify critically ischemic tissue (CIT) shortly after stroke onset. We tested if thresholded CT-CBF and CT-CBV maps are sufficiently accurate to substitute for DWI for estimating CIT volume. Methods Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation, and CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast-to-noise ratios (CNR) of ischemic regions on the DWI and CTP images were measured. Correlation and Bland-Altman analyses were used to assess reliability of CTP. Results Mean CNRs for DWI, CT-CBF and CT-CBV were 4.3, 0.9 and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R2=0.87 for CT-CBF; R2=0.83 for CT-CBV; p<0.001). Bland-Altman analyses revealed little systemic bias (−2.6 ml) but high measurement variability (95% CI ±56.7 ml) between mean CT-CBF and DWI lesion volumes, and systemic bias (−26 ml) and high measurement variability (95% CI ±64.0 ml) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. Conclusions The poor CNRs of CT-CBV and CT-CBF compared to DWI result in large measurement error making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than if DWI is used. PMID:25550366

  13. The effect of acute and chronic hypoxia on thoracic gas volume in anaesthetized rats.

    PubMed Central

    Barer, G R; Herget, J; Sloan, P J; Suggett, A J

    1978-01-01

    1. Thoracic gas volume at end expiration (functional residual capacity, FRC) was measured in chronically and acutely hypoxic anaesthetized rats by a plethysmograph method. 2. FRC, measured during air breathing, was 34-62% larger in rats which had been kept in an environmental chamber in 8, 10 or 12% O2 for 3 weeks than in littermate controls. FRC returned to normal after the rats had returned to air for 9 days. There was no constant difference in the pattern of breathing between control and chronically hypoxic rats. 3. Pressure-volume curves measured post mortem showed no difference in the volume of the lung at 25 cm H2O pressure or in the compliance of the lung between chronically hypoxic and control rats. Thus there was no gross mechanical change in the lung to account for the increase in FRC. 4. Acute hypoxia caused by breathing 12% O2 increased FRC in control but not in chronically hypoxic rats. The increase in FRC in control rats was abolished by combined blockade of the vagus nerves and carotid bodies (with procaine) but not by vagal blockade alone. 5. The combined vagal and carotid body blockade reduced FRC significantly in rats which had been in 10% O2 for 3 days but not in those which had been in 10% O2 for 21 days. 6. Lung area measured from radiographs was not reduced by a muscle relaxant in chronically hypoxic rats. Electromyograms from anterior intercostal muscles and the diaphragm showed no electrical activity in expiration in chronically hypoxic rats which might indicate an active muscular basis for their increased FRC. However when FRC was raised by acute hypoxia in control animals there was also no increase in electrical activity in expiration which could have explained their increase in lung volume. 7. We concluded that the increase in FRC during acute hypoxia in control rats was probably due to a reflex from the carotid body. The increase in FRC in chronically hypoxic rats, which was present while they breathed air, may have had an active

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

    PubMed

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

    2016-01-01

    This article defines the concept of program-induced cumulative overload (PICO), provides examples, and advises ways to mitigate the adverse effects. PICO is the excessive cumulative physical workload that can be imparted to military personnel by a military training program with an embedded physical training component. PICO can be acute (accumulating within a single day) or chronic (accumulating across the entirety of the program) and results in adverse outcomes for affected personnel, including detrimental fatigue, performance degradation, injuries, or illness. Strategies to mitigate PICO include focusing administration and logistic practices during the development and ongoing management of a trainee program and implementing known musculoskeletal injury prevention strategies. More training is not always better, and trainers need to consider the total amount of physical activity that military personnel experience across both operational training and physical training if PICO is to be mitigated. PMID:27450610

  15. Effects of acute physical exercise on hepatocyte volume and function in rat.

    PubMed

    Latour, M G; Brault, A; Huet, P M; Lavoie, J M

    1999-05-01

    The goal of the present experiment was to measure the volume of the different compartments in liver of exercised rats and to get some insights into the appropriate working of the hepatic function following exercise. Hence, livers from male rats were isolated and perfused after treadmill exercise or rest. This procedure was performed on rats that were overnight semifasted (50% food restriction) or well fed. To evaluate the hepatocyte cell volume, the multiple-indicator dilution curve technique was used after 40 min of perfusion. Radioactive tracers for red blood cells, sucrose, and water were used to measure liver vascular space, liver interstitial space, and water cellular space, respectively. The hepatocyte function was assessed by taurocholate and propanolol clearance. Oxygen consumption, intrahepatic resistance, bile secretion, and lactate dehydrogenase release estimated liver viability. Liver viability and hepatocyte function were not changed following exercise either in the fed or in the semifasted animals. As expected, liver glycogen levels were significantly (P < 0.01) reduced in the food-restricted rats. Consequently, liver glycogen levels following exercise were decreased significantly (P < 0.01) only in the fed rats. Despite this, exercise decreased the hepatocyte water space in both food-restricted and fed groups ( approximately 15%; P < 0.01) without altering the sinusoidal and interstitial space. The present data show that acute exercise decreased the hepatocyte volume and that this volume change is not entirely linked to a decrease in hepatic glycogen level. PMID:10233015

  16. Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome.

    PubMed

    Roupie, E; Dambrosio, M; Servillo, G; Mentec, H; el Atrous, S; Beydon, L; Brun-Buisson, C; Lemaire, F; Brochard, L

    1995-07-01

    Mechanical ventilation may promote overdistension-induced pulmonary lesions in patients with acute respiratory distress syndrome (ARDS). The static pressure-volume (P-V) curve of the respiratory system can be used to determine the lung volume and corresponding static airway pressure at which lung compliance begins to diminish (the upper inflection point, or UIP). This fall in compliance may indicate overdistension of lung units. We prospectively studied 42 patients receiving mechanical ventilation with an FIO2 of 0.5 or more for at least 24 h. According to the Lung Injury Score (LIS), 25 patients were classified as having ARDS (LIS > 2.5), while 17 patients constituted a non-ARDS control group. The P-V curve was obtained every 2 d. Mechanical ventilation initially used standard settings (volume-control mode, a positive end-expiratory pressure [PEEP] adjusted to the lower inflection point on the P-V curve, and a tidal volume [VT] of 10 ml/kg). The end-inspiratory plateau pressure (Pplat) was compared to the UIP, and VT was lowered when the Pplat was above the UIP. In the range of lung volume studied on the P-V curves (up to 1600 ml), a UIP could be shown in only one control patient (at 23 cm H2O). By contrast, a UIP was present on the P-V curve obtained from all patients with ARDS, corresponding to a mean airway pressure of 26 +/- 6 cm H2O, a lung volume of 850 +/- 200 ml above functional residual capacity and 610 +/- 235 ml above PEEP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7599810

  17. Evaluation of reduced sediment volume procedures for acute toxicity tests using the estuarine amphipod Leptocheirus plumulosus.

    PubMed

    Stanley, Jacob K; Kennedy, Alan J; Farrar, J Daniel; Mount, David R; Steevens, Jeffery A

    2010-12-01

    The volume of sediment required to perform a sediment toxicity bioassay is a major driver of the overall cost associated with that bioassay. Sediment volume affects bioassay cost because of sediment collection, transportation, storage, and disposal costs as well as labor costs associated with organism recovery at the conclusion of the exposure. The objective of the current study was to evaluate reduced sediment volume versions of the standard U.S. Environmental Protection Agency (U.S. EPA) 10-d acute Leptocheirus plumulosus method that uses a beaker size of 1,000 ml and 20 organisms. The test design used evaluated the effects of beaker size (250 and 100 ml) and associated sediment volume (75 and 30 ml, respectively) as well as organism loading density (10 and 20 organisms) on test endpoint responsiveness relative to the standard 10-d test method. These comparisons were completed with three different types of contaminated sediments: a field-collected polycyclic aromatic hydrocarbon (PAH)-contaminated sediment, a lead-spiked control sediment, and a control sediment spiked with mineral oil. Assessment criteria included test endpoint sensitivity, endpoint consistency, statistical power, water quality, and logistical assessments. Results indicate that the current U.S. EPA method is preferable to the reduced sediment volume methods we assessed, but that a 250-ml beaker/10 organism experimental design is of comparable utility and may be advantageous when reduced sediment volumes are desirable because of high contaminant (spiking studies) or sediment disposal costs. In addition, the results of the current study provide toxicity reference values for PAHs, lead, and an oil surrogate for petroleum hydrocarbons. PMID:20890914

  18. Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia

    PubMed Central

    Holliday, Malcolm A.; Kalayci, M. N.; Harrah, Jean

    1968-01-01

    Rats were made acutely hyper- or hyponatremic by infusion of hypertonic saline or water, respectively. Other rats were maintained in these states from 1 to 7 days to observe the effects of time. Brain tissue water, Na, Cl, and K were compared with serum Na and Cl concentration (NaE and ClE). The following observations are noted: Brain Cl content varies directly with ClE and brain Na content in the Cl space (Nae) varies directly with NaE, indicating little or no restraint on the inward or outward movement of Na or Cl from the Cl space of brain. The intracellular volume of brain fluid (Vi) derived as the difference between total water and Cl space, decreases with hypernatremia and increases with hyponatremia. The changes in Vi in the acute studies are not accompanied by any change in brain K content, or calculated intracellular Na content, and are approximately 0.6 the changes predicted from osmotic behavior of cells, which apply four assumptions: (a) NaE is proportional to osmolality; (b) brain osmolality remains equal to plasma osmolality; (c) Vi is osmotically active; and (d) there is no net gain or loss of solute from Vi. The validity of these assumptions is considered. When changes in osmolality are sustained, Vi is much closer to control values than when in the acute phase. K content increases in hypernatremia and decreases in hyponatremia. The changes in K content can account for some of the adjustment in Vi observed over the extended period of hyper- or hyponatremia. The regression of (Na + K)/v upon NaE describes a slope less than 1.0 and an intercept of (Na + K)/v equal to 40% of the control (Na + K)/v. These characteristics are interpreted to mean that significant quantities of Na and K in brain are osmotically inactive. The brain protects itself from acute volume changes in response to change in NaE by the freedom for Na and Cl to move from the Cl space, by Vi not changing acutely to the degree predicted from osmotic properties of cells in general, and by

  19. Increased tubuloglomerular feed-back mediated suppression of glomerular filtration during acute volume expansion in rats.

    PubMed Central

    Davis, J M; Häberle, D A; Kawata, T; Schmitt, E; Takabatake, T; Wohlfeil, S

    1988-01-01

    1. Volume expansion is currently believed to change the intrinsic properties of the juxtaglomerular apparatus such that the sensitivity of the tubuloglomerular feedback (TGF) mechanism is reduced, thus allowing glomerular filtration rate, and hence salt and water excretion, to rise. Recent studies conflict with this view and indeed the older literature reveals that the rise in glomerular filtration rate (GFR) under these conditions is far more modest than would be expected if TGF control were eliminated. 2. To investigate this problem, TGF control of filtration rate was examined by measuring single-nephron glomerular filtration rate (SNGFR) during loop of Henle perfusion at varying rates in rats under control conditions, after acute, moderate (4% of body weight), iso-oncotic volume expansion and in rats treated with antibodies to atrial natriuretic peptide (ANP) prior to the acute volume expansion. 3. With TGF control of filtration interrupted by filtrate collection from the proximal tubule, SNGFR in the expanded rats was massively increased compared with controls, although SNGFR measured in the distal tubule, and hence with TGF control intact, was only modestly increased, as was whole-kidney filtration rate. Loop perfusion at increasing rates up to 30 nl min-1 progressively decreased SNGFR in controls, and in the expanded rats the range over which control was exerted extended up to 60-80 nl min-1. For changes in loop flow around the spontaneous operating point, the sensitivity of the TGF mechanism, defined as delta SNGFR/delta loop flow, was similar in both groups. Treatment of rats with ANP antibodies prior to volume expansion substantially blunted the changes in renal salt and water excretion and the increase in SNGFR seen in the absence of loop perfusion. 4. These results are not consistent with a diminution of TGF function after volume expansion, rather with an enhancement. The latter is best accounted for by vasodilation of preglomerular resistance vessels on

  20. Effect of an acute increase in central blood volume on cerebral hemodynamics.

    PubMed

    Ogoh, Shigehiko; Hirasawa, Ai; Raven, Peter B; Rebuffat, Thomas; Denise, Pierre; Lericollais, Romain; Sugawara, Jun; Normand, Hervé

    2015-10-15

    Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV. PMID:26310936

  1. The Impact of Hospital/Surgeon Volume on Acute Renal Failure and Mortality in Liver Transplantation: A Nationwide Cohort Study

    PubMed Central

    Cheng, Chih-Wen; Liu, Fu-Chao; Lin, Jr-Rung; Tsai, Yung-Fong; Chen, Hsiu-Pin; Yu, Huang-Ping

    2016-01-01

    The aim of this study was to assess whether the case volume of surgeons and hospitals affects the rates of postoperative complications and survival after liver transplantation. This population-based retrospective cohort study included 2938 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. They were divided into two groups, according to the cumulative case volume of their operating surgeons and the case volume of their hospitals. The duration of intensive care unit stay and post-transplantation hospitalization, postoperative complications, and mortality were analyzed. The results showed that, in the low and high case volume surgeons groups, respectively, acute renal failure occurred at the rate of 14.11% and 5.86% (p<0.0001), and the overall mortality rates were 19.61% and 12.44% (p<0.0001). In the low and high case volume hospital groups, respectively, acute renal failure occurred in 11% and 7.11% of the recipients (p = 0.0004), and the overall mortality was 18.44% and 12.86% (p<0.0001). These findings suggest that liver transplantation recipients operated on higher case volume surgeons or in higher case volume hospitals have a lower rate of acute renal failure and mortality. PMID:27706183

  2. Association between i.v. thrombolysis volume and door-to-needle times in acute ischemic stroke.

    PubMed

    Groot, Adrien E; van Schaik, Ivo N; Visser, Marieke C; Nederkoorn, Paul J; Limburg, Martien; Aramideh, Majid; de Beer, Frank; Zwetsloot, Caspar P; Halkes, Patricia; de Kruijk, Jelle; Kruyt, Nyika D; van der Meulen, Willem; Spaander, Fianne; van der Ree, Taco; Kwa, Vincent I H; Van den Berg-Vos, Renske M; Roos, Yvo B; Coutinho, Jonathan M

    2016-04-01

    Centralization of intravenous thrombolysis (IVT) for acute ischemic stroke in high-volume centers is believed to improve the door-to-needle times (DNT), but limited data support this assumption. We examined the association between DNT and IVT volume in a large Dutch province. We identified consecutive patients treated with IVT between January 2009 and 2013. Based on annualized IVT volume, hospitals were categorized as low-volume (≤ 24), medium-volume (25-49) or high-volume (≥ 50). In logistic regression analysis, low-volume hospitals were used as reference category. Of 17,332 stroke patients from 11 participating hospitals, 1962 received IVT (11.3 %). We excluded 140 patients because of unknown DNT (n = 86) or in-hospital stroke (n = 54). There were two low-volume (total 101 patients), five medium-volume (747 patients) and four high-volume hospitals (974 patients). Median DNT was shorter in high-volume hospitals (30 min) than in medium-volume (42 min, p < 0.001) and low-volume hospitals (38 min, p < 0.001). Patients admitted to high-volume hospitals had a higher chance of DNT < 30 min (adjusted OR 3.13, 95 % CI 1.70-5.75), lower risk of symptomatic intracerebral hemorrhage (adjusted OR 0.39, 95 % CI 0.16-0.92), and a lower mortality risk (adjusted OR 0.45, 95 % CI 0.21-1.01), compared to low-volume centers. There was no difference in DNT between low- and medium-volume hospitals. Onset-to-needle times (ONT) did not differ between the groups. Hospitals in this Dutch province generally achieved short DNTs. Despite this overall good performance, higher IVT volumes were associated with shorter DNTs and lower complication risks. The ONT was not associated with IVT volume. PMID:26946499

  3. Volume regulatory loss of Na, Cl, and K from rat brain during acute hyponatremia

    SciTech Connect

    Melton, J.E.; Patlak, C.S.; Pettigrew, K.D.; Cserr, H.F.

    1987-04-01

    This study quantitatively evaluates the contribution of tissue Na, Cl, and K loss to brain volume regulation during acute dilutional hyponatremia (DH) and examines the mechanism of Na loss. DH was produced in pentobarbital sodium-anesthetized rats by intraperitoneal infusion of distilled water and brain water and electrolytes analyzed 30 min, 1 h, 3 h, 4 h, or 6 h later. The rate of Na and Cl loss was greatest during the first 30 min of DH. Net loss of Na and Cl was maximal after 3 h of DH. K loss was slower, achieving significance after 3 h. Electrolyte loss was sufficient to account for observed brain volume regulation after three or more hours of DH. Measurements of /sup 22/Na influx and efflux across the blood brain barrier showed that barrier permeability to Na is unchanged during DH. Analysis of results using a two-compartment model of plasma-brain exchange suggests that loss of brain Na during DH does not result solely from a shift of electrolyte across the blood-brain barrier to plasma, and thus provides indirect evidence for an additional pathway for Na loss, presumably via cerebrospinal fluid.

  4. Greater Volume of Acute Normovolemic Hemodilution May Aid in Reducing Blood Transfusions After Cardiac Surgery

    PubMed Central

    Goldberg, Joshua; Paugh, Paugh; Dickinson, Timothy A.; Fuller, John; Paone, Gaetano; Theurer, Patty F.; Shann, Kenneth G.; Sundt, Thoralf M.; Prager, Richard L.; Likosky, Donald S.

    2016-01-01

    Background Perioperative red blood cell transfusions (RBC) are associated with increased morbidity and mortality after cardiac surgery. Acute normovolemic hemodilution (ANH) is recommended to reduce perioperative transfusions; however, supporting data are limited and conflicting. We describe the relationship between ANH and RBC transfusions after cardiac surgery using a multi-center registry. Methods We analyzed 13,534 patients undergoing cardiac surgery between 2010 and 2014 at any of the 26 hospitals participating in a prospective cardiovascular perfusion database. The volume of ANH (no ANH, <400mL, 400–799mL, ≥800mL) was recorded and linked to each center’s surgical data. We report adjusted relative risks reflecting the association between the use and amount of ANH and the risk of perioperative RBC transfusion. Results were adjusted for preoperative risk factors, procedure, BSA, preoperative HCT, and center. Results ANH was used in 17% of the patients. ANH was associated with a reduction in RBC transfusions (RRadj 0.74, p <0.001). Patients having ≥800mL of ANH had the most profound reduction in RBC transfusions (RRadj 0.57, p<0.001). Platelet and plasma transfusions were also significantly lower with ANH. The ANH population had superior postoperative morbidity and mortality compared to the no ANH population. Conclusions There is a significant association between ANH and reduced perioperative RBC transfusion in cardiac surgery. Transfusion reduction is most profound with larger volumes of ANH. Our findings suggest the volume of ANH, rather than just its use, may be an important feature of a center’s blood conservation strategy. PMID:26206721

  5. Pediatric Acute Respiratory Distress Syndrome: Fluid Management in the PICU

    PubMed Central

    Ingelse, Sarah A.; Wösten-van Asperen, Roelie M.; Lemson, Joris; Daams, Joost G.; Bem, Reinout A.; van Woensel, Job B.

    2016-01-01

    The administration of an appropriate volume of intravenous fluids, while avoiding fluid overload, is a major challenge in the pediatric intensive care unit. Despite our efforts, fluid overload is a very common clinical observation in critically ill children, in particular in those with pediatric acute respiratory distress syndrome (PARDS). Patients with ARDS have widespread damage of the alveolar–capillary barrier, potentially making them vulnerable to fluid overload with the development of pulmonary edema leading to prolonged course of disease. Indeed, studies in adults with ARDS have shown that an increased cumulative fluid balance is associated with adverse outcome. However, age-related differences in the development and consequences of fluid overload in ARDS may exist due to disparities in immunologic response and body water distribution. This systematic review summarizes the current literature on fluid imbalance and management in PARDS, with special emphasis on potential differences with adult patients. It discusses the adverse effects associated with fluid overload and the corresponding possible pathophysiological mechanisms of its development. Our intent is to provide an incentive to develop age-specific fluid management protocols to improve PARDS outcomes. PMID:27047904

  6. The pathophysiology of hypertensive acute heart failure.

    PubMed

    Viau, David M; Sala-Mercado, Javier A; Spranger, Marty D; O'Leary, Donal S; Levy, Phillip D

    2015-12-01

    While acute heart failure (AHF) is often regarded as a single disorder, an evolving understanding recognises the existence of multiple phenotypes with varied pathophysiological alterations. Herein we discuss hypertensive AHF and provide insight into a mechanism where acute fluid redistribution is caused by a disturbance in the ventricular-vascular coupling relationship. In this relationship, acute alterations in vascular elasticity, vasoconstriction and reflected pulse waves lead to increases in cardiac work and contribute to decompensated LV function with associated subendocardial ischaemia and end-organ damage. Chronic predisposing factors (neurohormonal activity, nitric oxide insensitivity, arterial stiffening) and physiological stressors (sympathetic surge, volume overload, physical exertion) that are causally linked to acute symptom onset are discussed. Lastly, we review treatment options including both nitrovasodilators and promising novel therapeutics, and discuss future directions in the management of this phenotypic variant.

  7. Drug Therapy for Acute Heart Failure.

    PubMed

    Di Somma, Salvatore; Magrini, Laura

    2015-08-01

    Acute heart failure is globally one of most frequent reasons for hospitalization and still represents a challenge for the choice of the best treatment to improve patient outcome. According to current international guidelines, as soon as patients with acute heart failure arrive at the emergency department, the common therapeutic approach aims to improve their signs and symptoms, correct volume overload, and ameliorate cardiac hemodynamics by increasing vital organ perfusion. Recommended treatment for the early management of acute heart failure is characterized by the use of intravenous diuretics, oxygen, and vasodilators. Although these measures ameliorate the patient's symptoms, they do not favorably impact on short- and long-term mortality. Consequently, there is a pressing need for novel agents in acute heart failure treatment with the result that research in this field is increasing worldwide.

  8. Overload for ionized solutes in reversed-phase high-performance liquid chromatography.

    PubMed

    McCalley, David V

    2006-04-15

    Overloading occurs for submicrogram quantities of ionized solutes particularly when using low ionic strength mobile phases at low pH (e.g., formic acid), even with highly inert silica RP-HPLC columns of normal dimensions. Much higher loads can produce a sharp L-shaped peak with retention above the column void volume, in line with the hypothesis that a small number of high-energy sites fill first and are rapidly overloaded, followed by a much larger number of weaker sites. However, charged acids and bases show identical overloading behavior; overloading is reduced as the mobile-phase ionic strength is increased. These findings raise questions about the physical nature of the strong sites. The rapid overloading of silica and purely polymeric phases could be explained by mutual repulsion of ionic species or their inability to fully penetrate the hydrophobic structure of the phase. However, these alternative hypotheses cannot readily explain the high total saturation capacities obtained using frontal analysis. Ion pairing with trifluoroacetic acid may reduce overload, while the effect is less important for formate or phosphate buffers. A surface layer of acetonitrile is not a prerequisite for rapid overloading, as shown by studies using purely aqueous buffers. PMID:16615761

  9. Genetics Home Reference: African iron overload

    MedlinePlus

    ... of a genetic condition? Genetic and Rare Diseases Information Center Frequency African iron overload is common in rural areas of central and ... more about the gene associated with African iron overload SLC40A1 Related Information What is a gene? What is a gene ...

  10. Role of cardiac volume receptors in the control of ADH release during acute simulated weightlessness in man

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Benjamin, B. A.; Keil, L. C.; Sandler, H.

    1984-01-01

    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes, designed to induce central blood volume shifts in ten cardiac and one heart-lung transplant recipients, to assess the contribution of cardiac volume receptors in the control of ADH release during the initial acute phase of exposure to weightlessness. Each subject underwent 15 min of a sitting-control period (C) followed by 30 min of 6 deg headdown tilt (T) and 30 min of resumed sitting (S). Venous blood samples and cardiac dimensions were taken at 0 and 15 min of C; 5, 15, and 30 min of T; and 5, 15, and 30 min of S. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Heart rate and blood pressure were recorded every two min. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 ml in C to 106 ml in T and returned to 87 ml in S. Plasma ADH was reduced by 20 percent (P less than 0.05) with T, and returned to control levels with S. These responses were similar in six normal cardiac-innervated control subjects. These data may suggest that cardiac volume receptors are not the primary mechanism for the control of ADH release during acute central volume shifts in man.

  11. CXCR4 gene transfer prevents pressure overload induced heart failure

    PubMed Central

    LaRocca, Thomas J.; Jeong, Dongtak; Kohlbrenner, Erik; Lee, Ahyoung; Chen, JiQiu; Hajjar, Roger J.; Tarzami, Sima T.

    2012-01-01

    Stem cell and gene therapies are being pursued as strategies for repairing damaged cardiac tissue following myocardial infarction in an attempt to prevent heart failure. The chemokine receptor-4 (CXCR4) and its ligand, CXCL12, play a critical role in stem cell recruitment post-acute myocardial infarction. Whereas progenitor cell migration via the CXCL12/CXCR4 axis is well characterized, little is known about the molecular mechanisms of CXCR4 mediated modulation of cardiac hypertrophy and failure. We used gene therapy to test the effects of CXCR4 gene delivery on adverse ventricular remodeling due to pressure overload. We assessed the effect of cardiac overexpression of CXCR4 during trans-aortic constriction (TAC) using a cardiotropic adeno-associated viral vector (AAV9) carrying the CXCR4 gene. Cardiac overexpression of CXCR4 in mice with pressure overload prevented ventricular remodeling, preserved capillary density and maintained function as determined by echocardiography and in vivo hemodynamics. In isolated adult rat cardiac myocytes, CXCL12 treatment prevented isoproterenol induced hypertrophy and interrupted the calcineurin/NFAT pathway. Finally, a complex involving the L-type calcium channel, β2-adenoreceptor, and CXCR4 (Cav1.2/β2AR/CXCR4) was identified in healthy cardiac myocytes and was shown to dissociate as a consequence of heart failure. CXCR4 administered to the heart via gene transfer prevents pressure overload induced heart failure. The identification of CXCR4 participation in a Cav1.2-β2AR regulatory complex provides further insight into the mechanism by which CXCR4 modulates calcium homeostasis and chronic pressure overload responses in the cardiac myocyte. Together these results suggest AAV9.CXCR4 gene therapy is a potential therapeutic approach for congestive heart failure. PMID:22668785

  12. Hepatocellular carcinoma and African iron overload.

    PubMed Central

    Gangaidzo, I T; Gordeuk, V R

    1995-01-01

    Both hepatocellular carcinoma (HCC) and iron overload are important health problems in Africa. Chronic hepatitis B virus (HBV) infection is recognised as a major risk factor for HCC, but iron overload in Africans has not been considered in pathogenesis. Up to half the patients with HCC in Africa do not have any recognised risk factors such as preceding chronic HBV infection, and other risk factors remain unidentified. HCC is an important complication of HLA-linked haemochromatosis, an iron loading disorder found in Europeans. It is proposed that African iron overload might also be a risk factor for HCC. PMID:8549953

  13. [IRON OVERLOAD: BETTER UNDERSTANDING, BETTER CARE].

    PubMed

    Brissot, Pierre

    2015-12-01

    Chronic iron overload, either of genetic (hemochromatoses) or acquired (transfusions) origin, leads to frequent disorders, affecting both the quality of life and life expectancy. Major recent advances in the knowledge of iron metabolism, together with advances in biology, imaging and drug design have already significantly improved the diagnostic and therapeutic approaches. These conceptual and technological ameliorations should, in the near future, continue to benefit the clinical management of iron overloaded patients. PMID:26979029

  14. Lithium clearance in man: effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide.

    PubMed

    Atherton, J C; Green, R; Hughes, S; McFall, V; Sharples, J A; Solomon, L R; Wilson, L

    1987-12-01

    1. The effects of amiloride and frusemide on lithium clearance were studied during changes in dietary sodium chloride intake and during infusion of 0.9% NaCl in normal human volunteers. 2. Lithium and fractional lithium clearances were less on the low than on the high salt diet. Values for the medium salt diet were intermediate. Acute extracellular fluid volume expansion with 0.9% NaCl infusion and extracellular fluid volume contraction 3-4 h after intravenous frusemide caused lithium and fractional lithium clearances to increase and decrease respectively. 3. Amiloride caused small changes in lithium and fractional lithium clearances on a low salt diet, but was without effect when salt intake was medium or high. 4. Increases in lithium clearance occurred immediately after frusemide irrespective of dietary salt intake and in subjects infused with 0.9% NaCl. Only in salt-depleted subjects did frusemide cause a substantial increase in fractional lithium clearance. Changes induced under other circumstances were small. 5. It is concluded that the lithium clearance method for assessment of proximal tubule salt and water reabsorption can be used with some degree of confidence in certain circumstances (medium and high salt intake as well as in acute volume expansion) but may not be reliable when dietary salt intake is low. PMID:3690979

  15. The acute effect of drop jump protocols with different volumes and recovery time on countermovement jump performance.

    PubMed

    Chen, Zong-Rong; Wang, Yu-Han; Peng, Hsien-Te; Yu, Ching-Fang; Wang, Min-Hsien

    2013-01-01

    The aim of this study was to investigate the acute effect of (a) a drop jump (DJ) protocol with 1 set per 5 repetitions and (b) a DJ protocol with 2 sets per 5 repetitions on countermovement jump (CMJ) height performance in volleyball players at recovery times of (a) 2 minutes, (b) 6 minutes, and (c) 12 minutes. The subjects were 10 male Division I college volleyball players. They were instructed to perform a pretest of 3 CMJs and then randomly assigned to perform (a) a DJ protocol with 1 set per 5 repetitions and (b) a DJ protocol with 2 sets per 5 repetitions. After the DJ, 3 CMJs were completed in 2, 6, and 12 minutes. A 2-way repeated-measures analysis of variance was used to examine the differences between training volumes and recovery times in CMJ height (H(CMJ)) and maximum ground reaction force. Both DJ training volumes significantly increased the H(CMJ). The H(CMJ) at post 2 minutes was greater than those at the pretest (p = 0.008), post 6 minutes (p = 0.004), and post 12 minutes (p = 0.002). In addition, the H(CMJ) at post 6 minutes was significantly greater than that at post 12 minutes (p = 0.018). Drop jumps in lower volume (e.g., within 10 repetitions) and short recovery time (e.g., within 2 minutes) can produce a positive acute effect on CMJ performance. PMID:23249768

  16. Self Organized Spatial-Temporal Structure within the Fractured Vadose Zone: The Influence of Dynamic Overloading at Fracture Intersections

    SciTech Connect

    Randall A. Laviolette

    2004-09-01

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

  17. Evaluation of Reduced Sediment Volume Procedures for Acute Toxicity Tests Using the Estuarine Amphipod Leptocheirus plumulosus

    EPA Science Inventory

    The volume of sediment required to perform a sediment toxicity bioassay is a major driver of the overall cost associated with that bioassay. Sediment volume affects bioassay cost due to sediment collection, transportation, storage, and disposal costs as well as labor costs assoc...

  18. Cardiorenal-endocrine dynamics during and following volume expansion

    SciTech Connect

    Zimmerman, R.S.; Edwards, B.S.; Schwab, T.R.; Heublein, D.M.; Burnett, J.C. Jr.

    1987-02-01

    The relationship between atrial pressure, atrial natriuretic peptide (ANP), the renin-angiotensin-aldosterone system, and renal hemodynamic and excretory function was examined during and following acute 10% body weight saline volume expansion and measurements were made at 3.3, 6.6, and 10% body weight volume expansion in pentobarbital anesthetized dogs. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), fractional excretion of Na (FE/sub Na/), and ANP all increased in parallel during volume expansion. Plasma renin activity (PRA) and aldosterone decreased in parallel during 10% volume expansion. ANP, PRA and aldosterone were measured by radioimmunoassay. Following 10% volume expansion, saline was infused at the peak urine flow rate to maintain peak volume expansion. Despite continued saline infusion, RAP, PCWP, and ANP decreased in parallel. In contrast, FE/sub Na/ remained increased, and aldosterone and PRA remained depressed. These studies demonstrate that atrial pressures, ANP, and FE/sub Na/ increase in parallel during volume expansion; this suggests a role for ANP in modulating acute atrial volume overload. During stable volume expansion periods, however, despite a decrease in ANP levels, Na excretion remains elevated, suggesting that non-ANP mechanisms may be important in maintaining natriuresis during stable volume expansion.

  19. The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated With Intensity-Modulated Radiation Therapy

    SciTech Connect

    Aizer, Ayal A.; Anderson, Nicole S.; Oh, Steven C.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Peschel, Richard E.

    2011-02-01

    Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm{sup 3}, respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm{sup 3}) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm{sup 3} increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

  20. Triphasic multinutrient supplementation during acute resistance exercise improves session volume load and reduces muscle damage in strength-trained athletes.

    PubMed

    Bird, Stephen P; Mabon, Tom; Pryde, Mitchell; Feebrey, Sarah; Cannon, Jack

    2013-05-01

    We hypothesized that triphasic multinutrient supplementation during acute resistance exercise would enhance muscular performance, produce a more favorable anabolic profile, and reduce biochemical markers of muscle damage in strength-trained athletes. Fifteen male strength-trained athletes completed two acute lower-body resistance exercise sessions to fatigue 7 days apart. After a 4-hour fast, participants consumed either a multinutrient supplement (Musashi 1-2-3 Step System, Notting Hill, Australia) (SUPP) or placebo (PLA) beverage preexercise (PRE), during (DUR), and immediately postexercise (IP). Session volume loads were calculated as kilograms × repetitions. Lower-body peak power was measured using unloaded repeated countermovement jumps, and blood samples were collected to assess biochemistry, serum hormones, and muscle damage markers at PRE, DUR, IP, 30 minutes postexercise (P30), and 24 hours postexercise (P24h). The SUPP demonstrated increased glucose concentrations at DUR and IP compared with at PRE (P < .01), whereas PLA demonstrated higher glucose at P30 compared with at PRE (P < .001). Session volume load was higher for SUPP compared with PLA (P < .05). Cortisol increased at DUR, IP, and P30 compared with at PRE in both treatments (P < .05); however, SUPP also displayed lower cortisol at P24h compared with at PRE and PLA (P < .01). The total testosterone response to exercise was higher for PLA compared with SUPP (P < .01); however, total creatine kinase and C-reactive protein responses to exercise were lower for SUPP compared with PLA (P < .05). These data indicate that although triphasic multinutrient supplementation did not produce a more favorable anabolic profile, it improved acute resistance exercise performance while attenuating muscle damage in strength-trained athletes.

  1. Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose-volume relationships and role for inverse planning

    SciTech Connect

    Tho, Lye Mun . E-mail: l.tho@beatson.gla.ac.uk; Glegg, Martin; Paterson, Jennifer; Yap, Christina; MacLeod, Alice; McCabe, Marie; McDonald, Alexander C.

    2006-10-01

    Purpose: The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. Methods and Materials: Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervals (V{sub 5}, V{sub 1}, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. Results: VSB correlated strongly with diarrheal severity at every dose level (p < 0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p {<=} 0.05). No correlation was found with anorexia, nausea, vomiting, abdominal cramps, age, body mass index, sex, tumor position, or number of fields. Analysis of 8 patients showed that inverse planning reduced median dose to small bowel by 5.1 Gy (p = 0.008) and calculated late normal tissue complication probability (NTCP) by 67% (p = 0.016). We constructed a model using mathematical analysis to predict for acute diarrhea occurring at V{sub 5} and V{sub 15}. Conclusions: A strong dose-volume relationship exists between VSB and acute diarrhea at all dose levels during preoperative chemoradiotherapy. Our constructed model may be useful in predicting toxicity, and this has been derived without the confounding influence of surgical excision on bowel function. Inverse planning can reduce calculated dose to small bowel and late NTCP, and its clinical role warrants further

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

    PubMed

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

    2003-01-01

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

  3. [Acute Kidney Injury, Type - 3 cardiorenal syndrome, Biomarkers, Renal Replacement Therapy].

    PubMed

    Di Lullo, Luca; Bellasi, Antonio; Barbera, Vincenzo; Cozzolino, Mario; Russo, Domenico; De Pascalis, Antonio; Santoboni, Francesca; Villani, Annalisa; De Rosa, Silvia; Colafelice, Marco; Russo, Luigi; Ronco, Claudio

    2016-01-01

    Cardiovascular disease and major cardiovascular events represent main cause of death in both acute and chronic kidney disease patients. Kidney and heart failure are common and frequently co-exist This organ-organ interaction, also called organ cross-talk, leads to well-known definition of cardiorenal syndrome (CRS). Here we will describe cardiovascular involvement in patients with acute kidney injury (AKI). Also known as Type-3 CRS or acute reno-cardiac CRS, it occurs when AKI contributes and/or precipitates development of acute cardiac injury. AKI may directly or indirectly produces an acute cardiac event and it can be associated with volume overload, metabolic acidosis and electrolytes disorders such as hyperkalemia and hypocalcemia, coronary artery disease, left ventricular dysfunction and fibrosis which has been also described in patients with AKI with the consequence of direct negative effects on cardiac performance. PMID:27374388

  4. Influence of acute lung volume change on contractile properties of human diaphragm.

    PubMed

    Polkey, M I; Hamnegård, C H; Hughes, P D; Rafferty, G F; Green, M; Moxham, J

    1998-10-01

    The effect of stimulus frequency on the in vivo pressure generating capacity of the human diaphragm is unknown at lung volumes other than functional residual capacity. The transdiaphragmatic pressure (Pdi) produced by a pair of phrenic nerve stimuli may be viewed as the sum of the Pdi elicited by the first (T1 Pdi) and second (T2 Pdi) stimuli. We used bilateral anterior supramaximal magnetic phrenic nerve stimulation and a digital subtraction technique to obtain the T2 Pdi at interstimulus intervals of 999, 100, 50, 33, and 10 ms in eight normal subjects at lung volumes between residual volume and total lung capacity. The reduction in T2 Pdi that we observed as lung volume increased was greatest at long interstimulus intervals, whereas the T2 Pdi obtained with short interstimulus intervals remained relatively stable over the 50% of vital capacity around functional residual capacity. For all interstimulus intervals, the total pressure produced by the pair decreased as a function of increasing lung volume. These data demonstrate that, in the human diaphragm, hyperinflation has a disproportionately severe effect on the summation of pressure responses elicited by low-frequency stimulations; this effect is distinct from and additional to the known length-tension relationship. PMID:9760323

  5. Drugs preventing Na+ and Ca2+ overload.

    PubMed

    Ravens, U; Himmel, H M

    1999-03-01

    Cardiac intracellular Na+and Ca2+homeostasis is regulated by the concerted action of ion channels, pumps and exchangers. The Na+, K+-ATPase produces the electrochemical concentration gradient for Na+, which is the driving force for Ca2+removal from the cytosol via the Na+/Ca2+exchange. Reduction of this gradient by increased intracellular Na+concentration leads to cellular Ca2+overload resulting in arrhythmias and contractile dysfunction. Na+and Ca2+overload-associated arrhythmias can be produced experimentally by inhibition of Na+efflux (digitalis-induced intoxication) and by abnormal Na+influx via modulated Na+channels (veratridine, DPI 201-106; hypoxia) or via the Na+, H+exchanger. Theoretically, blockers of Na+and Ca2+channels, inhibitors of abnormal oscillatory release of Ca2+from internal stores or modulators of the Na+, Ca2+and Na+, H+exchanger activities could protect against cellular Na+and Ca2+overload. Three exemplary drugs that prevent Na+and Ca2+overload, i.e. the benzothiazolamine R56865, the methylenephenoxydioxy-derivative CP-060S, and the benzoyl-guanidine Hoe 642, a Na+, H+exchange blocker, are briefly reviewed with respect to their efficacy on digitalis-, veratridine- and ischaemia/reperfusion-induced arrhythmias. PMID:10094840

  6. [Bruxism and overload of periodontium and implants].

    PubMed

    Jacobs, R; De Laat, A

    2000-07-01

    Bruxism is responsible for occlusal tooth wear but can not induce nor aggravate gingivitis or periodontitis. Bruxism induces jiggling forces, which cause a clinical tooth hypermobility, radiologically seen as a widened periodontal space. Although there is no direct causal relation between bruxism and implant failure, implant overload may lead to fractures of the components and bone loss. PMID:11385782

  7. Performance During the Stress of Processing Overload.

    ERIC Educational Resources Information Center

    Martin, David W.

    Performance becomes degraded when the human processing system undergoes the stress of processing overload. Information processing models are often used to predict how performance will be affected. Single channel models hypothesize that information will either be lost in the queue or processed with delay. Single capacity models predict that for a…

  8. Shock absorber protects motive components against overloads

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Shock absorber with an output shaft, hollow gear, and a pair of springs forming a resilient driving connection between shaft and gear, operates when abnormally high torques are applied. This simple durable frictional device is valuable in rotating mechanisms subject to sudden overloads.

  9. Effect of acute saline volume expansion in the anaesthetised DeltaF508 cystic fibrosis mouse.

    PubMed

    Kibble, J D; Neal, A; Green, R; Colledge, W H; Taylor, C J

    2001-01-01

    It has been suggested that CFTR Cl(-) channels in the renal inner medullary collecting duct may be involved in mediating increased renal salt excretion during extracellular fluid volume expansion. To investigate this hypothesis, in-vivo clearance experiments were performed comparing wild-type (WT) and DeltaF508-CFTR transgenic mice (cftr (tm2Cam)). Control animals were given a 0.1-ml bolus of 0.9% saline, followed by I.V. infusion at 0.3 ml x h(-1). Volume expansion was applied by infusing a 1-ml bolus of 0.9% saline followed by infusion at 0.6 ml x h(-1). No significant differences in renal NaCl handling between WT mice ( C(Na)=1.2 +/- 0.3 microl x min(-1), C(Cl)=4.0 +/- 0.5 microl x min(-1)) and DeltaF508-CFTR mice ( C(Na)=1.7 +/- 0.5 microl x min(-1), C(Cl)=4.1 +/- 0.8 microl x min(-1)) were observed under control conditions. Volume expansion resulted in large significant increases in NaCl clearance in both WT mice ( C(Na)=7.0 +/- 0.9 microl x min(-1), C(Cl)=12.0 +/- 0.6 microl x min(-1)) and DeltaF508-CFTR mice ( C(Na)=7.2 +/- 1.6 microl x min(-1), C(Cl)=11.0 +/- 2.2 microl x min(-1)). However, there was no significant difference between WT and DeltaF508-CFTR mice. In conclusion, renal NaCl excretion is not significantly different under basal conditions and during saline volume expansion in DeltaF508-CFTR mice. The data suggest that CFTR is not a physiologically important mediator of volume natriuresis.

  10. Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome.

    PubMed

    Eisner, M D; Thompson, T; Hudson, L D; Luce, J M; Hayden, D; Schoenfeld, D; Matthay, M A

    2001-07-15

    In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.

  11. Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

    SciTech Connect

    Chen, Ronald C.; Mamon, Harvey J.; Ancukiewicz, Marek; Killoran, Joseph H.; Crowley, Elizabeth M.; Blaszkowsky, Lawrence S.; Wo, Jennifer Y.; Ryan, David P.; Hong, Theodore S.

    2012-07-15

    Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women's Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman's correlation. Potential associations between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.

  12. Determinants of acute mortality of Hippodamia convergens (Coleoptera: Coccinellidae) to ultra-low volume permethrin used for mosquito management

    PubMed Central

    Preftakes, Collin J.; Bodin, Jennifer L.; Brown, Christopher R.; Piccolomini, Alyssa M.; Schleier, Jerome J.

    2016-01-01

    There are relatively few experimental studies and risk assessments of the effects on non-target insects from ultra-low volume (ULV) insecticides used for management of adult mosquitoes. Therefore, we evaluated factors that may influence the ability of an insect to intercept the insecticide at the time of application by using Hippodamia convergens (Coleoptera: Coccinellidae) in field bioassay experiments in 2011 and 2015. Treatment factors included different distances, two cage heights (ground-level and 1.5 m above ground) to the point of the application, and covered vs. uncovered cage faces (2015 only). Insecticides used included a water-based formulation (Aqua-Reslin®) and an oil-based formulation (Permanone® 30-30) of permethrin. Cage height was highly significant both years, with much less acute (i.e., short-term exposure) mortality at ground-level compared with 1.5 m. In 2011, acute mortality was less at ground-level (mean = 3.2%, median = 0%) compared to 1.5 m (mean = 85.2%, median = 100%). Cage type also was highly significant, with less mortality in covered cages compared to uncovered cages. Mortality by cage height and cage type was as follows: ground level, covered cage (mean = 2.8%, median = 0.1%); ground level, uncovered cage (mean = 41.9%, median = 9.6%); 1.5 m, covered cage (mean = 6.8%, median = 0%); 1.5 m, uncovered cage (mean = 83.7%, median = 100%). Results suggest that acute mortality to non-target insects may vary considerably based on their height and their ability to directly intercept the insecticide as the aerosol passes through the area being sprayed. PMID:27366655

  13. Determinants of acute mortality of Hippodamia convergens (Coleoptera: Coccinellidae) to ultra-low volume permethrin used for mosquito management.

    PubMed

    Peterson, Robert K D; Preftakes, Collin J; Bodin, Jennifer L; Brown, Christopher R; Piccolomini, Alyssa M; Schleier, Jerome J

    2016-01-01

    There are relatively few experimental studies and risk assessments of the effects on non-target insects from ultra-low volume (ULV) insecticides used for management of adult mosquitoes. Therefore, we evaluated factors that may influence the ability of an insect to intercept the insecticide at the time of application by using Hippodamia convergens (Coleoptera: Coccinellidae) in field bioassay experiments in 2011 and 2015. Treatment factors included different distances, two cage heights (ground-level and 1.5 m above ground) to the point of the application, and covered vs. uncovered cage faces (2015 only). Insecticides used included a water-based formulation (Aqua-Reslin®) and an oil-based formulation (Permanone® 30-30) of permethrin. Cage height was highly significant both years, with much less acute (i.e., short-term exposure) mortality at ground-level compared with 1.5 m. In 2011, acute mortality was less at ground-level (mean = 3.2%, median = 0%) compared to 1.5 m (mean = 85.2%, median = 100%). Cage type also was highly significant, with less mortality in covered cages compared to uncovered cages. Mortality by cage height and cage type was as follows: ground level, covered cage (mean = 2.8%, median = 0.1%); ground level, uncovered cage (mean = 41.9%, median = 9.6%); 1.5 m, covered cage (mean = 6.8%, median = 0%); 1.5 m, uncovered cage (mean = 83.7%, median = 100%). Results suggest that acute mortality to non-target insects may vary considerably based on their height and their ability to directly intercept the insecticide as the aerosol passes through the area being sprayed. PMID:27366655

  14. 30 CFR 57.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  15. 30 CFR 57.12001 - Circuit overload protection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Circuit overload protection. 57.12001 Section... Electricity Surface and Underground § 57.12001 Circuit overload protection. Circuits shall be protected against excessive overloads by fuses or circuit breakers of the correct type and capacity....

  16. 30 CFR 57.12001 - Circuit overload protection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Circuit overload protection. 57.12001 Section... Electricity Surface and Underground § 57.12001 Circuit overload protection. Circuits shall be protected against excessive overloads by fuses or circuit breakers of the correct type and capacity....

  17. 30 CFR 57.12001 - Circuit overload protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  18. 30 CFR 57.12001 - Circuit overload protection.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Circuit overload protection. 57.12001 Section... Electricity Surface and Underground § 57.12001 Circuit overload protection. Circuits shall be protected against excessive overloads by fuses or circuit breakers of the correct type and capacity....

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

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

  20. Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Yancy, Clyde W.; Buckey, Jay C.; Lane, Lynda D.; Hargens, Alan R.; Blomqvist, C. G.

    1992-01-01

    A hypothesis is proposed that a temporal relationship exists between increases in cardiac filling pressure and plasma artrial natriuretic peptide (ANP) concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). To test the hypothesis, 30 ml/kg isotonic saline were infused in supine male subjects over 24 min and responses were monitored for 3 h postinfusion. Results show that at end infusion, mean arterial pressure (RAP), heart rate and plasma volume exhibited peak increases of 146, 23, and 27 percent, respectively. Mean plasma ANP and UV peaked (45 and 390 percent, respectively) at 30 min postinfusion. Most cardiovascular variables had returned toward control levels by 1 h postinfusion, and net reabsorption of extravascular fluid ensued. It is concluded that since ANP was not significantly increased until 30 min postinfusion, factors other than ANP initiate responses to intravascular fluid loading. These factors include increased vascular pressures, baroreceptor-mediated vasolidation, and hemodilution of plasma proteins. ANP is suggested to mediate, in part, the renal response to saline infusion.

  1. Valgus Extension Overload in Baseball Players.

    PubMed

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

    2016-01-01

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

  2. Valgus Extension Overload in Baseball Players.

    PubMed

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

    2016-01-01

    Repetitive throwing, such as in baseball pitching, applies massive stress on the elbow. This can often lead to a predictable constellation of elbow injuries, such as valgus extension overload syndrome (VEO). The following review of VEO provides an understanding of relevant anatomy, explanation of pathomechanics, key aspects to clinical evaluation, effective treatment options, and indications for surgery. In addition, we provide the senior author's (CSA) preferred arthroscopic technique for cases of VEO refractory to conservative management. PMID:26991567

  3. Blood volume of nonsplenectomized and splenectomized cats before and after acute hemorrhage

    SciTech Connect

    Breznock, E.M.; Strack, D.

    1982-10-01

    Blood volume (BV) was determined in awake, nonsplenectomized (NSPX) and splenectomized (SPX) cats before and after hemorrhage (6 ml/kg). Each NSPX cat had a determined BV at least 10 ml/kg greater than the same cat after splenectomy. The mean BV of SPX cats was 43.4 +/- 8.94. ml kg (4.3% of body weight). The calculated RBC masses of NSPX and SPX cats were 17.0 +/- 4.07 and 12.2 +/- 1.12 ml/kg, respectively. Each NSPX cat had apparent RBC masses of 5 ml/kg greater than that of the same cat after splenectomy was done. At 1 hour after a hemorrhage, the BV and RBC masses determined in SPX cats were 46.7 +/- 12.1 and 9.7 +/- 1.90 ml/kg, respectively. Extravascular-to-intravascular fluid flux (calculated from RBC masses and plasma protein dilution) was approximately 0.80% of body weight. The indirect method with /sup 51/Cr-labeled RBC for BV determination was accurate and precise in awake, SPX cats; in awake, NSPX cats, the /sup 51/Cr-labeled RBC dilution method was precise, but not accurate. The spleen in the cat resulted in marked overestimations of BV and RBC masses.

  4. Acute responses of circulating microRNAs to low-volume sprint interval cycling

    PubMed Central

    Cui, Shu Fang; Li, Wei; Niu, Jie; Zhang, Chen Yu; Chen, Xi; Ma, Ji Zheng

    2015-01-01

    Low-volume high-intensity interval training is an efficient and practical method of inducing physiological responses in various tissues to develop physical fitness and may also change the expression of circulating microRNAs (miRNAs). The purpose of the present study was to examine whether miRNAs for muscle, heart, somatic tissue and metabolism were affected by 30-s intervals of intensive sprint cycling. We also examined the relationship of these miRNAs to conventional biochemical and performance indices. Eighteen healthy young males performed sprint interval cycling. Circulating miRNAs in plasma were detected using TaqMan-based quantitative PCR and normalized to Let-7d/g/i. In addition, we determined the levels of insulin-like growth factor-I, testosterone and cortisol, and anaerobic capacity. Compared to plasma levels before exercise muscle-specific miR-1 (0.12 ± 0.02 vs. 0.09 ± 0.02), miR-133a (0.46 ± 0.10 vs. 0.31 ± 0.06), and miR-133b (0.19 ± 0.02 vs. 0.10 ± 0.01) decreased (all P < 0.05), while miR-206 and miR-499 remained unchanged. The levels of metabolism related miR-122 (0.62 ± 0.07 vs. 0.34 ± 0.03) and somatic tissues related miR-16 (1.74 ± 0.27 vs. 0.94 ± 0.12) also decreased (both P < 0.05). The post-exercise IGF-1 and cortisol concentrations were significantly increased, while testosterone concentrations did not. Plasma levels of miR-133b correlated to peak power (r = 0.712, P = 0.001) and miR-122 correlated to peak power ratio (r = 0.665, P = 0.003). In conclusion sprint exercise provokes genetic changes for RNA related to specific muscle or metabolism related miRNAs suggesting that miR-133b and miR-122 may be potential useful biomarkers for actual physiological strain or anaerobic capacity. Together, our findings on the circulating miRNAs may provide new insight into the physiological responses that are being performed during exercise and delineate mechanisms by which exercise confers distinct phenotypes and improves performance. PMID

  5. Could Mean Platelet Volume Be a Reliable Indicator for Acute Mesenteric Ischemia Diagnosis? A Case-Control Study

    PubMed Central

    Degerli, Vermi; Ergin, Isil; Ustuner, Mehmet Akif; Duran, Ozgur

    2016-01-01

    Objective. Acute mesenteric ischemia (AMI) is a disease, usually seen in elderly people and accompanied by comorbid diseases. Mean platelet volume (MPV), the significant indicator of platelet activation and function, is associated with AMI. In this study, we considered that we can use MPV as a reliable indicator in the diagnosis of AMI. Methods. This study was conducted among AMI patients with two control groups. Age, gender, MPV, platelet count, concomitant diseases, abdominal computed tomography, and patient outcomes were recorded for evaluation. Control group I contained 41 healthy patients whose ages-genders were matched. Control group II contained 41 patients with no AMI, whose ages-genders-concomitant diseases were matched. Results. Of the total 41 AMI patients, 22 were female and 19 were male. The average age of them was 72.12 ± 13.2 (44–91) years. MPV was significantly increased in the AMI (p = 0.001) and control group II (p < 0.001) in comparison with healthy control groups. In the comparison of the AMI patients with their matched controls for concomitant diseases, no statistical difference was found in the MPV values. Conclusion. MPV may be used as an indicator of AMI only if the patient has no concomitant diseases. The existence of a concomitant disease brings into question the reliability of high MPV values as a suitable indicator.

  6. Acceleration of Fatigue Crack Growth after Overload in Carbon Steel

    NASA Astrophysics Data System (ADS)

    Yamauchi, A.; Miyahara, H.; Makabe, C.; Miyazaki, T.

    The effects of an overload on fatigue crack growth behavior have been investigated by using carbon steel. Delayed retardation and acceleration of crack growth were both observed. These phenomena depended not only on overload conditions but also on the baseline stress conditions. Moreover, the mechanical properties of the materials affected the crack growth rate after overload. It was found that crack growth accelerated when tensile residual stress was distributed in front of the crack tip. The residual stress distribution is related to the crack opening geometry at the overload stage.

  7. Fibre-Specific Responses to Endurance and Low Volume High Intensity Interval Training: Striking Similarities in Acute and Chronic Adaptation

    PubMed Central

    Scribbans, Trisha D.; Edgett, Brittany A.; Vorobej, Kira; Mitchell, Andrew S.; Joanisse, Sophie D.; Matusiak, Jennifer B. L.; Parise, Gianni; Quadrilatero, Joe; Gurd, Brendon J.

    2014-01-01

    The current study involved the completion of two distinct experiments. Experiment 1 compared fibre specific and whole muscle responses to acute bouts of either low-volume high-intensity interval training (LV-HIT) or moderate-intensity continuous endurance exercise (END) in a randomized crossover design. Experiment 2 examined the impact of a six-week training intervention (END or LV-HIT; 4 days/week), on whole body and skeletal muscle fibre specific markers of aerobic and anaerobic capacity. Six recreationally active men (Age: 20.7±3.8 yrs; VO2peak: 51.9±5.1 mL/kg/min) reported to the lab on two separate occasions for experiment 1. Following a muscle biopsy taken in a fasted state, participants completed an acute bout of each exercise protocol (LV-HIT: 8, 20-second intervals at ∼170% of VO2peak separated by 10 seconds of rest; END: 30 minutes at ∼65% of VO2peak), immediately followed by a muscle biopsy. Glycogen content of type I and IIA fibres was significantly (p<0.05) reduced, while p-ACC was significantly increased (p<0.05) following both protocols. Nineteen recreationally active males (n = 16) and females (n = 3) were VO2peak-matched and assigned to either the LV-HIT (n = 10; 21±2 yrs) or END (n = 9; 20.7±3.8 yrs) group for experiment 2. After 6 weeks, both training protocols induced comparable increases in aerobic capacity (END: Pre: 48.3±6.0, Mid: 51.8±6.0, Post: 55.0±6.3 mL/kg/min LV-HIT: Pre: 47.9±8.1, Mid: 50.4±7.4, Post: 54.7±7.6 mL/kg/min), fibre-type specific oxidative and glycolytic capacity, glycogen and IMTG stores, and whole-muscle capillary density. Interestingly, only LV-HIT induced greater improvements in anaerobic performance and estimated whole-muscle glycolytic capacity. These results suggest that 30 minutes of END exercise at ∼65% VO2peak or 4 minutes of LV-HIT at ∼170% VO2peak induce comparable changes in the intra-myocellular environment (glycogen content and signaling activation); correspondingly, training

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

    PubMed

    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.

  9. Dietary fat overload reprograms brown fat mitochondria

    PubMed Central

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

    2015-01-01

    Chronic nutrient overload accelerates the onset of several aging-related diseases reducing life expectancy. Although the mechanisms by which overnutrition affects metabolic processes in many tissues are known, its role on BAT physiology is still unclear. Herein, we investigated the mitochondrial responses in BAT of female mice exposed to high fat diet (HFD) at different steps of life. Although adult mice showed an unchanged mitochondrial amount, both respiration and OxPHOS subunits were strongly affected. Differently, offspring pups exposed to HFD during pregnancy and lactation displayed reduced mitochondrial mass but high oxidative efficiency that, however, resulted in increased bioenergetics state of BAT rather than augmented uncoupling respiration. Interestingly, the metabolic responses triggered by HFD were accompanied by changes in mitochondrial dynamics characterized by decreased content of the fragmentation marker Drp1 both in mothers and offspring pups. HFD-induced inactivation of the FoxO1 transcription factor seemed to be the up-stream modulator of Drp1 levels in brown fat cells. Furthermore, HFD offspring pups weaned with normal diet only partially reverted the mitochondrial dysfunctions caused by HFD. Finally these mice failed in activating the thermogenic program upon cold exposure. Collectively our findings suggest that maternal dietary fat overload irreversibly commits BAT unresponsiveness to physiological stimuli such as cool temperature and this dysfunction in the early stage of life might negatively modulate health and lifespan. PMID:26483700

  10. [Acute respiratory distress syndrome after near-drowning (author's transl)].

    PubMed

    Tempel, G; Jelen, S; Forster, B; Gullotta, U; Daum, S

    1977-08-01

    After successful rescue from drowning there may develop a situation which is called secondary drowning, resulting in acute respiratory distress characterized by interstitial pulmonary oedema, hypoxaemia, hypercapnia and acidosis during drowning, direct alteration of the alveolar membrane by aspirated water and particulate matters and a volume overloading by adsorption and--not seldom--inept therapy. This situation requires mechanical ventilation and forced diuresis, combined with high doses of steroids, antibiotics and digitalis. We present the case of an eleven year old patient whose clinical course demonstrate the necessity of exact clinical observation after rescue from drowning. After development of acute respiratory distress only the immediate utilization of the therapeutic modalities of an intensive care may result in a satisfactory outcome. Four months later our patient had normal pulmonary function except for a moderate reduction of compliance.

  11. Comparison of Acute and Chronic Traumatic Brain Injury Using Semi-Automatic Multimodal Segmentation of MR Volumes

    PubMed Central

    Chambers, Micah C.; Alger, Jeffry R.; Filippou, Maria; Prastawa, Marcel W.; Wang, Bo; Hovda, David A.; Gerig, Guido; Toga, Arthur W.; Kikinis, Ron; Vespa, Paul M.; Van Horn, John D.

    2011-01-01

    Abstract Although neuroimaging is essential for prompt and proper management of traumatic brain injury (TBI), there is a regrettable and acute lack of robust methods for the visualization and assessment of TBI pathophysiology, especially for of the purpose of improving clinical outcome metrics. Until now, the application of automatic segmentation algorithms to TBI in a clinical setting has remained an elusive goal because existing methods have, for the most part, been insufficiently robust to faithfully capture TBI-related changes in brain anatomy. This article introduces and illustrates the combined use of multimodal TBI segmentation and time point comparison using 3D Slicer, a widely-used software environment whose TBI data processing solutions are openly available. For three representative TBI cases, semi-automatic tissue classification and 3D model generation are performed to perform intra-patient time point comparison of TBI using multimodal volumetrics and clinical atrophy measures. Identification and quantitative assessment of extra- and intra-cortical bleeding, lesions, edema, and diffuse axonal injury are demonstrated. The proposed tools allow cross-correlation of multimodal metrics from structural imaging (e.g., structural volume, atrophy measurements) with clinical outcome variables and other potential factors predictive of recovery. In addition, the workflows described are suitable for TBI clinical practice and patient monitoring, particularly for assessing damage extent and for the measurement of neuroanatomical change over time. With knowledge of general location, extent, and degree of change, such metrics can be associated with clinical measures and subsequently used to suggest viable treatment options. PMID:21787171

  12. Fluid and electrolyte overload in critically ill patients: An overview

    PubMed Central

    Besen, Bruno Adler Maccagnan Pinheiro; Gobatto, André Luiz Nunes; Melro, Lívia Maria Garcia; Maciel, Alexandre Toledo; Park, Marcelo

    2015-01-01

    Fluids are considered the cornerstone of therapy for many shock states, particularly states that are associated with relative or absolute hypovolemia. Fluids are also commonly used for many other purposes, such as renal protection from endogenous and exogenous substances, for the safe dilution of medications and as “maintenance” fluids. However, a large amount of evidence from the last decade has shown that fluids can have deleterious effects on several organ functions, both from excessive amounts of fluids and from their non-physiological electrolyte composition. Additionally, fluid prescription is more common in patients with systemic inflammatory response syndrome whose kidneys may have impaired mechanisms of electrolyte and free water excretion. These processes have been studied as separate entities (hypernatremia, hyperchloremic acidosis and progressive fluid accumulation) leading to worse outcomes in many clinical scenarios, including but not limited to acute kidney injury, worsening respiratory function, higher mortality and higher hospital and intensive care unit length-of-stays. In this review, we synthesize this evidence and describe this phenomenon as fluid and electrolyte overload with potentially deleterious effects. Finally, we propose a strategy to safely use fluids and thereafter wean patients from fluids, along with other caveats to be considered when dealing with fluids in the intensive care unit. PMID:25938027

  13. Engineering and the problem of moral overload.

    PubMed

    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

  14. Evaluation of thermal overload in boiler operators.

    PubMed

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

    2012-01-01

    The Brazilians educational institutions need a large energy demand for the operation of laundries, restaurants and accommodation of students. Much of that energy comes from steam generated in boilers with wood fuel. The laboral activity in boiler may present problems for the operator's health due to exposure to excessive heat, and its operation has a high degree of risk. This paper describes an analysis made the conditions of thermal environment in the operation of a B category boiler, located at a Higher Education Institution, located in the Zona da Mata Mineira The equipments used to collect data were Meter WBGT of the Heat Index; Meter of Wet Bulb Index and Globe Thermometer (WBGT); Politeste Instruments, an anemometer and an Infrared Thermometer. By the application of questionnaires, the second phase consisted of collecting data on environmental factors (temperature natural environment, globe temperature, relative humidity and air velocity). The study concluded that during the period evaluated, the activity had thermal overload. PMID:22316768

  15. Iron overload in cultured rat myocardial cells

    NASA Astrophysics Data System (ADS)

    Bauminger, E. R.; Iancu, T. C.; Link, G.; Pinson, A.; Hershko, C.

    1987-03-01

    In order to characterize the nature of iron deposits associated with iron overload in heart cells, Mössbauer spectroscopy and ultrastructural studies were performed in iron loaded heart cell cultures obtained from newborn rats grown in a medium containing 20 μg iron/ml. Maximal uptake of iron after 24 hrs was about 15%. Not more than 20% of the iron in these cells was stored in ferritin and the rest was found in smaller trivalent iron aggregates. With time there was a shift from smaller to larger aggregates. In chase samples there was only a very limited spontaneous release of iron from heart cells. Desferrioxamine, an iron chelating drug, removed a major part of the smaller aggregates, but did not remove ferritin iron.

  16. Evaluation of thermal overload in boiler operators.

    PubMed

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

    2012-01-01

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

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

    NASA Technical Reports Server (NTRS)

    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.

  18. Bioaugmentation of overloaded anaerobic digesters restores function and archaeal community.

    PubMed

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

    2015-03-01

    Adding beneficial microorganisms to anaerobic digesters for improved performance (i.e. bioaugmentation) has been shown to decrease recovery time after organic overload or toxicity upset. Compared to strictly anaerobic cultures, adding aerotolerant methanogenic cultures may be more practical since they exhibit higher methanogenic activity and can be easily dried and stored in ambient air for future shipping and use. In this study, anaerobic digesters were bioaugmented with both anaerobic and aerated, methanogenic propionate enrichment cultures after a transient organic overload. Digesters bioaugmented with anaerobic and moderately aerated cultures recovered 25 and 100 days before non-bioaugmented digesters, respectively. Increased methane production due to bioaugmentation continued a long time, with 50-120% increases 6 to 12 SRTs (60-120 days) after overload. In contrast to the anaerobic enrichment, the aerated enrichments were more effective as bioaugmentation cultures, resulting in faster recovery of upset digester methane and COD removal rates. Sixty days after overload, the bioaugmented digester archaeal community was not shifted, but was restored to one similar to the pre-overload community. In contrast, non-bioaugmented digester archaeal communities before and after overload were significantly different. Organisms most similar to Methanospirillum hungatei had higher relative abundance in well-operating, undisturbed and bioaugmented digesters, whereas organisms similar to Methanolinea tarda were more abundant in upset, non-bioaugmented digesters. Bioaugmentation is a beneficial approach to increase digester recovery rate after transient organic overload events. Moderately aerated, methanogenic propionate enrichment cultures were more beneficial augments than a strictly anaerobic enrichment. PMID:25528544

  19. Bioaugmentation of overloaded anaerobic digesters restores function and archaeal community.

    PubMed

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

    2015-03-01

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

  20. Clinical and Research Considerations for Patients With Hypertensive Acute Heart Failure: A Consensus Statement from the Society of Academic Emergency Medicine and the Heart Failure Society of America Acute Heart Failure Working Group.

    PubMed

    Collins, Sean P; Levy, Phillip D; Martindale, Jennifer L; Dunlap, Mark E; Storrow, Alan B; Pang, Peter S; Albert, Nancy M; Felker, G Michael; Fermann, Gregory J; Fonarow, Gregg C; Givertz, Michael M; Hollander, Judd E; Lanfear, David J; Lenihan, Daniel J; Lindenfeld, JoAnn M; Peacock, W Frank; Sawyer, Douglas B; Teerlink, John R; Butler, Javed

    2016-08-01

    Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF. PMID:27262665

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

    PubMed

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

    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(-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.

  2. Obesity versus osteoarthritis: beyond the mechanical overload

    PubMed Central

    Sartori-Cintra, Angélica Rossi; Aikawa, Priscila; Cintra, Dennys Esper Correa

    2014-01-01

    Obesity is currently considered a major public health problem in the world, already reaching epidemic characteristics, according to the World Health Organization. Excess weight is the major risk factor associated with various diseases, such as type 2 diabetes mellitus, hypertension, dyslipidemia and osteometabolic diseases, including osteoporosis and osteoarthritis. Osteoarthritis is the most prevalent rheumatic disease and the leading cause of physical disability and reduced quality of life of the population over 65 years. It mainly involves the joints that bear weight - knees and hips. However, along with the cases of obesity, its prevalence is increasing, and even in other joints, such as hands. Thus, it is assumed that the influence of obesity on the development of OA is beyond mechanical overload. The purpose of this review was to correlate the possible mechanisms underlying the genesis and development of these two diseases. Increased fat mass is directly proportional to excessive consumption of saturated fatty acids, responsible for systemic low-grade inflammation condition and insulin and leptin resistance. At high levels, leptin assumes inflammatory characteristics and acts in the articular cartilage, triggering the inflammatory process and changing homeostasis this tissue with consequent degeneration. We conclude that obesity is a risk factor for osteoarthritis and that physical activity and changes in diet composition can reverse the inflammatory and leptin resistance, reducing progression or preventing the onset of osteoarthritis. PMID:25184806

  3. High-volume hemofiltration and prone ventilation in subarachnoid hemorrhage complicated by severe acute respiratory distress syndrome and refractory septic shock

    PubMed Central

    Cornejo, Rodrigo; Romero, Carlos; Ugalde, Diego; Bustos, Patricio; Diaz, Gonzalo; Galvez, Ricardo; Llanos, Osvaldo; Tobar, Eduardo

    2014-01-01

    We report the successful treatment of two patients with aneurismal subarachnoid hemorrhage complicated by severe respiratory failure and refractory septic shock using simultaneous prone position ventilation and high-volume hemofiltration. These rescue therapies allowed the patients to overcome the critical situation without associated complications and with no detrimental effects on the intracranial and cerebral perfusion pressures. Prone position ventilation is now an accepted therapy for severe acute respiratory distress syndrome, and high-volume hemofiltration is a non-conventional hemodynamic support that has several potential mechanisms for improving septic shock. In this manuscript, we briefly review these therapies and the related evidence. When other conventional treatments are insufficient for providing safe limits of oxygenation and perfusion as part of basic neuroprotective care in subarachnoid hemorrhage patients, these rescue therapies should be considered on a case-by-case basis by an experienced critical care team. PMID:25028955

  4. Associations between Lifestyle Factors and Iron Overload in Korean Adults

    PubMed Central

    2016-01-01

    It has been suggested that iron overload, which indicates the accumulation of iron, generates cellular reactive oxygens and causes peroxide damages to the body. Such oxidative stresses, in a broader context, are also caused by lifestyles such as alcohol consumption and smoking. However, there are limited data on the association between these lifestyle factors and internal iron overload. In present study, we evaluated associations between lifestyle factors, such as smoking status, alcohol consumption, and physical activity, and serum markers of iron overload. In a population-based cross-sectional study including 2,347 Korean men and women aged 49–79 years, we assessed serum transferrin saturation (TSAT) levels and defined iron overload as TSAT levels > 50% for men and > 45% for women. After excluding persons with chronic diseases and iron deficiency, multivariate odds ratio (OR) and its 95% confidence interval (CI) were estimated to evaluate associations between lifestyle factors and iron overload in 1,973 participants. In all participants, we examined a significantly positive association between heavy alcohol consumption (> 30 g/day) and iron overload; heavy drinkers showed 1.6-fold higher OR (95% CI, 1.11–2.36) than non-drinkers. Stratified analysis by sex showed that this association was significant only among men. In addition, we observed a potential association between heavy smoking > 10 cigarettes/day and iron overload (p = 0.07). In stratified analysis by sex, we examined a significant association between smoking and iron overload only among women; former or current smokers had 1.9-fold higher OR (95% CI, 1.01–3.63) than never-smoker. Our findings suggest that heavy alcohol consumption and smoking may worsen iron accumulation in the body. PMID:27812516

  5. Effects of MMP-9 inhibition by doxycycline on proteome of lungs in high tidal volume mechanical ventilation-induced acute lung injury

    PubMed Central

    2010-01-01

    Background Although mechanical ventilation (MV) is a major supportive therapy for patients with acute respiratory distress syndrome, it may result in side effects including lung injury. In this study we hypothesize that MMP-9 inhibition by doxycycline might reduce MV-related lung damage. Using a proteomic approach we identified the pulmonary proteins altered in high volume ventilation-induced lung injury (VILI). Forty Wistar rats were randomized to an orally pretreated with doxycycline group (n = 20) or to a placebo group (n = 20) each of which was followed by instrumentation prior to either low or high tidal volume mechanical ventilation. Afterwards, animals were euthanized and lungs were harvested for subsequent analyses. Results Mechanical function and gas exchange parameters improved following treatment with doxycycline in the high volume ventilated group as compared to the placebo group. Nine pulmonary proteins have shown significant changes between the two biochemically analysed (high volume ventilated) groups. Treatment with doxycycline resulted in a decrease of pulmonary MMP-9 activity as well as in an increase in the levels of soluble receptor for advanced glycation endproduct, apoliporotein A-I, peroxiredoxin II, four molecular forms of albumin and two unnamed proteins. Using the pharmacoproteomic approach we have shown that treatment with doxycycline leads to an increase in levels of several proteins, which could potentially be part of a defense mechanism. Conclusion Administration of doxycycline might be a significant supportive therapeutic strategy in prevention of VILI. PMID:20205825

  6. Multimedia reviews: multimedia overload produces "symplexity".

    PubMed

    Zingrone, Frank

    2003-03-01

    We humans "know" from information mediated through our "natural senses." All outside signals come to us through some medium-sound waves, pressure and touch, light waves, radio and television waves, and so forth. McLuhan's famous mantra "The medium is the message" paradoxically highlighted the critical transformation of meaning when each type of medium-radio, television, drums, hand signals-by its very nature modifies the message it is transmitting. In this month's column Dr. Zingrone brings challenging new ideas to the field of human communication and vividly describes the communication distortions that occur when the overload of increasingly complex modern media results in a paradoxical diminution of meaning itself. He has coined a term for this unintended consequence and given it to his exciting new book, The Media Symplex: At the Edge of Meaning in the Age of Chaos (1). Many of us may recognize the effect created by this accelerating phenomenon-our stupefaction as we experience the onslaught of sound and visual signals produced by a television news screen, where an avalanche of rapidly changing, overlapping, and distorted visual images flash at our eyes while screeching, undulating synthetic "music" crashes about our ears. And in that chaos we struggle to find meaning,Dr. Zingrone, who worked with McLuhan and who has written extensively about his work (2,3), has succeeded in his new book to move the pioneering work of human communication scientists forward and thereby help us all to understand the developing paradox and danger of more communication yet less meaning. PMID:12610237

  7. Multimedia reviews: multimedia overload produces "symplexity".

    PubMed

    Zingrone, Frank

    2003-03-01

    We humans "know" from information mediated through our "natural senses." All outside signals come to us through some medium-sound waves, pressure and touch, light waves, radio and television waves, and so forth. McLuhan's famous mantra "The medium is the message" paradoxically highlighted the critical transformation of meaning when each type of medium-radio, television, drums, hand signals-by its very nature modifies the message it is transmitting. In this month's column Dr. Zingrone brings challenging new ideas to the field of human communication and vividly describes the communication distortions that occur when the overload of increasingly complex modern media results in a paradoxical diminution of meaning itself. He has coined a term for this unintended consequence and given it to his exciting new book, The Media Symplex: At the Edge of Meaning in the Age of Chaos (1). Many of us may recognize the effect created by this accelerating phenomenon-our stupefaction as we experience the onslaught of sound and visual signals produced by a television news screen, where an avalanche of rapidly changing, overlapping, and distorted visual images flash at our eyes while screeching, undulating synthetic "music" crashes about our ears. And in that chaos we struggle to find meaning,Dr. Zingrone, who worked with McLuhan and who has written extensively about his work (2,3), has succeeded in his new book to move the pioneering work of human communication scientists forward and thereby help us all to understand the developing paradox and danger of more communication yet less meaning.

  8. Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children

    PubMed Central

    Kilian, Yvonne; Wehmeier, Udo F.; Wahl, Patrick; Mester, Joachim; Hilberg, Thomas; Sperlich, Billy

    2016-01-01

    Aim: The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126) and the VEGF mRNA following an acute bout of HIIT and HVT in children. Methods:Twelve healthy competitive young male cyclists (14.4 ± 0.8 years; 57.9 ± 9.4 ml·min−1·kg−1 peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90–95% peak power output (PPO), each interval separated by 3 min of active recovery, and one high volume session (HVT) consisting of a constant load exercise for 90 min at 60% PPO. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min), and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126, and VEGF mRNA. Results: HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre-values, whereas HIIT showed no significant influence on the miRNAs compared to pre-values. VEGF mRNA significantly increased during and after HIIT (d1, 30′, 60′, 180′) and HVT (d3, 0′, 60′). Conclusion: Results of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126) in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues. PMID:27014090

  9. Interleukin-6 and associated cytokine responses to an acute bout of high-intensity interval exercise: the effect of exercise intensity and volume.

    PubMed

    Cullen, Tom; Thomas, Andrew W; Webb, Richard; Hughes, Michael G

    2016-08-01

    Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL-10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6-related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 ± 1.51) than LOW (1.40 ± 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise. PMID:27377137

  10. Interleukin-6 and associated cytokine responses to an acute bout of high-intensity interval exercise: the effect of exercise intensity and volume.

    PubMed

    Cullen, Tom; Thomas, Andrew W; Webb, Richard; Hughes, Michael G

    2016-08-01

    Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL-10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6-related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 ± 1.51) than LOW (1.40 ± 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise.

  11. The Impact of a Targeted Training Program on E-Mail System Processing Capabilities and Self-Perception of E-Mail Overload

    ERIC Educational Resources Information Center

    Einstein, Michael M.

    2014-01-01

    As business e-mail volumes continue to grow and employees spend increasingly larger portions of their day processing e-mail, there is strong evidence of the negative impacts of e-mail processing, especially with respect to e-mail overload. This study sought to determine whether a training program focused on select e-mail features and processing…

  12. A Descriptive Study of the Temporal Patterns of Volume and Contents Change in Human Acute Burn Edema: Application in Evidence-Based Intervention and Research Design.

    PubMed

    Edgar, Dale W; Fear, Mark; Wood, Fiona M

    2016-01-01

    Edema after burn contributes significantly to burn wound depth conversion. In humans after burn injury, there is a lack of detailed understanding of the contents and temporal changes in volume of acute tissue edema. The novel findings of these studies relate to the collection of edema fluid after partial-thickness burn injury. Edema volume peaks on day 1 after burn without formal fluid resuscitation. The studies indicated that the peak was on day 2 for a resuscitated burn. In contrast, animal studies suggest that the peak of edema occurs by or before day 1 after injury. The findings confirm the pitfalls of evidence derived from animal models and assuming direct transference to humans. Postburn edema was demonstrated to be a high-protein fluid (ie, ≥10 g/L) for the duration of the inflammatory period. The presence of high-protein edema presents greater challenges to clinicians developing novel treatment options. The rate of volume change over time tapered to insignificant levels after day 4 following burn. Greater than 98% of the edema contents was fluid. However, the size of particulate matter did not preclude it passing through patent lymphatic collectors. The results indicate a necessity for urgent postburn intervention, which should incorporate the active stimulation of the lymphatic system to improve efficacy of edema removal.

  13. A Descriptive Study of the Temporal Patterns of Volume and Contents Change in Human Acute Burn Edema: Application in Evidence-Based Intervention and Research Design.

    PubMed

    Edgar, Dale W; Fear, Mark; Wood, Fiona M

    2016-01-01

    Edema after burn contributes significantly to burn wound depth conversion. In humans after burn injury, there is a lack of detailed understanding of the contents and temporal changes in volume of acute tissue edema. The novel findings of these studies relate to the collection of edema fluid after partial-thickness burn injury. Edema volume peaks on day 1 after burn without formal fluid resuscitation. The studies indicated that the peak was on day 2 for a resuscitated burn. In contrast, animal studies suggest that the peak of edema occurs by or before day 1 after injury. The findings confirm the pitfalls of evidence derived from animal models and assuming direct transference to humans. Postburn edema was demonstrated to be a high-protein fluid (ie, ≥10 g/L) for the duration of the inflammatory period. The presence of high-protein edema presents greater challenges to clinicians developing novel treatment options. The rate of volume change over time tapered to insignificant levels after day 4 following burn. Greater than 98% of the edema contents was fluid. However, the size of particulate matter did not preclude it passing through patent lymphatic collectors. The results indicate a necessity for urgent postburn intervention, which should incorporate the active stimulation of the lymphatic system to improve efficacy of edema removal. PMID:27322367

  14. Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.

    PubMed

    Harjola, Veli-Pekka; Mebazaa, Alexandre; Čelutkienė, Jelena; Bettex, Dominique; Bueno, Hector; Chioncel, Ovidiu; Crespo-Leiro, Maria G; Falk, Volkmar; Filippatos, Gerasimos; Gibbs, Simon; Leite-Moreira, Adelino; Lassus, Johan; Masip, Josep; Mueller, Christian; Mullens, Wilfried; Naeije, Robert; Nordegraaf, Anton Vonk; Parissis, John; Riley, Jillian P; Ristic, Arsen; Rosano, Giuseppe; Rudiger, Alain; Ruschitzka, Frank; Seferovic, Petar; Sztrymf, Benjamin; Vieillard-Baron, Antoine; Yilmaz, Mehmet Birhan; Konstantinides, Stavros

    2016-03-01

    Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches. PMID:26995592

  15. Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.

    PubMed

    Harjola, Veli-Pekka; Mebazaa, Alexandre; Čelutkienė, Jelena; Bettex, Dominique; Bueno, Hector; Chioncel, Ovidiu; Crespo-Leiro, Maria G; Falk, Volkmar; Filippatos, Gerasimos; Gibbs, Simon; Leite-Moreira, Adelino; Lassus, Johan; Masip, Josep; Mueller, Christian; Mullens, Wilfried; Naeije, Robert; Nordegraaf, Anton Vonk; Parissis, John; Riley, Jillian P; Ristic, Arsen; Rosano, Giuseppe; Rudiger, Alain; Ruschitzka, Frank; Seferovic, Petar; Sztrymf, Benjamin; Vieillard-Baron, Antoine; Yilmaz, Mehmet Birhan; Konstantinides, Stavros

    2016-03-01

    Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches.

  16. Differential expression of stress-inducible proteins in chronic hepatic iron overload

    SciTech Connect

    Brown, Kyle E. Broadhurst, Kimberly A.; Mathahs, M. Meleah; Weydert, Jamie

    2007-09-01

    Introduction:: Oxidative stress can trigger a cellular stress response characterized by induction of antioxidants, acute phase reactants (APRs) and heat shock proteins (HSPs), which are presumed to play a role in limiting tissue damage. In rodents, hepatic iron overload causes oxidative stress that results in upregulation of antioxidant defenses with minimal progressive liver injury. The aim of this study was to determine whether iron overload modulates expression of other stress-responsive proteins such as APRs and HSPs that may confer protection against iron-induced damage in rodent liver. Methods:: Male rats received repeated injections of iron dextran or dextran alone over a 6-month period. Hepatic transcript levels for a panel of APRs and HSPs were quantitated by real-time PCR and protein expression was evaluated by Western blot and immunohistochemistry. Results:: Hepatic iron concentrations were increased > 50-fold in the iron-loaded rats compared to controls. Iron loading resulted in striking increases in mRNAs for Hsp32 (heme oxygenase-1; 12-fold increase vs. controls) and metallothionein-1 and -2 (both increased {approx} 6-fold). Transcripts for {alpha}1-acid glycoprotein, the major rat APR, were increased {approx} 3-fold, while expression of other classical APRs was unaltered. Surprisingly, although mRNA levels for the HSPs were not altered by iron, the abundance of Hsp25, Hsp70 and Hsp90 proteins was uniformly reduced in the iron-loaded livers, as were levels of NAD(P)H:quinone oxidoreductase 1, an Hsp70 client protein. Conclusions:: Chronic iron administration elicits a unique pattern of stress protein expression. These alterations may modulate hepatic responses to iron overload, as well as other injury processes.

  17. Effect of acute hyaluronidase treatment of the glycocalyx on tracer-based whole body vascular volume estimates in mice.

    PubMed

    VanTeeffelen, Jurgen W G E; Brands, Judith; Janssen, Ben J A; Vink, Hans

    2013-05-01

    The endothelial glycocalyx forms a hyaluronan-containing interface between the flowing blood and the endothelium throughout the body. By comparing the systemic distribution of a small glycocalyx-accessible tracer vs. a large circulating plasma tracer, the size-selective barrier properties of the glycocalyx have recently been utilized to estimate whole body glycocalyx volumes in humans and animals, but a comprehensive validation of this approach has been lacking at the moment. In the present study, we compared, in anesthetized, ventilated C57Bl/6 mice, the whole body distribution of small (40 kDa) dextrans (Texas Red labeled; Dex40) vs. that of intermediate (70 kDa) and large (500 kDa) dextrans (both FITC labeled; Dex70 and Dex500, respectively) using tracer dilution and vs. that of circulating plasma, as derived from the dilution of fluorescein-labeled red blood cells and large-vessel hematocrit. The contribution of the glycocalyx was evaluated by intravenous infusion of a bolus of the enzyme hyaluronidase. In saline-treated control mice, distribution volume (in ml) differed between tracers (P < 0.05; ANOVA) in the following order: Dex40 (0.97 ± 0.04) > Dex70 (0.90 ± 0.04) > Dex500 (0.81 ± 0.10) > plasma (0.71 ± 0.02), resulting in an inaccessible vascular volume, i.e., compared with the distribution volume of Dex40, of 0.03 ± 0.01, 0.15 ± 0.04, and 0.31 ± 0.05 ml for Dex70, Dex500, and plasma, respectively. In hyaluronidase-treated mice, Dex70 and Dex40 volumes were not different from each other, and inaccessible vascular volumes for Dex500 (0.03 ± 0.03) and plasma (0.14 ± 0.05) were smaller (P < 0.05) than those in control animals. Clearance of Dex70 and Dex500 from the circulation was enhanced (P < 0.05) in hyaluronidase-treated vs. control mice. These results indicate that the glycocalyx contributes to size-dependent differences in whole body vascular distribution of plasma solutes in mice. Whole body vascular volume measurements based on the

  18. Effect of acute hyaluronidase treatment of the glycocalyx on tracer-based whole body vascular volume estimates in mice.

    PubMed

    VanTeeffelen, Jurgen W G E; Brands, Judith; Janssen, Ben J A; Vink, Hans

    2013-05-01

    The endothelial glycocalyx forms a hyaluronan-containing interface between the flowing blood and the endothelium throughout the body. By comparing the systemic distribution of a small glycocalyx-accessible tracer vs. a large circulating plasma tracer, the size-selective barrier properties of the glycocalyx have recently been utilized to estimate whole body glycocalyx volumes in humans and animals, but a comprehensive validation of this approach has been lacking at the moment. In the present study, we compared, in anesthetized, ventilated C57Bl/6 mice, the whole body distribution of small (40 kDa) dextrans (Texas Red labeled; Dex40) vs. that of intermediate (70 kDa) and large (500 kDa) dextrans (both FITC labeled; Dex70 and Dex500, respectively) using tracer dilution and vs. that of circulating plasma, as derived from the dilution of fluorescein-labeled red blood cells and large-vessel hematocrit. The contribution of the glycocalyx was evaluated by intravenous infusion of a bolus of the enzyme hyaluronidase. In saline-treated control mice, distribution volume (in ml) differed between tracers (P < 0.05; ANOVA) in the following order: Dex40 (0.97 ± 0.04) > Dex70 (0.90 ± 0.04) > Dex500 (0.81 ± 0.10) > plasma (0.71 ± 0.02), resulting in an inaccessible vascular volume, i.e., compared with the distribution volume of Dex40, of 0.03 ± 0.01, 0.15 ± 0.04, and 0.31 ± 0.05 ml for Dex70, Dex500, and plasma, respectively. In hyaluronidase-treated mice, Dex70 and Dex40 volumes were not different from each other, and inaccessible vascular volumes for Dex500 (0.03 ± 0.03) and plasma (0.14 ± 0.05) were smaller (P < 0.05) than those in control animals. Clearance of Dex70 and Dex500 from the circulation was enhanced (P < 0.05) in hyaluronidase-treated vs. control mice. These results indicate that the glycocalyx contributes to size-dependent differences in whole body vascular distribution of plasma solutes in mice. Whole body vascular volume measurements based on the

  19. High-volume plasma exchange in a patient with acute liver failure due to non-exertional heat stroke in a sauna.

    PubMed

    Chen, Kuan-Jung; Chen, Tso-Hsiao; Sue, Yuh-Mou; Chen, Tzay-Jinn; Cheng, Chung-Yi

    2014-10-01

    Heat stroke is a life-threatening condition characterized by an increased core body temperature (over 40°C) and a systemic inflammatory response, which may lead to a syndrome of multiple organ dysfunction. Heat stroke may be due to either strenuous exercise or non-exercise-induced exposure to a high environmental temperature. Current management of heat stroke is mostly supportive, with an emphasis on cooling the core body temperature and preventing the development of multiple organ dysfunction. Prognosis of heat stroke depends on the severity of organ involvement. Here, we report a rare case of non-exercise-induced heat stroke in a 73-year-old male patient who was suffering from acute liver failure after prolonged exposure in a hot sauna room. We successfully managed this patient by administering high-volume plasma exchange, and the patient recovered completely after treatment.

  20. Orally active iron chelators in the treatment of iron overload.

    PubMed

    Olivieri, N F

    1996-03-01

    Data from several trials have provided evidence for the efficacy of deferiprone in the treatment of iron overload in thalassemia major. Deferiprone has now been shown to induce sustained decreases in tissue iron to concentrations that are associated with survival free of the complications of iron overload in deferoxamine-treated patients. Despite this evidence of efficacy, the risk of agranulocytosis mandates a careful evaluation of the risk of this drug in patients willing and able to use deferoxamine. The incidence of agranulocytosis associated with deferiprone is under study in a prospective multicenter trial in Canada, Italy, and the United States, under corporate sponsorship by Apotex Research in Canada. The results of this study should determine the risk associated with the use of this agent and may provide the data required for a US Food and Drug Administration decision regarding licensing of this agent for the treatment of iron overload, a goal supported by investigators worldwide.

  1. Salvaging transient data with overloads and zero offsets

    SciTech Connect

    Smallwood, D.O.; Cap, J.S.

    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.

  2. Is the circulating plasma volume sufficiently maintained? Fluid management of an aneurysmal subarachnoid hemorrhage in the acute phase.

    PubMed

    Mori, Tatsuro; Katayama, Yoichi; Igarashi, Takahiro; Moro, Nobuhiro; Kojima, Jun; Hirayama, Teruyasu

    2012-12-01

    Cerebral vasospasm is a well-known cause of mortality and morbidity following aneurysmal subarachnoid hemorrhage (SAH). Prevention of symptomatic cerebral vasospasm is the basic management after SAH. Numerous pharmaceutical therapies and endovascular treatments are available against cerebral vasospasm, but none of them have so far proven to improve the outcome. We have focused on maintaining the circulation volume in order to prevent cerebral vasospasm. But to maintain the central venous pressure, huge infusion volume was required, and hyponatremia was frequently observed due to natriuresis and osmotic diuresis. Excessive natriuresis and diuresis cannot be managed through sodium and water replacement, since sodium replacement induces further natriuresis and diuresis (desalination), and water replacement induces hyponatremia. We therefore administered fludrocortisone and hydrocortisone to inhibit excessive natriuresis and diuresis. The efficacy of sodium reabsorption therapy is extremely high to maintain the circulation volume that might have a therapeutic effect to prevent cerebral vasospasm. In this article, we review our institution's experience regarding the management of patients with aneurysmal SAH and also discuss the importance of water and sodium balance when managing such patients.

  3. Intradialytic hypertension during chronic haemodialysis and subclinical fluid overload assessed by bioimpedance spectroscopy

    PubMed Central

    Sebastian, Sajith; Filmalter, Christelle; Harvey, Justin; Chothia, Mogamat-Yazied

    2016-01-01

    Background Intradialytic hypertension (IDH) increases morbidity and mortality. The prevalence in South Africa is unknown. The pathogenesis is unclear, but it has been suggested that IDH may be due to subclinical fluid overload. The objective of this study was to determine the prevalence of IDH and to evaluate its association with fluid overload using bioimpedance spectroscopy (BIS). Methods A cross-sectional study involving 190 chronic haemodialysis patients in the Western Cape province of South Africa was conducted between January 2013 and May 2014. IDH was defined as a >10 mmHg increase in systolic blood pressure in at least four of six prior consecutive haemodialysis sessions. Results The prevalence of IDH was 28.4% (n = 54). There was a trend towards pre-dialysis overhydration in the IDH group when compared with controls {2.6 L [95% confidence interval (CI) 1.7–3.4] versus 1.8 L [95% CI 1.4–2.1], respectively; P = 0.06} as measured by BIS, but no difference in mean ultrafiltration (UF) volume (2.4 versus 2.6 L; P = 0.30). A trend towards greater use of antihypertensive drugs was noted in the IDH group [2.5 drugs (95% CI 2.15–2.87) versus 2.1 (95% CI 1.82–2.30); P = 0.05]. More participants in the IDH group received calcium channel blockers (54 versus 36; P = 0.03). Conclusions The prevalence of IDH in our treatment centres is much higher than previously reported. Subclinical fluid overload may be a major contributing factor to the mechanism of this condition. The use of BIS identifies patients who may benefit from additional UF. PMID:27478611

  4. The heart communicates with the kidney exclusively through the guanylyl cyclase-A receptor: acute handling of sodium and water in response to volume expansion.

    PubMed Central

    Kishimoto, I; Dubois, S K; Garbers, D L

    1996-01-01

    Disruption of guanylyl cyclase-A (GC-A) results in mice displaying an elevated blood pressure, which is not altered by high or low dietary salt. However, atrial natriuretic peptide (ANP), a proposed ligand for GC-A, has been suggested as critical for the maintenance of normal blood pressure during high salt intake. In this report, we show that infusion of ANP results in substantial natriuresis and diuresis in wild-type mice but fails to cause significant changes in sodium excretion or urine output in GC-A-deficient mice. ANP, therefore, appears to signal through GC-A in the kidney. Other natriuretic/diuretic factors could be released from the heart. Therefore, acute volume expansion was used as a means to cause release of granules from the atrium of the heart. That granule release occurred was confirmed by measurements of plasma ANP concentrations, which were markedly elevated in both wild-type and GC-A-null mice. After volume expansion, urine output as well as urinary sodium and cyclic GMP excretion increased rapidly and markedly in wild-type mice, but the rapid increases were abolished in GC-A-deficient animals. These results strongly suggest that natriuretic/diuretic factors released from the heart function exclusively through GC-A. PMID:8650246

  5. Comparison of epicardial fat volume by computed tomography in black versus white patients with acute chest pain.

    PubMed

    Apfaltrer, Paul; Schindler, Andreas; Schoepf, U Joseph; Nance, John W; Tricarico, Francesco; Ebersberger, Ullrich; McQuiston, Andrew D; Meyer, Mathias; Henzler, Thomas; Schoenberg, Stefan O; Bamberg, Fabian; Vliegenthart, Rozemarijn

    2014-02-01

    Disparities in the risk of coronary artery disease (CAD) between races may be influenced by differences in the thoracic adipose tissue. We compared computed tomography (CT)-derived volumes of epicardial adipose tissue (EAT), mediastinal adipose tissue (MAT), and pericoronary fat thickness (PFT) and correlations with CAD between black and white patients. This institutional review board-approved Health Insurance Portability and Accountability Act-compliant study included 372 age- and gender-matched black versus white patients (186 black, 54 ± 11 years, 50% men; 186 white, 54 ± 11 years, 50% men) who underwent CT for chest pain evaluation. EAT, MAT, and PFT were measured. The amount of coronary calcium was quantified as calcium score. CAD was defined as ≥50% coronary artery narrowing. EAT and MAT volumes were significantly lower in black than white patients (59 [twenty-fifth to seventy-fifth percentile 39 to 84] vs 97 [67 to 132] cm(3) and 44 [27 to 77] vs 87 [52 to 157] cm(3), for both p <0.001). Mean PFT in black patients was slightly lower than white patients (17.2 ± 3.2 vs 18.1 ± 3.4 mm, p <0.01). The relation between race and extent of adipose tissue remained significant after adjustment for cardiovascular risk factors. Significant correlations were observed between EAT and MAT volumes and calcium score in black and white patients (r = 0.19 to 0.26, p <0.01). For both races, the level of thoracic fat measurements was higher in present versus absent coronary calcification. A greater amount of thoracic fat was found with obstructive CAD only in white patients. In conclusion, CT-derived measurements of thoracic fat differ between symptomatic black and white patients, suggesting a differential relation between thoracic adipose tissue and CAD pathophysiology by race.

  6. Effects of experimental cardiac volume loading on left atrial phasic function in healthy dogs.

    PubMed

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

    2016-09-01

    OBJECTIVE To elucidate the relationship between acute volume overload and left atrial phasic function in healthy dogs. ANIMALS 6 healthy Beagles. PROCEDURES Dogs were anesthetized. A Swan-Ganz catheter was placed to measure mean pulmonary capillary wedge pressure (PCWP). Cardiac preload was increased by IV infusion with lactated Ringer solution at 150 mL/kg/h for 90 minutes. Transthoracic echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after volume loading began. At each echocardiographic assessment point, apical 4-chamber images were recorded and analyzed to derive time-left atrial area curves. Left atrial total (for reservoir function), passive (for conduit function), and active (for booster-pump function) fractional area changes were calculated from the curves. RESULTS Volume overload resulted in a significant increase from baseline in PCWP from 15 to 90 minutes after volume loading began. All fractional area changes at 15 to 90 minutes were significantly increased from baseline. In multiple regression analysis, quadratic regression models were better fitted to the relationships between PCWP and each of the total and active fractional area changes than were linear regression models. A linear regression model was better fitted to the relationship between PCWP and passive fractional area change. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that left atrial phasic function assessed on the basis of left atrial phasic areas was enhanced during experimental cardiac volume loading in healthy dogs. The effect of volume load should be considered when evaluating left atrial phasic function by indices derived from left atrial phasic sizes. PMID:27580106

  7. Loss of COMMD1 and copper overload disrupt zinc homeostasis and influence an autism-associated pathway at glutamatergic synapses.

    PubMed

    Baecker, Tanja; Mangus, Katharina; Pfaender, Stefanie; Chhabra, Resham; Boeckers, Tobias M; Grabrucker, Andreas M

    2014-08-01

    Recent studies suggest that synaptic pathology in autism spectrum disorder (ASD) might be caused by the disruption of a signaling pathway at excitatory glutamatergic synapses, which can be influenced by environmental factors. Some factors, such as prenatal zinc deficiency, dysfunction of metallothioneins as well as deletion of COMMD1, all affect brain metal-ion homeostasis and have been associated with ASD. Given that COMMD1 regulates copper levels and that copper and zinc have antagonistic properties, here, we followed the idea that copper overload might induce a local zinc deficiency affecting key players of a putative ASD pathway such as ProSAP/Shank proteins as reported before. Our results show that increased copper levels indeed interfere with intracellular zinc concentrations and affect synaptic ProSAP/Shank levels, which similarly are altered by manipulation of copper and zinc levels through overexpression and knockdown of COMMD1. In line with this, acute and prenatal copper overload lead to local zinc deficiencies in mice. Pups exposed to prenatal copper overload furthermore show a reduction in ProSAP/Shank protein levels in the brain as well as a decreased NMDAR subunit 1 concentration. Thus, it might be likely that brain metal ion status influences a distinct pathway in excitatory synapses associated with genetic forms of ASD.

  8. A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure

    PubMed Central

    Chang, Suchi; Shi, Jindong; Fu, Cuiping; Wu, Xu; Li, Shanqun

    2016-01-01

    Background COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. Objective We evaluated pressure-regulated volume control (PRVC) ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. Patients and methods Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation – volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2–4 hours and 48 hours. Results Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2), and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2) levels. The pH and PaCO2 levels at 2–4 hours were lower and higher, respectively, in the test group than those in the control group (P<0.05 for both); after 48 hours, blood gas analyses showed no statistical difference in any marker (P>0.05). Vital signs during 2–4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05). The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2–4 hours and 48 hours was significantly lower than that in the control group (P<0.05), while other variables were not significantly different between groups (P>0.05). Conclusion Among elderly COPD patients with respiratory failure, application of PRVC resulted in rapid improvement in arterial blood gas analyses while maintaining

  9. Digestive cells from Mytilus galloprovincialis show a partial regulatory volume decrease following acute hypotonic stress through mechanisms involving inorganic ions.

    PubMed

    Torre, Agata; Trischitta, Francesca; Corsaro, Carmelo; Mallamace, Domenico; Faggio, Caterina

    2013-08-01

    The response of isolated digestive cells of the digestive gland of Mytilus galloprovincialis to hypotonic shock was studied using videometric methods. The isolated cells exposed to a rapid change (from 1100 to 800 mosmol kg(-1) ) of the bathing solution osmolality swelled but thereafter underwent a regulatory volume decrease (RVD), tending to recover the original size. When the hypotonic stress was applied in the presence of quinine and glibenclamide, known inhibitors of swelling activated ion channels, the cells did not exhibit an RVD response; in addition, they showed a larger increase in size in respect to control cells. These observations suggest that the digestive cells of the digestive gland have the machinery to cope with the hyposmotic shock allowing them to exhibit a small but significant RVD preventing an excessive increase in cell size. The pharmacological treatment of digestive cells during the RVD experiments suggests that cell volume is regulated by K(+) and Cl(-) efflux followed by an obliged water efflux from the cell. The involvement of organic osmolytes such as taurine and betaine seems to be excluded by NMR measurement on digestive cells.

  10. Acute mannitol and saline volume expansion in the rat: effect on transepithelial potential difference in proximal tubules.

    PubMed

    Sugo, E; Györy, A Z

    1990-01-01

    1. Transepithelial potential difference (PDte) of proximal tubules was measured in rats under control conditions (C), and mannitol-saline and saline extracellular fluid volume expansion (MVE, SVE, respectively) under conditions of normal net lumen to basal sodium transport. 2. PDte was measured in kidneys bathed with Hartmann's solution or covered with mineral oil under both volume-expanded conditions together with their controls. 3. PDte was significantly lower in kidneys bathed with Hartmann's solution than those covered with oil. 4. In MVE rats, with mineral oil covering the kidneys, PDte (expressed as mean and s.e.m.) was for the control 2.20 +/- 0.05 (n = 45) mV and MVE 1.97 +/- 0.04 (n = 36) mV, lumen positive, a significant reduction of 10% (P less than 0.001). In SVE rats, with mineral oil covering the kidneys, PDte was for C = 2.42 +/- 0.05 (n = 74) mV and SVE = 1.93 +/- 0.03 (n = 67) mV, a significant reduction (P less than 0.001) of 20%. 5. According to thermodynamic considerations, neither of these changes is sufficient to explain the 50% inhibition of Na transport measured previously during MVE and SVE with autologous tubular fluid. The present results offer further evidence supporting the idea that the inhibition of Na transport during MVE and SVE is largely due to inhibition of the active Na transporting step.

  11. sup 1 H NMR study of renal trimethylamine responses to dehydration and acute volume loading in man

    SciTech Connect

    Avison, M.J.; Rothman, D.L.; Nixon, T.W.; Long, W.S.; Siegel, N.J. )

    1991-07-15

    The authors have used volume-localized {sup 1}H NMR spectroscopy to detect and measure changes in medullary trimethylamines (TMAs) in the human kidney in vivo. Localized water-suppressed {sup 1}H spectra were collected from a volume of interest located within the renal medulla by using a stimulated echo-based localization scheme. The principal resonances in the medullary {sup 1}H spectrum were residual water, lipid, and TMAs. The TMA line width was 7-15 Hz before filtering, and the signal-to-noise ratio was 40:1. In four normal volunteers, 15 hr of dehydration led to a significant increase in urine ismolality and decrease in body weight and an increase in medullary TMAs. A subsequent water load caused a transient water diuresis, a return to euvolemic body weight, and a significant reduction in medullary TMAs within 4 hr. These results suggest that TMAs may play an osmoregulatory role in the medulla of the normal human kidney.

  12. Nondestructive test determines overload destruction characteristics of current limiter fuses

    NASA Technical Reports Server (NTRS)

    Swartz, G. A.

    1968-01-01

    Nondestructive test predicts the time required for current limiters to blow /open the circuit/ when subjected to a given overload. The test method is based on an empirical relationship between the voltage rise across a current limiter for a fixed time interval and the time to blow.

  13. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  14. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  15. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  16. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  17. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  18. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  19. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  20. 30 CFR 56.12003 - Trailing cable overload protection.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Trailing cable overload protection. 56.12003 Section 56.12003 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  1. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  2. 30 CFR 56.12001 - Circuit overload protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuit overload protection. 56.12001 Section 56.12001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES...

  3. Shift Work, Role Overload, and the Transition to Parenthood

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  4. Information Overload and Viral Marketing: Countermeasures and Strategies

    NASA Astrophysics Data System (ADS)

    Cheng, Jiesi; Sun, Aaron; Zeng, Daniel

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

  5. Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

    PubMed Central

    2012-01-01

    Introduction Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality. Methods We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality. Results We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT. Conclusions Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments. PMID:23075459

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

    PubMed

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

    2008-02-01

    Fifteen healthy men performed a 5-week training program comprising four sets of seven unilateral, coupled concentric-eccentric knee extensions 2-3 times weekly. While eight men were assigned to training using a weight stack (WS) machine, seven men trained using a flywheel (FW) device, which inherently provides variable resistance and allows for eccentric overload. The design of these apparatuses ensured similar knee extensor muscle use and range of motion. Before and after training, maximal isometric force (MVC) was measured in tasks non-specific to the training modes. Volume of all individual quadriceps muscles was determined by magnetic resonance imaging. Performance across the 12 exercise sessions was measured using the inherent features of the devices. Whereas MVC increased (P < 0.05) at all angles measured in FW, such a change was less consistent in WS. There was a marked increase (P < 0.05) in task-specific performance (i.e., load lifted) in WS. Average work showed a non-significant 8.7% increase in FW. Quadriceps muscle volume increased (P < 0.025) in both groups after training. Although the more than twofold greater hypertrophy evident in FW (6.2%) was not statistically greater than that shown in WS (3.0%), all four individual quadriceps muscles of FW showed increased (P < 0.025) volume whereas in WS only m. rectus femoris was increased (P < 0.025). Collectively the results of this study suggest more robust muscular adaptations following flywheel than weight stack resistance exercise supporting the idea that eccentric overload offers a potent stimuli essential to optimize the benefits of resistance exercise. PMID:17926060

  7. Human albumin solution for patients with cirrhosis and acute on chronic liver failure: Beyond simple volume expansion

    PubMed Central

    Valerio, Christopher; Theocharidou, Eleni; Davenport, Andrew; Agarwal, Banwari

    2016-01-01

    To provide an overview of the properties of human serum albumin (HSA), and to review the evidence for the use of human albumin solution (HAS) in critical illness, sepsis and cirrhosis. A MEDLINE search was performed using the terms “human albumin”, “critical illness”, “sepsis” and “cirrhosis”. The references of retrieved articles were reviewed manually. Studies published between 1980 and 2014 were selected based on quality criteria. Data extraction was performed by all authors. HSA is the main plasma protein contributing greatly to its oncotic pressure. HSA demonstrates important binding properties for endogenous and exogenous toxins, drugs and drug metabolites that account for its anti-oxidant and anti-inflammatory properties. In disease states, hypoalbuminaemia is secondary to decreased HSA production, increased loss or transcapillary leakage into the interstitial space. HSA function can be also altered in disease with reduced albumin binding capacity and increased production of modified isoforms. HAS has been used as volume expander in critical illness, but received criticism due to cost and concerns regarding safety. More recent studies confirmed the safety of HAS, but failed to show any survival benefit compared to the cheaper crystalloid fluids, therefore limiting its use. On the contrary, in cirrhosis there is robust data to support the efficacy of HAS for the prevention of circulatory dysfunction post-large volume paracentesis and in the context of spontaneous bacterial peritonitis, and for the treatment of hepato-renal syndrome and hypervolaemic hyponatraemia. It is likely that not only the oncotic properties of HAS are beneficial in cirrhosis, but also its functional properties, as HAS replaces the dysfunctional HSA. The role of HAS as the resuscitation fluid of choice in critically ill patients with cirrhosis, beyond the established indications for HAS use, should be addressed in future studies. PMID:26981172

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

    PubMed

    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

  9. Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-07

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

  12. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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 2013-07-01 2013-07-01 false Electric equipment and circuits; overload...

  13. Quantification of diffusion-weighted images (DWI) and apparent diffusion coefficient maps (ADC) in the detection of acute stroke

    NASA Astrophysics Data System (ADS)

    Tulipano, P. Karina; Millar, William S.; Imielinska, Celina; Liu, Xin; Rosiene, Joel; D'Ambrosio, Anthony L.

    2006-03-01

    Magnetic resonance (MR) imaging is an imaging modality that is used in the management and diagnosis of acute stroke. Common MR imaging techniques such as diffusion weighted imaging (DWI) and apparent diffusion coefficient maps (ADC) are used routinely in the diagnosis of acute infarcts. However, advances in radiology information systems and imaging protocols have led to an overload of image information that can be difficult to manage and time consuming. Automated techniques to assist in the identification of acute ischemic stroke can prove beneficial to 1) the physician by providing a mechanism for early detection and 2) the patient by providing effective stroke therapy at an early stage. We have processed DW images and ADC maps using a novel automated Relative Difference Map (RDM) method that was tailored to the identification and delineation of the stroke region. Results indicate that the technique can delineate regions of acute infarctions on DW images and ADC maps. A formal evaluation of the RDM algorithm was performed by comparing accuracy measurements between 1) expert generated ground truths with the RDM delineated DWI infarcts and 2) RDM delineated DWI infarcts with RDM delineated ADC infarcts. The accuracy measurements indicate that the RDM delineated DWI infarcts are comparable to the expert generated ground truths. The true positive volume fraction value (TPVF), between RDM delineated DWI and ADC infarcts, is nonzero for all cases with an acute infarct while the value for non-acute cases remains zero.

  14. Acute Myosin Heavy Chain Isoform mRNA Expression in Response to Two Resistance Exercise Intensities With Equal Volume Load in Resistance-Trained Men.

    PubMed

    Schwarz, Neil A; Spillane, Mike B; McKinley, Sarah K; Andre, Thomas L; Gann, Joshua J; Willoughby, Darryn S

    2015-08-01

    The purpose of this study was to determine if resistance exercise intensity, in the context of equal volume load, differentially affected myosin heavy chain (MHC) isoform messenger RNA (mRNA) expression in resistance-trained men. In a crossover, uniform-balanced design, 10 male participants (23.7 ± 2.8 years, 178.8 ± 5.9 cm, 85.9 ± 9.2 kg) completed 2 lower-body resistance exercise sessions of different intensities with equal volume load. For the higher-intensity exercise session, participants performed 5 sets of 6 repetitions at 80% of 1 repetition maximum (1RM). For the lower-intensity exercise session, participants performed 3 sets of 16 repetitions at 50% of 1RM. Muscle samples from the vastus lateralis were acquired before exercise (PRE), 45 minutes postexercise (45MINPE), 3 hours postexercise (3HRPE), 24 hours postexercise (24HRPE), and 48 hours postexercise (48HRPE). Statistical analyses of mRNA expression were performed using separate 2 × 5 two-way repeated-measures analyses of variance for each criterion variable (p ≤ 0.05). There were no statistically significant interactions between intensity and time. Likewise, there were no significant differences between exercise intensity in MHC expression. Expression of mRNA for all MHC isoforms decreased at all postexercise time points, except 3HRPE (p = 0.051), compared with PRE following both exercise bouts (p ≤ 0.05). The results of this study found no difference in mRNA expression of MHC isoforms as a function of resistance exercise intensity. In addition, in contrast to results found in previous studies of untrained men, MHC mRNA expression seems to decrease in response to acute resistance exercise in previously resistance-trained men.

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

    NASA Astrophysics Data System (ADS)

    Miyagi, Katsunori; Oe, Etsuo; Yamagata, Naoki; Miyahara, Hideyuki

    A sudden capacity increase in demand during the summer peak, or in contingencies such as malfunctioning transformers, may cause overload for normal transformers. In this paper, on the basis of examples of overloaded transformer operation in distributing substations, thermal aging testing in oil was carried out under various overload patterns, such as short time overload and long time overload, but with the winding insulation paper's life loss kept constant. From the results, various characteristics such as mean degree of polymerization and productions of furfural and (CO2+CO), and their effects on the life loss of the insulation paper were obtained.

  16. Pumpless extracorporeal removal of carbon dioxide combined with ventilation using low tidal volume and high positive end-expiratory pressure in a patient with severe acute respiratory distress syndrome.

    PubMed

    Bein, T; Zimmermann, M; Hergeth, K; Ramming, M; Rupprecht, L; Schlitt, H J; Slutsky, A S

    2009-02-01

    The effects of the combination of a 'lowest' lung ventilation with extracorporeal elimination of carbon dioxide by interventional lung assist are described in a patient presenting with severe acute respiratory distress syndrome due to fulminant pneumonia. Reducing tidal volume to 3 ml.kg(-1) together with interventional lung assist resulted in a decrease in severe hypercapnia without alveolar collapse or hypoxaemia but with a decrease in serum levels of interleukin-6. This approach was applied for 12 days with recovery of the patient, without complications. Extracorporeal removal of carbon dioxide by interventional lung assist may be a useful tool to enable 'ultraprotective' ventilation in severe acute respiratory distress syndrome.

  17. Association Between Contrast Media Volume-Glomerular Filtration Rate Ratio and Contrast-Induced Acute Kidney Injury After Primary Percutaneous Coronary Intervention.

    PubMed

    Celik, Omer; Ozturk, Derya; Akin, Fatih; Ayca, Burak; Yalcın, Ahmet Arif; Erturk, Mehmet; Bıyık, Ismail; Ayaz, Ahmet; Akturk, Ibrahim Faruk; Enhos, Asım; Aslan, Serkan

    2015-07-01

    We hypothesized that contrast media volume-estimated glomerular filtration rate (CV-e-GFR) ratio may be a predictor of contrast media-induced acute kidney injury (CI-AKI). We investigated the associations between CV-e-GFR ratio and CI-AKI in 597 patients undergoing primary percutaneous coronary intervention (pPCI). An absolute ≥0.3 mg/dL increase in serum creatinine compared with baseline levels within 48 hours after the procedure was considered as CI-AKI; 78 (13.1%) of the 597 patients experienced CI-AKI. The amount of contrast during procedure was higher in the CI-AKI group than in those without CI-AKI (153 vs 135 mL, P = .003). The CV-e-GFR ratio was significantly higher in patients with CI-AKI than without (2.3 vs 1.5, P < .001). In multivariate analysis, independent predictors of CI-AKI were low left ventricular ejection fraction (P = .018, odds ratio [OR] = 0.966), e-GFR <60 mL/min (P = .012, OR = 2.558), and CV-e-GFR >2 (P < .001, OR = 5.917). In conclusion, CV-e-GFR ratio is significantly associated with CI-AKI after pPCI.

  18. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome.

    PubMed

    Boker, Abdulaziz; Graham, M Ruth; Walley, Keith R; McManus, Bruce M; Girling, Linda G; Walker, Elizabeth; Lefevre, Gerald R; Mutch, W Alan C

    2002-02-15

    We compared biologically variable ventilation (V (bv); n = 9) with control mode ventilation (V (c); n = 8) at low tidal volume (VT)--initial 6 ml/kg--in a porcine model of acute respiratory distress syndrome (ARDS). Hemodynamics, respiratory gases, airway pressures, and VT data were measured. Static P-V curves were generated at 5 h. Interleukin (IL)-8 and IL-10 were measured in serum and tracheal aspirate. By 5 h, higher Pa(O(2)) (173 +/- 30 mm Hg versus 119 +/- 23 mm Hg; mean +/- SD; p < 0.0001 group x time interaction [G x T]), lower shunt fraction (6 +/- 1% versus 9 +/- 3%; p = 0.0026, G x T) at lower peak airway pressure (21 +/- 2 versus 24 +/- 1 cm H(2)O; p = 0.0342; G x T) occurred with V (bv). IL-8 concentrations in tracheal aspirate and wet:dry weight ratios were inversely related; p = 0.011. With V (c), IL-8 concentrations were 3.75-fold greater at wet:dry weight ratio of 10. IL-10 concentrations did not differ between groups. In both groups, ventilation was on the linear portion of the P-V curve. With V (bv), VT variability demonstrated an inverse power law indicating fractal behavior. In this model of ARDS, V (bv) improved Pa(O(2)) at lower peak airway pressure and IL-8 levels compared with V (c).

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

    PubMed

    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.

  20. Oleanolic acid alleviated pressure overload-induced cardiac remodeling.

    PubMed

    Liao, Hai-Han; Zhang, Nan; Feng, Hong; Zhang, Ning; Ma, Zhen-Guo; Yang, Zheng; Yuan, Yuan; Bian, Zhou-Yan; Tang, Qi-Zhu

    2015-11-01

    Previous study has demonstrated that oleanolic acid (OA) possessing the anti-inflammatory and anti-oxidant properties blunted high-glucose-induced diabetic cardiomyopathy and ameliorated experimental autoimmune myocarditis in mice. However, little is known about its effects on pressure overload-induced cardiac remodeling. Herein, we investigated the effect of OA on cardiac remodeling and underlying mechanism. Mice, subjected to aortic banding (AB), were randomly assigned into control group and experimental group. OA premixed in diets was administered to mice after 3 days of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed after 8 weeks' treatment of OA. Histologic examination and molecular analyses were used to assess cardiac hypertrophy and tissue fibrosis. In addition, the inhibitory effects of OA on H9c2 cardiomyocytes and cardiac primary fibroblast responded to the stimulation of AngII were also investigated. OA ameliorated the systolic and diastolic dysfunction induced by pressure overload evidenced by echocardiography and catheter-based measurements. OA also decreased the mRNA expression of cardiac hypertrophy and fibrosis markers evidenced by RT-PCR. It has been shown in our study that pressure overload activated the phosphorylations of Akt, mTOR, p70s6k, S6, GSK3β, and FoxO3a, and treatment of OA attenuated the phosphorylation of these proteins. In addition, hypertrophy of cardiomyocytes and fibrosis markers induced by AngII was inhibited by OA in vitro. Our findings uncover that OA suppressed AB-induced cardiac hypertrophy, partly by inhibiting the activity of Akt/mTOR pathway, and suggest that treatment of OA may have a benefit on retarding the progress of cardiac remodeling under long terms of pressure overload. PMID:26215454

  1. Natural history and information overload: The case of Linnaeus.

    PubMed

    Müller-Wille, Staffan; Charmantier, Isabelle

    2012-03-01

    Natural History can be seen as a discipline paradigmatically engaged in 'data-driven research.' Historians of early modern science have begun to emphasize its crucial role in the Scientific Revolution, and some observers of present day genomics see it as engaged in a return to natural history practices. A key concept that was developed to understand the dynamics of early modern natural history is that of 'information overload.' Taxonomic systems, rules of nomenclature, and technical terminologies were developed in botany and zoology to catch up with the ever increasing amount of information on hitherto unknown plant and animal species. In our contribution, we want to expand on this concept. After all, the same people who complain about information overload are usually the ones who contribute to it most significantly. In order to understand this complex relationship, we will turn to the annotation practices of the Swedish naturalist Carl Linnaeus (1707-1778). The very tools that Linnaeus developed to contain and reduce information overload, as we aim to demonstrate, facilitated a veritable information explosion that led to the emergence of a new research object in botany: the so-called 'natural' system.

  2. Influence, information overload, and information technology in health care.

    PubMed

    Rebitzer, James B; Rege, Mari; Shepard, Christopher

    2008-01-01

    We investigate whether information technology (IT) can help physicians more efficiently acquire new knowledge in a clinical environment characterized by information overload. We combine analysis of data from a randomized trial with a theoretical model of the influence that IT has on the acquisition of new medical knowledge. Although the theoretical framework we develop is conventionally microeconomic, the model highlights the non-market and non-pecuniary influence activities that have been emphasized in the sociological literature on technology diffusion. We report three findings. First, empirical evidence and theoretical reasoning suggests that computer-based decision support will speed the diffusion of new medical knowledge when physicians are coping with information overload. Second, spillover effects will likely lead to "underinvestment" in this decision support technology. Third, alternative financing strategies common to new IT, such as the use of marketing dollars to pay for the decision support systems, may lead to undesirable outcomes if physician information overload is sufficiently severe and if there is significant ambiguity in how best to respond to the clinical issues identified by the computer. This is the first paper to analyze empirically and theoretically how computer-based decision support influences the acquisition of new knowledge by physicians. PMID:19548513

  3. Pathology of dietary carbonyl iron overload in rats.

    PubMed

    Park, C H; Bacon, B R; Brittenham, G M; Tavill, A S

    1987-11-01

    Serial light microscopic and ultrastructural studies were performed in rats with experimental iron overload produced by dietary supplementation with carbonyl (elemental) iron over a 12-month period. Hepatic iron increased rapidly to concentrations approximately 40 to 90 times those of control rats by 3 months. Within the liver, iron deposition was initially confined to periportal (zone 1) hepatocytes but subsequently extended to midzonal (zone 2) and centrilobular (zone 3) hepatocytes. Reticuloendothelial cell deposits of iron increased gradually and became prominent after 3 months. At this time, morphologic evidence of hepatocellular injury was mild and subtle with occasional foci of spotty necrosis and ultrastructural subcellular organelle damage. By 8 months, iron deposition was massive. Portal areas were enlarged with collections of iron-loaded macrophages and increased collagenous tissue. This portal fibrous tissue extended between periportal (zone 1) hepatocytes at sites of maximal iron deposition and around iron-loaded Kupffer cells and macrophages. At 12 months, the periportal (zone 1) fibrosis was more pronounced. These serial morphologic studies are the first to demonstrate the production of hepatic fibrosis by chronic dietary iron overload. This experimental model may reproduce important components of the pathophysiologic sequence of chronic liver damage seen in iron overload states in humans.

  4. Natural history and information overload: The case of Linnaeus

    PubMed Central

    Müller-Wille, Staffan; Charmantier, Isabelle

    2012-01-01

    Natural History can be seen as a discipline paradigmatically engaged in ‘data-driven research.’ Historians of early modern science have begun to emphasize its crucial role in the Scientific Revolution, and some observers of present day genomics see it as engaged in a return to natural history practices. A key concept that was developed to understand the dynamics of early modern natural history is that of ‘information overload.’ Taxonomic systems, rules of nomenclature, and technical terminologies were developed in botany and zoology to catch up with the ever increasing amount of information on hitherto unknown plant and animal species. In our contribution, we want to expand on this concept. After all, the same people who complain about information overload are usually the ones who contribute to it most significantly. In order to understand this complex relationship, we will turn to the annotation practices of the Swedish naturalist Carl Linnaeus (1707–1778). The very tools that Linnaeus developed to contain and reduce information overload, as we aim to demonstrate, facilitated a veritable information explosion that led to the emergence of a new research object in botany: the so-called ‘natural’ system. PMID:22326068

  5. Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload.

    PubMed Central

    Gross, J B; Myers, B M; Kost, L J; Kuntz, S M; LaRusso, N F

    1989-01-01

    We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload. Images PMID:2910913

  6. Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload

    SciTech Connect

    Gross, J.B. Jr.; Myers, B.M.; Kost, L.J.; Kuntz, S.M.; LaRusso, N.F.

    1989-01-01

    We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload.

  7. No fluid overload in male ultra-runners during a 100 km ultra-run.

    PubMed

    Knechtle, Beat; Senn, Oliver; Imoberdorf, Reinhard; Joleska, Irena; Wirth, Andrea; Knechtle, Patrizia; Rosemann, Thomas

    2011-01-01

    We investigated the change in body composition and hydration status in 27 male ultra-runners during a 100 km ultra-run. The athletes drank fluids ad libitum during the run; intake of calories, fluids, and electrolytes during performance were determined. Body mass decreased by 1.9 kg, haematocrit decreased, plasma [Na(+)] remained unchanged, and urinary specific gravity and plasma volume increased. Fluid intake was 0.52 (0.18) L/h and was related to running speed (r = 0.50; p = 0.0081). Δ body mass was associated with total fluid intake during the race (r = 0.49, p = 0.0095). Sodium intake amounted to 425 (478) mg/h and potassium intake to 140 (179) mg/h. Sodium and potassium intake were not related to either postrace concentration or change in plasma concentration. Sodium intake, however, was related to Δ urinary sodium concentration (r = 0.45, p = 0.0227). The increase in plasma volume was significantly and negatively related to both postrace plasma [Na(+)] (r = - 0.42, p = 0.0278) and the postrace potassium-to-sodium ratio in urine (r = - 0.44, p = 0.0218). To conclude, we found no fluid overload in these ultra-runners, the increase in plasma volume was most probably due to a stimulation of the renin-angiotensin-aldosterone system (RAAS) since sodium intake was not related to both the change in plasma [Na(+)] or postrace plasma [Na(+)]. PMID:21253973

  8. The perinatal thyroid in iodine deficient regions: risks of radioiodines--hazards of stable iodine overload. A study in the newborn rat.

    PubMed

    Hindié, E; Walker, F; Petiet, A; Bourahla, K; Galle, P; Colas-Linhart, N

    2001-05-01

    Administration of large quantities of stable iodine is an effective means of reducing the radiation burden on the thyroid in the event of a nuclear power-plant accident. Such administration may involve countries with low baseline dietary iodine intake. It is questioned whether stable iodine overload is safe, and in particular, what are its effects in newborn infants? Iodine-deficient newborn rats were submitted to a single acute administration of stable iodine (100 microg) on the second day of life. The effects on thyroid structure were studied, after 24 hr and after 7 days, using light microscopy. Compared to controls, the thyroids of animals submitted to stable iodine overload showed, 7 days after treatment, signs of acute toxicity including marked desquamation of epithelial cells and rupture of a large number of thyroid follicles. Our findings in iodine deficient newborn rats suggest that stable iodine overload may have side effects during perinatal life. This prophylactic measure should, therefore, be accompanied by follow-up of thyroid function. Thyroid hormones are critical for brain development, during the first period of life. PMID:11441946

  9. The Comparison of the Effects of Acute and Repeated Morphine Administration on Fast Synaptic Transmission in Magnocellular Neurons of Supraoptic Nucleus, Plasma Vasopressin Levels, and Urine Volume of Male Rats

    PubMed Central

    Yousefpour, Mitra; Naderi, Nima; Mansouri, Zahra; Janahmadi, Mahyar; Alizadeh, Amir-Mohammad; Motamedi, Fereshteh

    2014-01-01

    The activity of the magnocellular neurons (MCNs) of supraoptic nucleus (SON) is regulated by a variety of excitatory and inhibitory inputs. Opioids are one of the important compounds that affect these inputs at SON synapses. In this study, whole-cell patch clamp recording of SON neurons was used to investigate the effect of acute and repeated morphine administration on spontaneous inhibitory and excitatory post synaptic currents (sIPSCs and sEPSCs) in MCNs. While acute bath application of morphine to brain slice of intact rat produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency, repeated in-vivo administration of morphine produced opposite effect. Moreover, repetitive i.c.v. administration of morphine for three consecutive days caused significant increase in urine volume, but had no significant alteration in water consumption compared to control group. The increase in urine volume was consistent with a significant decrease in plasma arginine vasopressin (AVP) levels after repetitive i.p. morphine administration. The results suggest that acute administration of morphine stimulates whereas repeated administration of morphine inhibits the MCNs. Morphine-induced MCN inhibition could result in diminished plasma AVP levels and eventually an increase in urine volume of rats. PMID:25276199

  10. White Blood Cell Count to Mean Platelet Volume Ratio Is a Prognostic Factor in Patients with Non-ST Elevation Acute Coronary Syndrome with or without Metabolic Syndrome

    PubMed Central

    Dehghani, Mohammad Reza; Fakour, Sanam; Arjmand, Nasim

    2016-01-01

    Background and Objectives Leukocyte and platelet have been found to be associated with metabolic syndrome (MetS). We aimed to determine the usefulness of a novel marker named white blood cell count to mean platelet volume ratio (WMR) for predicting outcomes of non-ST elevation acute coronary syndrome (NSTE-ACS) with or without MetS. Subjects and Methods A total of 331 NSTE-ACS individuals (60±12.5 years, 57.4% male) were enrolled and followed for a median of 24 months. MetS was identified using the National Cholesterol Education Program Adult Treatment Panel III criteria. Results Patients were divided into two groups: high WMR (WMR≥720) and low WMR (WMR<720). Major adverse cardiovascular events (MACE) and MetS rates were significantly greater in the higher WMR group compared to those in the low WMR group (MACE: 14.3% vs. 25%, p=0.014; MetS: 50.9% vs. 75%, p<0.001). MetS was diagnosed in 62.2% of patients. MACE incidence in patients with or without MetS was comparable (p=0.737). Among MetS individuals, patients in the high WMR group had more MACE than the low WMR group (11.2% vs. 26.5%, p=0.007). However, MACE was comparable among non-MetS individuals (p=0.681). In multivariable Cox regression analysis, hazard ratios (HR) of MACE incidence for high-WMR in MetS individuals was 2.616 (95% confidence interval: 1.282–5.339, p=0.008). However, HR of MACE incidence for high WMR in non-MetS individuals was not significant. Conclusion Among NSTE-ACS patients without revascularization therapy, elevated admission WMR was associated with an increased risk of developing composite MACE in MetS individuals but not in non-MetS patients. PMID:27014354

  11. [Unexpected cause of acute renal failure in an 85-year-old woman].

    PubMed

    Fabbian, F; Stabellini, N; Catizone, L

    2008-01-01

    Acute postinfectious glomerulonephritis (APIGN) is usually diagnosed in young people, while in elderly people rapidly progressive forms appear to be the most important glomerular disease causing acute renal failure. We report on a 85-year-old woman with acute renal failure due to APIGN. An 85-year-old woman with a history of hypertension and cerebrovascular disease was hospitalized because of diarrhea and syncope associated with atrial fibrillation. She was found to have left lower lobe pneumonia. Serum creatinine was over 2 mg/dL. Fluids were given, without improvement in renal function but leading to volume overload instead. Within a few days serum creatinine reached a level of 5.4 mg/dL with reduction of urine output despite administration of diuretics. The patient developed hematuria and purpura of the feet. Serum IgA was high and the urine sediment showed casts. Methylprednisolone 125 mg i.v. was given for three days followed by prednisone 50 mg daily. The patient's clinical condition gradually improved and serum creatinine decreased to 1.9 mg/dL. Renal biopsy showed APIGN. During hospitalization, three major complications occurred: hemodynamic instability due to atrial fibrillation, Clostridium difficile colitis and urinary tract infections due to Enterococcus faecalis and Candida tropicans, all successfully treated. APIGN should be taken into account as a cause of acute renal failure in hospitalized elderly patients with many comorbidities. PMID:19048577

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

    ClinicalTrials.gov

    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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

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

    1993-05-01

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

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

    SciTech Connect

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

    1993-01-01

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

  16. Dietary iron overload in southern African rural blacks.

    PubMed

    Friedman, B M; Baynes, R D; Bothwell, T H; Gordeuk, V R; Macfarlane, B J; Lamparelli, R D; Robinson, E J; Sher, R; Hamberg, S

    1990-09-15

    A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Mitochondrial calcium overload is a key determinant in heart failure.

    PubMed

    Santulli, Gaetano; Xie, Wenjun; Reiken, Steven R; Marks, Andrew R

    2015-09-01

    Calcium (Ca2+) released from the sarcoplasmic reticulum (SR) is crucial for excitation-contraction (E-C) coupling. Mitochondria, the major source of energy, in the form of ATP, required for cardiac contractility, are closely interconnected with the SR, and Ca2+ is essential for optimal function of these organelles. However, Ca2+ accumulation can impair mitochondrial function, leading to reduced ATP production and increased release of reactive oxygen species (ROS). Oxidative stress contributes to heart failure (HF), but whether mitochondrial Ca2+ plays a mechanistic role in HF remains unresolved. Here, we show for the first time, to our knowledge, that diastolic SR Ca2+ leak causes mitochondrial Ca2+ overload and dysfunction in a murine model of postmyocardial infarction HF. There are two forms of Ca2+ release channels on cardiac SR: type 2 ryanodine receptors (RyR2s) and type 2 inositol 1,4,5-trisphosphate receptors (IP3R2s). Using murine models harboring RyR2 mutations that either cause or inhibit SR Ca2+ leak, we found that leaky RyR2 channels result in mitochondrial Ca2+ overload, dysmorphology, and malfunction. In contrast, cardiac-specific deletion of IP3R2 had no major effect on mitochondrial fitness in HF. Moreover, genetic enhancement of mitochondrial antioxidant activity improved mitochondrial function and reduced posttranslational modifications of RyR2 macromolecular complex. Our data demonstrate that leaky RyR2, but not IP3R2, channels cause mitochondrial Ca2+ overload and dysfunction in HF. PMID:26217001

  18. Use of magnetic resonance imaging to monitor iron overload.

    PubMed

    Wood, John C

    2014-08-01

    Treatment of iron overload requires robust estimates of total-body iron burden and its response to iron chelation therapy. Compliance with chelation therapy varies considerably among patients, and individual reporting is notoriously unreliable. Even with perfect compliance, intersubject variability in chelator effectiveness is extremely high, necessitating reliable iron estimates to guide dose titration. In addition, each chelator has a unique profile with respect to clearing iron stores from different organs. This article presents the tools available to clinicians to monitor their patients, focusing on noninvasive magnetic resonance imaging methods because they have become the de facto standard of care.

  19. Inherent overload protection for the series resonant converter

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

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

  20. The relevance of the rat lung response to particle overload for human risk assessment: a workshop consensus report.

    PubMed

    2000-01-01

    On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled "Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment." The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, nonfibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload." These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs can lead to lung cancer in humans via mechanisms similar to those of the rat, in the absence of mechanistic data to the contrary it must be assumed that the rat model can identify potential carcinogenic hazards to humans. Since the apparent responsiveness of the rat model at overload is dependent on coexistent chronic active inflammation and cell proliferation, at lower lung doses where chronic active inflammation and cell proliferation are not present, no lung cancer hazard is anticipated.

  1. Treatment of acute non-anion gap metabolic acidosis.

    PubMed

    Kraut, Jeffrey A; Kurtz, Ira

    2015-02-01

    Acute non-anion gap metabolic acidosis, also termed hyperchloremic acidosis, is frequently detected in seriously ill patients. The most common mechanisms leading to this acid-base disorder include loss of large quantities of base secondary to diarrhea and administration of large quantities of chloride-containing solutions in the treatment of hypovolemia and various shock states. The resultant acidic milieu can cause cellular dysfunction and contribute to poor clinical outcomes. The associated change in the chloride concentration in the distal tubule lumen might also play a role in reducing the glomerular filtration rate. Administration of base is often recommended for the treatment of acute non-anion gap acidosis. Importantly, the blood pH and/or serum bicarbonate concentration to guide the initiation of treatment has not been established for this type of metabolic acidosis; and most clinicians use guidelines derived from studies of high anion gap metabolic acidosis. Therapeutic complications resulting from base administration such as volume overload, exacerbation of hypertension and reduction in ionized calcium are likely to be as common as with high anion gap metabolic acidosis. On the other hand, exacerbation of intracellular acidosis due to the excessive generation of carbon dioxide might be less frequent than in high anion gap metabolic acidosis because of better tissue perfusion and the ability to eliminate carbon dioxide. Further basic and clinical research is needed to facilitate development of evidence-based guidelines for therapy of this important and increasingly common acid-base disorder.

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

    PubMed

    Klerings, Irma; Weinhandl, Alexandra S; Thaler, Kylie J

    2015-01-01

    The rapidly growing production of healthcare information - both scientific and popular - increasingly leads to a situation of information overload affecting all actors of the healthcare system and threatening to impede the adoption of evidence-based practice. In preparation for the 2015 Cochrane Colloquium in Vienna, we discuss the issues faced by three major actors of this system: patients, healthcare practitioners, and systematic reviewers. We analyze their situation through the concept of "filter failure", positing that the main problem is not that there is "too much information", but that the traditional means of managing and evaluating information are ill-suited to the realities of the digital age. Some of the major instances of filter failure are inadequate information retrieval systems for point-of-care settings, the problem of identifying all relevant evidence in an exceedingly diverse landscape of information resources, and the very basic lack of health information literacy, concerning not only the general public. Finally, we give an overview of proposed solutions to the problem of information overload. These new or adapted filtering systems include adapting review literature to the specific needs of practitioners or patients, technological improvements to information systems, strengthening the roles of intermediaries, as well as improving health literacy. PMID:26354128

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

    PubMed

    Klerings, Irma; Weinhandl, Alexandra S; Thaler, Kylie J

    2015-01-01

    The rapidly growing production of healthcare information - both scientific and popular - increasingly leads to a situation of information overload affecting all actors of the healthcare system and threatening to impede the adoption of evidence-based practice. In preparation for the 2015 Cochrane Colloquium in Vienna, we discuss the issues faced by three major actors of this system: patients, healthcare practitioners, and systematic reviewers. We analyze their situation through the concept of "filter failure", positing that the main problem is not that there is "too much information", but that the traditional means of managing and evaluating information are ill-suited to the realities of the digital age. Some of the major instances of filter failure are inadequate information retrieval systems for point-of-care settings, the problem of identifying all relevant evidence in an exceedingly diverse landscape of information resources, and the very basic lack of health information literacy, concerning not only the general public. Finally, we give an overview of proposed solutions to the problem of information overload. These new or adapted filtering systems include adapting review literature to the specific needs of practitioners or patients, technological improvements to information systems, strengthening the roles of intermediaries, as well as improving health literacy.

  4. Myocardial iron overload in thalassaemia major. How early to check?

    PubMed

    Borgna-Pignatti, Caterina; Meloni, Antonella; Guerrini, Giulia; Gulino, Letizia; Filosa, Aldo; Ruffo, Giovan B; Casini, Tommaso; Chiodi, Elisabetta; Lombardi, Massimo; Pepe, Alessia

    2014-02-01

    The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR) T2* screening in thalassaemia major (TM) is still uncertain. To clarify this point, we evaluated the prevalence of myocardial iron overload (MIO), function and fibrosis by CMR in TM patients younger than 10 years. We retrospectively selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia network. MIO was measured by T2* multislice multiecho technique. Biventricular function parameters were evaluated by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Patients' age ranged from 4·2 to 9·7 years. All scans were performed without sedation. Nine patients showed no MIO, 22 patients had heterogeneous MIO with a T2* global value ≥20 ms; two patients had heterogeneous MIO with a T2* global value <20 ms and two patients showed homogeneous MIO. No patient showed myocardial fibrosis. Among the patients with heart T2*<20 ms, the youngest was 6 years old, none showed heart dysfunction and the iron transfused was <35 g in all cases. Cardiac iron loading can occur much earlier than previously described. The first cardiac T2* assessment should be performed as early as feasible without sedation, especially if chelation is started late or if poor compliance is suspected.

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

    PubMed

    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.

  6. Fatty acids exacerbate tubulointerstitial injury in protein-overload proteinuria.

    PubMed

    Thomas, Mark E; Harris, Kevin P G; Walls, John; Furness, Peter N; Brunskill, Nigel J

    2002-10-01

    The role of the albumin-carried fatty acids in the induction of tubulointerstitial injury was studied in protein-overload proteinuria. Rats were injected with fatty acid-carrying BSA [FA(+)BSA], fatty acid-depleted BSA [FA(-)BSA], or saline. Macrophage infiltration was measured by immunohistochemical staining, apoptotic cells were detected by in situ end labeling, and proliferating cells were identified by in situ hybridization for histone mRNA. Macrophage infiltration was significantly greater in the FA(+)BSA group than in the FA(-)BSA and saline groups. The infiltrate was largely restricted to the outer cortex. Apoptosis was greater in the FA(+)BSA group than in the FA(-)BSA and saline groups. Compared with the saline group, apoptosis was significantly increased in the FA(+)BSA group but not in the FA(-)BSA group. Cortical cells proliferated significantly more in the FA(+)BSA and FA(-)BSA groups than in the saline group. FA(+)BSA is therefore a more potent inducer of macrophage infiltration and cell death than FA(-)BSA. The fatty acids carried on albumin may be the chief instigators of tubulointerstitial injury in protein-overload proteinuria. PMID:12217854

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

    PubMed Central

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

    2015-01-01

    Modern social media are becoming overloaded with information because of the rapidly-expanding number of information feeds. We analyze the user-generated content in Sina Weibo, and find evidence that the spread of popular messages often follow a mechanism that differs from the spread of disease, in contrast to common belief. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that for certain messages the chance of an individual to share the message is proportional to the fraction of its neighbours who shared it with him/her, which is a result of competition for attention. We model this process using a fractional susceptible infected recovered (FSIR) model, where the infection probability of a node is proportional to its fraction of infected neighbors. Our findings have dramatic implications for information contagion. For example, using the FSIR model we find that real-world social networks have a finite epidemic threshold in contrast to the zero threshold in disease epidemic models. This means that when individuals are overloaded with excess information feeds, the information either reaches out the population if it is above the critical epidemic threshold, or it would never be well received. PMID:26161956

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

    PubMed

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

    2015-01-01

    Modern social media are becoming overloaded with information because of the rapidly-expanding number of information feeds. We analyze the user-generated content in Sina Weibo, and find evidence that the spread of popular messages often follow a mechanism that differs from the spread of disease, in contrast to common belief. In this mechanism, an individual with more friends needs more repeated exposures to spread further the information. Moreover, our data suggest that for certain messages the chance of an individual to share the message is proportional to the fraction of its neighbours who shared it with him/her, which is a result of competition for attention. We model this process using a fractional susceptible infected recovered (FSIR) model, where the infection probability of a node is proportional to its fraction of infected neighbors. Our findings have dramatic implications for information contagion. For example, using the FSIR model we find that real-world social networks have a finite epidemic threshold in contrast to the zero threshold in disease epidemic models. This means that when individuals are overloaded with excess information feeds, the information either reaches out the population if it is above the critical epidemic threshold, or it would never be well received. PMID:26161956

  9. Immune overload: Parental attitudes toward combination and single antigen vaccines.

    PubMed

    Hulsey, Ella; Bland, Tami

    2015-05-21

    Parental concerns have led to a recent decline in immunization coverage, resulting in outbreaks of diseases that were once under control in the US. As the CDC vaccination schedule continues to increase in complexity, the number of required injections per office visit increases as well. Some parents perceive that there is trauma associated with the administration of multiple injections, and research shows that having multiple vaccines due in a single visit is associated with delays and lower immunization rates. Combination vaccines make vaccination more efficient by incorporating the antigens of several different diseases into a single injection, but many parents worry that they may overload the child's developing immune system and leave him or her susceptible to secondary infections. This literature review synthesizes current evidence regarding the parental fear of vaccine-induced immune system overload and the fear of vaccine-associated trauma, in an attempt to understand the scope and nature of these fears. Despite the wealth of knowledge about each of these fears individually, it is still unknown which is of greater concern and how this affects parental decision-making.

  10. Slow continuous ultrafiltration (SCUF)--the safe and efficient treatment for patients with cardiac failure and fluid overload.

    PubMed

    Wei, S S; Lee, W T; Woo, K T

    1995-06-01

    Slow Continuous ultrafiltration (SCUF) was first used in 1980 as an alternative mode of fluid removal for patients with oliguric acute renal dysfunction from whatever causes. The advantage of this treatment is that haemodynamic parameters remain stable in the presence of significant removal of fluid. We are describing our experience in 7 patients [age: 57 +/- 9 years; 4 male, 3 female] with cardiac failure and fluid overload who had undergone 8 sessions of SCUF. All of them had renal impairment and were resistant to diuretics. Blood lines were attached to a Kawasumi Renak-E dialyser (Cuprophane membrane) in series using Gambro AK10 dialysis blood pump. The following parameters were monitored: Blood pump (Qb): 175 +/- 26 ml/min, time (T): 393 +/- minutes. Venous pressure averaged a55 +/- 24 mmHg. We achieved ultrafiltration of 2,189 +/- 699 ml/session or 5.5 +/- 1.7 ml/hr. There was no significant change in blood pressure [systolic pre: 143 +/- 14, post: 136 +/- 13 mmHg, not significant; diastolic pre: 87 +/- 10, post: 83 + 10 mmHg, not significant and pulse rate [pre: 87 +/- 9 vs post: 84 +/- 2 per minute, not significant. Heparin dosage averaged 274 +/- 26 IU/hr during the SCUF. We conclude that SCUF is beneficial to diuretic resistant patients with cardiac failure and fluid overload in whom dialysis treatment is not required.

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

    PubMed

    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 < 0.001; RVEDV: 17 ± 6 vs. 12 ± 6 %; p = 0.003). TPM mass was related to the RVFW mass in patients (baseline: R = 0.65; p < 0.001; follow-up: R = 0.80; p < 0.001) and controls (R = 0.76; p < 0.001). In PAH and controls, exclusion of TPM from the assessment resulted in altered RV mass, volumes and function than when included (all p < 0.01). Changes in RV 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.

  12. Estrogen Inhibits Mast Cell Chymase Release to Prevent Pressure Overload-Induced Adverse Cardiac Remodeling

    PubMed Central

    Li, Jianping; Jubair, Shaiban; Janicki, Joseph S.

    2014-01-01

    Estrogen regulation of myocardial chymase and chymase effects on cardiac remodeling are unknown. To test the hypothesis that estrogen prevents pressure overload-induced adverse cardiac remodeling by inhibiting mast cell chymase release, transverse aortic constriction or sham surgery was performed in 7-week-old intact and ovariectomized rats. Three days prior to creating the constriction, additional groups of ovariectomized rats began receiving 17β-Estradiol, a chymase inhibitor, or a mast cell stabilizer. Left ventricular function, cardiomyocyte size, collagen volume fraction, mast cell density and degranulation, and myocardial and plasma chymase levels were assessed 18 days post-surgery. Aortic constriction resulted in ventricular hypertrophy in intact and ovariectomized groups while collagen volume fraction was increased only in ovariectomized rats. Chymase protein content was increased by aortic constriction in the intact and ovariectomized groups with the magnitude of the increase being greater in ovariectomized rats. Mast cell density and degranulation, plasma chymase levels and myocardial active transforming growth factor- 1 levels were increased by aortic constriction only in ovariectomized rats. Estrogen replacement markedly attenuated the constriction-increased myocardial chymase, mast cell density and degranulation, plasma chymase and myocardial active transforming growth factor- 1 as well as prevented ventricular hypertrophy and increased collagen volume fraction. Chymostatin attenuated the aortic constriction induced ventricular hypertrophy and collagen volume fraction in the ovariectomized rats similar to that achieved by estrogen replacement. Nedocromil yielded similar effects except for the reduction of chymase content. We conclude that the estrogen-inhibited release of mast cell chymase is responsible for the cardioprotection against transverse aortic constriction-induced adverse cardiac remodeling. PMID:25403608

  13. Estrogen inhibits mast cell chymase release to prevent pressure overload-induced adverse cardiac remodeling.

    PubMed

    Li, Jianping; Jubair, Shaiban; Janicki, Joseph S

    2015-02-01

    Estrogen regulation of myocardial chymase and chymase effects on cardiac remodeling are unknown. To test the hypothesis that estrogen prevents pressure overload-induced adverse cardiac remodeling by inhibiting mast cell (MC) chymase release, transverse aortic constriction or sham surgery was performed in 7-week-old intact and ovariectomized (OVX) rats. Three days before creating the constriction, additional groups of OVX rats began receiving 17β-estradiol, a chymase inhibitor, or a MC stabilizer. Left ventricular function, cardiomyocyte size, collagen volume fraction, MC density and degranulation, and myocardial and plasma chymase levels were assessed 18 days postsurgery. Aortic constriction resulted in ventricular hypertrophy in intact and OVX groups, whereas collagen volume fraction was increased only in OVX rats. Chymase protein content was increased by aortic constriction in the intact and OVX groups, with the magnitude of the increase being greater in OVX rats. MC density and degranulation, plasma chymase levels, and myocardial active transforming growth factor-β1 levels were increased by aortic constriction only in OVX rats. Estrogen replacement markedly attenuated the constriction-increased myocardial chymase, MC density and degranulation, plasma chymase, and myocardial active transforming growth factor-β1, as well as prevented ventricular hypertrophy and increased collagen volume fraction. Chymostatin attenuated the aortic constriction-induced ventricular hypertrophy and collagen volume fraction in the OVX rats similar to that achieved by estrogen replacement. Nedocromil yielded similar effects, except for the reduction of chymase content. We conclude that the estrogen-inhibited release of MC chymase is responsible for the cardioprotection against transverse aortic constriction-induced adverse cardiac remodeling.

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

    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

  17. Determination of Serum Ferritin Glycosylation in Hyperferritinemia Associated to Iron Overload and Inflammation.

    PubMed Central

    Gasser, Bethina Isasi

    2009-01-01

    Background Serum ferritin is a commonly used clinical biochemical parameter and hyperferritinemia is used as a surrogate marker for iron overload, acute or chronic inflammation, malignancy or cell death. The aim of the present study was to develop purification strategies of ferritin from sera to determine if micro-heterogeneity of serum ferritin can be used to differentiate the underlying cause of the hyperferritinemia. Patients, Materials and Methods Sera from patients with hemochromatosis, rheumatologic diseases, aceruloplasminemia, ferroportin disease or iron loading anemia have been collected and stored and ferritin purified by negative affinity followed by ion exchange and size exclusion chromatography. Purified serum ferritin was analyzed by western blotting and MALDI TOF mass spectrometry and the spectra compared with the results from ferritin isolated from human liver, spleen and placenta. Results By Western blotting a major band of 19kD has been found in most sera, suggesting that the L-ferritin is the predominant isoform present in serum regardless of the cause of hyperferritinemia. Multistep chromatography can be used for significant enrichment and purification of ferritin from serum, which can be further analyzed by MALDI TOF MS. Tryptic digestion and peptide mass finger-printing by MALDI TOF MS of ferritin purified from human tissues shows differential spectra. Discussion and conclusions Analysis of ferritin micro-heterogeneity by MALDI TOF allows determination of the tissue origin of ferritin, which could be applied in the differential diagnostic workup of hyperferritinemia.

  18. Inhibition of transforming growth factor-beta signaling induces left ventricular dilation and dysfunction in the pressure-overloaded heart.

    PubMed

    Lucas, Jason A; Zhang, Yun; Li, Peng; Gong, Kaizheng; Miller, Andrew P; Hassan, Erum; Hage, Fadi; Xing, Dongqi; Wells, Bryan; Oparil, Suzanne; Chen, Yiu-Fai

    2010-02-01

    This study utilized a transgenic mouse model that expresses an inducible dominant-negative mutation of the transforming growth factor (TGF)-beta type II receptor (DnTGFbetaRII) to define the structural and functional responses of the left ventricle (LV) to pressure-overload stress in the absence of an intact TGF-beta signaling cascade. DnTGFbetaRII and nontransgenic (NTG) control mice (male, 8-10 wk) were randomized to receive Zn(2+) (25 mM ZnSO(4) in drinking H(2)O to induce DnTGFbetaRII gene expression) or control tap H(2)O and then further randomized to undergo transverse aortic constriction (TAC) or sham surgery. At 7 days post-TAC, interstitial nonmyocyte proliferation (Ki67 staining) was greatly reduced in LV of DnTGFbetaRII+Zn(2+) mice compared with the other TAC groups. At 28 and 120 days post-TAC, collagen deposition (picrosirius-red staining) in LV was attenuated in DnTGFbetaRII+Zn(2+) mice compared with the other TAC groups. LV end systolic diameter and end systolic and end diastolic volumes were markedly increased, while ejection fraction and fractional shortening were significantly decreased in TAC-DnTGFbetaRII+Zn(2+) mice compared with the other groups at 120 days post-TAC. These data indicate that interruption of TGF-beta signaling attenuates pressure-overload-induced interstitial nonmyocyte proliferation and collagen deposition and promotes LV dilation and dysfunction in the pressure-overloaded heart, thus creating a novel model of dilated cardiomyopathy. PMID:19933419

  19. 30 CFR 75.518-2 - Incandescent lamps, overload and short circuit protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

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

    ERIC Educational Resources Information Center

    West, Lindsey M.

    2014-01-01

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

  1. 77 FR 11598 - Thermal Overload Protection for Electric Motors on Motor-Operated Valves

    Federal Register 2010, 2011, 2012, 2013, 2014

    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... (NRC or Commission) is issuing a revision to Regulatory Guide (RG) 1.106, ``Thermal Overload...

  2. Managing Information Overload for Senior Leaders in the 21st Century

    ERIC Educational Resources Information Center

    Jackson, Jason M.

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    Chen, Chun-Ying; Pedersen, Susan; Murphy, Karen L.

    2011-01-01

    Many studies report information overload as one of the main problems that students encounter in online learning via computer-mediated communication. This study aimed to explore the sources of online students' information overload and offer suggestions for increasing students' cognitive resources for learning. Participants were 12 graduate students…

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

    ERIC Educational Resources Information Center

    Chan, Siu Y.

    2001-01-01

    Discussion of information overload focuses on a study of masters degree students at a Hong Kong university that investigated the effectiveness of graphs as decision aids to reduce adverse effects of information overload on decision quality. Results of a simulation of a business prediction task with a sample of business managers are presented.…

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

    ERIC Educational Resources Information Center

    Allen, David K.; Shoard, M.

    2005-01-01

    Introduction: We report on a small-scale research project which examined the impact of mobile technologies on the users' experience of information overload. The project focused on a group of worker who have had relatively little attention in both the mobile technology and information overload literatures: senior managers. Method: The case study…

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    ERIC Educational Resources Information Center

    Pearson, Quinn M.

    2008-01-01

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

  10. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electric equipment and circuits; overload and short circuit protection. 75.518 Section 75.518 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Equipment-General § 75.518 Electric equipment and circuits; overload and short circuit protection....

  11. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electric equipment and circuits; overload and short circuit protection. 75.518 Section 75.518 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Equipment-General § 75.518 Electric equipment and circuits; overload and short circuit protection....

  12. 30 CFR 77.506 - Electric equipment and circuits; overload and short-circuit protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short-circuit protection. 77.506 Section 77.506 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... circuits; overload and short-circuit protection. Automatic circuit-breaking devices or fuses of the...

  13. 30 CFR 77.506 - Electric equipment and circuits; overload and short-circuit protection.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electric equipment and circuits; overload and short-circuit protection. 77.506 Section 77.506 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... circuits; overload and short-circuit protection. Automatic circuit-breaking devices or fuses of the...

  14. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short circuit protection. 75.518 Section 75.518 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Equipment-General § 75.518 Electric equipment and circuits; overload and short circuit protection....

  15. 30 CFR 77.506 - Electric equipment and circuits; overload and short-circuit protection.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electric equipment and circuits; overload and short-circuit protection. 77.506 Section 77.506 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... circuits; overload and short-circuit protection. Automatic circuit-breaking devices or fuses of the...

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

    PubMed

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

    2016-08-01

    Stressful, busy days have been linked with increases in angry and withdrawn marital behavior. The process by which stressors in 1 domain, such as work, affect an individual's behavior in another domain, such as the marital relationship, is known as. 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

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

    ERIC Educational Resources Information Center

    Rodriguez, Jacinto

    2013-01-01

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

  18. 30 CFR 77.506 - Electric equipment and circuits; overload and short-circuit protection.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electric equipment and circuits; overload and short-circuit protection. 77.506 Section 77.506 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... circuits; overload and short-circuit protection. Automatic circuit-breaking devices or fuses of the...

  19. 30 CFR 75.518 - Electric equipment and circuits; overload and short circuit protection.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electric equipment and circuits; overload and short circuit protection. 75.518 Section 75.518 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Equipment-General § 75.518 Electric equipment and circuits; overload and short circuit protection....

  20. Clinical and Research Considerations for Patients With Hypertensive Acute Heart Failure: A Consensus Statement from the Society for Academic Emergency Medicine and the Heart Failure Society of America Acute Heart Failure Working Group.

    PubMed

    Collins, Sean P; Levy, Phillip D; Martindale, Jennifer L; Dunlap, Mark E; Storrow, Alan B; Pang, Peter S; Albert, Nancy M; Felker, G Michael; Fermann, Gregory J; Fonarow, Gregg C; Givertz, Michael M; Hollander, Judd E; Lanfear, David E; Lenihan, Daniel J; Lindenfeld, JoAnn M; Peacock, W Frank; Sawyer, Douglas B; Teerlink, John R; Butler, Javed

    2016-08-01

    Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease that is based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF. PMID:27286136

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

    PubMed

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

    2016-01-01

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

  2. Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload.

    PubMed

    Altamura, Sandro; Kessler, Regina; Gröne, Hermann-Josef; Gretz, Norbert; Hentze, Matthias W; Galy, Bruno; Muckenthaler, Martina U

    2014-08-01

    The regulatory axis between the iron hormone hepcidin and its receptor, the iron exporter ferroportin (FPN), is central to iron homeostasis. Mutations preventing hepcidin-mediated degradation of FPN cause systemic iron overload. We have introduced a point mutation (C326S) into the murine Fpn locus, resembling human hereditary hemochromatosis type 4, including elevated plasma iron and ferritin levels, high transferrin saturation, hepatic iron overload, and iron depletion of duodenal enterocytes and reticuloendothelial macrophages. Unlike other mouse models of iron overload, homozygous C326S mice die between 7 and 14 months of age. Pancreatic acinar cells display marked iron accumulation, oxidative damage and degeneration, associated with failure of the exocrine pancreas and severe body weight loss. Rescue experiments reveal iron overload and exocrine pancreatic failure as leading causes of death. This work uncovers the critical importance of the hepcidin-ferroportin regulatory axis for life and unveils the sensitivity of the exocrine pancreas to iron overload.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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

  5. Iron excretion in iron dextran-overloaded mice

    PubMed Central

    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

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

    PubMed Central

    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

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  8. Hemodynamic and radionuclide effects of acute captopril therapy for heart failure: changes in left and right ventricular volumes and function at rest and during exercise

    SciTech Connect

    Massie, B.; Kramer, B.L.; Topic, N.; Henderson, S.G.

    1982-06-01

    Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responses at rest were decreases in left and right ventricular end-diastolic volumes from 388 + 81 to 350 + 77 ml (p < 0.01) and from 52 + 26 to 43 + 20 volume units (p < 0.01), respectively, and in their corresponding filling pressures, from 24 + 10 to 17 + 9 mm Hg and 10 + 5 to and + 5 mm Hg (both p < 0.01). Altough stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 + 6% to 22 + 5% and from 25 + 9% to 29 + 11%, respectively (both p < 0.01). During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. Thus, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.

  9. Hemodynamic and radionuclide effects of acute captopril therapy for heart failure: changes in left and right ventricular volumes and function at rest and during exercise

    SciTech Connect

    Massie, B.; Kramer, B.L.; Topic, N.; Henderson, S.G.

    1982-06-01

    Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg of oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responses at rest were decreases in left and right ventricular end-diastolic volumes from 388 +/- 81 to 350 +/- 77 ml and from 52 +/- 26 to 43 +/- 20 volume units, respectively, and in their corresponding filling pressures, from 24 +/- 10 to 17 +/- 9 mm Hg and 10 +/- 5 to 6 +/- 5 mm Hg. Although stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 +/- 6% to 22+/- 5% and from 25 +/- 9% to 29 +/- 11%, respectively. During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. This, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.

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

    PubMed

    Espinoza, A; Morales, S; Arredondo, M

    2014-06-01

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

  11. A Treatment Planning and Acute Toxicity Comparison of Two Pelvic Nodal Volume Delineation Techniques and Delivery Comparison of Intensity-Modulated Radiotherapy Versus Volumetric Modulated Arc Therapy for Hypofractionated High-Risk Prostate Cancer Radiotherapy

    SciTech Connect

    Myrehaug, Sten; Chan, Gordon; Craig, Tim; Weinberg, Vivian; Cheng, Chun; Roach, Mack; Cheung, Patrick; Sahgal, Arjun

    2012-03-15

    Purpose: To perform a comparison of two pelvic lymph node volume delineation strategies used in intensity-modulated radiotherapy (IMRT) for high risk prostate cancer and to determine the role of volumetric modulated arc therapy (VMAT). Methods and Materials: Eighteen consecutive patients accrued to an ongoing clinical trial were identified according to either the nodal contouring strategy as described based on lymphotropic nanoparticle-enhanced magnetic resonance imaging technology (9 patients) or the current Radiation Therapy Oncology Group (RTOG) consensus guidelines (9 patients). Radiation consisted of 45 Gy to prostate, seminal vesicles, and lymph nodes, with a simultaneous integrated boost to the prostate alone, to a total dose of 67.5 Gy delivered in 25 fractions. Prospective acute genitourinary and gastrointestinal toxicities were compared at baseline, during radiotherapy, and 3 months after radiotherapy. Each patient was retrospectively replanned using the opposite method of nodal contouring, and plans were normalized for dosimetric comparison. VMAT plans were also generated according to the RTOG method for comparison. Results: RTOG plans resulted in a significantly lower rate of genitourinary frequency 3 months after treatment. The dosimetric comparison showed that the RTOG plans resulted in both favorable planning target volume (PTV) coverage and lower organs at risk (OARs) and integral (ID) doses. VMAT required two to three arcs to achieve adequate treatment plans, we did not observe consistent dosimetric benefits to either the PTV or the OARs, and a higher ID was observed. However, treatment times were significantly shorter with VMAT. Conclusion: The RTOG guidelines for pelvic nodal volume delineation results in favorable dosimetry and acceptable acute toxicities for both the target and OARs. We are unable to conclude that VMAT provides a benefit compared with IMRT.

  12. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  13. Cognitive overload and communication in two healthcare settings.

    PubMed

    Cicourel, Aaron V

    2004-01-01

    The confluence of organizational social interaction and cognitive information processing constraints create 'noisy' conditions in institutionalized settings. Attentional and memory limitations always influence the ability of participants to comprehend each other's communication. Two organizational settings (a medical specialty clinic and periodontal office) will be used to explore a few features of healthcare delivery that are often ignored in studies of such systems. Scheduling appointments, for example, creates stress for both patients and healthcare personnel but is often an unexamined aspect of healthcare delivery that has become both challenging and often irritating for all concerned. For example, when patients call, someone at a general scheduling center or the particular clinic or office of an individual physician or dentist or a group practice will answer the call with a menu of options, or the caller may be asked to leave message. When a patient leaves a clinic or surgery office after a visit, they may be allowed to make a new appointment. The term 'cognitive overload' is a ubiquitous element of all healthcare systems and refers to organizationally induced and constrained limited capacity processing inherent in the way improvised discourse practices, and annotative devices or artifacts (such as written notes or some related strategy) become an integral part of everyday healthcare delivery. PMID:16808687

  14. Game-Theoretic Models of Information Overload in Social Networks

    NASA Astrophysics Data System (ADS)

    Borgs, Christian; Chayes, Jennifer; Karrer, Brian; Meeder, Brendan; Ravi, R.; Reagans, Ray; Sayedi, Amin

    We study the effect of information overload on user engagement in an asymmetric social network like Twitter. We introduce simple game-theoretic models that capture rate competition between celebrities producing updates in such networks where users non-strategically choose a subset of celebrities to follow based on the utility derived from high quality updates as well as disutility derived from having to wade through too many updates. Our two variants model the two behaviors of users dropping some potential connections (followership model) or leaving the network altogether (engagement model). We show that under a simple formulation of celebrity rate competition, there is no pure strategy Nash equilibrium under the first model. We then identify special cases in both models when pure rate equilibria exist for the celebrities: For the followership model, we show existence of a pure rate equilibrium when there is a global ranking of the celebrities in terms of the quality of their updates to users. This result also generalizes to the case when there is a partial order consistent with all the linear orders of the celebrities based on their qualities to the users. Furthermore, these equilibria can be computed in polynomial time. For the engagement model, pure rate equilibria exist when all users are interested in the same number of celebrities, or when they are interested in at most two. Finally, we also give a finite though inefficient procedure to determine if pure equilibria exist in the general case of the followership model.

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

    PubMed

    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

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

    PubMed Central

    Muller, Mees; Heeck, Kier

    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

  17. Entry overload, emergency department overcrowding, and ambulance bypass

    PubMed Central

    Fatovich, D; Hirsch, R

    2003-01-01

    Objectives: To describe an experience of emergency department (ED) overcrowding and ambulance bypass. Methods: A prospective observational study at Royal Perth Hospital, a major teaching hospital. Episodes of ambulance bypass and their characteristics were recorded. Results: From 1 July 1999 to 30 June 2001, there were 141 episodes of ambulance bypass (mean duration 187 min, range 35–995). Monday was the most common day with 39 (28%) episodes. Entry block alone was the most common reason bypass was activated (n=38, 30.4%). The mean number of patients in ED at these times was 40 (occupancy 174%), including nine in the corridor, seven awaiting admission, and 14 waiting to be seen. Episodes attributable to entry block were typically preceded by a presentation rate of ⩾10 patients per hour for ⩾2 hours (OR 6.2, 95% CI 4.3 to 8.5). Mid-afternoon to early evening was the most common time for activation. Ambulance bypass is increasing in frequency and duration. Conclusions: Entry overload resulting in entry block results from overwhelming numbers of patients presenting to the ED in a short space of time. Entry block impairs access to emergency care. Unless something is done in the near future, the general public may no longer be able to rely on EDs for quality and timely emergency care. A "whole of system" approach is necessary to tackle the problem. PMID:12954675

  18. Overload and neovascularization of shoulder tendons in volleyball players

    PubMed Central

    2012-01-01

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

  19. [Effect of long flying overloads with moderate values on functional capacity of airplane crew members].

    PubMed

    Zasiad'ko, K I; Lapa, V V; Lemeshchenko, N A; Iasnyĭ, S I

    2008-01-01

    The influence of long (up to 5 min) flying overloads with moderate values (2-5 U, at the increase and descent rate of 0,6-1,5 U/s) on the functional state and activities of airplane crewmembers was studied during the real flights. It was established that the influence of such overloads causes the unfavorable changes in the functional state and decrease in the effectiveness of crewmembers' (especially of a navigator-operator) actions. It was shown that the use of measure complex (during the flight the crewmembers use anti-overload dress, the pilot informs the navigator-operator about beginning of maneuvering, trainings on statoergometer to improve the crewmembers' static physical endurance) allows increasing the crews' psychophysiologic capacity during the maneuvers accompanied with the effect of complex flying overloads with moderate values. PMID:18350795

  20. The Acute Effects of Changes to AV Delay on Blood Pressure and Stroke Volume: Potential Implications for Design of Pacemaker Optimization Protocols

    PubMed Central

    Manisty, Charlotte H.; Al-Hussaini, Ali; Unsworth, Beth; Baruah, Resham; Pabari, Punam A.; Mayet, Jamil; Hughes, Alun D.; Whinnett, Zachary I.; Francis, Darrel P.

    2012-01-01

    Background Atrioventricular (AV) delay optimization of biventricular pacemakers (cardiac resynchronization therapy, CRT) may maximise hemodynamic benefit, but consumes specialist time to conduct echocardiographically. Non-invasive blood pressure monitoring is a potentially-automatable alternative, but it is unknown whether it gives the same information, and similar precision (signal-to-noise ratio). Moreover, the immediate blood pressure increment on optimization has been reported to decay away: it is unclear whether this is the result of an (undesirable) fall in stroke volume or a (desirable) compensatory relief of peripheral vasoconstriction. Methods and Results To discriminate between these alternative mechanisms, we measured simultaneous beat-to-beat stroke volume (flow) using Doppler echocardiography, and blood pressure (BP) using finger photoplethysmography, during and after atrioventricular delay changes from 40 to 120 ms in 19 subjects with cardiac pacemakers. BP and stroke volume both increased immediately (p<0.001, within one heartbeat). BP showed a clear decline a few seconds later (average rate −0.65mmHg/beat, r=0.95 [95% CI 0.86 to 0.98]); in contrast, stroke volume did not decline (p=0.87). The immediate BP increment correlated strongly with the stroke volume increment (r=0.74, p<0.001). Signal-to-noise ratio was threefold better for BP than stroke volume (6.8±3.5 versus 2.3±1.4, p<0.001). Conclusions Improving atrioventricular delay immediately increases blood pressure, but the effect begins to decay within a few seconds. Reassuringly this is due to compensatory vasodilatation rather than reduction in cardiac function. Pacemaker optimization will never be reliable unless there is adequate signal-to-noise ratio. Using BP rather than Doppler minimises noise. The early phase – before vascular compensation – has the richest signal lode. PMID:22095639

  1. Modelling training response in elite female gymnasts and optimal strategies of overload training and taper.

    PubMed

    Sanchez, Anthony M J; Galbès, Olivier; Fabre-Guery, Frédérique; Thomas, Luc; Douillard, Aymeric; Py, Guillaume; Busso, Thierry; Candau, Robin B

    2013-01-01

    The aim of the study is the modelling of training responses with a variable dose-response model in a sport discipline that requires highly complex coordination. We propose a method to optimise the training programme plan using the potential maximal performance gain associated with overload and tapering periods. Data from five female elite gymnasts were collected over a 3-month training period. The relationship between training amounts and performance was then assessed with a non-linear model. The optimal magnitude of training load reduction and its duration were investigated with and without an overload period using simulation procedures based on individual responses to training. The correlation between actual and modelled performances was significant (R² = 0.81 ± 0.02, P < 0.01). The standard error was 2.7%. Simulations revealed that taper preceded by an overload period allows a higher performance to be achieved compared to an absence of overload period (106.3 ± 0.3% vs. 105.1 ± 0.3%). With respect to the pre-taper load, the model predicts that optimal load reductions during taper were 48.4 ± 0.7% and 42.5 ± 1.0% for overloading and non-overloading strategies, respectively. Moreover, optimal durations of the taper period were 34 ± 0.5 days and 22 ± 0.5 days for overloading and non-overloading strategies, respectively. In conclusion, the study showed that the variable dose-response model describes precisely the training response in gymnasts. PMID:23656356

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

    PubMed

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

    2015-01-01

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

  3. Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model

    PubMed Central

    ZHANG, ZEYU; LIU, DAN; YI, BO; LIAO, ZHANGPING; TANG, LEI; YIN, DONG; HE, MING

    2014-01-01

    We previously demonstrated that iron overload induces liver damage by causing the formation of reactive oxygen species (ROS). Taurine is a potent free radical scavenger that attenuates the damage caused by excessive oxygen free radicals. Therefore, the aim of the present study was to investigate whether taurine could reduce the hepatotoxicity of iron overload with regard to ROS production. Mice were intraperitoneally injected with iron 5 days/week for 13 weeks to achieve iron overload. It was found that iron overload resulted in liver dysfunction, increased apoptosis and elevated oxidative stress. Taurine supplementation increased liver taurine levels by 40% and led to improved liver function, as well as a reduction in apoptosis, ROS formation and mitochondrial swelling and an attenuation in the loss of the mitochondrial membrane potential. Treatment with taurine mediated a reduction in oxidative stress in iron-overloaded mice, attenuated liver lipid peroxidation, elevated antioxidant enzyme activities and maintained reduced glutathione levels. These results indicate that taurine reduces iron-induced hepatic oxidative stress, preserves liver function and inhibits hepatocyte apoptosis. Therefore, taurine may be a potential therapeutic drug to reduce liver damage caused by iron overload. PMID:25201602

  4. [Iron deficiency and overload. Implications in oxidative stress and cardiovascular health].

    PubMed

    Toxqui, L; De Piero, A; Courtois, V; Bastida, S; Sánchez-Muniz, F J; Vaquero, Ma P

    2010-01-01

    Although iron is an essential mineral for maintaining good health, excessive amounts are toxic. Nowadays, much interest is focused on the mechanisms and regulation of iron metabolism by down-regulation of the hormone hepcidin. The HAMP gene encodes for hepcidin appears to be exceptionally preserved. Disorders of iron metabolism could lead to iron overload, mainly causing the rare disease hereditary hemochromatosis, or on the other hand, iron deficiency and iron deficiency anaemia. Currently, these alterations constitute an important problem of public health. The genetic variation implicated in iron overload and iron deficiency anaemia, involves mutations in several genes such as HFE, TFR2,HAMP, HJV, Tf and TMPRSS6. Iron has the capacity to accept and donate electrons easily and can catalyze reactions of free radicals production. Therefore, iron overload causes lipid peroxidation and increases cardiovascular risk. Recently, a relationship between iron metabolism and insulin resistance and obesity has been described. In contrast, regarding a possible relationship between iron deficiency anaemia and cardiovascular disease, many aspects remain controversial. This review presents an overview of the most recent information concerning iron metabolism, iron bioavailability and iron overload/deficiency related diseases. The relation between iron and cardiovascular risk, in iron overload and in iron deficiency situations, is also examined. Finally, strategies to modify dietary iron bioavailability in order to prevent iron deficiency or alleviate iron overload are suggested.

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

    PubMed

    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

  6. Acute Genital Edema during Peritoneal Dialysis: A Review for Surgeons.

    PubMed

    Jorge, Juaquito; Haggerty, Stephen P

    2015-11-01

    Acute genital edema (AGE) is an infrequent but disruptive complication in patients on continuous ambulatory peritoneal dialysis. It is a common manifestation of dialysate leakage caused by inguinal, umbilical, femoral, or incisional hernias; peritoneal tears; leaks around the dialysis catheter; trauma; fluid overload; and malignancy. The evaluation of AGE begins with a history and physical exam. However, the physical exam in these patients is often indeterminate. Several diagnostic measures exist to evaluate and guide management of AGE occurring during continuous ambulatory peritoneal dialysis but little agreement exists on an optimum method. We have conducted a review of the literature on the evaluation and management of AGE and present a summary of the data. CT peritoneography and peritoneal scintigraphy have been used extensively to evaluate AGE although no comparative studies exist. MRI peritoneography has also been described. CT peritoneography offers more anatomical detail but may not be as sensitive as peritoneal scintigraphy in detecting a peritoneal fluid leak as the cause for AGE. CT is also more costly and subjects the patient to more radiation. MRI is a noncontrast study without radiation risk, but has not been studied to the same degree. If testing is equivocal or bilateral hernias are suspected, diagnostic laparoscopy is helpful and can be combined with hernia repair. Whether the etiology is a leak or tear, low-volume peritoneal dialysis (PD) or cessation of PD for two to four weeks will allow closure. However, hernias almost always require operative repair with mesh usually without disrupting PD.

  7. Electrical short circuit and current overload tests on aircraft wiring

    NASA Technical Reports Server (NTRS)

    Cahill, Patricia

    1995-01-01

    The findings of electrical short circuit and current overload tests performed on commercial aircraft wiring are presented. A series of bench-scale tests were conducted to evaluate circuit breaker response to overcurrent and to determine if the wire showed any visible signs of thermal degradation due to overcurrent. Three types of wire used in commercial aircraft were evaluated: MIL-W-22759/34 (150 C rated), MIL-W-81381/12 (200 C rated), and BMS 1360 (260 C rated). A second series of tests evaluated circuit breaker response to short circuits and ticking faults. These tests were also meant to determine if the three test wires behaved differently under these conditions and if a short circuit or ticking fault could start a fire. It is concluded that circuit breakers provided reliable overcurrent protection. Circuit breakers may not protect wire from ticking faults but can protect wire from direct shorts. These tests indicated that the appearance of a wire subjected to a current that totally degrades the insulation looks identical to a wire subjected to a fire; however the 'fire exposed' conductor was more brittle than the conductor degraded by overcurrent. Preliminary testing indicates that direct short circuits are not likely to start a fire. Preliminary testing indicated that direct short circuits do not erode insulation and conductor to the extent that ticking faults did. Circuit breakers may not safeguard against the ignition of flammable materials by ticking faults. The flammability of materials near ticking faults is far more important than the rating of the wire insulation material.

  8. Metabolomic Analysis of Pressure-overloaded and Infarcted Mouse Hearts

    PubMed Central

    Sansbury, Brian E.; De Martino, Angelica M.; Xie, Zhengzhi; Brooks, Alan C.; Brainard, Robert E.; Watson, Lewis J.; DeFilippis, Andrew P.; Cummins, Timothy D.; Harbeson, Matthew A.; Brittian, Kenneth R.; Prabhu, Sumanth D.; Bhatnagar, Aruni; Jones, Steven P.; Hill, Bradford G.

    2014-01-01

    Background Cardiac hypertrophy and heart failure are associated with metabolic dysregulation and a state of chronic energy deficiency. Although several disparate changes in individual metabolic pathways have been described, there has been no global assessment of metabolomic changes in hypertrophic and failing hearts in vivo. Here, we investigated the impact of pressure overload and infarction on myocardial metabolism. Methods and Results Male C57BL/6J mice were subjected to transverse aortic constriction (TAC) or permanent coronary occlusion (myocardial infarction; MI). A combination of LC/MS/MS and GC/MS techniques was used to measure 288 metabolites in these hearts. Both TAC and MI were associated with profound changes in myocardial metabolism affecting up to 40% of all metabolites measured. Prominent changes in branched amino acids acids (BCAAs) were observed after 1 week of TAC and 5 days after MI. Changes in BCAAs after MI were associated with myocardial insulin resistance. Longer duration of TAC and MI led to a decrease in purines, acylcarnitines, fatty acids and several lysolipid and sphingolipid species, but a marked increase in pyrimidines as well as ascorbate, heme and other indices of oxidative stress. Cardiac remodeling and contractile dysfunction in hypertrophied hearts were associated also with large increases in myocardial, but not plasma, levels of the polyamines putrescine and spermidine as well as the collagen breakdown product prolylhydroxyproline. Conclusions These findings reveal extensive metabolic remodeling common to both hypertrophic and failing hearts that are indicative of extensive extracellular matrix remodeling, insulin resistance and perturbations in amino acid, lipid and nucleotide metabolism. PMID:24762972

  9. Characterization and accumulation of ferritin in hepatocyte nuclei of mice with iron overload

    SciTech Connect

    Smith, A.G.; Carthew, P.; Francis, J.E.; Edwards, R.E.; Dinsdale, D. )

    1990-12-01

    After a single subcutaneous dose of iron-dextran (600 mg of iron/kg), iron overload developed in C57BL/10ScSn mice. At 4, 24 and 78 wk liver nonheme iron concentrations were 67-, 42- and 21-fold higher than controls, respectively. Much of the iron was in macrophages, but hepatocytes were also strongly positive for Perls' stainable iron. One feature was the development of iron-positive nuclear inclusions in hepatocytes. After a delay of at least 8 wk when no stainable iron was evident, a maximum of 37% of periportal hepatocytes contained inclusions by 24 wk. Although this proportion remained constant for the remainder of the study, the size of the inclusions (which were not membrane-limited) increased to greater than 3 microns in diameter, occupying greater than 25% of the nuclear volume. The presence of iron in the inclusions was confirmed by energy dispersive x-ray microanalysis. Immunocytochemical studies showed that the iron was present as aggregates of ferritin. Quantitation of nonaggregated ferritin molecules by image analyses after electron microscopy demonstrated that within 4 wk ferritin levels in cytoplasm and nucleoplasm had greatly increased but that there was a concentration gradient of approximately one order of magnitude across the nuclear envelope. These findings are consistent with the hypothesis that in iron-loaded mouse hepatocytes there is a slow passage of ferritin-molecules through the nuclear pores; the gradient is maintained by the continual aggregation of ferritin within the nucleus. Intranuclear ferritin may provide a source of iron for catalyzing hydroxyl radical formation in nuclei during some toxic, carcinogenic and aging processes.

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

    PubMed

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

    2005-09-01

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

  11. Genome-linked toxic responses to dietary iron overload.

    PubMed

    Whittaker, P; Dunkel, V C; Bucci, T J; Kusewitt, D F; Thurman, J D; Warbritton, A; Wolff, G L

    1997-01-01

    Genome-related differences to Fe overload between and within rodent species were evaluated in the present study. Male B6C3F1 mice, yellow and black C5YSF1 mice, and Fischer 344 (F344) rats were fed AIN-76A diets containing 35 (control), 1,500, 3,500, 5,000, or 10,000 micrograms carbonyl Fe/g for 12 wk. No effects on body weight gain were observed in the B6C3F1 and black C5YSF1 mice, whereas at all doses of Fe above the control, weight gain was reduced in yellow C5YSF1 mice and F344 rats. At the 10,000 micrograms Fe/g dose, 9 of 12 rats died, but there was no mortality among the mice. In all animals, there was a dose-related increase in liver nonheme Fe, and the Fe was stored in hepatocytes predominantly in the periportal region. There was significant hypertrophy of the hepatocytes in both B6C3F1 mice and F344 rats fed the 10,000 micrograms Fe/g diet. PCNA assays showed significant stimulatory effects of the high dose of Fe on hepatocyte proliferation in the F344 rats and the C5YSF1 mice but not in the B6C3F1 mice. In the rat, there was pancreatic atrophy with loss of both endocrine and exocrine tissue. Morphometric evaluation of pancreas showed fewer beta cells in B6C3F1 and yellow C5YSF1 mice but not in the black C5YSF1 mice. There were fewer islets in the yellow C5YSF1 mice, and total and mean islet areas were smaller than in the control mice. Rats in the 10,000 micrograms Fe/g dose group had markedly exacerbated dose-dependent nephropathy and changes in glomerular and tubular epithelium associated with Fe accumulation. The rats also showed degeneration of the germinal epithelium of the testis, formation of multinucleated giant cells, and lack of mature sperm. PMID:9437799

  12. Biological responses to overload training in endurance sports.

    PubMed

    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

  13. Acute Effects of Caffeine on Heart Rate Variability, Blood Pressure and Tidal Volume in Paraplegic and Tetraplegic Compared to Able-Bodied Individuals: A Randomized, Blinded Trial

    PubMed Central

    Flueck, Joelle Leonie; Schaufelberger, Fabienne; Lienert, Martina; Schäfer Olstad, Daniela; Wilhelm, Matthias; Perret, Claudio

    2016-01-01

    Caffeine increases sympathetic nerve activity in healthy individuals. Such modulation of nervous system activity can be tracked by assessing the heart rate variability. This study aimed to investigate the influence of caffeine on time- and frequency-domain heart rate variability parameters, blood pressure and tidal volume in paraplegic and tetraplegic compared to able-bodied participants. Heart rate variability was measured in supine and sitting position pre and post ingestion of either placebo or 6 mg caffeine in 12 able-bodied, 9 paraplegic and 7 tetraplegic participants in a placebo-controlled, randomized and double-blind study design. Metronomic breathing was applied (0.25 Hz) and tidal volume was recorded during heart rate variability assessment. Blood pressure, plasma caffeine and epinephrine concentrations were analyzed pre and post ingestion. Most parameters of heart rate variability did not significantly change post caffeine ingestion compared to placebo. Tidal volume significantly increased post caffeine ingestion in able-bodied (p = 0.021) and paraplegic (p = 0.036) but not in tetraplegic participants (p = 0.34). Systolic and diastolic blood pressure increased significantly post caffeine in able-bodied (systolic: p = 0.003; diastolic: p = 0.021) and tetraplegic (systolic: p = 0.043; diastolic: p = 0.042) but not in paraplegic participants (systolic: p = 0.09; diastolic: p = 0.33). Plasma caffeine concentrations were significantly increased post caffeine ingestion in all three groups of participants (p<0.05). Plasma epinephrine concentrations increased significantly in able-bodied (p = 0.002) and paraplegic (p = 0.032) but not in tetraplegic participants (p = 0.63). The influence of caffeine on the autonomic nervous system seems to depend on the level of lesion and the extent of the impairment. Therefore, tetraplegic participants may be less influenced by caffeine ingestion. Trial Registration ClinicalTrials.gov NCT02083328 PMID:27776149

  14. Bmp6 Expression in Murine Liver Non Parenchymal Cells: A Mechanism to Control their High Iron Exporter Activity and Protect Hepatocytes from Iron Overload?

    PubMed Central

    Rausa, Marco; Pagani, Alessia; Nai, Antonella; Campanella, Alessandro; Gilberti, Maria Enrica; Apostoli, Pietro; Camaschella, Clara; Silvestri, Laura

    2015-01-01

    Bmp6 is the main activator of hepcidin, the liver hormone that negatively regulates plasma iron influx by degrading the sole iron exporter ferroportin in enterocytes and macrophages. Bmp6 expression is modulated by iron but the molecular mechanisms are unknown. Although hepcidin is expressed almost exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild type mice whose diet was modified in iron content in acute or chronic manner and in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1 expression in both HCs and NPCs was inversely related, as expected. When hepcidin expression is abnormal in murine models of iron overload (Hjv KO mice) and deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1. Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low. Conversely, despite body iron overload and high expression of Bmp6 in NPCs from Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells ferritin L was only slightly increased, but the iron content was not, suggesting that Bmp6 in these cells reflects the high intracellular iron import and export. We propose that NPCs, sensing the iron flux, not only increase hepcidin through Bmp6 with a paracrine mechanism to control systemic iron homeostasis but, controlling hepcidin, they regulate their own ferroportin, inducing iron retention or release and further modulating Bmp6 production in an autocrine manner. This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production. PMID:25860887

  15. Bmp6 expression in murine liver non parenchymal cells: a mechanism to control their high iron exporter activity and protect hepatocytes from iron overload?

    PubMed

    Rausa, Marco; Pagani, Alessia; Nai, Antonella; Campanella, Alessandro; Gilberti, Maria Enrica; Apostoli, Pietro; Camaschella, Clara; Silvestri, Laura

    2015-01-01

    Bmp6 is the main activator of hepcidin, the liver hormone that negatively regulates plasma iron influx by degrading the sole iron exporter ferroportin in enterocytes and macrophages. Bmp6 expression is modulated by iron but the molecular mechanisms are unknown. Although hepcidin is expressed almost exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild type mice whose diet was modified in iron content in acute or chronic manner and in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1 expression in both HCs and NPCs was inversely related, as expected. When hepcidin expression is abnormal in murine models of iron overload (Hjv KO mice) and deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1. Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low. Conversely, despite body iron overload and high expression of Bmp6 in NPCs from Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells ferritin L was only slightly increased, but the iron content was not, suggesting that Bmp6 in these cells reflects the high intracellular iron import and export. We propose that NPCs, sensing the iron flux, not only increase hepcidin through Bmp6 with a paracrine mechanism to control systemic iron homeostasis but, controlling hepcidin, they regulate their own ferroportin, inducing iron retention or release and further modulating Bmp6 production in an autocrine manner. This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production.

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

    PubMed

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

    2014-09-01

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

  17. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  18. Oral exfoliative cytology as a screening tool for iron overload in β-thalassemia patients

    PubMed Central

    Rathore, Ajit Singh; Keshri, Neha; Shetty, Devi Charan; Juneja, Saurabh

    2016-01-01

    Background: Increased iron overload is frequent problem in thalassemia patients, and this is monitored by serum ferritin levels or chemical assessment of the iron levels in liver tissue. However, repeated monitoring of serum ferritin levels to assess the iron overload is an invasive procedure associated with practical problems. Aims: To use Perl's Prussian blue reaction to evaluate the iron overload in beta-thalassemia patients by staining the oral cytosmears. Materials and Methods: The study comprised 35 patients diagnosed with beta-thalassemia. Cytosmears were prepared from exfoliated oral epithelial cells, fixed in 70% ethanol and stained with Perl's Prussian blue stain for detection of blue colored granules in the cytoplasm. Results: 29/35 (82.9%) cases showed a positive reaction for Perl's Prussian blue reaction while 6/35 (17%) cases did not show the presence of blue colored granules in the oral cytosmears. The presence of iron detected by Perl's Prussian blue reaction correlated with serum ferritin level (P < 0.05). Conclusion: Perl's Prussian blue reaction can be used to evaluate the iron overload in beta-thalassemia patients by staining the oral cytosmears. It is a simple and noninvasive method for assessment of iron overload in such patients. PMID:26958519

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

    PubMed Central

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

    2008-01-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2016-03-15

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

  2. Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. Evidence for mediation by tubuloglomerular feedback.

    PubMed Central

    Galla, J H; Bonduris, D N; Sanders, P W; Luke, R G

    1984-01-01

    We have recently described reduced superficial nephron glomerular filtration rate (SNGFR) in chloride-depletion alkalosis (CDA) without volume depletion. To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyses against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HCO3. Extracellular fluid (ECF) volume was assessed by blood pressure, hematocrit, plasma protein concentration, and 125I-albumin space; none of these variables differed among the four groups. Micropuncture of the latest proximal and earliest distal convolutions was carried out. As CDA intensified from CON to CDA-3 (plasma tCO2 25 +/- 1 to 43 +/- 1 meq/L; P less than 0.01), distally determined SNGFR declined progressively (40.9 +/- 1.7 to 28.3 +/- 1.8 nl/min; P less than 0.01), while in early distal tubule fluid, flow rate (8.6 +/- 0.7 to 3.4 +/- 0.6 nl/min) and Cl concentration (36 +/- 2 to 19 +/- 3 meq/L) decreased and osmolality (110 +/- 5 to 208 +/- 12 mosmol/kg) increased (P less than 0.01), and, in the loop segment, Cl reabsorption decreased progressively (2,009 +/- 112 to 765 +/- 128 peq/min; P less than 0.01). In early distal tubule fluid, Cl concentration correlated positively and osmolality negatively with distally determined SNGFR (P less than 0.05). Proximally determined SNGFRs did not differ among the four groups. Proximal tubule stop-flow pressure responses to increasing rates of orthograde perfusion of the loop segment from 0 to 40 nl/min did not differ between groups CON and CDA-2. We interpret these data to show that reductions in SNGFR in CDA in the rat can occur by tubuloglomerular feedback (TGF) in the absence of differences in ECF volume or of alterations in TGF sensitivity during metabolic alkalosis. Of the proposed signals for TGF sensed by the macula densa

  3. Relation between acute and late irradiation impairment of four basic tastes and irradiated tongue volume in patients with head-and-neck cancer

    SciTech Connect

    Yamashita, Hideomi . E-mail: yamachan07291973@yahoo.co.jp; Nakagawa, Keiichi; Nakamura, Naoki; Abe, Keiko; Asakage, Takahiro; Ohmoto, Makoto; Okada, Shinji; Matsumoto, Ichiro; Hosoi, Yoshio; Sasano, Nakashi; Yamakawa, Sen; Ohtomo, Kuni

    2006-12-01

    Purpose: Taste loss is a major cause of morbidity in patients undergoing head-and-neck irradiation. The relationship between the time course and the degree of taste disorder was studied in both acute and late phases. Methods and Materials: Taste ability was measured by the taste threshold for the four basic tastes using a filter paper disc method in patients before, during, and after radiotherapy. The subjects were divided into two groups. In Group A, Radiation fields included most of the tongue (n = 100), and in Group B Radiation fields did not include the tip of the tongue (n = 18). Results: In Group A, there was a significant impairment of the threshold of all four basic tastes at 3 weeks after starting radiotherapy (RT), and this impairment remained at 8 weeks (p < 0.05). This was not seen in Group B. In Group A, there was no significant difference in the patterns of taste sensitivity change between the high-dose (>20 Gy) and low-dose ({<=}20 Gy) groups. In the late phase, recovery of taste loss was seen in both groups since 4 months after completing RT. Conclusions: Unless the anterior part of the tongue was irradiated, taste loss was not observed during RT. When the anterior part of the tongue was irradiated, a difference by radiation dose was not observed in the taste loss pattern. Additionally, radiation-induced taste dysfunction appears to be a temporal effect.

  4. Information Diffusion in Facebook-Like Social Networks Under Information Overload

    NASA Astrophysics Data System (ADS)

    Li, Pei; Xing, Kai; Wang, Dapeng; Zhang, Xin; Wang, Hui

    2013-07-01

    Research on social networks has received remarkable attention, since many people use social networks to broadcast information and stay connected with their friends. However, due to the information overload in social networks, it becomes increasingly difficult for users to find useful information. This paper takes Facebook-like social networks into account, and models the process of information diffusion under information overload. The term view scope is introduced to model the user information-processing capability under information overload, and the average number of times a message appears in view scopes after it is generated is proposed to characterize the information diffusion efficiency. Through theoretical analysis, we find that factors such as network structure and view scope number have no impact on the information diffusion efficiency, which is a surprising result. To verify the results, we conduct simulations and provide the simulation results, which are consistent with the theoretical analysis results perfectly.

  5. Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice.

    PubMed

    Sebastiani, Giada; Pantopoulos, Kostas

    2011-10-01

    In healthy subjects, the rate of dietary iron absorption, as well as the amount and distribution of body iron are tightly controlled by hepcidin, the iron regulatory hormone. Disruption of systemic iron homeostasis leads to pathological conditions, ranging from anemias caused by iron deficiency or defective iron traffic, to iron overload (hemochromatosis). Other iron-related disorders are caused by misregulation of cellular iron metabolism, which results in local accumulation of the metal in mitochondria. Brain iron overload is observed in neurodegenerative disorders. Secondary hemochromatosis develops as a complication of another disease. For example, repeated blood transfusions, a standard treatment of various anemias characterized by ineffective erythropoiesis, promote transfusional siderosis, while chronic liver diseases are often associated with mild to moderate secondary iron overload. In this critical review, we discuss pathophysiological and clinical aspects of all types of iron metabolism disorders (265 references).

  6. An alternating current superconductor susceptometric system to evaluate liver iron overload

    NASA Astrophysics Data System (ADS)

    Carneiro, A. A. O.; Fernandes, J. P.; Zago, M. A.; Covas, D. T.; Ángulo, I. L.; Baffa, O.

    2003-06-01

    An ac susceptometric system to quantify liver iron overload composed of a second order axial gradiometer coil coupled to a rf superconducting quantum interference device detector and a large field coil array is presented. A homogeneous ac magnetizing field with low frequency (7.7 Hz) and low intensity (114 μT) is used. Preliminary measurements over a group of 34 normal individuals and 20 patients with iron overload show the ability of the instrument to perform the measurement and to distinguish normal and pathological individuals. The diamagnetic signature of the surrounding tissues is minimized using a special water bag on the torso. In summary it was shown that with a relatively simple instrumentation it was possible to build a superconducting susceptometer dedicated to quantify in vivo iron concentrations, which is clinically important information in the assessment and management of patients with liver iron overload, mainly those who regularly receive blood transfusion.

  7. Iron overload impairs proliferation of erythroid progenitors cells (BFU-E) from patients with myelodysplastic syndromes.

    PubMed

    Hartmann, Julia; Braulke, Friederike; Sinzig, Ursula; Wulf, Gerald; Maas, Jens Holger; Konietschke, Frank; Haase, Detlef

    2013-03-01

    In patients with myelodysplastic syndromes (MDS) iron overload caused by long-term red blood cell transfusions is an important factor for comorbidity especially in low-risk MDS. In this report we present the results of a comparative study based on colony formation assays of hematopoietic cells in MDS patients with and without iron overload. We demonstrate that iron overload suppresses the proliferation of erythroid progenitors cells (BFU-E), while the myeloid compartment (CFU-GM) was not found to be affected. Even patients with slightly elevated ferritin values show an impaired proliferation capacity in comparison to patients with normal ferritin levels. Furthermore, we show that this negative impact is reversible by sufficient iron chelation therapy.

  8. Reducing Information Overload in Large Seismic Data Sets

    SciTech Connect

    HAMPTON,JEFFERY W.; YOUNG,CHRISTOPHER J.; MERCHANT,BION J.; CARR,DORTHE B.; AGUILAR-CHANG,JULIO

    2000-08-02

    Event catalogs for seismic data can become very large. Furthermore, as researchers collect multiple catalogs and reconcile them into a single catalog that is stored in a relational database, the reconciled set becomes even larger. The sheer number of these events makes searching for relevant events to compare with events of interest problematic. Information overload in this form can lead to the data sets being under-utilized and/or used incorrectly or inconsistently. Thus, efforts have been initiated to research techniques and strategies for helping researchers to make better use of large data sets. In this paper, the authors present their efforts to do so in two ways: (1) the Event Search Engine, which is a waveform correlation tool and (2) some content analysis tools, which area combination of custom-built and commercial off-the-shelf tools for accessing, managing, and querying seismic data stored in a relational database. The current Event Search Engine is based on a hierarchical clustering tool known as the dendrogram tool, which is written as a MatSeis graphical user interface. The dendrogram tool allows the user to build dendrogram diagrams for a set of waveforms by controlling phase windowing, down-sampling, filtering, enveloping, and the clustering method (e.g. single linkage, complete linkage, flexible method). It also allows the clustering to be based on two or more stations simultaneously, which is important to bridge gaps in the sparsely recorded event sets anticipated in such a large reconciled event set. Current efforts are focusing on tools to help the researcher winnow the clusters defined using the dendrogram tool down to the minimum optimal identification set. This will become critical as the number of reference events in the reconciled event set continually grows. The dendrogram tool is part of the MatSeis analysis package, which is available on the Nuclear Explosion Monitoring Research and Engineering Program Web Site. As part of the research

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Nakada, Satoshi; Ogasawara, Riki; Kawada, Shigeo; Maekawa, Takahiro; Ishii, Naokata

    2016-01-01

    External loads applied to skeletal muscle cause increases in the protein translation rate, which leads to muscle hypertrophy. Although some studies have demonstrated that increases in the capacity and efficiency of translation are involved in this process, it remains unclear how these two factors are related to the magnitude of muscle hypertrophy. The present study aimed to clarify the roles played by the capacity and efficiency of translation in muscle hypertrophy. We used an improved synergist ablation in which the magnitude of compensatory hypertrophy could be controlled by partial removal of synergist muscles. Male rats were assigned to four groups in which the plantaris muscle was unilaterally subjected to weak (WK), moderate (MO), middle (MI), and strong (ST) overloading by four types of synergist ablation. Fourteen days after surgery, the weight of the plantaris muscle per body weight increased by 8%, 22%, 32% and 45%, in the WK, MO, MI and ST groups, respectively. Five days after surgery, 18+28S rRNA content (an indicator of translational capacity) increased with increasing overload, with increases of 1.8-fold (MO), 2.2-fold (MI), and 2.5-fold (ST), respectively, relative to non-overloaded muscle (NL) in the WK group. rRNA content showed a strong correlation with relative muscle weight measured 14 days after surgery (r = 0.98). The phosphorylated form of p70S6K (a positive regulator of translational efficiency) showed a marked increase in the MO group, but no further increase was observed with further increase in overload (increases of 22.6-fold (MO), 17.4-fold (MI), and 18.2-fold (ST), respectively, relative to NL in the WK group). These results indicate that increases in ribosome biogenesis at the early phase of overloading are strongly dependent on the amount of overloading, and may play an important role in increasing the translational capacity for further gain of muscular size. PMID:26824605

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

    NASA Astrophysics Data System (ADS)

    Marcauteanu, Corina; Negrutiu, Meda; Sinescu, Cosmin; Demjan, Enikö; Hughes, Michael; Bradu, Adrian; Dobre, George; Podoleanu, Adrian G.

    2009-07-01

    The aim of this study is the early detection and monitoring of occlusal overload in bruxing patients. En-Face Optical coherence tomography (eF-OCT) and fluorescence microscopy (FM) were used for the imaging of several anterior teeth extracted from patients with light active bruxism. We found a characteristic pattern of enamel cracks, that reached the tooth surface. We concluded that the combination of the en-Face OCT and FM is a promising non-invasive alternative technique for reliable monitoring of occlusal overload.

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

    PubMed

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

    2013-01-01

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

  13. Iron Overload Leading to Torsades de Pointes in β-Thalassemia and Long QT Syndrome.

    PubMed

    Refaat, Marwan M; El Hage, Lea; Steffensen, Annette Buur; Hotait, Mostafa; Schmitt, Nicole; Scheinman, Melvin; Badhwar, Nitish

    2016-03-01

    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 laevis oocytes showed loss of function of the IKs current. The authors hypothesize that iron overload combined with the KCNQ1 gene mutation leads to prolongation of QTc and torsades de pointes. PMID:26920202

  14. 30 CFR 75.518-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    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...

  15. 30 CFR 77.506-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-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...

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

    ERIC Educational Resources Information Center

    Salyers, Jessica L.

    2013-01-01

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

  17. 30 CFR 75.518-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 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...

  18. 30 CFR 77.506-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-1 Electric equipment and circuits; overload and short circuit protection; minimum requirements... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electric equipment and circuits; overload and short circuit protection; minimum requirements. 77.506-1 Section 77.506-1 Mineral Resources MINE...

  19. 30 CFR 77.506-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-1 Electric equipment and circuits; overload and short circuit protection; minimum requirements... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electric equipment and circuits; overload and short circuit protection; minimum requirements. 77.506-1 Section 77.506-1 Mineral Resources MINE...

  20. 30 CFR 77.506-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-1 Electric equipment and circuits; overload and short circuit protection; minimum requirements... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electric equipment and circuits; overload and short circuit protection; minimum requirements. 77.506-1 Section 77.506-1 Mineral Resources MINE...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 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...

  2. 30 CFR 75.518-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 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...

  3. 30 CFR 75.518-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 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...

  4. Conflicting Physiological and Genomic Cardiopulmonary Effects of Recruitment Maneuvers in Murine Acute Lung Injury

    PubMed Central

    Mekontso Dessap, Armand; Voiriot, Guillaume; Zhou, Tong; Marcos, Elisabeth; Dudek, Steven M.; Jacobson, Jeff R.; Machado, Roberto; Adnot, Serge; Brochard, Laurent; Maitre, Bernard

    2012-01-01

    Low tidal volume ventilation, although promoting atelectasis, is a protective strategy against ventilator-induced lung injury. Deep inflation (DI) recruitment maneuvers restore lung volumes, but potentially compromise lung parenchymal and vascular function via repetitive overdistention. Our objective was to examine cardiopulmonary physiological and transcriptional consequences of recruitment maneuvers. C57/BL6 mice challenged with either PBS or LPS via aspiration were placed on mechanical ventilation (5 h) using low tidal volume inflation (TI; 8 μl/g) alone or in combination with intermittent DIs (0.75 ml twice/min). Lung mechanics during TI ventilation significantly deteriorated, as assessed by forced oscillation technique and pressure–volume curves. DI mitigated the TI-induced alterations in lung mechanics, but induced a significant rise in right ventricle systolic pressures and pulmonary vascular resistances, especially in LPS-challenged animals. In addition, DI exacerbated the LPS-induced genome-wide lung inflammatory transcriptome, with prominent dysregulation of a gene cluster involving vascular processes, as well as increases in cytokine concentrations in bronchoalveolar lavage fluid and plasma. Gene ontology analyses of right ventricular tissue expression profiles also identified inflammatory signatures, as well as apoptosis and membrane organization ontologies, as potential elements in the response to acute pressure overload. Our results, although confirming the improvement in lung mechanics offered by DI, highlight a detrimental impact in sustaining inflammatory response and exacerbating lung vascular dysfunction, events contributing to increases in right ventricle afterload. These novel insights should be integrated into the clinical assessment of the risk/benefit of recruitment maneuver strategies. PMID:22135358

  5. Biomechanics and histology of bovine claw suspensory tissue in early acute laminitis.

    PubMed

    Danscher, A M; Toelboell, T H; Wattle, O

    2010-01-01

    Weakening of the suspensory tissue supporting the pedal bone is the central issue in the theory of acute bovine laminitis, but this aspect has never been tested. The objective of this study was to investigate the effect of laminitis on the suspensory tissue. The hypothesis was that clinical and histological signs of acute laminitis are associated with decreased strength of the suspensory tissue of the bovine claw. Nonpregnant dairy heifers (n=10) received oral oligofructose overload (17 g/kg of body weight) and were killed 24 (n=4) and 72h (n=6) after overload. Control heifers (n=6) received tap water and were killed at 72 or 96h. Clinical, orthopedic, and histological examinations were carried out to confirm the occurrence of laminitis. After euthanasia, 2 adjacent tissue samples including the horn wall, lamellar layer, dermis, and pedal bone were cut from the dorso-abaxial aspect of each claw. Tissue samples were kept on ice until mounted on a mechanical testing frame, fixed by horn and bone, and loaded to failure. A stress displacement curve was generated and measurements of physiological support (force needed to displace 1mm beyond first resistance) and maximal support (force needed to break the tissue) were recorded. Heifers treated with oligofructose developed clinical signs consistent with ruminal and systemic acidosis after treatment as well as acute laminitis, characterized by weight shifting (35% of observations vs. 6% in controls), moderate lameness (100 vs. 17%, score of 3 out of 5 at 72h), and reaction to hoof testing (30 and 50% at 48 and 72h, respectively, vs. 0% in controls). Histological examination of claws from heifers killed 72h after overload showed changes consistent with acute laminitis, including stretched lamellae, wider basal cells with low chromatin density, and a thick, wavy, and blurry appearance of the basement membrane. Biomechanical results showed no effect of oligofructose overload on physiological support of the suspensory tissue

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

    SciTech Connect

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

    2007-01-01

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

  7. The Effects of Technological Overload on Children: An Art Therapist's Perspective

    ERIC Educational Resources Information Center

    Klorer, P. Gussie

    2009-01-01

    Children today are continually bombarded with visual and auditory stimulation, and many make their connections in cyberspace to the detriment of real-time face-to-face encounters with other people. The negative effects of multitasking and technological overload on children and adolescents are discussed in this viewpoint article from the…

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

    PubMed Central

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

    2015-01-01

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

  9. Estimation of iron overloads using oral exfoliative cytology in beta-thalassemia major patients

    PubMed Central

    Leekha, Swati; Nayar, Amit Kumar; Bakshi, Preeti; Sharma, Aman; Parhar, Swati; Soni, Sugandhi

    2016-01-01

    Background: Iron overload is a medical condition that occurs when too much of the mineral iron builds up inside the body and produces a toxic reaction. Thalassemia is a genetic disorder of hemoglobin synthesis, which requires regular blood transfusion therapy, and the lack of specific excretory pathways for iron in humans leads to iron overload in the body tissues. It is a major cause of morbidity and mortality in these patients. The estimation of iron levels in exfoliated buccal mucosal cells may provide a simple, noninvasive, and a safe procedure for estimating the iron overload by using the Perls’ Prussian blue stain. Methods: Smears were obtained from buccal mucosa of 40 randomly selected beta-thalassemia major patients and 40 healthy subjects as controls. Smears were stained with Perls’ Prussian blue method. Blood samples were taken for estimation of serum ferritin levels. Images of smears were analyzed using the software image J software version 1.47v and correlated with serum ferritin. Results: Perls’ positivity was observed in 87.5% of thalassemic patients with a positive correlation to serum ferritin levels. Conclusion: The use of exfoliative buccal mucosal cells for the evaluation of iron overloads in the body provides us with a diagnostic medium that is noninvasive, easy to collect, store, and transport, cost effective, and above all reliable. PMID:27081394

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  12. [The clinical significance of glycosylated ferritin in iron overloads and hematopoietic malignancies].

    PubMed

    Takakuwa, Y; Miyazawa, K; Yoshikawa, O; Toyama, K

    1994-08-01

    Serum ferritin concentration had been known to represent the amount of total body iron and has been clinically used as a parameter to evaluate the iron storage pool in a whole body. Glycosylated (secreted) and non-glycosylated (non-secreted) forms of serum ferritin (sFt) have been reported by others based on the difference in their affinity to concanavalin-A binding. In this report, we assessed the amount of glycosylated serum ferritin (Glyco-sFt) and the ratio (%) of Glyco-sFt/in hematopoietic disorders including iron overloads (n = 10), leukemias (n = 36), malignant lymphomas (n = 10), multiple myelomas (n = 3) and myelodysplastic syndromes (n = 12). A high percentage of Glyco-sFt was observed in normal healthy controls (n = 18, 78.1 +/- 7.4%) and iron-overloads (61.1 +/- 17.8%) as compared with that in hematopoietic malignancies (43.8 +/- 23.4%, p < 0.001). The amount of Glyco-sFt in iron-overloads was higher than that in hematopoietic malignancies with hyperferritinemia (p < 0.005). These data demonstrated that the same part of serum ferritin in hematopoietic malignancies was the non-secreted form and appeared to be derived from tumor cell lysis. We conclude that assessment of Glyco-Ft is a useful parameter to distinguish iron-overloads from malignant hematopoietic disorders both displaying hyperferritinemia.

  13. When Enough Is Not Enough: Information Overload and Metacognitive Decisions to Stop Studying Information

    ERIC Educational Resources Information Center

    Murayama, Kou; Blake, Adam B.; Kerr, Tyson; Castel, Alan D.

    2016-01-01

    People are often exposed to more information than they can actually remember. Despite this frequent form of information overload, little is known about how much information people choose to remember. Using a novel "stop" paradigm, the current research examined whether and how people choose to stop receiving new--possibly…

  14. Exploring the Influence of Information Overload on Middle Management Decision-Making in Organizations

    ERIC Educational Resources Information Center

    Carlevale, Edward A.

    2010-01-01

    This phenomenological study was an exploration of information overload and how it influenced middle management decision-making in a single organization. In-depth interviews were used to gather lived experiences of 22 middle managers at XYZ Defense Company in California. Data were analyzed using both HyperRESEARCH TM 2.8 software and a manual…

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

    ERIC Educational Resources Information Center

    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.…

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

    PubMed Central

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

    2013-01-01

    ABSTRACT To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions. PMID:24488397

  17. Antagonism of the thromboxane-prostanoid receptor is cardioprotective against right ventricular pressure overload.

    PubMed

    West, James D; Voss, Bryan M; Pavliv, Leo; de Caestecker, Mark; Hemnes, Anna R; Carrier, Erica J

    2016-06-01

    Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH) and is a significant cause of morbidity and mortality in other forms of pulmonary hypertension. There are no approved therapies directed at preserving RV function. F-series and E-series isoprostanes are increased in heart failure and PAH, correlate to the severity of disease, and can signal through the thromboxane-prostanoid (TP) receptor, with effects from vasoconstriction to fibrosis. The goal of these studies was to determine whether blockade of the TP receptor with the antagonist CPI211 was beneficial therapeutically in PAH-induced RV dysfunction. Mice with RV dysfunction due to pressure overload by pulmonary artery banding (PAB) were given vehicle or CPI211. Two weeks after PAB, CPI211-treated mice were protected from fibrosis with pressure overload. Gene expression arrays and immunoblotting, quantitative histology and morphometry, and flow cytometric analysis were used to determine the mechanism of CPI211 protection. TP receptor inhibition caused a near normalization of fibrotic area, prevented cellular hypertrophy while allowing increased RV mass, increased expression of antifibrotic thrombospondin-4, and blocked induction of the profibrotic transforming growth factor β (TGF-β) pathway. A thromboxane synthase inhibitor or low-dose aspirin failed to replicate these results, which suggests that a ligand other than thromboxane mediates fibrosis through the TP receptor after pressure overload. This study suggests that TP receptor antagonism may improve RV adaptation in situations of pressure overload by decreasing fibrosis and TGF-β signaling.

  18. Choosing To Examine Electronic Information: A Message Ranking Model To Minimize Information Overload.

    ERIC Educational Resources Information Center

    Losee, Robert M., Jr.

    Designed to minimize information overload in telecommunications systems, the formal model developed in this paper predicts the usefulness of a message based on the available message features, and may be used to rank messages by expected importance or economic worth. The assumptions of binary and two Poisson independent probabilistic distributions…

  19. Pressure overload-induced cardiac hypertrophy response requires janus kinase 2-histone deacetylase 2 signaling.

    PubMed

    Ying, Huang; Xu, Mao-Chun; Tan, Jing-Hua; Shen, Jing-Hua; Wang, Hao; Zhang, Dai-Fu

    2014-01-01

    Pressure overload induces cardiac hypertrophy through activation of Janus kinase 2 (Jak2), however, the underlying mechanisms remain largely unknown. In the current study, we tested whether histone deacetylase 2 (HDAC2) was involved in the process. We found that angiotensin II (Ang-II)-induced re-expression of fetal genes (Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) in cultured cardiomyocytes was prevented by the Jak2 inhibitor AG-490 and HDAC2 inhibitor Trichostatin-A (TSA), or by Jak2/HDAC2 siRNA knockdown. On the other hand, myocardial cells with Jak2 or HDAC2 over-expression were hyper-sensitive to Ang-II. In vivo, pressure overload by transverse aorta binding (AB) induced a significant cardiac hypertrophic response as well as re-expression of ANP and BNP in mice heart, which were markedly reduced by AG-490 and TSA. Significantly, AG-490, the Jak2 inhibitor, largely suppressed pressure overload-/Ang-II-induced HDAC2 nuclear exportation in vivo and in vitro. Meanwhile, TSA or HDAC2 siRNA knockdown reduced Ang-II-induced ANP/BNP expression in Jak2 over-expressed H9c2 cardiomyocytes. Together, these results suggest that HDAC2 might be a downstream effector of Jak2 to mediate cardiac hypertrophic response by pressure overload or Ang-II. PMID:25380525

  20. Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload.

    PubMed Central

    Houglum, K; Filip, M; Witztum, J L; Chojkier, M

    1990-01-01

    In hepatic iron overload, iron-catalyzed lipid peroxidation has been implicated in the mechanisms of hepatocellular injury. Lipid peroxidation may produce reactive aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which may form aldehyde-protein adducts. We investigated whether lipid peroxidation occurred in rats fed a diet containing 3% carbonyl iron for 5-13 wk, and if this resulted in the formation of MDA- and 4-HNE- protein adducts. Chronic iron feeding resulted in hepatic iron overload (greater than 10-fold) and concomitantly induced a 2-fold increase in hepatic lipid peroxidation. Using an antiserum specific for MDA-lysine protein adducts, we demonstrated by immunohistochemistry the presence of aldehyde-protein adducts in the cytosol of periportal hepatocytes, which co-localized with iron. In addition, MDA- and 4-HNE-lysine adducts were found in plasma proteins of animals with iron overload. Only MDA adducts were detected in albumin, while other plasma proteins including a approximately 120-kD protein had both MDA and 4-HNE adducts. In this animal model of hepatic iron overload, injury occurs primarily in periportal hepatocytes, where MDA-lysine protein adducts and excess iron co-localized. Images PMID:2123889

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 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...

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

    ERIC Educational Resources Information Center

    Hellar, David Benjamin

    2009-01-01

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

  3. 21 CFR 890.5575 - Powered external limb overload warning device.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Powered external limb overload warning device. 890.5575 Section 890.5575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices §...

  4. 21 CFR 890.5575 - Powered external limb overload warning device.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Powered external limb overload warning device. 890.5575 Section 890.5575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices §...

  5. 21 CFR 890.5575 - Powered external limb overload warning device.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Powered external limb overload warning device. 890.5575 Section 890.5575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices §...

  6. 21 CFR 890.5575 - Powered external limb overload warning device.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Powered external limb overload warning device. 890.5575 Section 890.5575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices §...

  7. 21 CFR 890.5575 - Powered external limb overload warning device.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Powered external limb overload warning device. 890.5575 Section 890.5575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices §...

  8. Fatty emaciation: a case report of suspected fat overload syndrome in oral refeeding.

    PubMed

    Macher, Arielle D; Palazuelos, Daniel; Maviglia, Saverio M

    2012-07-01

    Refeeding syndrome has been observed in patients receiving nutrition after a prolonged period of malnourishment and is characterized by multiple metabolic derangements. Besides hypophosphatemia and hypoglycemia, lipemia has been described in association with parenteral nutrition administration to the malnourished. The authors describe one anorexic patient who developed lipemia during oral refeeding, followed by a precipitous drop in hematocrit suggestive of fat overload syndrome.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

    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

  11. The impact of pressure overload on coronary vascular changes following myocardial infarction in rats.

    PubMed

    Chen, Jiqiu; Petrov, Artiom; Yaniz-Galende, Elisa; Liang, Lifan; de Haas, Hans J; Narula, Jagat; Hajjar, Roger J

    2013-03-01

    This study investigates the impact of pressure overload on vascular changes after myocardial infarction (MI) in rats. To evaluate the effect of pressure overload, MI was induced in three groups: 1) left coronary artery ligation for 1 mo (MI-1m), 2) ischemia 30 min/reperfusion for 1 mo (I/R-1m), and 3) ischemia-reperfusion (I/R) was performed after pressure overload induced by aortic banding for 2 mo; 1 mo post-I/R, aortic constriction was released (Ab+I/R+DeAb). Heart function was assessed by echocardiography and in vivo hemodynamics. Resin casting and three-dimensional imaging with microcomputed tomography were used to characterize changes in coronary vasculature. TTC (triphenyltetrazohum chloride) staining and Masson's Trichrome were conducted in parallel experiments. In normal rats, MI induced by I/R and permanent occlusion was transmural or subendocardial. Occluded arterial branches vanished in MI-1m rats. A short residual tail was retained, distal to the occluded site in the ischemic area in I/R-1m hearts. Vascular pathological changes in transmural MI mostly occurred in ischemic areas and remote vasculature remained normal. In pressure overloaded rats, I/R injury induced a sub-MI in which ischemia was transmural, but myocardium in the involved area had survived. The ischemic arterial branches were preserved even though the capillaries were significantly diminished and the pathological changes were extended to remote areas, characterized by fibrosis, atrial thrombus, and pulmonary edema in the Ab+I/R+DeAb group. Pressure overload could increase vascular tolerance to I/R injury, but also trigger severe global ventricular fibrosis and results in atrial thrombus and pulmonary edema. PMID:23275620

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

    PubMed

    Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

    2016-01-15

    We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis.

  13. Transient two-phase CFD simulation of overload pressure pulsation in a prototype sized Francis turbine considering the waterway dynamics

    NASA Astrophysics Data System (ADS)

    Mössinger, P.; Conrad, P.; Jung, A.

    2014-03-01

    At high load operation points, Francis turbines generally produce large cavitation volumes of central vortex character in the draft tube. In order to gain a deeper understanding of the flow behaviour at high load conditions a combined 1D-3D transient two-phase numerical investigation at prototype size was carried out and these results were compared with measured site data. A one-dimensional model to capture hydroacoustic effects along a pipeline will be presented. The corresponding PDEs were solved using an implicit finite difference scheme on a staggered grid. In contrast to previous studies this model is coupled to the commercial software ANSYS CFX through an interface which exchanges pressure and discharge data within every time step until convergence. Results of the one-dimensional approach as well as the coupled solution were validated with commercial one-dimensional software (SIMSEN) and a full threedimensional calculation for hydroacoustic test cases. Unlike former investigations the described 1D-3D approach is used to compare site data with a numerical analysis at prototype size focused on the amplitude and frequency of the pressure pulsation at overload condition. The combined model is able to capture the occurring phase change in the draft tube as well as the propagating pressure oscillation through the hydraulic system without solving for the whole penstock in a 3D manner, thus saving time and computational resources.

  14. Nonalcoholic Fatty Liver Disease Is Associated With Higher 1-year All-Cause Rehospitalization Rates in Patients Admitted for Acute Heart Failure

    PubMed Central

    Valbusa, Filippo; Bonapace, Stefano; Grillo, Cristina; Scala, Luca; Chiampan, Andrea; Rossi, Andrea; Zoppini, Giacomo; Lonardo, Amedeo; Arcaro, Guido; Byrne, Christopher D.; Targher, Giovanni

    2016-01-01

    Abstract Repeat hospitalization due to acute heart failure (HF) is a global public health problem that markedly impacts on health resource use. Identifying novel predictors of rehospitalization would help physicians to determine the optimal postdischarge plan for preventing HF rehospitalization. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for many heart diseases, including HF. We assessed whether NAFLD at hospital admission predicts 1-year all-cause rehospitalization in patients with acute HF. We enrolled all patients consecutively admitted for acute HF to our General Medicine Division, from January 2013 to April 2014, after excluding patients with acute myocardial infarction, severe heart valve diseases, malignancy, known liver diseases, and those with volume overload related to extracardiac causes. NAFLD was diagnosed by ultrasonography and exclusion of competing etiologies. The primary outcome of the study was the 1-year all-cause rehospitalization rate. Among the 107 patients enrolled in the study, the cumulative rehospitalization rate was 12.1% at 1 month, 25.2% at 3 months, 29.9% at 6 months, and 38.3% at 1 year. Patients with NAFLD had markedly higher 1-year rehospitalization rates than those without NAFLD (58% vs 21% at 1 y; P < 0.001 by the log-rank test). Cox regression analysis revealed that NAFLD was associated with a 5.5-fold increased risk of rehospitalization (adjusted hazard ratio 5.56, 95% confidence interval 2.46–12.1, P < 0.001) after adjustment for multiple HF risk factors and potential confounders. In conclusion, NAFLD was independently associated with higher 1-year rehospitalization in patients hospitalized for acute HF. PMID:26886619

  15. Employees' Perceptions of Email Communication, Volume and Management Strategies in an Australian University

    ERIC Educational Resources Information Center

    Pignata, Silvia; Lushington, Kurt; Sloan, Jeremy; Buchanan, Fiona

    2015-01-01

    Despite email playing a central role in university business, little is known about the strategies used by staff to manage email and the factors contributing to email overload. In a mixed method study undertaken in one Australian university comparing academic (n = 193) and professional (n = 278) staff, we found that while email volume was higher in…

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

    PubMed

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

    2013-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25922644

  20. The Overexpression of Twinkle Helicase Ameliorates the Progression of Cardiac Fibrosis and Heart Failure in Pressure Overload Model in Mice

    PubMed Central

    Tanaka, Atsushi; Ide, Tomomi; Fujino, Takeo; Onitsuka, Ken; Ikeda, Masataka; Takehara, Takako; Hata, Yuko; Ylikallio, Emil; Tyynismaa, Henna; Suomalainen, Anu; Sunagawa, Kenji

    2013-01-01

    Myocardial mitochondrial DNA (mtDNA) copy number decreases in heart failure. In post-myocardial infarction mice, increasing mtDNA copy number by overexpressing mitochondrial transcription factor attenuates mtDNA deficiency and ameliorates pathological remodeling thereby markedly improving survival. However, the functional significance of increased mtDNA copy number in hypertensive heart disease remains unknown. We addressed this question using transgenic mice that overexpress Twinkle helicase (Twinkle; Tg), the mtDNA helicase, and examined whether Twinkle overexpression protects the heart from left ventricular (LV) remodeling and failure after pressure overload created by transverse aortic constriction (TAC). Twinkle overexpression increased mtDNA copy number by 2.2±0.1-fold. Heart weight, LV diastolic volume and wall thickness were comparable between Tg and wild type littermates (WT) at 28 days after TAC operation. LV end-diastolic pressure increased in WT after TAC (8.6±2.8 mmHg), and this increase was attenuated in Tg (4.6±2.6 mmHg). Impaired LV fractional shortening after TAC operation was also suppressed in Tg, as measured by echocardiography (WT: 16.2±7.2% vs Tg: 20.7±6.2%). These LV functional improvements were accompanied by a decrease in interstitial fibrosis (WT: 10.6±1.1% vs Tg: 3.0±0.6%). In in vitro studies, overexpressing Twinkle using an adenovirus vector in cultured cardiac fibroblasts significantly suppressed mRNA of collagen 1a, collagen 3a and connective tissue growth factor, and angiotensin II-induced transforming growth factor β1 expression. The findings suggest that Twinkle overexpression prevents LV function deterioration. In conclusion, Twinkle overexpression increases mtDNA copy number and ameliorates the progression of LV fibrosis and heart failure in a mouse pressure overload model. Increasing mtDNA copy number by Twinkle overexpression could be a novel therapeutic strategy for hypertensive heart disease. PMID:23840758

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  3. Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment

    NASA Technical Reports Server (NTRS)

    McCall, G. E.; Allen, D. L.; Linderman, J. K.; Grindeland, R. E.; Roy, R. R.; Mukku, V. R.; Edgerton, V. R.

    1998-01-01

    The purpose of this study was to determine the effects of functional overload (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I) administration on myonuclear number and domain size in rat soleus muscle fibers. Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius muscles and, after 7 days of recovery, were injected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receiving saline vehicle served as controls (Con group). Muscle wet weight was 32% greater in the FO than in the Con group: 162 +/- 8 vs. 123 +/- 16 mg. Muscle weight in the FO + GH/IGF-I group (196 +/- 14 mg) was 59 and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 +/- 445 microm2) was increased compared with the Con (2,044 +/- 108 microm2) and FO (2,267 +/- 301 microm2) groups. The difference in fiber size between the FO and Con groups was not significant. Mean myonuclear number increased in FO (187 +/- 15 myonuclei/mm) and FO + GH/IGF-I (217 +/- 23 myonuclei/mm) rats compared with Con (155 +/- 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume per myonucleus (myonuclear domain) was similar across groups. These results demonstrate that the larger mean muscle weight and fiber cross-sectional area occurred when FO was combined with GH/IGF-I administration and that myonuclear number increased concomitantly with fiber volume. Thus there appears to be some mechanism(s) that maintains the myonuclear domain when a fiber hypertrophies.

  4. High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

    PubMed Central

    2011-01-01

    Background To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI) and resultant systemic inflammatory responses. Methods Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV) with either a low tidal volume (Vt) of 6 mL/kg and 5 cm H2O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis) or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis). Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D) weight ratios, histological lung injury and plasma mediator concentrations were measured. Results Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed. Conclusions During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of mediators. PMID:22204611

  5. Acute respiratory distress syndrome following cardiovascular surgery: current concepts and novel therapeutic approaches

    PubMed Central

    Hoegl, Sandra; Zwissler, Bernhard; Eltzschig, Holger K.; Vohwinkel, Christine

    2015-01-01

    Purpose of review This review gives an update on current treatment options and novel concepts on the prevention and treatment of the acute respiratory distress syndrome (ARDS) in cardiovascular surgery patients. Recent findings The only proven beneficial therapeutic options in ARDS are those that help to prevent further ventilator-induced lung injury, such as prone position, use of lung-protective ventilation strategies, and extracorporeal membrane oxygenation. In the future also new approaches like mesenchymal cell therapy, activation of hypoxia-elicited transcription factors or targeting of purinergic signaling may be successful outside the experimental setting. Owing to the so far limited treatment options, it is of great importance to determine patients at risk for developing ARDS already perioperatively. In this context, serum biomarkers and lung injury prediction scores could be useful. Summary Preventing ARDS as a severe complication in the cardiovascular surgery setting may help to reduce morbidity and mortality. As cardiovascular surgery patients are of greater risk to develop ARDS, preventive interventions should be implemented early on. Especially, use of low tidal volumes, avoiding of fluid overload and restrictive blood transfusion regimes may help to prevent ARDS. PMID:26598954

  6. B-type natriuretic peptide-directed ultrafiltration improves care in acutely hospitalized dialysis patients.

    PubMed

    Tapolyai, Mihály; Uysal, Aşkin; Maeweathers, Gail; Bahta, Elias; Dossabhoy, Neville R

    2009-01-01

    In an observational study in 19 consecutive acutely hospitalized dialysis patients, ultrafiltration (UF) volume was determined by B-type natriuretic peptide (BNP) levels. Patients were ultrafiltrated daily until they achieved a target BNP level <500 pg/mL. The UF volumes ranged from 2 to 5 L per session. All patients were male veterans aged 68+/-11 years (mean +/- SD), 74% were diabetic, 47% were African Americans, 58% underwent prevalent dialysis, and 53% had an arteriovenous fistula. Left ventricular ejection fraction on 2-dimensional echocardiography was 43.8%+/-27.9% (n=16). The admission BNP was 2412+/-1479 pg/mL (range, 561-5000 pg/mL) and BNP at hospital discharge was 1245+/-1173 pg/mL (range, 345-5000 pg/mL) (nonparametric Wilcoxon P=.0013). Admission weight was 88.9+/-27.9 kg and at discharge was 78.1+/-25.6 kg (P=.0002). The number of antihypertensive medications taken was 3.8+/-2.0 at admission and 2.3+/-1.7 at discharge (P=.0005). The number of patients with >2 blood pressure medications decreased from 14 to 6 (Fisher exact test, P=.02). The systolic/diastolic/mean arterial blood pressure decreased from admission to discharge (153.6+/-43.8/80.6+/-21.8/102.4+/-27.3 to 132.1+/-27.9/68.9+/-14.6/89.9+/-16.5 mm Hg; P=.0222/.0139/.0329, respectively). Although all patients were volume-overloaded at admission according to BNP criteria (>500), only 42% were identified as having heart failure. BNP-directed UF is safe because it minimizes symptomatic hypotension, identifies occult congestive heart failure in a large number of patients, and significantly reduces blood pressure in addition to reducing body weight and number of medications used. PMID:19522962

  7. Fractures related to occlusal overload with single posterior implants: a clinical report.

    PubMed

    Conrad, Heather J; Schulte, John K; Vallee, Mark C

    2008-04-01

    This clinical report describes 2 patient situations in which fractures related to occlusal overload occurred with a single posterior implants. The initial clinical presentation of both patients appeared to be screw loosening, but upon further examination, implant and abutment fractures were identified. Several factors are described that have been implicated in the etiology of implant fractures, including occlusal overload, implant location, inadequate fit of the prosthesis, design of the prosthesis, progressive bone loss, metal fatigue, implant diameter, manufacturing defects, and galvanic activity. This article describes the management of implant and abutment fractures and discusses possible mechanisms of failure for the patient situations presented. Careful treatment planning and execution of implant therapy is necessary to minimize the risk of implant and component fractures. PMID:18395533

  8. Iron overload, cardiac and other factors affecting pregnancy in thalassemia major.

    PubMed

    Tsironi, Maria; Karagiorga, Markissia; Aessopos, Athanasios

    2010-06-01

    The reproductive thalassemic population is growing older and doctors confront the challenge of the thalassemic pregnancy. Pregnancy is characterized by dynamic multiple system changes, resulting in increased basal oxygen consumption, changes in energy substrate use by different organs and increased susceptibility to oxidative stress, while homozygous transfusion-dependent beta-thalassemia (beta-thal) patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload. Pregnant thalassemic patients require significantly larger amount of total blood transfusion during pregnancy and iron overload increases the oxidative stress of pregnancy, while the risk for cardiovascular events, in a high cardiac output state, is augmented and chelation treatment is generally avoided due to the potential teratogenicity. Pregnancy in thalassemia major should be considered high risk, and be cared for by an expert team with special caution and sensitivity.

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

    NASA Technical Reports Server (NTRS)

    Koszarny, Z.; Maziarka, S.

    1981-01-01

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

  10. Analysis of transformer loss evaluation and economic considerations in transformer overloading calculations

    SciTech Connect

    Sen, P.K.; Pansuwan, S.; Nelson, J.P.

    1999-11-01

    Economic considerations of possible overloading the transformer and accepting the reduced life expectancy due to higher hot spot temperature rise must be evaluated carefully against the delay in transformer replacement or addition of a second transformer to increase the capacity. This is a very significant question and quite often asked by the system planner, however, without much success in getting a practical answer. This paper, in two parts will address these interrelated economic issues. Part one deals with the loss evaluation methodology. The second part will deal with the design and economic aspects of transformer overloading, possible loss of life expectancy and the corresponding replacement strategy. The analyses will be done using simple mathematical modeling so that the practicing engineers can make quick. decisive but meaningful decisions.

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

    NASA Astrophysics Data System (ADS)

    Koszarny, Z.; Maziarka, S.

    1981-05-01

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

  12. Overload and work-family conflict among Australian dual-career families: moderating effects of support.

    PubMed

    Elloy, David F; Mackie, Beth

    2002-12-01

    Individuals in dual-career situations have become increasingly common all over the world. For couples dealing with multiple demands, this lifestyle often generates stresses and strains at home and at work, which can have negative consequences for organizations. Most empirical research into this lifestyle has been conducted in the United States and Britain, and very little in Australia. This particular study, based on data from an Australian sample of 65 dual-career couples, analyzed the relation between overload and work-family conflict and the moderating effects of support (supervisor, coworkers, and friends). Results confirm that overload was significantly related to work-family conflict but no moderating effects were found for support. Limitations of the study and an organizational role in managing the work-family interface dual-career couples are discussed.

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

    PubMed

    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. PMID:26021458

  14. Antagonism of the thromboxane-prostanoid receptor is cardioprotective against right ventricular pressure overload.

    PubMed

    West, James D; Voss, Bryan M; Pavliv, Leo; de Caestecker, Mark; Hemnes, Anna R; Carrier, Erica J

    2016-06-01

    Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH) and is a significant cause of morbidity and mortality in other forms of pulmonary hypertension. There are no approved therapies directed at preserving RV function. F-series and E-series isoprostanes are increased in heart failure and PAH, correlate to the severity of disease, and can signal through the thromboxane-prostanoid (TP) receptor, with effects from vasoconstriction to fibrosis. The goal of these studies was to determine whether blockade of the TP receptor with the antagonist CPI211 was beneficial therapeutically in PAH-induced RV dysfunction. Mice with RV dysfunction due to pressure overload by pulmonary artery banding (PAB) were given vehicle or CPI211. Two weeks after PAB, CPI211-treated mice were protected from fibrosis with pressure overload. Gene expression arrays and immunoblotting, quantitative histology and morphometry, and flow cytometric analysis were used to determine the mechanism of CPI211 protection. TP receptor inhibition caused a near normalization of fibrotic area, prevented cellular hypertrophy while allowing increased RV mass, increased expression of antifibrotic thrombospondin-4, and blocked induction of the profibrotic transforming growth factor β (TGF-β) pathway. A thromboxane synthase inhibitor or low-dose aspirin failed to replicate these results, which suggests that a ligand other than thromboxane mediates fibrosis through the TP receptor after pressure overload. This study suggests that TP receptor antagonism may improve RV adaptation in situations of pressure overload by decreasing fibrosis and TGF-β signaling. PMID:27252848

  15. Antagonism of the thromboxane-prostanoid receptor is cardioprotective against right ventricular pressure overload

    PubMed Central

    Voss, Bryan M.; Pavliv, Leo; de Caestecker, Mark; Hemnes, Anna R.; Carrier, Erica J.

    2016-01-01

    Abstract Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH) and is a significant cause of morbidity and mortality in other forms of pulmonary hypertension. There are no approved therapies directed at preserving RV function. F-series and E-series isoprostanes are increased in heart failure and PAH, correlate to the severity of disease, and can signal through the thromboxane-prostanoid (TP) receptor, with effects from vasoconstriction to fibrosis. The goal of these studies was to determine whether blockade of the TP receptor with the antagonist CPI211 was beneficial therapeutically in PAH-induced RV dysfunction. Mice with RV dysfunction due to pressure overload by pulmonary artery banding (PAB) were given vehicle or CPI211. Two weeks after PAB, CPI211-treated mice were protected from fibrosis with pressure overload. Gene expression arrays and immunoblotting, quantitative histology and morphometry, and flow cytometric analysis were used to determine the mechanism of CPI211 protection. TP receptor inhibition caused a near normalization of fibrotic area, prevented cellular hypertrophy while allowing increased RV mass, increased expression of antifibrotic thrombospondin-4, and blocked induction of the profibrotic transforming growth factor β (TGF-β) pathway. A thromboxane synthase inhibitor or low-dose aspirin failed to replicate these results, which suggests that a ligand other than thromboxane mediates fibrosis through the TP receptor after pressure overload. This study suggests that TP receptor antagonism may improve RV adaptation in situations of pressure overload by decreasing fibrosis and TGF-β signaling. PMID:27252848

  16. Continuing treatment with Salvia miltiorrhiza injection attenuates myocardial fibrosis in chronic iron-overloaded mice.

    PubMed

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

    2015-01-01

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

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

    PubMed

    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.

  18. Chronic iron overload in rats induces oval cells in the liver.

    PubMed Central

    Smith, P. G.; Yeoh, G. C.

    1996-01-01

    Liver damage induced by a variety of agents including hepatocarcinogens, alcohol, and virus induces proliferation of oval cells. In this study, iron overloading of the liver is used as a means of inducing liver damage over an extended period to ascertain whether it promotes the appearance of oval cells. Rats were fed a 2% carbonyl-iron-supplemented diet for 3 or 6 months. Extensive iron deposits appeared periportally in hepatocytes and some Kupffer cells. Iron deposition was less pronounced pericentrally. Small oval-like cells, morphologically and immunocytochemically similar to CDE-derived oval cells, were identified and quantified. They first emerged periportally and subsequently in small tracts or foci nearer central regions and stained positively for alpha-fetoprotein, pi-class glutathione S-transferase, and the embryonic form of pyruvate kinase. They contained very few iron deposits and were classified as iron free. The major difference between CDE- and iron-overload-derived oval cells was that the latter were negative for transferrin. This study shows that cellular changes occurring in iron-overloaded rat liver are similar to those observed in rats placed on a hepatocarcinogenic diet and in rats chronically exposed to alcohol. Images Figure 1 Figure 2 Figure 3 PMID:8701979

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

    PubMed

    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.

  20. The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

    PubMed Central

    Hu, Liang; Feng, Yu; Wang, Song; Zhang, Wei-yan; Yin, Ning; Mo, Xu-Ming

    2016-01-01

    Background Pulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknown. Methods and Results We investigated the role of succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH induced by pressure overload in SD rats. GPR91 was shown to be located in cardiomyocytes. In the sham and PAB rats, succinate treatment further aggravated RVH, up-regulated RVH-associated genes and increased p-Akt/t-Akt levels in vivo. In vitro, succinate treatment up-regulated the levels of the hypertrophic gene marker anp and p-Akt/t-Akt in cardiomyocytes. All these effects were inhibited by the PI3K antagonist wortmannin both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared to that in human RVH. Conclusions Our findings indicate that succinate-GPR91 signaling may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. Therefore, GPR91 may be a novel therapeutic target for treating pressure overload-induced RVH. PMID:26824665

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

    PubMed

    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.

  2. Dietary phosphorus overload aggravates the phenotype of the dystrophin-deficient mdx mouse.

    PubMed

    Wada, Eiji; Yoshida, Mizuko; Kojima, Yoriko; Nonaka, Ikuya; Ohashi, Kazuya; Nagata, Yosuke; Shiozuka, Masataka; Date, Munehiro; Higashi, Tetsuo; Nishino, Ichizo; Matsuda, Ryoichi

    2014-11-01

    Duchenne muscular dystrophy is a lethal X-linked disease with no effective treatment. Progressive muscle degeneration, increased macrophage infiltration, and ectopic calcification are characteristic features of the mdx mouse, a murine model of Duchenne muscular dystrophy. Because dietary phosphorus/phosphate consumption is increasing and adverse effects of phosphate overloading have been reported in several disease conditions, we examined the effects of dietary phosphorus intake in mdx mice phenotypes. On weaning, control and mdx mice were fed diets containing 0.7, 1.0, or 2.0 g phosphorus per 100 g until they were 90 days old. Dystrophic phenotypes were evaluated in cryosections of quadriceps and tibialis anterior muscles, and maximal forces and voluntary activity were measured. Ectopic calcification was analyzed by electron microscopy to determine the cells initially responsible for calcium deposition in skeletal muscle. Dietary phosphorus overload dramatically exacerbated the dystrophic phenotypes of mdx mice by increasing inflammation associated with infiltration of M1 macrophages. In contrast, minimal muscle necrosis and inflammation were observed in exercised mdx mice fed a low-phosphorus diet, suggesting potential beneficial therapeutic effects of lowering dietary phosphorus intake on disease progression. To our knowledge, this is the first report showing that dietary phosphorus intake directly affects muscle pathological characteristics of mdx mice. Dietary phosphorus overloading promoted dystrophic disease progression in mdx mice, whereas restricting dietary phosphorus intake improved muscle pathological characteristics and function.

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

    PubMed Central

    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

  4. Modeling of Information Diffusion in Twitter-Like Social Networks under Information Overload

    PubMed Central

    Li, Wei

    2014-01-01

    Due to the existence of information overload in social networks, it becomes increasingly difficult for users to find useful information according to their interests. This paper takes Twitter-like social networks into account and proposes models to characterize the process of information diffusion under information overload. Users are classified into different types according to their in-degrees and out-degrees, and user behaviors are generalized into two categories: generating and forwarding. View scope is introduced to model the user information-processing capability under information overload, and the average number of times a message appears in view scopes after it is generated by a given type user is adopted to characterize the information diffusion efficiency, which is calculated theoretically. To verify the accuracy of theoretical analysis results, we conduct simulations and provide the simulation results, which are consistent with the theoretical analysis results perfectly. These results are of importance to understand the diffusion dynamics in social networks, and this analysis framework can be extended to consider more realistic situations. PMID:24795541

  5. Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes.

    PubMed

    Ono, Yukiya; Ishigami, Masatoshi; Hayashi, Kazuhiko; Wakusawa, Shinya; Hayashi, Hisao; Kumagai, Kotaro; Morotomi, Natsuko; Yamashita, Tetsuji; Kawanaka, Miwa; Watanabe, Minemori; Ozawa, Hiroaki; Tai, Mayumi; Miyajima, Hiroaki; Yoshioka, Kentarou; Hirooka, Yoshiki; Goto, Hidemi

    2015-06-28

    In biology, redox reactions are essential and sometimes harmful, and therefore, iron metabolism is tightly regulated by cuproproteins. Since the state of copper in iron overload syndromes remains unclear, we investigated whether copper metabolism is altered in these syndromes. Eleven patients with iron overload syndromes participated in this study. The clinical diagnoses were aceruloplasminemia (n=2), hemochromatosis (n=5), ferroportin disease (n=2), and receiving excess intravenous iron supplementation (n=2). Liver specimens were analyzed using a light microscope and transmission electron microscope equipped with an X-ray analyzer. In addition to a large amount of iron associated with oxygen and phosphorus, the iron-rich hemosiderins of hepatocytes and Kupffer cells contained small amounts of copper and sulfur, regardless of disease etiology. Two-dimensional imaging clearly showed that cuproproteins were distributed homogenously with iron complexes within hemosiderins. Copper stasis was unlikely in noncirrhotic patients. The enhanced induction of cuproproteins by excess iron may contribute to copper accumulation in hemosiderins. In conclusion, we have demonstrated that copper accumulates in hemosiderins in iron overload conditions, perhaps due to alterations in copper metabolism. PMID:26356991

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

    PubMed Central

    Meng, Xiawei; Zhao, Yulong

    2016-01-01

    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. PMID:27005627

  7. Functional Role of HSP47 in the Periodontal Ligament Subjected to Occlusal Overload in Mice

    PubMed Central

    Mimura, Hiroaki; Takaya, Tatsuo; Matsuda, Saeka; Nakano, Keisuke; Muraoka, Rina; Tomida, Mihoko; Okafuji, Norimasa; Fujii, Takeo; Kawakami, Toshiyuki

    2016-01-01

    We carried out an experiment to induce traumatic occlusion in mice periodontal tissue and analyzed the expression of HSP47. Continuous traumatic occlusion resulted to damage and remodeling of periodontal ligament as well as increase in osteoclasts and bone resorption. Four days after traumatic occlusion, osteoclasts did not increase but Howship's lacunae became enlarged. That is, the persistent occlusal overload can destroy collagen fibers in the periodontal ligament. This was evident by the increased in HSP47 expression with the occlusal overload. HSP47 is maintained in fibroblasts for repair of damaged collagen fibers. On the other hand, osteoclasts continue to increase although the load was released. The osteoclasts that appeared on the alveolar bone surface were likely due to sustained activity. The increase in osteoclasts was estimated to occur after load application at day 4. HSP47 continued to increase until day 6 in experiment 2 but then reduced at day 10. Therefore, HSP47 appears after a period of certain activities to repair damaged collagen fibers, and the activity was returned to a state of equilibrium at day 30 with significantly diminished expression. Thus, the results suggest that HSP47 is actively involved in homeostasis of periodontal tissue subjected to occlusal overload. PMID:27076780

  8. Biochemical Competition Makes Fatty-Acid β-Oxidation Vulnerable to Substrate Overload

    PubMed Central

    van Eunen, Karen; Simons, Sereh M. J.; Gerding, Albert; Bleeker, Aycha; den Besten, Gijs; Touw, Catharina M. L.; Houten, Sander M.; Groen, Bert K.; Krab, Klaas; Reijngoud, Dirk-Jan; Bakker, Barbara M.

    2013-01-01

    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. PMID:23966849

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Triggering the succinate receptor GPR91 enhances pressure overload-induced right ventricular hypertrophy

    PubMed Central

    Yang, Lei; Yu, Di; Fan, Huan-Huan; Feng, Yu; Hu, Liang; Zhang, Wei-Yan; Zhou, Kai; Mo, Xu-Ming

    2014-01-01

    Background: Pulmonary arterial hypertension (PAH) leads to pressure overload in the right ventricle (RV) and induces right ventricular hypertrophy (RVH). GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, which increases in RVH; however, its role remains unknown. Methods and results: We studied succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH in the SD rats due to pressure overload. We report that GPR91 was located in cardiomyocytes. We found that the expressions of GPR91 and p-Akt in the RV significantly increased in the PAB model compared with the sham. In the PAB rats, the treatment of succinate further increased the p-Akt levels and aggravated RVH in vivo. In in vitro studies, succinate stimulated the up-regulation of the hypertrophic gene marker anp. All these effects were inhibited by the antagonist of PI3K, wortmannin, both in vivo and in vitro. Finally, we found that the GPR91-PI3K/Akt axis was also up-regulated compared with the sham in human RVH. Conclusions: Our results suggest that succinate-GPR91 is involved in RVH via PI3K/Akt signaling in vivo and in vitro. GPR91 may be a novel therapeutic target for RVH induced by pressure overload. PMID:25337184

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

    PubMed

    van Eunen, Karen; Simons, Sereh M J; Gerding, Albert; Bleeker, Aycha; den Besten, Gijs; Touw, Catharina M L; Houten, Sander M; Groen, Bert K; Krab, Klaas; Reijngoud, Dirk-Jan; Bakker, Barbara M

    2013-01-01

    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.

  13. Low molecular weight fucoidan protects renal tubular cells from injury induced by albumin overload

    PubMed Central

    Jia, Yingli; Sun, Yi; Weng, Lin; Li, Yingjie; Zhang, Quanbin; Zhou, Hong; Yang, Baoxue

    2016-01-01

    Albuminuria is a causative and aggravating factor for progressive renal damage in chronic kidney disease (CKD). The aim of this study was to determine if low molecular weight fucoidan (LMWF) could protect renal function and tubular cells from albumin overload caused injury. Treatment with 10 mg/g bovine serum albumin caused renal dysfunction, morphological changes, and overexpression of inflammation and fibrosis associated proteins in 129S2/Sv mice. LMWF (100 mg/kg) protected against kidney injury and renal dysfunction with decreased blood creatinine by 34% and urea nitrogen by 25%, increased creatinine clearance by 48%, and decreased significantly urinary albumin concentration. In vitro proximal tubule epithelial cell (NRK-52E) model showed that LMWF dose-dependently inhibited overexpression of proinflammatory and profibrotic factors, oxidative stress and apoptosis caused by albumin overload. These experimental results indicate that LMWF protects against albumin overload caused renal injury by inhibiting inflammation, fibrosis, oxidative stress and apoptosis, which suggests that LMWF could be a promising candidate drug for preventing CKD. PMID:27545472

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Provider Role Attitudes, Marital Satisfaction, Role Overload, and Housework: A Dyadic Approach

    PubMed Central

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

    2010-01-01

    Treating the marital dyad as the unit of analysis, this study examined the within-couple patterning of 272 dual-earner spouses’ provider role attitudes and their longitudinal associations with marital satisfaction, role overload, and the division of housework. Based on the congruence of husbands’ and wives’ provider role attitudes, couples were classified into one of four types: (1) main-secondary, (2) coprovider, (3) ambivalent coprovider, and (4) mismatched couples. Nearly half of all spouses differed in their attitudes about breadwinning. A series of mixed model ANCOVAs revealed significant between- and within-couple differences in human capital characteristics, spouses’ perceptions of marital satisfaction and role overload, and the division of housework across 3 years of measurement. Coprovider couples reported higher levels of marital satisfaction and a more equitable division of housework than the other couple groups. Wives in the ambivalent coprovider couples’ group reported higher levels of role overload than their husbands to a greater extent than was found in the other couple groups. As the first study to adopt a dyadic approach that considers the meanings that both spouses in dual-earner couples ascribe to paid employment, these findings advance understanding of how dual-earner spouses’ provider role attitudes serve as contexts for marital quality, behavior, and role-related stress. PMID:20954767

  16. Marginal peri-implantitis due to occlusal overload. A case report.

    PubMed

    Uribe, Roberto; Peñarrocha, Miguel; Sanchis, Jose María; García, Oscar

    2004-01-01

    The etiology of marginal peri-implantitis describes an infectious factor and a biomechanical factor resulting from occlusal overload. Clinical and experimental articles oriented to the biomechanical factor are scarce, so as the studies about the histology associated to periimplantitis. We present a case of marginal peri-implantitis on an implant in the mandibular molar zone caused by occlusal overload, which led to an osseous defect on the marginal crest. The treatment was composed of occlusal adjustment, removal of contaminated surgical tissue, and autogenous bone graft, which varies from the common treatment of infectious peri-implantitis. Histologic analysis of peri-implantitis tissue reveals a juxtaepithelial lympho-plasmocytorious infiltrate and a central zone of dense fibro-connective tissue with scanty inflammatory cells, which differs from the chronic inflammatory tissue associated with infectious peri-implantitis. Clinical and radiographic followup control after 12 months evidenced the remission of the symptoms and bone regeneration on the marginal crest. We consider that in the treatment of marginal peri-implantitis, it is necessary to continue the studies on the histological differences between the infectious types and those that are caused by occlusal overload.

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

    PubMed

    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

  18. Thymoquinone, a bioactive component of Nigella sativa, normalizes insulin secretion from pancreatic β-cells under glucose overload via regulation of malonyl-CoA.

    PubMed

    Gray, Joshua P; Burgos, Delaine Zayasbazan; Yuan, Tao; Seeram, Navindra; Rebar, Rebecca; Follmer, Rebecca; Heart, Emma A

    2016-03-15

    Thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) is a major bioactive component of Nigella sativa, a plant used in traditional medicine to treat a variety of symptoms, including elevated blood glucose levels in type 2 diabetic patients. Normalization of elevated blood glucose depends on both glucose disposal by peripheral tissues and glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. We employed clonal β-cells and rodent islets to investigate the effects of thymoquinone (TQ) and Nigella sativa extracts (NSEs) on GSIS and cataplerotic metabolic pathways implicated in the regulation of GSIS. TQ and NSE regulated NAD(P)H/NAD(P)(+) ratios via a quinone-dependent redox cycling mechanism. TQ content was positively correlated with the degree of redox cycling activity of NSE extracts, suggesting that TQ is a major component engaged in mediating NSE-dependent redox cycling. Both acute and chronic exposure to TQ and NSE enhanced GSIS and were associated with the ability of TQ and NSE to increase the ATP/ADP ratio. Furthermore, TQ ameliorated the impairment of GSIS following chronic exposure of β-cells to glucose overload. This protective action was associated with the TQ-dependent normalization of chronic accumulation of malonyl-CoA, elevation of acetyl-CoA carboxylase (ACC), fatty acid synthase, and fatty acid-binding proteins following chronic glucose overload. Together, these data suggest that TQ modulates the β-cell redox circuitry and enhances the sensitivity of β-cell metabolic pathways to glucose and GSIS under normal conditions as well as under hyperglycemia. This action is associated with the ability of TQ to regulate carbohydrate-to-lipid flux via downregulation of ACC and malonyl-CoA.

  19. Transcriptional activation of LON Gene by a new form of mitochondrial stress: A role for the nuclear respiratory factor 2 in StAR overload response (SOR).

    PubMed

    Bahat, Assaf; Perlberg, Shira; Melamed-Book, Naomi; Isaac, Sara; Eden, Amir; Lauria, Ines; Langer, Thomas; Orly, Joseph

    2015-06-15

    High output of steroid hormone synthesis in steroidogenic cells of the adrenal cortex and the gonads requires the expression of the steroidogenic acute regulatory protein (StAR) that facilitates cholesterol mobilization to the mitochondrial inner membrane where the CYP11A1/P450scc enzyme complex converts the sterol to the first steroid. Earlier studies have shown that StAR is active while pausing on the cytosolic face of the outer mitochondrial membrane while subsequent import of the protein into the matrix terminates the cholesterol mobilization activity. Consequently, during repeated activity cycles, high level of post-active StAR accumulates in the mitochondrial matrix. To prevent functional damage due to such protein overload effect, StAR is degraded by a sequence of three to four ATP-dependent proteases of the mitochondria protein quality control system, including LON and the m-AAA membranous proteases AFG3L2 and SPG7/paraplegin. Furthermore, StAR expression in both peri-ovulatory ovarian cells, or under ectopic expression in cell line models, results in up to 3-fold enrichment of the mitochondrial proteases and their transcripts. We named this novel form of mitochondrial stress as StAR overload response (SOR). To better understand the SOR mechanism at the transcriptional level we analyzed first the unexplored properties of the proximal promoter of the LON gene. Our findings suggest that the human nuclear respiratory factor 2 (NRF-2), also known as GA binding protein (GABP), is responsible for 88% of the proximal promoter activity, including the observed increase of transcription in the presence of StAR. Further studies are expected to reveal if common transcriptional determinants coordinate the SOR induced transcription of all the genes encoding the SOR proteases.

  20. Thymoquinone, a bioactive component of Nigella sativa, normalizes insulin secretion from pancreatic β-cells under glucose overload via regulation of malonyl-CoA.

    PubMed

    Gray, Joshua P; Burgos, Delaine Zayasbazan; Yuan, Tao; Seeram, Navindra; Rebar, Rebecca; Follmer, Rebecca; Heart, Emma A

    2016-03-15

    Thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) is a major bioactive component of Nigella sativa, a plant used in traditional medicine to treat a variety of symptoms, including elevated blood glucose levels in type 2 diabetic patients. Normalization of elevated blood glucose depends on both glucose disposal by peripheral tissues and glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. We employed clonal β-cells and rodent islets to investigate the effects of thymoquinone (TQ) and Nigella sativa extracts (NSEs) on GSIS and cataplerotic metabolic pathways implicated in the regulation of GSIS. TQ and NSE regulated NAD(P)H/NAD(P)(+) ratios via a quinone-dependent redox cycling mechanism. TQ content was positively correlated with the degree of redox cycling activity of NSE extracts, suggesting that TQ is a major component engaged in mediating NSE-dependent redox cycling. Both acute and chronic exposure to TQ and NSE enhanced GSIS and were associated with the ability of TQ and NSE to increase the ATP/ADP ratio. Furthermore, TQ ameliorated the impairment of GSIS following chronic exposure of β-cells to glucose overload. This protective action was associated with the TQ-dependent normalization of chronic accumulation of malonyl-CoA, elevation of acetyl-CoA carboxylase (ACC), fatty acid synthase, and fatty acid-binding proteins following chronic glucose overload. Together, these data suggest that TQ modulates the β-cell redox circuitry and enhances the sensitivity of β-cell metabolic pathways to glucose and GSIS under normal conditions as well as under hyperglycemia. This action is associated with the ability of TQ to regulate carbohydrate-to-lipid flux via downregulation of ACC and malonyl-CoA. PMID:26786775

  1. [The relationship between the heart and the kidney in acute heart failure: doubts of the cardiologist and the nephrologist's point of view].

    PubMed

    Di Tano, Giuseppe; Misuraca, Gianfranco; Ronco, Claudio; Zoccali, Carmine; Frigerio, Maria

    2012-04-01

    The pathophysiological interactions that link the heart and kidney in heart failure are multiple and complex. This issue constitutes one of the most vexing and difficult challenges facing cardiologists. In the setting of acute decompensated heart failure, worsening renal function has traditionally been directly associated with poor clinical prognosis and complicates treatment. In the last years, many reports suggest that worsening renal failure may represent the final common pathway of several mechanistically distinct processes, with different prognostic implications. In the clinical scenario, the clinical significance of transient worsening of renal function may be different as compared with irreversible or progressive renal failure. In addition, it can represent a relatively normal response to treatment-induced physiological derangements such as a reduction in renal perfusion and/or intravascular volume. We here focus on these highlights, with special reference to the diagnostic criteria of renal dysfunction and the management of fluid overload. Two expert nephrologists were asked to answer a few important clinical questions: how should renal dysfunction be recognized and monitored? Are there therapies to counteract it and when, and more importantly, for whom should be applied? Their answers serve as touchstones for cardiologists to provide better individualized care for their patients with acute heart failure. Only a multidisciplinary and collaborative management of cardio-renal interactions will help to mitigate the difficult day-to-day clinical practice and improve our understanding of this condition through a concerted and constructive approach.

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

    PubMed Central

    Chalmers, Anna W; Shammo, Jamile M

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    Myocardial hypertrophy is one of the basic mechanisms by which the heart compensates for hemodynamic overload. The mechanisms by which hemodynamic overload is transduced by the cardiac muscle cell and translated into cardiac hypertrophy are not completely understood. Candidates include activation of the renin-angiotensin system (RAS) and angiotensin II receptor (AT1) stimulation. In this study, we tested the hypothesis that load, independent of the RAS, is sufficient to stimulate cardiac growth. Four groups of cats were studied: 14 normal controls, 20 pulmonary artery-banded (PAB) cats, 7 PAB cats in whom the AT1 was concomitantly and continuously blocked with losartan, and 8 PAB cats in whom the angiotensin-converting enzyme (ACE) was concomitantly and continuously blocked with captopril. Losartan cats had at least a one-log order increase in the ED50 of the blood pressure response to angiotensin II infusion. Right ventricular (RV) hypertrophy was assessed using the RV mass-to-body weight ratio and ventricular cardiocyte size. RV hemodynamic overload was assessed by measuring RV systolic and diastolic pressures. Neither the extent of RV pressure overload nor RV hypertrophy that resulted from PAB was affected by AT1 blockade with losartan or ACE inhibition with captopril. RV systolic pressure was increased from 21 +/- 3 mmHg in normals to 68 +/- 4 mmHg in PAB, 65 +/- 5 mmHg in PAB plus losartan and 62 +/- 3 mmHg in PAB plus captopril. RV-to-body weight ratio increased from 0.52 +/- 0.04 g/kg in normals to 1.11 +/- 0.06 g/kg in PAB, 1.06 +/- 0.06 g/kg in PAB plus losartan and 1.06 +/- 0.06 g/kg in PAB plus captopril. Thus 1) pharmacological modulation of the RAS with losartan and captopril did not change the extent of the hemodynamic overload or the hypertrophic response induced by PAB; 2) neither RAS activation nor angiotensin II receptor stimulation is an obligatory and necessary component of the signaling pathway that acts as an intermediary coupling load to the

  4. Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

    PubMed Central

    Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica

    2014-01-01

    Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response. PMID:25013355

  5. Time course of changes in the mechanical properties of the canine right and left ventricles during hypertrophy caused by pressure overload.

    PubMed

    Mirsky, I; Laks, M M

    1980-04-01

    We developed a mathematical model of the right and left ventricles to determine whether there is a change in the mechanical properties of muscle during the hypertrophy process resulting from pulmonary arterial banding. Pressure-volume data were obtained from 10 normal dog hearts and 8 dog hearts in which the pulmonary artery was banded for periods of 2--40 weeks. These data were applied to the model, and the time course of wall stress and muscle stiffness was quantified for both ventricles. The results demonstrate that (1) myocardial stiffness is increased in pressure-overload hypertrophy (2) normal right and left ventricular muscle exhibits similar mechanical properties and (3) the relationships between wall stresses and the volume/mass ratios to the period of banding are biphasic. We concluded that (1) increase in muscle stiffness is due to several factors. In the early stages of hypertrophy, it may be predominantly due to fibrosis and, in the later stages, to substantial increases in muscle mass. (2) The progressive increase in muscle stiffness concomitant with the increase in muscle mass may be due to the presence of myocardial cellular projections and fibrosis. (3) The appropriate timing for surgical/medical intervention should take place before low volume:mass ratios and, hence, low wall stresses are attained. PMID:6444557

  6. Markers for vulnerability in acute porphyria. A hypothesis paper.

    PubMed

    Thunell, S; Andersson, C; Carlmark, B; Floderus, Y; Grönqvist, S O; Harper, P; Henrichson, A; Lindh, U

    1995-04-01

    Previously symptomatic and permanently asymptomatic carriers of a gene mutation for acute intermittent porphyria as well as matched controls were screened with regard to a series of variables of possible relevance to the development of porphyric symptoms. The basis for the study was a concept of acute porphyria as a condition of a permanent system overload of oxidative stress, with long term effects on hepatic and renal tissue, and with instances of periodic overload of free radicals giving rise to acute neurologic involvement. Leukocyte concentrations of manganese, calcium, iron and zinc, as well as erythrocyte calcium differed between the groups, acute intermittent porphyria gene carriers, irrespective of previous porphyric illness, showing significantly higher levels than the controls. Manganese was found to be the most discriminative component of all the 78 variables investigated, accounting for about 98 per cent of the variance between the groups. An increment, by a factor of four, in cellular manganese is suggestive of an increase, in acute intermittent porphyria, of a manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or mitochondrial superoxide dismutase. The best fit into the model considered is provided by a theory focused on superoxide dismutase, induced in response to superoxide anion radical produced from aminolaevulinic acid. In porphyria gene carriers seemingly resistant to porphyric manifestations, an increase in potentially prooxidant cellular iron is matched by a proportional increment in manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase induction. This mechanism is not operative in porphyric individuals prone to development of neuropsychiatric symptoms. In acute intermittent porphyria with a history of porphyric illness there is a positive correlation between erythrocyte manganese and serum folate and a negative correlation between leukocyte ferrochelatase activity and serum cobalamin

  7. Markers for vulnerability in acute porphyria. A hypothesis paper.

    PubMed

    Thunell, S; Andersson, C; Carlmark, B; Floderus, Y; Grönqvist, S O; Harper, P; Henrichson, A; Lindh, U

    1995-04-01

    Previously symptomatic and permanently asymptomatic carriers of a gene mutation for acute intermittent porphyria as well as matched controls were screened with regard to a series of variables of possible relevance to the development of porphyric symptoms. The basis for the study was a concept of acute porphyria as a condition of a permanent system overload of oxidative stress, with long term effects on hepatic and renal tissue, and with instances of periodic overload of free radicals giving rise to acute neurologic involvement. Leukocyte concentrations of manganese, calcium, iron and zinc, as well as erythrocyte calcium differed between the groups, acute intermittent porphyria gene carriers, irrespective of previous porphyric illness, showing significantly higher levels than the controls. Manganese was found to be the most discriminative component of all the 78 variables investigated, accounting for about 98 per cent of the variance between the groups. An increment, by a factor of four, in cellular manganese is suggestive of an increase, in acute intermittent porphyria, of a manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or mitochondrial superoxide dismutase. The best fit into the model considered is provided by a theory focused on superoxide dismutase, induced in response to superoxide anion radical produced from aminolaevulinic acid. In porphyria gene carriers seemingly resistant to porphyric manifestations, an increase in potentially prooxidant cellular iron is matched by a proportional increment in manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase induction. This mechanism is not operative in porphyric individuals prone to development of neuropsychiatric symptoms. In acute intermittent porphyria with a history of porphyric illness there is a positive correlation between erythrocyte manganese and serum folate and a negative correlation between leukocyte ferrochelatase activity and serum cobalamin

  8. Lack of association between chronic exposure to biomass fuel smoke and markers of right ventricular pressure overload at high altitude

    PubMed Central

    Caravedo, Maria A.; Painschab, Matthew S.; Davila-Roman, Victor G.; De Ferrari, Aldo; Gilman, Robert H.; Vasquez-Villar, Angel D.; Pollard, Suzanne L.; Miranda, J. Jaime; Checkley, William

    2014-01-01

    Background Chronic exposure to biomass fuel smoke has been implicated in the development of pulmonary hypertension and right ventricular pressure/volume overload through activation of inflammation, increase in vascular resistance and endothelial dysfunction. We sought to compare N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and echocardiography-derived pulmonary artery systolic pressure (PASP) levels in a high-altitude population-based study in Peru with and without chronic exposure to biomass fuel smoke. Methods NT-pro-BNP levels were measured in 519 adults (275 with and 244 without chronic exposure to biomass fuel smoke). Participants answered sociodemographics and clinical history questionnaires, underwent a clinical examination and blood testing for cardiopulmonary biomarkers. PASP was measured in a subgroup of 153 (31%) subjects. Results The study group consisted of 280 men (54%) and 239 women (46%). Average age was 56 years and average body mass index was 27 kg/m2. In multivariable analysis, there was no association between chronic exposure to biomass fuel smoke and NT-pro-BNP (p=0.31) or PASP (p=0.31). In the subgroup in which both NT-pro-BNP levels and PASP were measured, there was strong evidence of an association between these two variables (ρ=0.24, 95% CI 0.09-0.39; p=0.003). We found that age, high sensitivity C-reactive protein, being male and systolic blood pressure were positively associated with NT-pro-BNP levels whereas body mass index, LDL/HDL ratio and HOMA-IR were negatively associated (all p<0.01). Conclusions In this population-based study in a high-altitude setting, neither NT-pro-BNP levels nor echocardiography-derived PASP were associated with chronic exposure to biomass fuel smoke. PMID:25440802

  9. ACE inhibition prevents diastolic Ca2+ overload and loss of myofilament Ca2+ sensitivity after myocardial infarction

    PubMed Central

    Zalvidea, Santiago; Andre, Lucas; Loyer, Xavier; Cassan, Cécile; Sainte-Marie, Yannis; Thireau, Jérôme; Sjaastad, Ivar; Heymes, Christophe; Pasquié, Jean-Luc; Cazorla, Olivier; Aimond, Franck; Richard, Sylvain

    2012-01-01

    Prevention of adverse cardiac remodeling after myocardial infarction (MI) remains a therapeutic challenge. Angiotensin-converting enzyme inhibitors (ACE-I) are a well-established first-line treatment. ACE-I delay fibrosis, but little is known about their molecular effects on cardiomyocytes. We investigated the effects of the ACE-I delapril on cardiomyocytes in a mouse model of heart failure (HF) after MI. Mice were randomly assigned to three groups: Sham, MI, and MI-D (6 weeks of treatment with a non-hypotensive dose of delapril started 24h after MI). Echocardiography and pressure-volume loops revealed that MI induced hypertrophy and dilatation, and altered both contraction and relaxation of the left ventricle. At the cellular level, MI cardiomyocytes exhibited reduced contraction, slowed relaxation, increased diastolic Ca2+ levels, decreased Ca2+-transient amplitude, and diminished Ca2+ sensitivity of myofilaments. In MI-D mice, however, both mortality and cardiac remodeling were decreased when compared to non-treated MI mice. Delapril maintained cardiomyocyte contraction and relaxation, prevented diastolic Ca2+ overload and retained the normal Ca2+ sensitivity of contractile proteins. Delapril maintained SERCA2a activity through normalization of P-PLB/PLB (for both Ser16-PLB and Thr17-PLB) and PLB/SERCA2a ratios in cardiomyocytes, favoring normal reuptake of Ca2+ in the sarcoplasmic reticulum. In addition, delapril prevented defective cTnI function by normalizing the expression of PKC, enhanced in MI mice. In conclusion, early therapy with delapril after MI preserved the normal contraction/relaxation cycle of surviving cardiomyocytes with multiple direct effects on key intracellular mechanisms contributing to preserve cardiac function. PMID:22280358

  10. Controversies and problems of volume control and hypertension in haemodialysis.

    PubMed

    Ok, Ercan; Asci, Gulay; Chazot, Charles; Ozkahya, Mehmet; Mees, Evert J Dorhout

    2016-07-16

    Extracellular volume overload and hypertension are important contributors to the high risk of cardiovascular mortality in patients undergoing haemodialysis. Hypertension is present in more than 90% of patients at the initiation of haemodialysis and persists in more than two-thirds, despite use of several antihypertensive medications. High blood pressure is a risk factor for the development of left ventricular hypertrophy, heart failure, and mortality, although there are controversies with some study findings showing poor survival with low-but not high-blood pressure. The most frequent cause of hypertension in patients undergoing haemodialysis is volume overload, which is associated with poor cardiovascular outcomes itself independent of blood pressure. Although antihypertensive medications might not be successful to control blood pressure, extracellular volume reduction by persistent ultrafiltration and dietary salt restriction can produce favourable results with good blood pressure control. More frequent or longer haemodialysis can facilitate volume and blood pressure control. However, successful volume and blood pressure control is also possible in patients undergoing conventional haemodialysis.

  11. Acute tubular necrosis

    MedlinePlus

    ... in the following cases: Decreased mental status Fluid overload Increased potassium level Pericarditis Removal of toxins that ... to achieve this important distinction for online health information and services. Learn more about A.D.A. ...

  12. Blog Overload

    ERIC Educational Resources Information Center

    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…

  13. Moderate alcohol consumption does not impair overload-induced muscle hypertrophy and protein synthesis.

    PubMed

    Steiner, Jennifer L; Gordon, Bradley S; Lang, Charles H

    2015-03-01

    Chronic alcohol consumption leads to muscle weakness and atrophy in part by suppressing protein synthesis and mTORC1-mediated signaling. However, it is unknown whether moderate alcohol consumption also prevents overload-induced muscle growth and related anabolic signaling. Hypertrophy of the plantaris muscle was induced by removal of a section of the gastrocnemius and soleus muscles from one leg of C57BL/6 adult male mice while the contralateral leg remained intact as the sham control. A nutritionally complete alcohol-containing liquid diet (EtOH) or isocaloric, alcohol-free liquid diet (Con) was provided for 14 days post-surgery. EtOH intake was increased progressively (day 1-5) before being maintained at ~20 g/day/kg BW. The plantaris muscle from the sham and OL leg was removed after 14 days at which time there was no difference in body weight between Con and EtOH-fed mice. OL increased muscle weight (90%) and protein synthesis (125%) in both Con and EtOH mice. The overload-induced increase in mTOR (Ser2448), 4E-BP1 (Thr37/46), S6K1 (Thr389), rpS6 (Ser240/244), and eEF2 (Thr56) were comparable in muscle from Con and EtOH mice. Modulation of signaling upstream of mTORC1 including REDD1 protein expression, Akt (Thr308), PRAS40 (Thr246), and ERK (Thr202/Tyr204) also did not differ between Con and EtOH mice. Markers of autophagy (ULK1, p62, and LC3) suggested inhibition of autophagy with overload and activation with alcohol feeding. These data show that moderate alcohol consumption does not impair muscle growth, and therefore imply that resistance exercise may be an effective therapeutic modality for alcoholic-related muscle disease. PMID:25780086

  14. β-cell metabolic alterations under chronic nutrient overload in rat and human islets.

    PubMed

    Vernier, Stephanie; Chiu, Angela; Schober, Joseph; Weber, Theresa; Nguyen, Phuong; Luer, Mark; McPherson, Timothy; Wanda, Paul E; Marshall, Connie A; Rohatgi, Nidhi; McDaniel, Michael L; Greenberg, Andrew S; Kwon, Guim

    2012-01-01

    The aim of this study was to assess multifactorial β-cell responses to metabolic perturbations in primary rat and human islets. Treatment of dispersed rat islet cells with elevated glucose and free fatty acids (FFAs, oleate:palmitate = 1:1 v/v) resulted in increases in the size and the number of lipid droplets in β-cells in a time- and concentration-dependent manner. Glucose and FFAs synergistically stimulated the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1). A potent mTORC1 inhibitor, rapamycin (25 nM), significantly reduced triglyceride accumulation in rat islets. Importantly, lipid droplets accumulated only in β-cells but not in α-cells in an mTORC1-dependent manner. Nutrient activation of mTORC1 upregulated the expression of adipose differentiation related protein (ADRP), known to stabilize lipid droplets. Rat islet size and new DNA synthesis also increased under nutrient overload. Insulin secretion into the culture medium increased steadily over a 4-day period without any significant difference between glucose (10 mM) alone and the combination of glucose (10 mM) and FFAs (240 μM). Insulin content and insulin biosynthesis, however, were significantly reduced under the combination of nutrients compared with glucose alone. Elevated nutrients also stimulated lipid droplet formation in human islets in an mTORC1-dependent manner. Unlike rat islets, however, human islets did not increase in size under nutrient overload despite a normal response to nutrients in releasing insulin. The different responses of islet cell growth under nutrient overload appear to impact insulin biosynthesis and storage differently in rat and human islets. PMID:23247575

  15. Sympathectomy or doxazosin, but not propranolol, blunt myocardial interstitial fibrosis in pressure-overload hypertrophy.

    PubMed

    Perlini, Stefano; Palladini, Giuseppina; Ferrero, Ivana; Tozzi, Rossana; Fallarini, Silvia; Facoetti, Angelica; Nano, Rosanna; Clari, Francesca; Busca, Giuseppe; Fogari, Roberto; Ferrari, Alberto U

    2005-11-01

    The adaptive changes that develop in the pressure-overloaded left ventricular (LV) myocardium include cardiomyocyte hypertrophy and interstitial fibrosis. Although the former is known to depend to a sizeable extent on sympathetic (over)activity, little information exists whether the same applies to the latter, ie, whether excess catecholamine exposure contributes to the imbalance between collagen deposition by fibroblasts and degradation by matrix metalloproteases (MMPs), eventually leading to LV collagen accumulation. Sprague-Dawley rats were subjected to abdominal aortic banding (B) or sham operation (S) and treated with beta-blockade (Bb, oral propranolol, 40 mg/kg per day), chemical sympathectomy (Sx, 6-hydroxydopamine, 150 mg/kg intraperitoneal twice per week) or vehicle (Vh). Ten weeks later, systolic blood pressure, LV weight, collagen abundance (computer-aided histology), zymographic matrix metalloproteinase (MMP)-2 activity and its specific tissue inhibitor concentration (TIMP-2) were measured. Both sympathectomy and beta-blockade failed to attenuate the banding-induced blood pressure elevation but significantly attenuated the attendant LV hypertrophy. As expected, pressure-overload hypertrophy was associated with interstitial fibrosis (collagen: 4.37+/-1.23% BVh versus 1.23+/-0.44% SVh, P<0.05), which was abolished by sympathectomy (2.55+/-1.31%, P=not significant versus SSx) but left unchanged by beta-blockade (4.11+/-1.23%, P<0.05 versus both SBb and BSx). beta-blockade, but not sympathectomy, was also associated with an increased TIMP-2/MMP-2 ratio (P<0.05), indicating reduced interstitial collagenolytic activity. In separate groups of banded and sham-operated rats, treatment with the alpha-receptor blocker doxazosin (10 mg/kg per day) displayed similar antifibrotic and biochemical effects as sympathectomy. Thus in the course of experimental pressure overload, the sympathetic nervous system plays a major pro-fibrotic role, which is mediated via alpha

  16. Phosphate overload directly induces systemic inflammation and malnutrition as well as vascular calcification in uremia.

    PubMed

    Yamada, Shunsuke; Tokumoto, Masanori; Tatsumoto, Narihito; Taniguchi, Masatomo; Noguchi, Hideko; Nakano, Toshiaki; Masutani, Kosuke; Ooboshi, Hiroaki; Tsuruya, Kazuhiko; Kitazono, Takanari

    2014-06-15

    Hyperphosphatemia contributes to increased cardiovascular mortality through vascular calcification (VC) in patients with chronic kidney disease (CKD). Malnutrition and inflammation are also closely linked to an increased risk of cardiovascular death in CKD. However, the effects of Pi overload on inflammation and malnutrition remain to be elucidated. The aim of the present study was to investigate the effects of dietary Pi loading on the interactions among inflammation, malnutrition, and VC in CKD. We used control rats fed normal diets and adenine-induced CKD rats fed diets with different Pi concentrations ranging from 0.3% to 1.2% for 8 wk. CKD rats showed dietary Pi concentration-dependent increases in serum and tissue levels of TNF-α and urinary and tissue levels of oxidative stress markers and developed malnutrition (decrease in body weight, serum albumin, and urinary creatinine excretion), VC, and premature death without affecting kidney function. Treatment with 6% lanthanum carbonate blunted almost all changes induced by Pi overload. Regression analysis showed that serum Pi levels closely correlated with the extent of inflammation, malnutrition, and VC. Also, in cultured human vascular smooth muscle cells, high-Pi medium directly increased the expression of TNF-α in advance of the increase in osteochondrogenic markers. Our data suggest that dietary Pi overload induces systemic inflammation and malnutrition, accompanied by VC and premature death in CKD, and that inhibition of Pi loading through dietary or pharmacological interventions or anti-inflammatory therapy may be a promising treatment for the prevention of malnutrition-inflammation-atherosclerosis syndrome.

  17. Sodium molybdate prevents hypertension and vascular prostanoid imbalance in fructose-overloaded rats.

    PubMed

    Peredo, H A; Andrade, V; Donoso, A S; Lee, H J; Puyó, A M

    2013-10-01

    (1) Fructose (F) overload produces elevated blood pressure (BP), hyperglycaemia, hypertriglyceridemia and insulin resistance, resembling human metabolic syndrome. Previously, we found altered vascular prostanoid (PR) production in this model. (2) Sodium molybdate (Mo), as well as sodium tungstate, causes insulin-like effects and normalizes plasma glucose levels in streptozotocin-treated diabetic rats. We studied the effects of Mo on BP, metabolic parameters and release of PR from the mesenteric vascular bed (MVB) in F-overloaded rats. (3) Four groups of male Sprague-Dawley rats were analysed: Control, tap water to drink; F, F solution 10% W/V to drink; CMo, Mo 100 mg kg day(-1) and FMo, both treatments. After 9 weeks, the animals were killed and MVBs removed and the released PRs measured. (4) F increased BP, glycemia, triglyceridemia and insulinemia. Mo treatment prevented the increases in BP and glycemia, but did not modify triglyceridemia or insulinemia. In addition, Mo decreased BP in controls. (5) Prostaglandins (PG) F2 alpha and E2, PG 6-ketoF1 alpha and thromboxane (TX) B2 , as well as inactive metabolites of prostacyclin (PGI2 ) and TXA2 were detected. F decreased the production of vasodilator PRs PGI2 and PGE2 in MVB. Mo prevented these alterations and increased PGE2 in controls. Vasoconstrict or PRs PGF2 alpha and TXA2 release was not modified. (6) Mo treatment, beyond its known lowering effect on glycemia, prevents the reduction in the vascular release of vasodilator PR observed in this model. This could be one of the mechanisms by which Mo avoids the increase in BP caused by F overload in the rat.

  18. Mapping and load response of overload strain fields: Synchrotron X-ray measurements

    SciTech Connect

    Shukla, V; Jisrawi, N M; Sadangi, R K; Pao, P S; Horvath, K; Sadananda, K; Ignatov, A; Skaritka, J; Tsakalakos, T

    2009-02-05

    High energy synchrotron X-ray diffraction measurements have been performed to provide quantitative microscopic guidance for modeling of fatigue crack growth. Specifically we report local strain mapping, along with in situ loading strain response, results on 4140 steel fatigue specimens exhibiting the crack growth retardation 'overload effect'. Detailed, 2D, {epsilon}{gamma}{gamma}-strain field mapping shows that a single overload (OL) cycle creates a compressive strain field extending millimeters above and below the crack plane. The OL strain field structures are shown to persist after the crack tip has grown well beyond the OL position. The specimen exhibiting the maximal crack growth rate retardation following overload exhibits a tensile residual strain region at the crack tip. Strain field results, on in situ tensile loaded specimens, show a striking critical threshold load, F{sub c}, phenomenon in their strain response. At loads below F{sub c} the strain response is dominated by a rapid suppression of the compressive OL feature with modest response at the crack tip. At loads above F{sub c} the strain response at the OL position terminates and the response at the crack tip becomes large. This threshold load response behavior is shown to exhibit lower F{sub c} values, and dramatically enhanced rates of strain change with load as the crack tip propagates farther beyond the OL position. The OL strain feature behind the crack tip also is shown to be suppressed by removing the opposing crack faces via an electron discharge cut passing through the crack tip. Finally unique 2D strain field mapping (imaging) results, through the depth of the specimen, of the fatigue crack front and the OL feature in the wake are also presented.

  19. Iron Overload Causes Alterations of E-Cadherin in the Liver.

    PubMed

    Fujikura, Y; Krijt, J; Povýšil, C; Mělková, Z; Přikryl, P; Vokurka, M; Nečas, E

    2016-01-01

    Iron overload causes tissue damage in the liver, but its initial effects at the molecular and cellular level are not well understood. Epithelial cadherin (E-cad) is a major adhesion protein in adherens junctions and is associated with several signal transduction pathways. Dysfunction of E-cad causes instability of adherens junctions, which leads to cell invasion, cell migration, and carcinogenesis. We found in liver samples from iron-overloaded mice that the apparent molecular mass of E-cad was reduced from 125 to 115 kDa in sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions and immunoblotting, and that the cellular expression of E-cad was decreased in immunohistochemistry. The mRNA level of E-cad, however, did not change significantly, suggesting that the alterations are posttranslational. Interestingly, incubation of control liver extracts with Fe2+ alone also produced the same mobility shift. Neither an oxidant nor an antioxidant influenced this shift in vitro, suggesting that reactive oxygen species, which are generated by iron and known to cause damage to macromolecules, are not involved. Treatment of the 115 kDa E-cad with deferoxamine, an iron chelator, thus removing Fe2+, shifted the molecular mass back to 125 kDa, demonstrating that the shift is reversible. The observation also implies that the alteration that causes the mobility shift is not due to transcriptional control, deglycosylation, and proteolysis. This reversible mobility shift of E-cad has not been previously known. The alteration of E-cad that causes the mobility shift might be an initial step to liver diseases by iron overload. PMID:27516188

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

    SciTech Connect

    Ledee, Dolena R.; Smith, Lincoln; Kajimoto, Masaki; Bruce, Margaret; Isern, Nancy G.; Xu, Chun; Portman, Michael A.; Olson, Aaron

    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.

  1. Pathophysiology of acute heart failure: a world to know.

    PubMed

    Sánchez-Marteles, M; Rubio Gracia, J; Giménez López, I

    2016-01-01

    Our understanding of the pathophysiological mechanisms of heart failure (HF) has changed considerably in recent years, progressing from a merely haemodynamic viewpoint to a concept of systemic and multifactorial involvement in which numerous mechanisms interact and concatenate. The effects of these mechanisms go beyond the heart itself, to other organs of vital importance such as the kidneys, liver and lungs. Despite this, the pathophysiology of acute HF still has aspects that elude our deeper understanding. Haemodynamic overload, venous congestion, neurohormonal systems, natriuretic peptides, inflammation, oxidative stress and its repercussion on cardiac and vascular remodelling are currently considered the main players in acute HF. Starting with the concept of acute HF, this review provides updates on the various mechanisms involved in this disease.

  2. Role of Cardiovascular Disease-associated iron overload in Libby amphibole-induced acute pulmonary injury and inflammation

    EPA Science Inventory

    Pulmonary toxicity induced by asbestos is thought to be mediated through redox-cycling of fiber-bound and bioavailable iron (Fe). We hypothesized that Libby amphibole (LA)-induced cute lung injury will be exacerbated in rat models of cardiovascular disease (CVD)-associated Fe-ove...

  3. Fractography of induction-hardened steel fractured in fatigue and overload

    SciTech Connect

    Santos, C.G.; Laird, C.

    1997-07-01

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

  4. Acute gastroenteritis.

    PubMed

    Graves, Nancy S

    2013-09-01

    Acute gastroenteritis is a common infectious disease syndrome, causing a combination of nausea, vomiting, diarrhea, and abdominal pain. There are more than 350 million cases of acute gastroenteritis in the United States annually and 48 million of these cases are caused by foodborne bacteria. Traveler's diarrhea affects more than half of people traveling from developed countries to developing countries. In adult and pediatric patients, the prevalence of Clostridium difficile is increasing. Contact precautions, public health education, and prudent use of antibiotics are necessary goals in decreasing the prevalence of Clostridium difficle. Preventing dehydration or providing appropriate rehydration is the primary supportive treatment of acute gastroenteritis.

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

    PubMed

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

    2012-06-01

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

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

    PubMed

    Ballak, Sam B; Busé-Pot, Tinelies; Harding, Peter J; Yap, Moi H; Deldicque, Louise; de Haan, Arnold; Jaspers, Richard T; Degens, Hans

    2016-04-01

    We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity. PMID:26970774

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

    PubMed

    Ballak, Sam B; Busé-Pot, Tinelies; Harding, Peter J; Yap, Moi H; Deldicque, Louise; de Haan, Arnold; Jaspers, Richard T; Degens, Hans

    2016-04-01

    We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

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

    PubMed

    Fisher, David M

    2014-07-01

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

  9. [Ascites and acute kidney injury].

    PubMed

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years. PMID:27571467

  10. [Ascites and acute kidney injury].

    PubMed

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.

  11. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is almost always caused by viruses that attack the lining of the bronchial tree ... infection. As your body fights back against these viruses, more swelling occurs and more mucus is produced. ...

  12. Acute Pericarditis

    MedlinePlus

    ... large pericardial effusions). Acute pericarditis usually responds to colchicine or NSAIDs (such as aspirin and ibuprofen ) taken ... reduce pain but relieves it by reducing inflammation. Colchicine also decreases the chance of pericarditis returning later. ...

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

    PubMed Central

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

    2013-01-01

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

  14. Pirfenidone exhibits cardioprotective effects by regulating myocardial fibrosis and vascular permeability in pressure-overloaded hearts.

    PubMed

    Yamagami, Kiyoshi; Oka, Toru; Wang, Qi; Ishizu, Takamaru; Lee, Jong-Kook; Miwa, Keiko; Akazawa, Hiroshi; Naito, Atsuhiko T; Sakata, Yasushi; Komuro, Issei

    2015-08-01

    Although cardiac fibrosis causes heart failure, its molecular mechanisms remain elusive. In this study, we investigated the mechanisms of cardiac fibrosis and examined the effects of the antifibrotic drug pirfenidone (PFD) on chronic heart failure. To understand the responsible mechanisms, we generated an in vivo pressure-overloaded heart failure model via transverse aortic constriction (TAC) and examined the effects of PFD on chronic-phase cardiac fibrosis and function. In the vehicle group, contractile dysfunction and left ventricle fibrosis progressed further from 4 to 8 wk after TAC but were prevented by PFD treatment beginning 4 wk after TAC. We isolated cardiac fibroblasts and vascular endothelial cells from the left ventricles of adult male mice and investigated the cell-type-specific effects of PFD. Transforming growth factor-β induced upregulated collagen 1 expression via p38 phosphorylation and downregulated claudin 5 (Cldn5) expression in cardiac fibroblasts and endothelial cells, respectively; both processes were inhibited by PFD. Moreover, PFD inhibited changes in the collagen 1 and Cldn5 expression levels, resulting in reduced fibrosis and serum albumin leakage into the interstitial space during the chronic phase in TAC hearts. In conclusion, PFD inhibited cardiac fibrosis by suppressing both collagen expression and the increased vascular permeability induced by pressure overload.

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

    PubMed

    Lavin, Shana R

    2012-09-01

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

  16. Impact of Oxidative Stress in Premature Aging and Iron Overload in Hemodialysis Patients

    PubMed Central

    Hernández Vázquez, Wendy Ivett; Solorio-Meza, Sergio; Albarrán-Tamayo, Froylán; Ramos-Rodríguez, Edna; Benítez- Bribiesca, Luis

    2016-01-01

    Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS (p = 0.008), carbonyls (p = 0.0004), and urea (p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels (r = −0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis (r = −0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length. PMID:27800120

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

    PubMed Central

    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. PMID:26770287

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

    PubMed

    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

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

    PubMed

    Lavin, Shana R

    2012-09-01

    Phenolic compounds are bioactive chemicals found in all vascular plants but are difficult to characterize and quantify, and comparative analyses on these compounds are challenging due to chemical structure complexity and inconsistent laboratory methodologies employed historically. These chemicals can elicit beneficial or toxic effects in consumers, depending on the compound, dose and the species of the consumer. In particular, plant phenolic compounds such as tannins can reduce the utilization of iron in mammalian and avian consumers. Multiple zoo-managed wild animal species are sensitive to iron overload, and these species tend to be offered diets higher in iron than most of the plant browse consumed by these animals in the wild and in captivity. Furthermore, these animals likely consume diets higher in polyphenols in the wild as compared with in managed settings. Thus, in addition to reducing dietary iron concentrations in captivity, supplementing diets with phenolic compounds capable of safely chelating iron in the intestinal lumen may reduce the incidence of iron overload in these animal species. It is recommended to investigate various sources and types of phenolic compounds for use in diets intended for iron-sensitive species. Candidate compounds should be screened both in vitro and in vivo using model species to reduce the risk of toxicity in target species. In particular, it would be important to assess potential compounds in terms of 1) biological activity including iron-binding capacity, 2) accessibility, 3) palatability, and 4) physiological effects on the consumer, including changes in nutritional and antioxidant statuses. PMID:23156709

  20. Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats.

    PubMed

    Whittaker, P; Hines, F A; Robl, M G; Dunkel, V C

    1996-01-01

    The effects of increasing dietary levels of Fe on the histopathology of liver, pancreas, spleen, and heart were examined in a rat model for iron overload. Sprague-Dawley rats were fed diets containing 35, 350, 3,500, or 20,000 micrograms Fe/g, and, after 12 wk, there was a direct correlation between increased liver nonheme Fe and lipid peroxidation measured by the lipid-conjugated diene assay. Histopathological examination of tissues revealed the following: (a) hepatocellular hemosiderosis in all groups of rats, with a dose-related accumulation of cytoplasmic Fe-positive material predominantly in hepatocytes located in the periportal region (Zone 1), (b) myocardial degeneration and necrosis (cardiomyopathy) with hemosiderin in interstitial macrophages or in myocardial fibers of animals with heart damage, (c) splenic lymphoid atrophy affecting the marginal zone of the white pulp and hemosiderin deposition in the sinusoidal macrophages, and (d) pancreatic atrophy with loss of both the endocrine and exocrine pancreatic tissue in those animals receiving 3,500 and 20,000 micrograms Fe/g of diet. The toxic effects of Fe overload in this rat model include cellular apoptosis or necrosis in heart, spleen, and pancreas and, when coupled with the findings on lipid peroxidation, suggests that oxidative stress is involved in the pathogenesis of the lesions.

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Thermographic Assessment of Eccentric Overload Training Within Three Days of a Running Session.

    PubMed

    Sanz-López, Fernando; Martínez-Amat, Antonio; Hita-Contreras, Fidel; Valero-Campo, Carlos; Berzosa, César

    2016-02-01

    The aim of this study was to analyze the changes in patellar and Achilles tendons between a group trained using eccentric overload and an untrained group within 3 days of a running session. To this end, infrared thermography (IRT) will be used. Twenty healthy male subjects were divided into 2 groups. One group performed a 6-week squat training in the flywheel before the running session. During the running intervention, both groups ran in 3 different days, for 1 hour each, at 80% maximal heart rate. Before, just after, and after 10 minutes of the running intervention, participants were assessed using IRT. Eccentrically trained groups showed a statistically significant difference (analysis of variance, p = 0.0049) expressed as a smaller bilateral increase in temperature in the patellar tendon just before the first running day (right side, 0.11 °C; left side, 0.29 °C). On the other days of running and in the Achilles tendon groups, similar changes were observed: an increase in the temperature after running and no significant difference between contralateral limbs. Our results point at eccentric overload training providing a better adaptation for the first day of running. IRT is an easy-to-apply noninvasive tool to analyze and compare the effects of performance on tendon tissues.

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

    PubMed Central

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

    2016-01-01

    Cancer cells typically display higher than normal levels of reactive oxygen species (ROS), which may promote cancer development and progression but may also render the cancer cells more vulnerable to further ROS insult. Indeed, many of the current anticancer therapeutics kill cancer cells via induction of oxidative stress, though they target both cancer and normal cells. Recently, alantolactone (ATL), a natural sesquiterpene lactone, has been shown to induce apoptosis by increasing ROS levels specifically in cancer cells; however, the molecular mechanisms linking ROS overproduction to apoptosis remain unclear. Here we show that the ATL-induced ROS overload in human SW480 and SW1116 colorectal cancer cells was followed by a prominent accumulation of cellular oxidized guanine (8-oxoG) and immediate increase in the number of DNA strand breaks, indicating that increased ROS resulted in extensive oxidative DNA damage. Consequently, the G1/S-CDK suppresser CDKN1B (p21) and pro-apoptotic proteins Bax and activated caspase-3 were upregulated, while anti-apoptotic Bcl-2 was downregulated, which were followed by cell cycle arrest at G1 and marked apoptosis in ATL-treated cancer but not non-cancer cells. These results suggest that the ATL-induced ROS overload triggers cell death through induction of massive oxidative DNA damage and subsequent activation of the intrinsic apoptosis pathway. PMID:27089328

  4. Synthesis of polymers containing 3-hydroxypyridin-4-one bidentate ligands for treatment of iron overload

    PubMed Central

    Saghaie, Lotfollah; Liu, Dy; Hider, Robert C

    2015-01-01

    Iron overload is a clinical problem which can be prevented by using iron chelating agents. An alternative method of relieving iron overload is to reduce iron absorption from the intestine by administering specific iron chelating agents, which can bind iron to form nonabsorbable complexes. Based on this strategy, a series of polymeric ligands containing the chelating moiety 3-hydroxypyridin-4-ones (HPOs) were synthesized. The synthetic route involves the benzylation of hydroxyl group of (2-methyl-3-hydroxypyran-4-one (maltol) and conversion of benzylated maltol to 3-benzyloxypyridin-4-one derivatives by using three suitable primary amines (2,6-diaminohexanoic acid (lysine) and 1,6-diaminohexane and 5-aminopentanol). The resulted compounds incorporated into polymer by copolymerization with acryloyl chloride using 2, 2’-azobisisobutyronitrile (AIBN) as the initiator. Finally, the benzyl groups of polymers were removed by catalytic hydrogenation (Pd/C). In this work, three final polymers of HPO derivatives namely poly-2-propylamido-6-(3- hydroxy -1,4-dihydro-2-methy-4-oxopyrid-1-yl) hexanoic acid, 6-(3-hydroxy-1, 4-dihydro-2-methyl-4-oxopyrid-1-yl) hexyl-1-polypropylamide and 5-(3-hydroxy-1-,4-dihydro-2-methyl-4-oxopyrid-1-yl)-1-polyacrylate pentane were synthesized. Identification and structural elucidation of compounds were achieved by proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR) and infrared (IR) spectroscopy. PMID:26600863

  5. Thermographic Assessment of Eccentric Overload Training Within Three Days of a Running Session.

    PubMed

    Sanz-López, Fernando; Martínez-Amat, Antonio; Hita-Contreras, Fidel; Valero-Campo, Carlos; Berzosa, César

    2016-02-01

    The aim of this study was to analyze the changes in patellar and Achilles tendons between a group trained using eccentric overload and an untrained group within 3 days of a running session. To this end, infrared thermography (IRT) will be used. Twenty healthy male subjects were divided into 2 groups. One group performed a 6-week squat training in the flywheel before the running session. During the running intervention, both groups ran in 3 different days, for 1 hour each, at 80% maximal heart rate. Before, just after, and after 10 minutes of the running intervention, participants were assessed using IRT. Eccentrically trained groups showed a statistically significant difference (analysis of variance, p = 0.0049) expressed as a smaller bilateral increase in temperature in the patellar tendon just before the first running day (right side, 0.11 °C; left side, 0.29 °C). On the other days of running and in the Achilles tendon groups, similar changes were observed: an increase in the temperature after running and no significant difference between contralateral limbs. Our results point at eccentric overload training providing a better adaptation for the first day of running. IRT is an easy-to-apply noninvasive tool to analyze and compare the effects of performance on tendon tissues. PMID:26110350

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

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

    Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4–induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise. PMID:25336758

  8. Activation of the hypoxia-inducible factor-1 in overloaded temporomandibular joint, and induction of osteoclastogenesis.

    PubMed

    Shirakura, Maya; Tanimoto, Keiji; Eguchi, Hidetaka; Miyauchi, Mutsumi; Nakamura, Hideaki; Hiyama, Keiko; Tanimoto, Kotaro; Tanaka, Eiji; Takata, Takashi; Tanne, Kazuo

    2010-03-19

    Vascular endothelial growth factor (Vegf) was previously shown to be expressed specifically in the condylar cartilage of temporomandibular joint-osteoarthritis (TMJ-OA) model rats. Here we demonstrate for the first time that hypoxia-inducible factor-1alpha (Hif-1alpha) is activated in mature chondrocytes of temporomandibular joint-osteoarthritis (TMJ-OA) model rat by mechanical overload, and that activated Hif-1 in chondrocytes can induce osteoclastogenesis via repression of osteoprotegerin (Opg) expression. In rat TMJs, degeneration of the condylar cartilage became prominent in proportion to the duration of overloading. Hif-1alpha expression was observed specifically in mature and hypertrophic chondrocytes, and Hif-1alpha-positivity, level of Vegf expression, and tartrate-resistant acid phosphatase (TRAP)-positive cell numbers all increased in the same manner. When ATDC5 cells induced differentiation by insulin were cultured under hypoxia, Hif-1alpha induction was observed in mature stage, but not in immature stage. Inductions of Hif-1-target genes showed a similar expression pattern. In addition, expression of Opg decreased in hypoxia, and Hif-1alpha played a role, in part, in its regulation. PMID:20171183

  9. Management of iron overload before, during, and after hematopoietic stem cell transplantation for thalassemia major.

    PubMed

    Angelucci, Emanuele; Pilo, Federica

    2016-03-01

    Solid evidence has established the negative impact of high iron burden and related tissue damage on the outcome of hemopoietic stem cell transplantation for thalassemia major. Recent improvements in our knowledge of iron metabolism have been focused on elevated non-transferrin-bound iron and labile plasma iron levels in the peritransplantation period as potential contributors to tissue toxicity and subsequent adverse transplant outcome. As mouse models have shown, iron overload can injure bone marrow hematopoiesis by increasing reactive oxygen species. The Pesaro experience, conducted in the deferoxamine-only era, clearly defined three iron-related factors (liver fibrosis, hepatomegaly, and quality of lifelong chelation) as significantly affecting transplant outcome. The detrimental effect of iron has only been clarified in recent years. Active interventional strategies are ongoing. Although successful hematopoietic stem cell transplantation clinically resolves the thalassemia marrow defect, patients still remain carriers of iron overload and of all the clinical complications acquired during prior years of transfusion therapy. Therefore, adequate "iron diagnosis" and management is mandatory after hemopoietic stem cell transplantation. In transplanted thalassemia patients, body iron should be returned to within the normal range. Phlebotomy is the gold standard to reduce iron burden; though deferoxamine is a proven, acceptable alternative, clinical investigations on deferasirox are ongoing. PMID:26999450

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. Activation of endothelial nitric oxide synthase by a vanadium compound ameliorates pressure overload-induced cardiac injury in ovariectomized rats.

    PubMed

    Bhuiyan, Md Shenuarin; Shioda, Norifumi; Shibuya, Masatoshi; Iwabuchi, Yoshiharu; Fukunaga, Kohji

    2009-01-01

    We here investigated the effect of bis(1-oxy-2-pyridinethiolato) oxovanadium (IV), [VO(OPT)], against myocardial hypertrophy and cardiac functional recovery in pressure overload-induced hypertrophy in ovariectomized female rats and defined mechanisms underlying its cardioprotective action. Wistar rats subjected to bilateral ovariectomy were further treated with abdominal aortic stenosis. VO(OPT) (containing 1.25 and 2.50 mg of vanadium per kg) was administered orally once a day for 14 days starting from 2 weeks after aortic banding. Treatment with VO(OPT) significantly inhibited pressure overload-induced increase both in the heart weight:body weight ratio and the lung weight:body weight ratio. VO(OPT) also attenuated hypertrophy-induced impaired left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular contractility (+/-dp/dt(max)). VO(OPT) treatment significantly restored pressure overload-induced impaired endothelial NO synthase activity with concomitant increased phosphorylation of endothelial NO synthase (Ser1179). Moreover, VO(OPT) treatment significantly restored pressure overload-induced reduced Akt activity, as indicated by increased phosphorylation at Ser473 and at Thr308. Treatment with VO(OPT) also secondarily inhibited calpastatin and dystrophin breakdown and decreased myosin light chain phosphorylation. Finally, VO(OPT) treatment significantly attenuated mortality after repeated isoproterenol administration in pressure overloaded-ovariectomized rats. Taken together, VO(OPT) attenuates cardiac myocytes hypertrophy in vivo in pressure overload-induced hypertrophy in ovariectomized rats and prevents the process from hypertrophy to heart failure. These effects are mediated by inhibition of calpastatin and dystrophin breakdown in addition to increased Akt and endothelial NO synthase activities.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    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

  17. Acute myocardial infarction in rats.

    PubMed

    Wu, Yewen; Yin, Xing; Wijaya, Cori; Huang, Ming-He; McConnell, Bradley K

    2011-01-01

    With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial

  18. Physiology of cell volume regulation in vertebrates.

    PubMed

    Hoffmann, Else K; Lambert, Ian H; Pedersen, Stine F

    2009-01-01

    The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most cases, activation of volume regulatory osmolyte transport. After acute swelling, cell volume is regulated by the process of regulatory volume decrease (RVD), which involves the activation of KCl cotransport and of channels mediating K(+), Cl(-), and taurine efflux. Conversely, after acute shrinkage, cell volume is regulated by the process of regulatory volume increase (RVI), which is mediated primarily by Na(+)/H(+) exchange, Na(+)-K(+)-2Cl(-) cotransport, and Na(+) channels. Here, we review in detail the current knowledge regarding the molecular identity of these transport pathways and their regulation by, e.g., membrane deformation, ionic strength, Ca(2+), protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review. PMID:19126758

  19. Porphyria cutanea tarda associated with HFE C282Y homozygosity, iron overload, and use of a contraceptive vaginal ring

    PubMed Central

    Barton, James C.; Edwards, Corwin Q.

    2016-01-01

    Porphyria cutanea tarda (PCT) is characterized by decreased uroporphyrinogen decarboxylase activity in hepatocytes, uroporphyrin I and heptacarboxyl porphyrin III accumulation, photosensitivity dermatitis, and increased storage iron. In women, estrogen therapy, including oral contraceptives, postmenopausal hormone replacement, and tamoxifen for breast cancer treatment, is a risk factor for PCT. We report the case of a woman who presented with PCT, HFE C282Y homozygosity, and hepatic iron overload and was using a contraceptive vaginal ring containing ethinyl estradiol, an estrogen. We discuss this case in the context of characteristics of other persons with PCT, including common HFE mutations, iron overload, and estrogen exposure. PMID:26908385

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

    NASA Technical Reports Server (NTRS)

    Max, S. R.; Rance, N.

    1983-01-01

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

  1. Performance-based contracting and the moderating influence of caseworker role overload on service provision in child welfare

    PubMed Central

    Chuang, Emmeline; Wells, Rebecca; Green, Sherri; Reiter, Kristin

    2012-01-01

    Although performance-based contracts have become increasingly popular in child welfare, administrators are developing these contracts with little empirically guided information about how internal work conditions may influence the services families receive. This study examines how child welfare caseworker role overload moderates associations between child welfare agencies’ use of performance-based contracting and services provided to families. Analyses using data from the National Survey of Child and Adolescent Well-Being suggest that when caseworkers experience high role overload, use of performance-based contracts may decrease caregivers’ likelihood of receiving necessary social and behavioral health services. These findings and their implications are discussed. PMID:22347768

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

    PubMed Central

    Lima, Cintia Taniguti; Silva, Juliane Cristina de Souza; Viegas, Katia Aparecida da Silva; Oliveira, Thais Cristina de Souza; de Lima, Rariane Silva; de Souza, Leandro Ezequiel; Aragão, Danielle; Casarini, Dulce Elena; Irigoyen, Maria Claudia; Lacchini, Silvia

    2015-01-01

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

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

    SciTech Connect

    Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Zhou, Heng; Xu, Dachun; Shan, Tichao; Zhang, Fan; Guo, Yuan; Chen, Yuguo; Wu, Dawei

    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

  4. Iron overload-related heart failure in a patient with transfusion-dependent myelodysplastic syndrome reversed by intensive combined chelation therapy.

    PubMed

    Pinto, Valeria; Balocco, Manuela; Ambaglio, Ilaria; Derchi, Giorgio; Malcovati, Luca; Forni, Gian Luca

    2015-11-01

    Patients with transfusion-dependent myelodysplastic syndromes (MDS) have an increased risk of cardiac events, due to both chronic anemia and iron overload. Here, we report the recovery of cardiac function after an intensive iron chelation therapy in a MDS patient who had developed heart failure due to iron overload.

  5. Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment.

    PubMed

    Kimmel, Robin A; Dobler, Stefan; Schmitner, Nicole; Walsen, Tanja; Freudenblum, Julia; Meyer, Dirk

    2015-01-01

    Diabetes mellitus is characterized by disrupted glucose homeostasis due to loss or dysfunction of insulin-producing beta cells. In this work, we characterize pancreatic islet development and function in zebrafish mutant for pdx1, a gene which in humans is linked to genetic forms of diabetes and is associated with increased susceptibility to Type 2 diabetes. Pdx1 mutant zebrafish have the key diabetic features of reduced beta cells, decreased insulin and elevated glucose. The hyperglycemia responds to pharmacologic anti-diabetic treatment and, as often seen in mammalian diabetes models, beta cells of pdx1 mutants show sensitivity to nutrient overload. This unique genetic model of diabetes provides a new tool for elucidating the mechanisms behind hyperglycemic pathologies and will allow the testing of novel therapeutic interventions in a model organism that is amenable to high-throughput approaches. PMID:26384018

  6. Perceptual overloading reveals illusory contour perception without awareness of the inducers.

    PubMed

    Persuh, Marjan; Emmanouil, Tatiana Aloi; Ro, Tony

    2016-08-01

    Unconscious perception is frequently examined by restricting visual input (e.g., using short stimulus durations followed by masking) to prevent that information from entering visual awareness. Failures to demonstrate perception without awareness may thus be a consequence of this restricted input rather than of limitations in unconscious perception. Here, we demonstrate a novel method that circumvents these significant drawbacks inherent in other methods. Using this new perceptual overloading technique (POT), in which stimuli are repeatedly presented in alternation with a stream of variable masks, we demonstrate illusory contour perception and modal completion even when subjects are completely unaware of the inducing elements. In addition to demonstrating a powerful new method to study consciousness by effectively gating robust visual input from visual awareness, we show that more complex contextual effects, previously considered to be a privilege only of conscious vision, can occur without awareness. PMID:27250361

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

    SciTech Connect

    Bosche, Bert; Schäfer, Matthias; Graf, Rudolf; Härtel, Frauke V.; Schäfer, Ute; Noll, Thomas

    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. Suppression of store overload-induced calcium release by hydroxylated metabolites of carvedilol.

    PubMed

    Malig, Thomas; Xiao, Zhichao; Chen, S R Wayne; Back, Thomas G

    2016-01-01

    Carvedilol is a drug widely used in the treatment of heart failure and associated cardiac arrhythmias. A unique action of carvedilol is its suppression of store overload-induced calcium release (SOICR) through the cardiac ryanodine receptor (RyR2), which can trigger ventricular arrhythmias. Since the effects of carvedilol metabolites on SOICR have not yet been investigated, three carvedilol metabolites hydroxylated at the 3-, 4' and 5'-positions were synthesized and assayed for SOICR inhibition in mutant HEK 293 cells expressing the RyR2 mutant R4496C. This cell line is especially prone to SOICR and calcium release through the defective RyR2 channel was measured with a calcium-sensitive fluorescent dye. These results revealed that the 3- and 4'-hydroxy derivatives are slightly more effective than carvedilol in suppressing SOICR, while the 5'-analog proved slightly less active. Metabolic deactivation of carvedilol via these hydroxylation pathways is therefore insignificant.

  9. Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment

    PubMed Central

    Kimmel, Robin A.; Dobler, Stefan; Schmitner, Nicole; Walsen, Tanja; Freudenblum, Julia; Meyer, Dirk

    2015-01-01

    Diabetes mellitus is characterized by disrupted glucose homeostasis due to loss or dysfunction of insulin-producing beta cells. In this work, we characterize pancreatic islet development and function in zebrafish mutant for pdx1, a gene which in humans is linked to genetic forms of diabetes and is associated with increased susceptibility to Type 2 diabetes. Pdx1 mutant zebrafish have the key diabetic features of reduced beta cells, decreased insulin and elevated glucose. The hyperglycemia responds to pharmacologic anti-diabetic treatment and, as often seen in mammalian diabetes models, beta cells of pdx1 mutants show sensitivity to nutrient overload. This unique genetic model of diabetes provides a new tool for elucidating the mechanisms behind hyperglycemic pathologies and will allow the testing of novel therapeutic interventions in a model organism that is amenable to high-throughput approaches. PMID:26384018

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

    PubMed Central

    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

  11. Antioxidative effects of lactic acid bacteria on the colonic mucosa of iron-overloaded mice.

    PubMed

    Ito, Masahiko; Ohishi, Kenji; Yoshida, Yasuto; Yokoi, Wakae; Sawada, Haruji

    2003-07-16

    The antioxidative effects of lactic acid bacteria on lipid peroxidation in the colonic mucosa were investigated. Among 49 strains of lactic acid bacteria, Streptococcus thermophilus YIT 2001 showed the highest inhibitory activity against lipid peroxidation in liposomes induced by ferrous iron. Feeding a diet containing 0.4% St. thermophilus YIT 2001 (2 x 10(8) colony-forming units per mouse per day) for 2 weeks caused a significant decrease of lipid peroxide (thiobarbituric acid reactive substance) in the colonic mucosa of iron-overloaded mice (0.07% Fe in the diet). The mucosal lipid peroxide level did not correlate with the soluble iron concentration of the cecal contents. Therefore, it is suggested that the antioxidative effect of St. thermophilus YIT 2001 in the colonic mucosa was not due to the removal of ferrous iron from the reaction system of lipid peroxidation. PMID:12848525

  12. Novel Carvedilol Analogs that Suppress Store Overload Induced Ca2+ Release

    PubMed Central

    Smith, Chris D.; Wang, Aixia; Vembaiyan, Kannan; Zhang, Jingqun; Xie, Cuihong; Zhou, Qiang; Wu, Guogen; Wayne Chen, S. R.; Back, Thomas G.

    2013-01-01

    Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part due to its ability to inhibit store overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization and bioassay of ca. 100 compounds based on the carvedilol motif in order to identify features that correlate with and optimize SOICR inhibition. A single cell bioassay was employed based on the RyR2-R4496C mutant HEK-293 cell line, in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the β-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits. PMID:24124794

  13. The effect of rear-seat overloading in a car crash: pathological and kinematics evidences.

    PubMed

    Luchini, Duccio; Sammicheli, Michele; Cortucci, Cristiano

    2013-09-01

    Seat belts have been shown to decrease the incidence of lethal lesions to the head, chest, and abdomen. Since the introduction of seat belts, it is reported that the incidence of traumatic lesions in these body parts is reduced. In the meantime, the characteristic lesions to the chest and abdomen caused by the use of seat belts are described (J Trauma. 2007;62(6):1473-1480).Reported is a peculiar case of an oblique front-to-rear car collision, in which overloading of the rear seat with packages pushed forward the passenger front seat in an abnormal way, causing fatal thoracic and abdominal lesions.The authors underline that the seat belt protection device is defeated if front seats are damaged by heavy unanchored bags on the rear seat or on the rear parcel shelf of a motor vehicle.

  14. Health implications of iron overload: the role of diet and genotype.

    PubMed

    Heath, Anne-Louise M; Fairweather-Tait, Susan J

    2003-02-01

    The relationship between high dietary iron intake, mutations of the HFE gene, and iron status, and their effects on human health are reviewed. Prolonged high dietary intakes of iron are unlikely to result in iron overload in the general population. Homozygotes for the C282Y mutation of the HFE gene have elevated body iron levels. Heterozygotes have normal iron stores but some may be at increased risk for cardiovascular disease. There is no convincing evidence that elevated iron status increases the risk of coronary heart disease or type 2 diabetes, but high iron intakes may increase the risk of colorectal cancer. The dietary levels of iron associated with health risks in different HFE genotypes must be determined.

  15. Novel Representation of Clinical Information in the ICU: Developing User Interfaces which Reduce Information Overload.

    PubMed

    Pickering, B W; Herasevich, V; Ahmed, A; Gajic, O

    2010-01-01

    The introduction of electronic medical records (EMR) and computerized physician order entry (CPOE) into the intensive care unit (ICU) is transforming the way health care providers currently work. The challenge facing developers of EMR's is to create products which add value to systems of health care delivery. As EMR's become more prevalent, the potential impact they have on the quality and safety, both negative and positive, will be amplified. In this paper we outline the key barriers to effective use of EMR and describe the methodology, using a worked example of the output. AWARE (Ambient Warning and Response Evaluation), is a physician led, electronic-environment enhancement program in an academic, tertiary care institution's ICU. The development process is focused on reducing information overload, improving efficiency and eliminating medical error in the ICU.

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

    PubMed Central

    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

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

    PubMed

    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 dosedependent 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

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

    PubMed

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

    2011-07-15

    Copper is dangerous when it is present in excess, mainly because it can participate in the Fenton reaction, which produces radical species. As a consequence of copper pollution, people are involuntarily exposed to a copper overload under sub-clinical and sub-symptomatological conditions, which may be very difficult to detect. Thus, we investigated (i) the possible use of the chelator molecules carnosine and neocuproine to prevent the Cu overload-induced damage on cellular lipids and proteins, as tested in human cell culture systems, and (ii) the differential response of these two chelating agents in relation to their protective action, and the type of copper ion involved in the process, by using two types of human cultured cells (HepG2 and A-549). Cu treatment clearly enhanced (p<0.01) the formation of protein carbonyls, thiobarbituric acid-reactive substances (TBARS) and the concentration of nitrate plus nitrites, with a concomitant decrease in cell survival, as estimated by the trypan dye exclusion test and lactate dehydrogenase leakage. Simultaneous treatment with Cu and carnosine or neocuproine indicated that carnosine is more efficient than neocuproine in protecting both types of cells from the effect of cupric ions on both the cell-associated damages and the decrease in the cellular viability. This observation was supported by the fact that carnosine is not only a complexing agent for Cu(II), but also an effective antioxidant that can dismutate superoxide radicals, scavenge hydroxyl radicals and neutralize TBARS formation. Carnosine should be investigated in more detail in order to establish its putative utility as an agent to prevent copper-associated damages in biological systems.

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

    PubMed

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

    1996-01-01

    This study was designed to explore the daily lived experiences of a group of employed, low-income Mexican women in their maternal and spousal roles. The participants were 41 auxiliary nurses recruited from two large urban hospitals in Mexico. Data were collected through the Women's Roles Interview Protocol (WRIP), which solicited the participants' perceptions of the satisfaction and stresses they experienced in their roles as mothers and spouses, and their descriptions of the coping strategies and the resources they used to deal with stressful life experiences related to these roles. Data analysis consisted of a qualitative thematic analysis of the narrative responses to open-ended questions in the WRIP. Satisfying aspects of the maternal and spousal roles, as identified by the participants, included giving to and receiving from their children and being valued and supported by their partners. Spousal approval of their work was also satisfying. These employed mothers, however, experienced many stressful aspects of functioning in multiple roles, including lack of resources, being absent from their children, self-doubt about their maternal role functioning, role overload and spousal absences. The women coped by juggling priorities and utilizing family resources. From the data analysis, the investigators developed a conceptual framework for understanding these women's experiences with parenting and marriage. The centrality of the family, a sense of value and empowerment as women in maternal and spousal roles, and the reality of role overload are discussed within the Mexican culture context of machismo, its female counterpart hembrismo, and family life. Implications for women's health are framed within a context of family and work. PMID:8708228

  20. Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats

    PubMed Central

    2012-01-01

    Background Higher aluminum (Al) content in infant formula and its effects on neonatal brain development are a cause for concern. This study aimed to evaluate the distribution and concentration of Al in neonatal rat brain following Al treatment, and oxidative stress in brain tissues induced by Al overload. Methods Postnatal day 3 (PND 3) rat pups (n =46) received intraperitoneal injection of aluminum chloride (AlCl3), at dosages of 0, 7, and 35 mg/kg body wt (control, low Al (LA), and high Al (HA), respectively), over 14 d. Results Aluminum concentrations were significantly higher in the hippocampus (751.0 ± 225.8 ng/g v.s. 294.9 ± 180.8 ng/g; p < 0.05), diencephalon (79.6 ± 20.7 ng/g v.s. 20.4 ± 9.6 ng/g; p < 0.05), and cerebellum (144.8 ± 36.2 ng/g v.s. 83.1 ± 15.2 ng/g; p < 0.05) in the HA group compared to the control. The hippocampus, diencephalon, cerebellum, and brain stem of HA animals displayed significantly higher levels of lipid peroxidative products (TBARS) than the same regions in the controls. However, the average superoxide dismutase (SOD) activities in the cerebral cortex, hippocampus, cerebellum, and brain stem were lower in the HA group compared to the control. The HA animals demonstrated increased catalase activity in the diencephalon, and increased glutathione peroxidase (GPx) activity in the cerebral cortex, hippocampus, cerebellum, and brain stem, compared to controls. Conclusion Aluminum overload increases oxidative stress (H2O2) in the hippocampus, diencephalon, cerebellum, and brain stem in neonatal rats. PMID:22613782

  1. Archaeal community composition affects the function of anaerobic co-digesters in response to organic overload

    SciTech Connect

    Lerm, S.; Kleyboecker, A.; Miethling-Graff, R.; Alawi, M.; Kasina, M.; Liebrich, M.; Wuerdemann, H.

    2012-03-15

    Highlights: Black-Right-Pointing-Pointer Two types of methanogens are necessary to respond successfully to perturbation. Black-Right-Pointing-Pointer Diversity of methanogens correlates with the VFA concentration and methane yield. Black-Right-Pointing-Pointer Aggregates indicate tight spatial relationship between minerals and microorganisms. - Abstract: Microbial community diversity in two thermophilic laboratory-scale and three full-scale anaerobic co-digesters was analysed by genetic profiling based on PCR-amplified partial 16S rRNA genes. In parallel operated laboratory reactors a stepwise increase of the organic loading rate (OLR) resulted in a decrease of methane production and an accumulation of volatile fatty acids (VFAs). However, almost threefold different OLRs were necessary to inhibit the gas production in the reactors. During stable reactor performance, no significant differences in the bacterial community structures were detected, except for in the archaeal communities. Sequencing of archaeal PCR products revealed a dominance of the acetoclastic methanogen Methanosarcina thermophila, while hydrogenotrophic methanogens were of minor importance and differed additionally in their abundance between reactors. As a consequence of the perturbation, changes in bacterial and archaeal populations were observed. After organic overload, hydrogenotrophic methanogens (Methanospirillum hungatei and Methanoculleus receptaculi) became more dominant, especially in the reactor attributed by a higher OLR capacity. In addition, aggregates composed of mineral and organic layers formed during organic overload and indicated tight spatial relationships between minerals and microbial processes that may support de-acidification processes in over-acidified sludge. Comparative analyses of mesophilic stationary phase full-scale reactors additionally indicated a correlation between the diversity of methanogens and the VFA concentration combined with the methane yield. This study

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

    PubMed

    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.

  3. Endothelial lipase modulates pressure overload-induced heart failure through alternative pathway for fatty acid uptake.

    PubMed

    Nakajima, Hideto; Ishida, Tatsuro; Satomi-Kobayashi, Seimi; Mori, Kenta; Hara, Tetsuya; Sasaki, Naoto; Yasuda, Tomoyuki; Toh, Ryuji; Tanaka, Hidekazu; Kawai, Hiroya; Hirata, Ken-ichi

    2013-05-01

    Lipoprotein lipase has been considered as the only enzyme capable of generating lipid-derived fatty acids for cardiac energy. Endothelial lipase is another member of the triglyceride lipase family and hydrolyzes high-density lipoproteins. Although endothelial lipase is expressed in the heart, its function remains unclear. We assessed the role of endothelial lipase in the genesis of heart failure. Pressure overload-induced cardiac hypertrophy was generated in endothelial lipase(-/-) and wild-type mice by ascending aortic banding. Endothelial lipase expression in cardiac tissues was markedly elevated in the early phase of cardiac hypertrophy in wild-type mice, whereas lipoprotein lipase expression was significantly reduced. Endothelial lipase(-/-) mice showed more severe systolic dysfunction with left-ventricular dilatation compared with wild-type mice in response to pressure overload. The expression of mitochondrial fatty acid oxidation-related genes, such as carnitine palmitoyltransferase-1 and medium-chain acyl coenzyme A dehydrogenase, was significantly lower in the heart of endothelial lipase(-/-) mice than in wild-type mice. Also, endothelial lipase(-/-) mice had lower myocardial adenosine triphosphate levels than wild-type mice after aortic banding. In cultured cardiomyocytes, endothelial lipase was upregulated by inflammatory stimuli, whereas lipoprotein lipase was downregulated. Endothelial lipase-overexpression in cardiomyocytes resulted in an upregulation of fatty acid oxidation-related enzymes and intracellular adenosine triphosphate accumulation in the presence of high-density lipoprotein. Endothelial lipase may act as an alternative candidate to provide fatty acids to the heart and regulate cardiac function. This effect seemed relevant particularly in the diseased heart, where lipoprotein lipase action is downregulated. PMID:23460280

  4. MicroRNAs and liver cancer associated with iron overload: therapeutic targets unravelled.

    PubMed

    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.

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

    EPA Science Inventory

    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...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... short circuit protection; minimum requirements. 77.506-1 Section 77.506-1 Mineral Resources MINE SAFETY..., SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.506-1 Electric equipment and circuits; overload and short circuit protection; minimum...

  7. The Influence of Perceived Information Overload on Student Participation and Knowledge Construction in Computer-Mediated Communication

    ERIC Educational Resources Information Center

    Chen, Chun-Ying; Pedersen, Susan; Murphy, Karen L.

    2012-01-01

    Computer-mediated communication (CMC) has been used widely to engage learners in academic discourse for knowledge construction. Due to the features of the task environment, one of the main problems caused by the medium is information overload (IO). Yet the literature is unclear about the impact of IO on student learning. This study therefore…

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

    PubMed

    Lu, Nai-Hao; Chen, Chao; He, Ying-Jie; Tian, Rong; Xiao, Qiang; Peng, Yi-Yuan

    2013-01-01

    Flavonoids have been widely reported to protect liver injury in iron-overload diseases, where the mechanism of this therapeutic action is dependent on their antioxidant effects, including free radical scavenging and metal-chelating. In this study, in contrast to the significant decrease in iron content, quercetin (Qu) from lower diet (0.3%, w/w) showed pro-oxidant ability on protein carbonyl formation and exhibited unobvious effect on iron-overload rat liver injury. Furthermore, the anti- and pro-oxidant activities of Qu on hemoglobin (Hb)-dependent redox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate, Hb-induced protein oxidation) were investigated to illustrate the elevated protein oxidation in lower Qu-treated iron-overload rat. It was found that superoxide (O₂·⁻) and hydrogen peroxide (H₂O₂) were generated during the reaction between Qu and Hb. Qu, however, effectively reduced ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. Moreover, Qu could significantly aggravate Hb-H₂O₂-induced protein oxidation at low concentrations and exhibit protective effects at high concentrations. Different from the classic antioxidant mechanisms of Qu, the dual effects on Hb redox reactions in vitro, therefore, may provide new insights into the physiological and pharmacological implications of Qu with iron-overload disease.

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

    PubMed Central

    Portela, Luciana Fernandes; Rotenberg, Lucia; Almeida, Ana Luiza Pereira; Landsbergis, Paul; Griep, Rosane Harter

    2013-01-01

    Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP) alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers. PMID:24287860

  10. Effects of chronic overload on muscle hypertrophy and mTOR signaling in adult and aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two-thirds of the gas...

  11. The influence of domestic overload on the association between job strain and ambulatory blood pressure among female nursing workers.

    PubMed

    Portela, Luciana Fernandes; Rotenberg, Lucia; Almeida, Ana Luiza Pereira; Landsbergis, Paul; Griep, Rosane Harter

    2013-11-27

    Evidence suggests that the workplace plays an important etiologic role in blood pressure (BP) alterations. Associations in female samples are controversial, and the domestic environment is hypothesized to be an important factor in this relationship. This study assessed the association between job strain and BP within a sample of female nursing workers, considering the potential role of domestic overload. A cross-sectional study was conducted in a group of 175 daytime workers who wore an ambulatory BP monitor for 24 h during a working day. Mean systolic and diastolic BP were calculated. Job strain was evaluated using the Demand-Control Model. Domestic overload was based on the level of responsibility in relation to four household tasks and on the number of beneficiaries. After adjustments no significant association between high job strain and BP was detected. Stratified analyses revealed that women exposed to both domestic overload and high job strain had higher systolic BP at home. These results indicate a possible interaction between domestic overload and job strain on BP levels and revealed the importance of domestic work, which is rarely considered in studies of female workers.

  12. Quantum volume

    NASA Astrophysics Data System (ADS)

    Ryabov, V. A.

    2015-08-01

    Quantum systems in a mechanical embedding, the breathing mode of a small particles, optomechanical system, etc. are far not the full list of examples in which the volume exhibits quantum behavior. Traditional consideration suggests strain in small systems as a result of a collective movement of particles, rather than the dynamics of the volume as an independent variable. The aim of this work is to show that some problem here might be essentially simplified by introducing periodic boundary conditions. At this case, the volume is considered as the independent dynamical variable driven by the internal pressure. For this purpose, the concept of quantum volume based on Schrödinger’s equation in 𝕋3 manifold is proposed. It is used to explore several 1D model systems: An ensemble of free particles under external pressure, quantum manometer and a quantum breathing mode. In particular, the influence of the pressure of free particle on quantum oscillator is determined. It is shown also that correction to the spectrum of the breathing mode due to internal degrees of freedom is determined by the off-diagonal matrix elements of the quantum stress. The new treatment not using the “force” theorem is proposed for the quantum stress tensor. In the general case of flexible quantum 3D dynamics, quantum deformations of different type might be introduced similarly to monopole mode.

  13. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  14. Erythrocyte membrane fatty acid composition is related to overloaded plasma ferritin in Chinese males with angiographic coronary artery disease.

    PubMed

    Li, Zhongxia; Li, Xinrui; Zhang, Yuan; Feng, Xiang; Yang, Fang; Su, Dongfang; Qiu, Jian; Ling, Wenhua; Yang, Yan

    2013-10-01

    Not only is iron deficiency an abnormal iron status, but iron overload is also harmful for human health. It has been reported that overloaded iron stores are positively associated with increased coronary artery disease (CAD) risk, which is called the "iron-heart hypothesis". Previous studies evaluating the relationships between fatty acids (FAs) and body iron status only focused on participants with iron deficiency. However, whether FA composition is related to overloaded iron remains unclear. Therefore, this study was designed to investigate the relationships between erythrocyte membrane FA (Ery-FA) composition and overloaded body iron status as measured by plasma ferritin levels in Chinese CAD patients. A total of 446 subjects with angiographically identified CAD (mean age 63.1 years, 76.9% males) were recruited in a hospital between 2009 and 2010. Ery-FAs were measured by gas chromatography and the activities of FA desaturases, which are involved in the de novo synthesis of unsaturated FAs, were evaluated by using FA product-to-precursor ratios. Results showed that the average iron status was a bit overloaded in the population (median ferritin levels of 234.1 ng mL(-1) and 40.4% males of overload). Moreover, in males, saturated FAs (SFAs) were positively correlated (22 : 0, r = 0.182, p = 0.001; 24 : 0, r = 0.214, p < 0.001), whereas monounsaturated FAs (MUFAs) and n-6 polyunsaturated FAs (PUFAs) were negatively correlated (18 : 1n-9, r = -0.120, p = 0.028; 18 : 2n-6, r = -0.216, p < 0.001) with plasma ferritin levels. A negative correlation (r < 0, p < 0.05) between stearoyl-CoA desaturase (SCD) activity and ferritin levels was also found in males. However, all the significant association