Osteoblast-secreted collagen upregulates paracrine Sonic hedgehog signaling by prostate cancer cells and enhances osteoblast differentiation

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Zunich Samantha M

2012-07-01

Full Text Available Abstract Background Induction of osteoblast differentiation by paracrine Sonic hedgehog (Shh signaling may be a mechanism through which Shh-expressing prostate cancer cells initiate changes in the bone microenvironment and promote metastases. A hallmark of osteoblast differentiation is the formation of matrix whose predominant protein is type 1 collagen. We investigated the formation of a collagen matrix by osteoblasts cultured with prostate cancer cells, and its effects on interactions between prostate cancer cells and osteoblasts. Results In the presence of exogenous ascorbic acid (AA, a co-factor in collagen synthesis, mouse MC3T3 pre-osteoblasts in mixed cultures with human LNCaP prostate cancer cells or LNCaP cells modified to overexpress Shh (LNShh cells formed collagen matrix with distinct fibril ultrastructural characteristics. AA increased the activity of alkaline phosphatase and the expression of the alkaline phosphatase gene Akp2, markers of osteoblast differentiation, in MC3T3 pre-osteoblasts cultured with LNCaP or LNShh cells. However, the AA-stimulated increase in Akp2 expression in MC3T3 pre-osteoblasts cultured with LNShh cells far exceeded the levels observed in MC3T3 cells cultured with either LNCaP cells with AA or LNShh cells without AA. Therefore, AA and Shh exert a synergistic effect on osteoblast differentiation. We determined whether the effect of AA on LNShh cell-induced osteoblast differentiation was mediated by Shh signaling. AA increased the expression of Gli1 and Ptc1, target genes of the Shh pathway, in MC3T3 pre-osteoblasts cultured with LNShh cells to at least twice their levels without AA. The ability of AA to upregulate Shh signaling and enhance alkaline phosphatase activity was blocked in MC3T3 cells that expressed a dominant negative form of the transcription factor GLI1. The AA-stimulated increase in Shh signaling and Shh-induced osteoblast differentiation was also inhibited by the specific collagen synthesis

Ciliopathy proteins regulate paracrine signaling by modulating proteasomal degradation of mediators

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Liu, Yangfan P.; Tsai, I-Chun; Morleo, Manuela; Oh, Edwin C.; Leitch, Carmen C.; Massa, Filomena; Lee, Byung-Hoon; Parker, David S.; Finley, Daniel; Zaghloul, Norann A.; Franco, Brunella; Katsanis, Nicholas

2014-01-01

Cilia are critical mediators of paracrine signaling; however, it is unknown whether proteins that contribute to ciliopathies converge on multiple paracrine pathways through a common mechanism. Here, we show that loss of cilopathy-associated proteins Bardet-Biedl syndrome 4 (BBS4) or oral-facial-digital syndrome 1 (OFD1) results in the accumulation of signaling mediators normally targeted for proteasomal degradation. In WT cells, several BBS proteins and OFD1 interacted with proteasomal subunits, and loss of either BBS4 or OFD1 led to depletion of multiple subunits from the centrosomal proteasome. Furthermore, overexpression of proteasomal regulatory components or treatment with proteasomal activators sulforaphane (SFN) and mevalonolactone (MVA) ameliorated signaling defects in cells lacking BBS1, BBS4, and OFD1, in morphant zebrafish embryos, and in induced neurons from Ofd1-deficient mice. Finally, we tested the hypothesis that other proteasome-dependent pathways not known to be associated with ciliopathies are defective in the absence of ciliopathy proteins. We found that loss of BBS1, BBS4, or OFD1 led to decreased NF-κB activity and concomitant IκBβ accumulation and that these defects were ameliorated with SFN treatment. Taken together, our data indicate that basal body proteasomal regulation governs paracrine signaling pathways and suggest that augmenting proteasomal function might benefit ciliopathy patients. PMID:24691443

How emotion context modulates unconscious goal activation during motor force exertion.

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Blakemore, Rebekah L; Neveu, Rémi; Vuilleumier, Patrik

2017-02-01

Priming participants with emotional or action-related concepts influences goal formation and motor force output during effort exertion tasks, even without awareness of priming information. However, little is known about neural processes underpinning how emotional cues interact with action (or inaction) goals to motivate (or demotivate) motor behaviour. In a novel functional neuroimaging paradigm, visible emotional images followed by subliminal action or inaction word primes were presented before participants performed a maximal force exertion. In neutral emotional contexts, maximum force was lower following inaction than action primes. However, arousing emotional images had interactive motivational effects on the motor system: Unpleasant images prior to inaction primes increased force output (enhanced effort exertion) relative to control primes, and engaged a motivation-related network involving ventral striatum, extended amygdala, as well as right inferior frontal cortex. Conversely, pleasant images presented before action (versus control) primes decreased force and activated regions of the default-mode network, including inferior parietal lobule and medial prefrontal cortex. These findings show that emotional context can determine how unconscious goal representations influence motivational processes and are transformed into actual motor output, without direct rewarding contingencies. Furthermore, they provide insight into altered motor behaviour in psychopathological disorders with dysfunctional motivational processes. Copyright © 2016 Elsevier Inc. All rights reserved.

Endothelial actions of atrial and B-type natriuretic peptides.

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Kuhn, Michaela

2012-05-01

The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

Adult mouse epicardium modulates myocardial injury by secreting paracrine factors

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Zhou, Bin; Honor, Leah B.; He, Huamei; Ma, Qing; Oh, Jin-Hee; Butterfield, Catherine; Lin, Ruei-Zeng; Melero-Martin, Juan M.; Dolmatova, Elena; Duffy, Heather S.; von Gise, Alexander; Zhou, Pingzhu; Hu, Yong Wu; Wang, Gang; Zhang, Bing; Wang, Lianchun; Hall, Jennifer L.; Moses, Marsha A.; McGowan, Francis X.; Pu, William T.

2011-01-01

The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection. PMID:21505261

Phenobarbital but not diazepam reduces AMPA/Kainate receptor mediated currents and exerts opposite actions on initial seizures in the neonatal rat hippocampus

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Romain eNardou

2011-07-01

Full Text Available Diazepam (DZP and phenobarbital (PB are extensively used as first and second line drugs to treat acute seizures in neonates and their actions are thought to be mediated by increasing the actions of GABAergic signals. Yet, their efficacy is variable with occasional failure or even aggravation of recurrent seizures questioning whether other mechanisms are not involved in their actions. We have now compared the effects of DZP and PB on ictal-like events (ILEs in an in vitro model of mirror focus (MF. Using the three-compartment chamber with the two immature hippocampi and their commissural fibers placed in 3 different compartments, kainate was applied to one hippocampus and PB or DZP to the contralateral one, either after one ILE or after many recurrent ILEs that produce an epileptogenic MF. We report that in contrast to PB, DZP aggravated propagating ILEs from the start and did not prevent the formation of MF. PB reduced and DZP increased the network driven Giant Depolarising Potentials suggesting that PB may exert additional actions that are not mediated by GABA signalling. In keeping with this, PB but not DZP reduced field potentials recorded in the presence of GABA and NMDA receptor antagonists. These effects are mediated by a direct action on AMPA/Kainate receptors since PB: i reduced AMPA/Kainate receptor mediated currents induced by focal applications of glutamate ; ii reduced the amplitude and the frequency of AMPA but not NMDA receptor mediated miniature EPSCs; iii augmented the number of AMPA receptor mediated EPSCs failures evoked by minimal stimulation. These effects persisted in MF. Therefore, PB exerts its anticonvulsive actions partly by reducing AMPA/Kainate receptors mediated EPSCs in addition to the pro-GABA effects. We suggest that PB may have advantage over DZP in the treatment of initial neonatal seizures since the additional reduction of glutamate receptors mediated signals may reduce the severity of neonatal seizures.

Endothelin-3 production by human rhabdomyosarcoma: a possible new marker with a paracrine role.

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Palladini, Arianna; Astolfi, Annalisa; Croci, Stefania; De Giovanni, Carla; Nicoletti, Giordano; Rosolen, Angelo; Sartori, Francesca; Lollini, Pier-Luigi; Landuzzi, Lorena; Nanni, Patrizia

2006-03-01

Several autocrine and paracrine growth factor circuits have been found in human rhabdomyosarcoma cells. In this study we show that endothelin-3 (ET-3), a vasoactive peptide, is produced by human rhabdomyosarcoma cell lines, whereas it is not expressed by human sarcoma cell lines of non-muscle origin. We did not find evidence of a significant autocrine loop; nevertheless ET-3 produced by rhabdomyosarcoma cells can act as a paracrine factor, since it promotes migration of endothelial cells. Moreover ET-3 is present in plasma of mice bearing xenografts of human rhabdomyosarcoma cells, and may be potential new marker of the human rhabdomyosarcoma to be studied further.

Microbioreactor arrays for full factorial screening of exogenous and paracrine factors in human embryonic stem cell differentiation.

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Drew M Titmarsh

Full Text Available Timed exposure of pluripotent stem cell cultures to exogenous molecules is widely used to drive differentiation towards desired cell lineages. However, screening differentiation conditions in conventional static cultures can become impractical in large parameter spaces, and is intrinsically limited by poor spatiotemporal control of the microenvironment that also makes it impossible to determine whether exogenous factors act directly or through paracrine-dependent mechanisms. We detail here the development of a continuous flow microbioreactor array platform that combines full-factorial multiplexing of input factors with progressive accumulation of paracrine factors through serially-connected culture chambers, and further, the use of this system to explore the combinatorial parameter space of both exogenous and paracrine factors involved in human embryonic stem cell (hESC differentiation to a MIXL1-GFP(+ primitive streak-like population. We show that well known inducers of primitive streak (BMP, Activin and Wnt signals do not simply act directly on hESC to induce MIXL1 expression, but that this requires accumulation of surplus, endogenous factors; and, that conditioned medium or FGF-2 supplementation is able to offset this. Our approach further reveals the presence of a paracrine, negative feedback loop to the MIXL1-GFP(+ population, which can be overcome with GSK-3β inhibitors (BIO or CHIR99021, implicating secreted Wnt inhibitory signals such as DKKs and sFRPs as candidate effectors. Importantly, modulating paracrine effects identified in microbioreactor arrays by supplementing FGF-2 and CHIR in conventional static culture vessels resulted in improved differentiation outcomes. We therefore demonstrate that this microbioreactor array platform uniquely enables the identification and decoding of complex soluble factor signalling hierarchies, and that this not only challenges prevailing strategies for extrinsic control of hESC differentiation, but

Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells

International Nuclear Information System (INIS)

Nakanishi, Chiaki; Yamagishi, Masakazu; Yamahara, Kenichi; Hagino, Ikuo; Mori, Hidezo; Sawa, Yoshiki; Yagihara, Toshikatsu; Kitamura, Soichiro; Nagaya, Noritoshi

2008-01-01

Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as β-myosin heavy chain (β-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation

Muscle as an endocrine organ: focus on muscle-derived interleukin-6

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Febbraio, M.A.; Pedersen, Bente Klarlund

2008-01-01

Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "myokines." Recent...... period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease...

Carvacrol promotes angiogenic paracrine potential and endothelial differentiation of human mesenchymal stem cells at low concentrations.

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Matluobi, Danial; Araghi, Atefeh; Maragheh, Behnaz Faramarzian Azimi; Rezabakhsh, Aysa; Soltani, Sina; Khaksar, Majid; Siavashi, Vahid; Feyzi, Adel; Bagheri, Hesam Saghaei; Rahbarghazi, Reza; Montazersaheb, Soheila

2018-01-01

Phenolic monoterpene compound, named Carvacrol, has been found to exert different biological outcomes. It has been accepted that the angiogenic activity of human mesenchymal stem cells was crucial in the pursuit of appropriate regeneration. In the current experiment, we investigated the contribution of Carvacrol on the angiogenic behavior of primary human mesenchymal stem cells. Mesenchymal stem cells were exposed to Carvacrol in a dose ranging from 25 to 200μM for 48h. We measured cell survival rate by MTT assay and migration rate by a scratch test. The oxidative status was monitored by measuring SOD, GPx activity. The endothelial differentiation was studied by evaluating the level of VE-cadherin and vWF by real-time PCR and ELISA analyses. The content of VEGF and tubulogenesis behavior was monitored in vitro. We also conducted Matrigel plug in vivo CAM assay to assess the angiogenic potential of conditioned media from human mesenchymal stem cells after exposure to Carvacrol. Carvacrol was able to increase mesenchymal stem cell survival and migration rate (pcells by detecting vWF and VE-cadherin expression (pmesenchymal stem cells conditioned media improved angiogenesis tube formation in vitro (pmesenchymal stem cells by modulating cell differentiation and paracrine angiogenic response. Copyright © 2017 Elsevier Inc. All rights reserved.

Decidual Stromal Cell Response to Paracrine Signals from the Trophoblast: Amplification of Immune and Angiogenic Modulators

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Hess, AP; Hamilton, AE; Talbi, S

2007-01-01

During the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important...... a functional genomics approach to investigate these paracrine interactions. Human endometrial stromal cells were decidualized with progesterone and were further treated with conditioned media (CM) from human trophoblasts (TCM) or, as a control, with conditioned media (CCM) from non-decidualized stromal cells...... regulated groups. The data demonstrate a significant induction of pro-inflammatory cytokines and chemokines, as well as angiogenic/static factors in decidualized endometrial stromal cells in response to trophoblast-secreted products. The data suggest that the trophoblast acts to alter the local immune...

Autocrine and Paracrine Mechanisms Promoting Chemoresistance in Cholangiocarcinoma

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Massimiliano Cadamuro

2017-01-01

Full Text Available Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat malignancy in humans. Mechanisms of chemoresistance by neoplastic cholangiocytes include evasion of drug-induced apoptosis mediated by autocrine and paracrine cues released in the tumor microenvironment. Here, recent evidence regarding molecular mechanisms of chemoresistance is reviewed, as well as associations between well-developed chemoresistance and activation of the cancer stem cell compartment. It is concluded that improved understanding of the complex interplay between apoptosis signaling and the promotion of cell survival represent potentially productive areas for active investigation, with the ultimate aim of encouraging future studies to unveil new, effective strategies able to overcome current limitations on treatment.

Lung-derived growth factors: possible paracrine effectors of fetal lung development

International Nuclear Information System (INIS)

Montes, A.M.

1985-01-01

A potential role for paracrine secretions in lung organogenesis has been hypothesized (Alescio and Piperno, 1957). These studies present direct support for the paracrine model by demonstrating the presence of locally produced mitogenic/maturational factors in fetal rat lung tissue. Conditioned serum free medium (CSFM) from nineteen-day fetal rat lung cultures was shown to contain several bioactive peptides as detected by 3 H-Thymidine incorporation into chick embryo and rat lung fibroblasts, as well as 14 C-choline incorporation into surfactant in mixed cell cultures. Using ion-exchange chromatography and Sephadex gel filtration, a partially purified mitogen, 11-III, was obtained. The partially purified 11-III stimulates mitosis in chick embryo fibroblasts and post-natal rat lung fibroblasts. Multiplication in fetal rat lung fibroblasts cultures is stimulated only when these are pre-incubated with a competence factor or unprocessed CSFM. This suggests the existence of an endogenously produced competence factor important in the regulation of fetal lung growth. Preparation 11-III does not possess surfactant stimulating activity as assessed by 3 H-choline incorporation into lipids in predominantly type-II cell cultures. These data demonstrate the presence of a maturational/mitogenic factor, influencing type-II mixed cell cultures. In addition, 11-III had been shown to play an autocrine role stimulating the proliferation of fetal lung fibroblasts. Finally, these data suggest the existence of a local produced competence factor

Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

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Ying An

2011-01-01

Full Text Available Ying An, Qun Chen, Ning QuanDepartment of Oral Biology, Ohio State University, Columbus, OH, USAAbstract: Interleukin-1 (IL-1 is a critical neuroinflammatory mediator in the central nervous system (CNS. In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1β is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1β stimulation. The three astrocyte cell lines responded to IL-1ß stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1β stimulation. The brain endothelial cells showed strongest response to IL-1β by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-κB pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.Keywords: astrocyte, microglia, endothelial cells, signal transduction pathways, gene expression 

Vasohibin 2 promotes human luminal breast cancer angiogenesis in a non-paracrine manner via transcriptional activation of fibroblast growth factor 2.

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Tu, Min; Lu, Cheng; Lv, Nan; Wei, Jishu; Lu, Zipeng; Xi, Chunhua; Chen, Jianmin; Guo, Feng; Jiang, Kuirong; Li, Qiang; Wu, Junli; Song, Guoxin; Wang, Shui; Gao, Wentao; Miao, Yi

2016-12-28

Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts via paracrine mechanisms. Here, we investigated the angiogenic function and mechanism of action of VASH2 in 200 human breast cancer tissues by performing immunohistochemical staining, western blot, indirect sandwich enzyme-linked immunosorbent assay (ELISA), and a semi-quantitative sandwich-based antibody array. Breast cancer cells stably overexpressing VASH2 or with knocked-down VASH2 were established and used for in vivo and in vitro models. In human luminal tissue, but not in HER2-positive or basal-like breast cancer tissues, VASH2 was positively correlated with CD31-positive microvascular density, induced angiogenesis in xenograft tumors, and promoted human umbilical vein endothelial cell tube formation in vitro. VASH2 expression was absent in the concentrated conditioned medium collected from knocked-down VASH2 and VASH2-overexpressing luminal breast cancer cells. Further, VASH2 regulated the expression of fibroblast growth factor 2 (FGF2) in human luminal breast cancer cells, and the pro-angiogenic effect induced by VASH2 overexpression was blocked by FGF2 neutralization in vitro. Additionally, dual luciferase reporter assay and Chromatin immunoprecipitation analysis results showed that FGF2 promoter was transcriptionally activated by VASH2 via histone modifications. In conclusion, VASH2 expression is positively correlated with FGF2 expression and promotes angiogenesis in human luminal breast cancer by transcriptional activation of fibroblast growth factor 2 through non-paracrine mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Paracrine and autocrine signals promoting full chondrogenic differentiation of a mesoblastic cell line.

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Locker, Morgane; Kellermann, Odile; Boucquey, Marie; Khun, Huot; Huerre, Michel; Poliard, Anne

2004-01-01

The pluripotent mesoblastic C1 cell line was used under serum-free culture conditions to investigate how paracrine and autocrine signals cooperate to drive chondrogenesis. Sequential addition of two systemic hormones, dexamethasone and triiodothyronine, permits full chondrogenic differentiation. The cell intrinsic activation of the BMP signaling pathway and Sox9 expression occurring on mesoblastic condensation is insufficient for recruitment of the progenitors. Dexamethasone-dependent Sox9 upregulation is essential for chondrogenesis. Differentiation of lineage stem cells relies on cell autonomous regulations modulated by external signals. We used the pluripotent mesoblastic C1 cell line under serum-free culture conditions to investigate how paracrine and autocrine signals cooperate to induce differentiation of a precursor clone along the chondrogenic lineage. C1 cells, cultured as aggregates, were induced toward chondrogenesis by addition of 10(-7) M dexamethasone in serum-free medium. After 30 days, dexamethasone was replaced by 10 nM triiodothyronine to promote final hypertrophic conversion. Mature and hypertrophic phenotypes were characterized by immunocytochemistry using specific antibodies against types II and X collagens, respectively. Type II collagen, bone morphogenetic proteins (BMPs), BMP receptors, Smads, and Sox9 expression were monitored by reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot, and/or Western blot analysis. Once C1 cells have formed nodules, sequential addition of two systemic hormones is sufficient to promote full chondrogenic differentiation. In response to dexamethasone, nearly 100% of the C1 precursors engage in chondrogenesis and convert within 30 days into mature chondrocytes, which triggers a typical cartilage matrix. On day 25, a switch in type II procollagen mRNA splicing acted as a limiting step in the acquisition of the mature chondrocyte phenotype. On day 30, substitution of dexamethasone with

Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

NARCIS (Netherlands)

Homberg, Judith R.; Olivier, Jocelien D. A.; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

2011-01-01

The selective serotonin reuptake inhibitor (SSRI) Prozac (R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

NARCIS (Netherlands)

Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

2011-01-01

The selective serotonin reuptake inhibitor (SSRI) Prozac(R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

NARCIS (Netherlands)

Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

2011-01-01

The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby

Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

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Kenichiro Ishii

2018-04-01

Full Text Available Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers.

Bone marrow transplantation rescues intestinal mucosa after whole body radiation via paracrine mechanisms

International Nuclear Information System (INIS)

Chang, Ya Hui; Lin, Li-Mei; Lou, Chi-Wen; Chou, Chuan-Kai; Ch’ang, Hui-Ju

2012-01-01

Purpose: Our previous study reveals bone marrow transplantation (BMT) recruits host marrow-derived myelomonocytic cells to radiation-injured intestine, enhancing stromal proliferation, leading secondarily to epithelial regeneration. In this study, we propose BMT ameliorates intestinal damage via paracrine mechanisms. Materials and methods: Angiogenic cytokines within the intestinal mucosa of mice after whole body irradiation (WBI) with or without BMT were measured by cytokine array and ELISA. BM conditioned medium (BMCM) with or without treatment with neutralizing antibodies to angiogenic cytokines were continuously infused into mice for three days after radiation. Carrageenan was used to deplete myelomonocytic cells of mice. Results: BMT increased VEGF, bFGF and other angiogenic and chemotactic cytokines in the intestinal mucosa within 24 h after WBI. Infusion of BMCM ameliorated radiation-induced intestinal damage with improved stromal activity and prolonged survival of mice. Neutralization of bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating effect to the intestine. Pretreatment of carrageenan to recipient mice reversed some of the cytokine levels, including VEGF, bFGF and IGF within the intestinal mucosa after BMT. Conclusions: Our result suggests BMT recruits host myelomonocytic cells and enhances intestinal stroma proliferation after radiation by secreting cytokines enhancing angiogenesis and chemotaxis. Host myelomonocytic cells further uplift the paracrine effect to enhance intestinal mucosal recovery.

Paracrine interactions of cancer-associated fibroblasts, macrophages and endothelial cells: tumor allies and foes.

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Ronca, Roberto; Van Ginderachter, Jo A; Turtoi, Andrei

2018-01-01

Tumor stroma is composed of many cellular subtypes, of which the most abundant are fibroblasts, macrophages and endothelial cells. During the process of tissue injury, these three cellular subtypes must coordinate their activity to efficiently contribute to tissue regeneration. In tumor, this mechanism is hijacked by cancer cells, which rewire the interaction of stromal cells to benefit tumor development. The present review aims at summarizing most relevant information concerning both pro-tumorigenic and anti-tumorigenic actions implicating the three stromal cell subtypes as well as their mutual interactions. Although stromal cells are generally regarded as tumor-supportive and at will manipulated by cancer cells, several novel studies point at many defaults in cancer cell-mediated stromal reprograming. Indeed, parts of initial tissue-protective and homeostatic functions of the stromal cells remain in place even after tumor development. Both tumor-supportive and tumor-suppressive functions have been well described for macrophages, whereas similar results are emerging for fibroblasts and endothelial cells. Recent success of immunotherapies have finally brought the long awaited proof that stroma is key for efficient tumor targeting. However, a better understanding of paracrine stromal interactions is needed in order to encourage drug development not only aiming at disruption of tumor-supportive communication but also re-enforcing, existing, tumor-suppressive mechanisms.

Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis.

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Sieh, Shirly; Taubenberger, Anna V; Lehman, Melanie L; Clements, Judith A; Nelson, Colleen C; Hutmacher, Dietmar W

2014-06-01

As microenvironmental factors such as three-dimensionality and cell-matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to

Plant natriuretic peptides are apoplastic and paracrine stress response molecules

KAUST Repository

Wang, Yuhua

2011-04-07

Higher plants contain biologically active proteins that are recognized by antibodies against human atrial natriuretic peptide (ANP). We identified and isolated two Arabidopsis thaliana immunoreactive plant natriuretic peptide (PNP)-encoding genes, AtPNP-A and AtPNP-B, which are distantly related members of the expansin superfamily and have a role in the regulation of homeostasis in abiotic and biotic stresses, and have shown that AtPNP-A modulates the effects of ABA on stomata. Arabidopsis PNP (PNP-A) is mainly expressed in leaf mesophyll cells, and in protoplast assays we demonstrate that it is secreted using AtPNP-A:green fluorescent protein (GFP) reporter constructs and flow cytometry. Transient reporter assays provide evidence that AtPNP-A expression is enhanced by heat, osmotica and salt, and that AtPNP-A itself can enhance its own expression, thereby generating a response signature diagnostic for paracrine action and potentially also autocrine effects. Expression of native AtPNP-A is enhanced by osmotica and transiently by salt. Although AtPNP-A expression is induced by salt and osmotica, ABA does not significantly modulate AtPNP-A levels nor does recombinant AtPNP-A affect reporter expression of the ABA-responsive RD29A gene. Together, these results provide experimental evidence that AtPNP-A is stress responsive, secreted into the apoplastic space and can enhance its own expression. Furthermore, our findings support the idea that AtPNP-A, together with ABA, is an important component in complex plant stress responses and that, much like in animals, peptide signaling molecules can create diverse and modular signals essential for growth, development and defense under rapidly changing environmental conditions. © 2011 The Author.

Interleukin-6: a bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells.

Science.gov (United States)

Delk, Nikki A; Farach-Carson, Mary C

2012-04-01

Autophagy reallocates nutrients and clears normal cells of damaged proteins and organelles. In the context of metastatic disease, invading cancer cells hijack autophagic processes to survive and adapt in the host microenvironment. We sought to understand how autophagy is regulated in the metastatic niche for prostate cancer (PCa) cells where bone marrow stromal cell (BMSC) paracrine signaling induces PCa neuroendocrine differentiation (NED). In PCa, this transdifferentiation of metastatic PCa cells to neuronal-like cells correlates with advanced disease. Because autophagy provides a survival advantage for cancer cells and promotes cell differentiation, we hypothesized that autophagy mediates PCa NED in the bone. Thus, we determined the ability of paracrine factors in conditioned media (CM) from two separate BMSC subtypes, HS5 and HS27a, to induce autophagy in C4-2 and C4-2B bone metastatic PCa cells by characterizing the autophagy marker, LC3. Unlike HS27a CM, HS5 CM induced LC3 accumulation in PCa cells, suggesting autophagy was induced and indicating that HS5 and HS27a secrete a different milieu of paracrine factors that influence PCa autophagy. We identified interleukin-6 (IL-6), a cytokine more highly expressed in HS5 cells than in HS27a cells, as a paracrine factor that regulates PCa autophagy. Pharmacological inhibition of STAT3 activity did not attenuate LC3 accumulation, implying that IL-6 regulates NED and autophagy through different pathways. Finally, chloroquine inhibition of autophagic flux blocked PCa NED; hence autophagic flux maintains NED. Our studies imply that autophagy is cytoprotective for PCa cells in the bone, thus targeting autophagy is a potential therapeutic strategy.

Perspectives on Exertional Rhabdomyolysis.

Science.gov (United States)

Rawson, Eric S; Clarkson, Priscilla M; Tarnopolsky, Mark A

2017-03-01

Exertional (exercise-induced) rhabdomyolysis is a potentially life threatening condition that has been the subject of research, intense discussion, and media attention. The causes of rhabdomyolysis are numerous and can include direct muscle injury, unaccustomed exercise, ischemia, extreme temperatures, electrolyte abnormalities, endocrinologic conditions, genetic disorders, autoimmune disorders, infections, drugs, toxins, and venoms. The objective of this article is to review the literature on exertional rhabdomyolysis, identify precipitating factors, and examine the role of the dietary supplement creatine monohydrate. PubMed and SPORTDiscus databases were searched using the terms rhabdomyolysis, muscle damage, creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Additionally, the references of papers identified through this search were examined for relevant studies. A meta-analysis was not performed. Although the prevalence of rhabdomyolysis is low, instances still occur where exercise is improperly prescribed or used as punishment, or incomplete medical history is taken, and exertional rhabdomyolysis occurs. Creatine monohydrate does not appear to be a precipitating factor for exertional rhabdomyolysis. Healthcare professionals should be able to recognize the basic signs of exertional rhabdomyolysis so prompt treatment can be administered. For the risk of rhabdomyolysis to remain low, exercise testing and prescription must be properly conducted based on professional standards.

The definition of exertion-related cardiac events.

Science.gov (United States)

Rai, M; Thompson, P D

2011-02-01

Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.

A Fuzzy Logic-Based Personalized Method to Classify Perceived Exertion in Workplaces Using a Wearable Heart Rate Sensor

OpenAIRE

Pancardo, Pablo; Hernández-Nolasco, J. A.; Acosta-Escalante, Francisco

2018-01-01

Knowing the perceived exertion of workers during their physical activities facilitates the decision-making of supervisors regarding the worker allocation in the appropriate job, actions to prevent accidents, and reassignment of tasks, among others. However, although wearable heart rate sensors represent an effective way to capture perceived exertion, ergonomic methods are generic and they do not consider the diffuse nature of the ranges that classify the efforts. Personalized monitoring is ne...

The endocrine and paracrine control of menstruation.

Science.gov (United States)

Henriet, Patrick; Gaide Chevronnay, Héloïse P; Marbaix, Etienne

2012-07-25

During the reproductive life, the human endometrium undergoes cycles of substantial remodeling including, at menstruation, a massive but delimited tissue breakdown immediately followed by scarless repair. The present review aims at summarizing the current knowledge on the endocrine and paracrine control of menstruation in the light of recent observations that undermine obsolete dogmas. Menstruation can be globally considered as a response to falling progesterone concentration. However, tissue breakdown is heterogeneous and tightly controlled in space and time by a complex network of regulators and effectors, including cytokines, chemokines, proteases and various components of an inflammatory response. Moreover, menstruation must be regarded as part of a complex and integrated mechanism of tissue remodeling including features that precede and follow tissue lysis, i.e. decidualization and immediate post-menstrual regeneration. The understanding of the regulation of menstruation is of major basic and clinical interest. Indeed, these mechanisms largely overlap with those controlling other histopathological occurrences of tissue remodeling, such as development and cancer, and inappropriate control of menstrual features is a major potential cause of two frequent endometrial pathologies (i.e. abnormal uterine bleeding and endometriosis). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice.

Science.gov (United States)

Queiroga, Cláudia S F; Alves, Raquel M A; Conde, Sílvia V; Alves, Paula M; Vieira, Helena L A

2016-08-15

The neuroprotective role of carbon monoxide (CO) has been studied in a cell-autonomous mode. Herein, a new concept is disclosed - CO affects astrocyte-neuron communication in a paracrine manner to promote neuroprotection. Neuronal survival was assessed when co-cultured with astrocytes that had been pre-treated or not with CO. The CO-pre-treated astrocytes reduced neuronal cell death, and the cellular mechanisms were investigated, focusing on purinergic signaling. CO modulates astrocytic metabolism and extracellular ATP content in the co-culture medium. Moreover, several antagonists of P1 adenosine and P2 ATP receptors partially reverted CO-induced neuroprotection through astrocytes. Likewise, knocking down expression of the neuronal P1 adenosine receptor A2A-R (encoded by Adora2a) reverted the neuroprotective effects of CO-exposed astrocytes. The neuroprotection of CO-treated astrocytes also decreased following prevention of ATP or adenosine release from astrocytic cells and inhibition of extracellular ATP metabolism into adenosine. Finally, the neuronal downstream event involves TrkB (also known as NTRK2) receptors and BDNF. Pharmacological and genetic inhibition of TrkB receptors reverts neuroprotection triggered by CO-treated astrocytes. Furthermore, the neuronal ratio of BDNF to pro-BDNF increased in the presence of CO-treated astrocytes and decreased whenever A2A-R expression was silenced. In summary, CO prevents neuronal cell death in a paracrine manner by targeting astrocytic metabolism through purinergic signaling. © 2016. Published by The Company of Biologists Ltd.

Does mental exertion alter maximal muscle activation?

Directory of Open Access Journals (Sweden)

Vianney eRozand

2014-09-01

Full Text Available Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 minutes each: i high mental exertion (incongruent Stroop task, ii moderate mental exertion (congruent Stroop task, iii low mental exertion (watching a movie. In each condition, mental exertion was combined with ten intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 minutes. Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors.

Exertional dyspnoea in obesity

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Vipa Bernhardt

2016-12-01

Full Text Available The purpose of cardiopulmonary exercise testing (CPET in the obese person, as in any cardiopulmonary exercise test, is to determine the patient's exercise tolerance, and to help identify and/or distinguish between the various physiological factors that could contribute to exercise intolerance. Unexplained dyspnoea on exertion is a common reason for CPET, but it is an extremely complex symptom to explain. Sometimes obesity is the simple answer by elimination of other possibilities. Thus, distinguishing among multiple clinical causes for exertional dyspnoea depends on the ability to eliminate possibilities while recognising response patterns that are unique to the obese patient. This includes the otherwise healthy obese patient, as well as the obese patient with potentially multiple cardiopulmonary limitations. Despite obvious limitations in lung function, metabolic disease and/or cardiovascular dysfunction, obesity may be the most likely reason for exertional dyspnoea. In this article, we will review the more common cardiopulmonary responses to exercise in the otherwise healthy obese adult with special emphasis on dyspnoea on exertion.

The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells

DEFF Research Database (Denmark)

Hemmingsen, Mette; Vedel, Søren; Skafte-Pedersen, Peder

2013-01-01

Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment...

A Fuzzy Logic-Based Personalized Method to Classify Perceived Exertion in Workplaces Using a Wearable Heart Rate Sensor

Directory of Open Access Journals (Sweden)

Pablo Pancardo

2018-01-01

Full Text Available Knowing the perceived exertion of workers during their physical activities facilitates the decision-making of supervisors regarding the worker allocation in the appropriate job, actions to prevent accidents, and reassignment of tasks, among others. However, although wearable heart rate sensors represent an effective way to capture perceived exertion, ergonomic methods are generic and they do not consider the diffuse nature of the ranges that classify the efforts. Personalized monitoring is needed to enable a real and efficient classification of perceived individual efforts. In this paper, we propose a heart rate-based personalized method to assess perceived exertion; our method uses fuzzy logic as an option to manage imprecision and uncertainty in involved variables. We applied some experiments to cleaning staff and obtained results that highlight the importance of a custom method to classify perceived exertion of people doing physical work.

The paracrine feedback loop between vitamin D₃ (1,25(OH)₂D₃) and PTHrP in prehypertrophic chondrocytes

NARCIS (Netherlands)

Bach, Frances C; Rutten, Kirsten; Hendriks, Kristyanne; Riemers, Frank M; Cornelissen, Peter; de Bruin, Alain; Arkesteijn, Ger J; Wubbolts, Richard; Horton, William A; Penning, Louis C; Tryfonidou, Marianna A

2014-01-01

The endocrine feedback loop between vitamin D3(1,25(OH)2D3) and parathyroid hormone (PTH) plays a central role in skeletal development. PTH-related protein (PTHrP) shares homology and its receptor (PTHR1) with PTH. The aim of this study was to investigate whether there is a functional paracrine

Exerting Capacity.

Science.gov (United States)

Leger, J Michael; Phillips, Carolyn A

2017-05-01

Patient safety has been at the forefront of nursing research since the release of the Institute of Medicine's report estimating the number of preventable adverse events in hospital settings; yet no research to date has incorporated the perspectives of bedside nurses using classical grounded theory (CGT) methodology. This CGT study explored the perceptions of bedside registered nurses regarding patient safety in adult acute care hospitals. Data analysis used three techniques unique to CGT-the constant comparative method, coding, and memoing-to explore the values, realities, and beliefs of bedside nurses about patient safety. The analysis resulted in a substantive theory, Exerting Capacity, which explained how bedside nurses balance the demands of keeping their patients safe. Exerting Capacity has implications for health care organization leaders, nursing leaders, and bedside nurses; it also has indications for future research into the concept of patient safety.

TLR3 Ligand Poly(I:C Exerts Distinct Actions in Synovial Fibroblasts When Delivered by Extracellular Vesicles

Directory of Open Access Journals (Sweden)

Mojca Frank-Bertoncelj

2018-01-01

Full Text Available Extracellular vesicles (EV can modulate the responses of cells to toll-like receptor (TLR ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis. We have used as model the effects on RA SFs, of EV released from monocyte U937 cells and peripheral blood mononuclear cells upon stimulation with Poly(I:C, a synthetic analog of dsRNA. We show that EV released from unstimulated cells and Poly(I:C-stimulated U937 cells [Poly(I:C EV] differ in size but bind similar amounts of Annexin V and express comparable levels of MAC-1, the receptor for dsRNA, on the vesicular membranes. Specifically, Poly(I:C EV contain or associate with Poly(I:C and at least partially protect Poly(I:C from RNAse III degradation. Poly(I:C EV shuttle Poly(I:C to SFs and reproduce the proinflammatory and antiviral gene responses of SFs to direct stimulation with Poly(I:C. Poly(I:C EV, however, halt the death receptor-induced apoptosis in SFs, thereby inverting the proapoptotic nature of Poly(I:C. These prosurvival effects sharply contrast with the high toxicity of cationic liposome-delivered Poly(I:C and may reflect the route of Poly(I:C delivery via EV or the fine-tuning of Poly(I:C actions by molecular cargo in EV. The demonstration that EV may safeguard extracellular dsRNA and allow dsRNA to exert antiapoptotic effects on SFs highlights the potential of EV to amplify the pathogenicity of dsRNA in arthritis beyond inflammation (by concurrently enhancing the

Paracrine Maturation and Migration of SH-SY5Y Cells by Dental Pulp Stem Cells

OpenAIRE

Gervois, Pascal; Wolfs, Esther; Dillen, Yörg; Hilkens, Petra; Ratajczak, Jessica; Driesen, Ronald; Vangansewinkel, Tim; Bronckaers, Annelies; Brône, Bert; Struys, Tom; Lambrichts, Ivo

2017-01-01

Neurological disorders are characterized by neurodegeneration and/or loss of neuronal function, which cannot be adequately repaired by the host. Therefore, there is need for novel treatment options such as cell-based therapies that aim to salvage or reconstitute the lost tissue or that stimulate host repair. The present study aimed to evaluate the paracrine effects of human dental pulp stem cells (hDPSCs) on the migration and neural maturation of human SH-SY5Y neuroblastoma cells. The hDPSC s...

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

International Nuclear Information System (INIS)

Brady, Robert T.; O'Brien, Fergal J.; Hoey, David A.

2015-01-01

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

Energy Technology Data Exchange (ETDEWEB)

Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

2015-03-27

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

Aberrant Hedgehog ligands induce progressive pancreatic fibrosis by paracrine activation of myofibroblasts and ductular cells in transgenic zebrafish.

Directory of Open Access Journals (Sweden)

In Hye Jung

Full Text Available Hedgehog (Hh signaling is frequently up-regulated in fibrogenic pancreatic diseases including chronic pancreatitis and pancreatic cancer. Although recent series suggest exclusive paracrine activation of stromal cells by Hh ligands from epithelial components, debates still exist on how Hh signaling works in pathologic conditions. To explore how Hh signaling affects the pancreas, we investigated transgenic phenotypes in zebrafish that over-express either Indian Hh or Sonic Hh along with green fluorescence protein (GFP to enable real-time observation, or GFP alone as control, at the ptf1a domain. Transgenic embryos and zebrafish were serially followed for transgenic phenotypes, and investigated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR, in situ hybridization, and immunohistochemistry. Over-expression of Ihh or Shh reveals virtually identical phenotypes. Hh induces morphologic changes in a developing pancreas without derangement in acinar differentiation. In older zebrafish, Hh induces progressive pancreatic fibrosis intermingled with proliferating ductular structures, which is accompanied by the destruction of the acinar structures. Both myofibroblasts and ductular are activated and proliferated by paracrine Hh signaling, showing restricted expression of Hh downstream components including Patched1 (Ptc1, Smoothened (Smo, and Gli1/2 in those Hh-responsive cells. Hh ligands induce matrix metalloproteinases (MMPs, especially MMP9 in all Hh-responsive cells, and transform growth factor-ß1 (TGFß1 only in ductular cells. Aberrant Hh over-expression, however, does not induce pancreatic tumors. On treatment with inhibitors, embryonic phenotypes are reversed by either cyclopamine or Hedgehog Primary Inhibitor-4 (HPI-4. Pancreatic fibrosis is only prevented by HPI-4. Our study provides strong evidence of Hh signaling which induces pancreatic fibrosis through paracrine activation of Hh-responsive cells in vivo. Induction of

Predictions for optimal mitigation of paracrine inhibitory signalling in haemopoietic stem cell cultures.

Science.gov (United States)

Berry, Joseph D; Godara, Pankaj; Liovic, Petar; Haylock, David N

2015-04-16

Recent studies in the literature have highlighted the critical role played by cell signalling in determining haemopoietic stem cell (HSC) fate within ex vivo culture systems. Stimulatory signals can enhance proliferation and promote differentiation, whilst inhibitory signals can significantly limit culture output. Numerical models of various mitigation strategies are presented and applied to determine effectiveness of these strategies toward mitigation of paracrine inhibitory signalling inherent in these culture systems. The strategies assessed include mixing, media-exchange, fed-batch and perfusion. The models predict that significant spatial concentration gradients exist in typical cell cultures, with important consequences for subsequent cell expansion. Media exchange is shown to be the most effective mitigation strategy, but remains labour intensive and difficult to scale-up for large culture systems. The fed-batch strategy is only effective at very small Peclet number, and its effect is diminished as the cell culture volume grows. Conversely, mixing is effective at high Peclet number, and ineffective at low Peclet number. The models predict that cell expansion in fed-batch cultures becomes independent of increasing dilution rate, consistent with experimental results previously reported in the literature. In contrast, the models predict that increasing the flow rate in perfused cultures will lead to increased cell expansion, indicating the suitability of perfusion for use as an automated, tunable strategy. The effect of initial cell seeding density is also investigated, with the model showing that perfusion outperforms dilution for all densities considered. The models predict that the impact of inhibitory signalling in HSC cultures can be mitigated against using media manipulation strategies, with the optimal strategy dependent upon the protein diffusion time-scale relative to the media manipulation time-scale. The key messages from this study can be applied to

Design Strategies for Balancing Exertion Games

DEFF Research Database (Denmark)

Jensen, Mads Møller; Grønbæk, Kaj

2016-01-01

In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however, it is un......In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however......, it is unclear how balancing mechanisms should be applied in exertion games, where physical and digital elements are fused. In this paper, we present an exertion game and three approaches for balancing it; a physical, an explicit-digital and an implicit-digital balancing approach. A user study that compares...... these three approaches is used to investigate the qualities and challenges within each approach and explore how the player experience is affected by them. Based on these findings, we suggest four design strategies for balancing exertion games, so that players will stay engaged in the game and contain...

National Athletic Trainers' Association Position Statement: Exertional Heat Illnesses.

Science.gov (United States)

Casa, Douglas J; DeMartini, Julie K; Bergeron, Michael F; Csillan, Dave; Eichner, E Randy; Lopez, Rebecca M; Ferrara, Michael S; Miller, Kevin C; O'Connor, Francis; Sawka, Michael N; Yeargin, Susan W

2015-09-01

To present best-practice recommendations for the prevention, recognition, and treatment of exertional heat illnesses (EHIs) and to describe the relevant physiology of thermoregulation. Certified athletic trainers recognize and treat athletes with EHIs, often in high-risk environments. Although the proper recognition and successful treatment strategies are well documented, EHIs continue to plague athletes, and exertional heat stroke remains one of the leading causes of sudden death during sport. The recommendations presented in this document provide athletic trainers and allied health providers with an integrated scientific and clinically applicable approach to the prevention, recognition, treatment of, and return-to-activity guidelines for EHIs. These recommendations are given so that proper recognition and treatment can be accomplished in order to maximize the safety and performance of athletes. Athletic trainers and other allied health care professionals should use these recommendations to establish onsite emergency action plans for their venues and athletes. The primary goal of athlete safety is addressed through the appropriate prevention strategies, proper recognition tactics, and effective treatment plans for EHIs. Athletic trainers and other allied health care professionals must be properly educated and prepared to respond in an expedient manner to alleviate symptoms and minimize the morbidity and mortality associated with these illnesses.

Molecular imaging of the paracrine proangiogenic effects of progenitor cell therapy in limb ischemia.

Science.gov (United States)

Ryu, Jae Choon; Davidson, Brian P; Xie, Aris; Qi, Yue; Zha, Daogang; Belcik, J Todd; Caplan, Evan S; Woda, Juliana M; Hedrick, Catherine C; Hanna, Richard N; Lehman, Nicholas; Zhao, Yan; Ting, Anthony; Lindner, Jonathan R

2013-02-12

Stem cells are thought to enhance vascular remodeling in ischemic tissue in part through paracrine effects. Using molecular imaging, we tested the hypothesis that treatment of limb ischemia with multipotential adult progenitor cells (MAPCs) promotes recovery of blood flow through the recruitment of proangiogenic monocytes. Hind-limb ischemia was produced in mice by iliac artery ligation, and MAPCs were administered intramuscularly on day 1. Optical imaging of luciferase-transfected MAPCs indicated that cells survived for 1 week. Contrast-enhanced ultrasound on days 3, 7, and 21 showed a more complete recovery of blood flow and greater expansion of microvascular blood volume in MAPC-treated mice than in controls. Fluorescent microangiography demonstrated more complete distribution of flow to microvascular units in MAPC-treated mice. On ultrasound molecular imaging, expression of endothelial P-selectin and intravascular recruitment of CX(3)CR-1-positive monocytes were significantly higher in MAPC-treated mice than in the control groups at days 3 and 7 after arterial ligation. Muscle immunohistology showed a >10-fold-greater infiltration of monocytes in MAPC-treated than control-treated ischemic limbs at all time points. Intravital microscopy of ischemic or tumor necrosis factor-α-treated cremaster muscle demonstrated that MAPCs migrate to perimicrovascular locations and potentiate selectin-dependent leukocyte rolling. In vitro migration of human CD14(+) monocytes was 10-fold greater in response to MAPC-conditioned than basal media. In limb ischemia, MAPCs stimulate the recruitment of proangiogenic monocytes through endothelial activation and enhanced chemotaxis. These responses are sustained beyond the MAPC lifespan, suggesting that paracrine effects promote flow recovery by rebalancing the immune response toward a more regenerative phenotype.

Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture

DEFF Research Database (Denmark)

Follin, Bjarke; Juhl, Morten; Cohen, Smadar

2016-01-01

Mesenchymal stromal/stem cells (MSCs) have been investigated extensively through the past years, proving to have great clinical therapeutic potential. In vitro cultivation of MSCs in three-dimensional (3D) culture systems, such as scaffolds, hydrogels, or spheroids, have recently gained attention...... for tissue engineering applications. Studies on MSC spheroids demonstrated that such cultivation increased the paracrine immunomodulatory potential of the MSCs, accompanied by phenotypic alterations. In this review, we gather results from recent experimental studies on the immunomodulatory abilities of MSCs...... when cultured as spheroids or in biomaterials like scaffolds or hydrogels compared to regular two-dimensional (2D) culture and show that alterations occurring to MSCs in spheroids also occur in MSCs in biomaterials. We provide a brief description of known mechanisms of MSC immunomodulatory capacity...

c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling.

Directory of Open Access Journals (Sweden)

Nanako Kawaguchi

2010-12-01

Full Text Available Resident c-kit positive (c-kitpos cardiac stem cells (CSCs could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential.We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs.c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway.

When exercise causes exertional rhabdomyolysis.

Science.gov (United States)

Furman, Janet

2015-04-01

Exertional rhabdomyolysis is a clinical condition caused by intense, repetitive exercise or a sudden increase in exercise in an untrained person, although rhabdomyolysis can occur in trained athletes. In many cases, the presentation of early, uncomplicated rhabdomyolysis is subtle, but serious complications such as renal failure, compartment syndrome, and dysrhythmias may arise if severe exertional rhabdomyolysis is undiagnosed or untreated. Management is further complicated by the lack of concrete management guidelines for treating rhabdomyolysis and returning patients to activity.

Zinc as a paracrine effector in pancreatic islet cell death.

Science.gov (United States)

Kim, B J; Kim, Y H; Kim, S; Kim, J W; Koh, J Y; Oh, S H; Lee, M K; Kim, K W; Lee, M S

2000-03-01

Because of a huge amount of Zn2+ in secretory granules of pancreatic islet beta-cells, Zn2+ released in certain conditions might affect the function or survival of islet cells. We studied potential paracrine effects of endogenous Zn2+ on beta-cell death. Zn2+ induced insulinoma/islet cell death in a dose-dependent manner. Chelation of released endogenous Zn2+ by CaEDTA significantly decreased streptozotocin (STZ)-induced islet cell death in an in vitro culture system simulating in vivo circumstances but not in the conventional culture system. Zn2+ chelation in vivo by continuous CaEDTA infusion significantly decreased the incidence of diabetes after STZ administration. N-(6-methoxy-quinolyl)-para-toluene-sulfonamide staining revealed that Zn2+ was densely deposited in degenerating islet cells 24 h after STZ treatment, which was decreased by CaEDTA infusion. We show here that Zn2+ is not a passive element for insulin storage but an active participant in islet cell death in certain conditions, which in time might contribute to the development of diabetes in aged people.

The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.

Science.gov (United States)

Bavik, Claes; Coleman, Ilsa; Dean, James P; Knudsen, Beatrice; Plymate, Steven; Nelson, Peter S

2006-01-15

The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate

Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

DEFF Research Database (Denmark)

Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

2015-01-01

of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation......BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...

Exertion Testing in Youth with Mild Traumatic Brain Injury/Concussion.

Science.gov (United States)

Dematteo, Carol; Volterman, Kimberly A; Breithaupt, Peter G; Claridge, Everett A; Adamich, John; Timmons, Brian W

2015-11-01

The decision regarding return to activity (RTA) after mild traumatic brain injuries/concussion is one of the most difficult and controversial areas in concussion management, particularly for youth. This study investigated how youth with postconcussion syndrome (PCS) are affected by exertion and whether standardized exertion testing using the McMaster All-Out Progressive Continuous Cycling Test can contribute to clinical decision making for safe RTA. Fifty-four youth (8.5-18.3 yr) with a previously confirmed concussion participated in the study. Each participant performed exertion testing on a cycle ergometer and completed a Postconcussion Symptom scale at the following time points: before exertion (baseline), 5 and 30 min, and 24 h after exertion. A modified Postconcussion Symptom scale was administered at 2-min intervals during exertion. Participants had a mean ± SD symptom duration of 6.3 ± 6.9 months after the most recent concussive injury, with a median of 4.1 months (range, 0.7-35 months). Sixty-three percent of participants had symptoms during exertion testing. Symptom profile (number and severity) significantly affected perception of exertion at 50% peak mechanical power. During acute assessment of symptoms (30-min after exertion), headache (P = 0.39), nausea (P = 0.63), and dizziness (P = 0.35) did not change. However, both the number and severity of symptoms significantly improved over 24 h, with 56.8% of youth showing improvements. The time from the most recent injury had a significant effect on the symptom score at baseline, 30 min after exertion, and 24 h after exertion. Exertion testing has an important role in the evaluation of symptoms and readiness to RTA, particularly in youth who are slow to recover. Overall, controlled exertion seemed to lesson symptoms for most youth.

Exertional Rhabdomyolysis after Spinning.

Science.gov (United States)

Jeong, Youjin; Kweon, Hyuk-Jung; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

2016-11-01

Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24-48 hours after attending a spinning class at a local gymnasium. Paired with key laboratory findings, her symptoms were suggestive of rhabdomyolysis. She required hospital admission to sustain renal function through fluid resuscitation therapy and fluid balance monitoring. Because exertional rhabdomyolysis may occur in any unfit but otherwise healthy individual who indulges in stationary cycling, the potential health risks of this activity must be considered.

20 CFR 404.1567 - Physical exertion requirements.

Science.gov (United States)

2010-04-01

... activities. If someone can do light work, we determine that he or she can also do sedentary work, unless... Physical exertion requirements. To determine the physical exertion requirements of work in the national... making disability determinations under this subpart, we use the following definitions: (a) Sedentary work...

20 CFR 416.967 - Physical exertion requirements.

Science.gov (United States)

2010-04-01

... activities. If someone can do light work, we determine that he or she can also do sedentary work, unless... Physical exertion requirements. To determine the physical exertion requirments of work in the national... making disability determinations under this subpart, we use the following definitions: (a) Sedentary work...

Regulation of insulin-like growth factor (IGF) I receptor expression during muscle cell differentiation. Potential autocrine role of IGF-II.

OpenAIRE

Rosenthal, S M; Brunetti, A; Brown, E J; Mamula, P W; Goldfine, I D

1991-01-01

Muscle is an important target tissue for insulin-like growth factor (IGF) action. The presence of specific, high affinity IGF receptors, as well as the expression of IGF peptides and binding proteins by muscle suggest that a significant component of IGF action in this tissue is mediated through autocrine and/or paracrine mechanisms. To explore autocrine/paracrine action of IGFs in muscle, we studied the regulation of the IGF-I receptor and the expression of IGF peptides during differentiation...

Paracrine Apoptotic Effect of p53 Mediated by Tumor Suppressor Par-4

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Ravshan Burikhanov

2014-01-01

Full Text Available The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53−/− or Par-4−/− mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 induced Par-4 secretion by suppressing the expression of its binding partner, UACA, which sequesters Par-4. Thus, normal cells can be empowered by p53 activation to induce Par-4 secretion for the inhibition of therapy-resistant tumors.

Paracrine-mediated osteoclastogenesis by the osteosarcoma MG63 cell line: is RANKL/RANK signalling really important?

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Costa-Rodrigues, J; Teixeira, C A; Fernandes, M H

2011-08-01

Although in the past little attention has been paid to the influence of osteosarcoma cells in osteoclast function, recent studies suggest a close relationship between osteosarcoma aggressiveness and osteoclastic activity. The present study addresses the paracrine effects of MG63 cells, a human osteosarcoma-derived cell line, on the differentiation of peripheral blood osteoclast precursor cells (PBMC). PBMC were cultured for 21 days in the presence of conditioned media from MG63 cell cultures (CM) collected at 48 h (CM_MG1), 7 days (CM_MG2) and 14 days (CM_MG3). MG63 cell cultures displayed the expression of ALP and BMP-2 and, also, the osteoclastogenic genes M-CSF and RANKL, although with a low expression of RANKL. PBMC cultures supplemented with CM presented an evident osteoclastogenic behavior, which was dependent on the culture period of the MG63 cells. The inductive effect appeared to be more relevant for the differentiation and activation genes, c-myc and c-src, and lower for genes associated with osteoclast function. In addition, PBMC cultures displayed increased functional parameters, including calcium phosphate resorbing activity. Assessment of the PBMC cultures in the presence of U0126, PDTC, and indomethacin suggested that in addition to MEK and NFkB pathways, other signaling mechanisms, probably not involving RANKL/RANK interaction, might be activated in the presence of conditioned medium from MG63. In conclusion, MG63 cell line appears to induce a significant paracrine-mediated osteoclastogenic response. Understanding the mechanisms underlying the interaction of osteosarcoma cells and osteoclasts may contribute to the development of new potential approaches in the treatment of such bone metabolic diseases.

Suppression of DHT-induced paracrine stimulation of endothelial cell growth by estrogens via prostate cancer cells.

Science.gov (United States)

Wen, Juan; Zhao, Yuan; Li, Jinghe; Weng, Chunyan; Cai, Jingjing; Yang, Kan; Yuan, Hong; Imperato-McGinley, Julianne; Zhu, Yuan-Shan

2013-07-01

Androgen modulation of angiogenesis in prostate cancer may be not directly mediated by androgen receptor (AR) as AR is not detected in the prostatic endothelial cells. We examined the paracrine stimulation of cell proliferation by prostate tumor cells and its modulation by androgen and estrogens in a murine endothelial cell line (MEC) that does not express AR. Tumor cell conditioned media (TCM) collected from LAPC-4 or LNCaP prostatic tumor cells produced a time- and concentration-dependent induction of cell growth in MECs, which was parallel to the VEGF concentration in the TCM. This TCM-induced cell growth in MECs was enhanced by the treatment of prostatic tumor cells with dihydrotestosterone (DHT). Both the TCM-stimulation and DHT-enhancement effects in MECs were completely blocked by SU5416, a specific VEGF receptor antagonist. Co-administration of 17α-estradiol or 17β-estradiol with DHT in prostatic tumor cells completely inhibited the DHT-enhancement effect while treatment with DHT, 17α-estradiol or 17β-estradiol did not produce any significant direct effect in MECs. Moreover, administration of 17α-estradiol or 17β-estradiol in xenograft animals with LAPC-4 or LNCaP prostate tumor significantly decreased the microvessel number in the tumor tissues. Our study indicated that prostate tumor cells regulate endothelial cell growth through a paracrine mechanism, which is mainly mediated by VEGF; and DHT is able to modulate endothelial cell growth via tumor cells, which is inhibited by 17α-estradiol and 17β-estradiol. Thus, both17α-estradiol and 17β-estradiol are potential agents for anti-angiogenesis therapy in androgen-responsive prostate cancer. Copyright © 2013 Wiley Periodicals, Inc.

Musical agency reduces perceived exertion during strenuous physical performance.

Science.gov (United States)

Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

2013-10-29

Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting.

Hedgehog-mediated paracrine interaction between hepatic stellate cells and marrow-derived mesenchymal stem cells

International Nuclear Information System (INIS)

Lin Nan; Tang Zhaofeng; Deng Meihai; Zhong Yuesi; Lin Jizong; Yang Xuhui; Xiang Peng; Xu Ruiyun

2008-01-01

During liver injury, bone marrow-derived mesenchymal stem cells (MSCs) can migrate and differentiate into hepatocytes. Hepatic stellate cell (SC) activation is a pivotal event in the development of liver fibrosis. Therefore, we hypothesized that SCs may play an important role in regulating MSC proliferation and differentiation through the paracrine signaling pathway. We demonstrate that MSCs and SCs both express hedgehog (Hh) pathway components, including its ligands, receptors, and target genes. Transwell co-cultures of SCs and MSCs showed that the SCs produced sonic hedgehog (Shh), which enhanced the proliferation and differentiation of MSCs. These findings demonstrate that SCs indirectly modulate the activity of MSCs in vitro via the Hh pathway, and provide a plausible explanation for the mechanisms of transplanted MSCs in the treatment of liver fibrosis

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

International Nuclear Information System (INIS)

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.

2013-01-01

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

Energy Technology Data Exchange (ETDEWEB)

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

2013-08-15

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

Curcumin Triggers p16-Dependent Senescence in Active Breast Cancer-Associated Fibroblasts and Suppresses Their Paracrine Procarcinogenic Effects

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Siti-Fauziah Hendrayani

2013-06-01

Full Text Available Activated cancer-associated fibroblasts (CAFs or myofibroblasts not only facilitate tumor growth and spread but also affect tumor response to therapeutic agents. Therefore, it became clear that efficient therapeutic regimens should also take into account the presence of these supportive cells and inhibit their paracrine effects. To this end, we tested the effect of low concentrations of curcumin, a pharmacologically safe natural product, on patient-derived primary breast CAF cells. We have shown that curcumin treatment upregulates p16INK4A and other tumor suppressor proteins while inactivates the JAK2/STAT3 pathway. This reduced the level of alpha-smooth muscle actin (α-SMA and the migration/invasion abilities of these cells. Furthermore, curcumin suppressed the expression/secretion of stromal cell-derived factor-1 (SDF-1, interleukin-6 (IL-6, matrix metalloproteinase-2 (MMP-2, MMP-9, and transforming growth factor-β, which impeded their paracrine procarcinogenic potential. Intriguingly, these effects were sustained even after curcumin withdrawal and cell splitting. Therefore, using different markers of senescence [senescence-associated β-galactosidase (SA-β-gal activity, Ki-67 and Lamin B1 levels, and bromodeoxyuridine incorporation], we have shown that curcumin markedly suppresses Lamin B1 and triggers DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts. Importantly, this curcumin-related senescence was p16INK4A-dependent and occurred with no associated inflammatory secretory phenotype. These results indicate the possible inactivation of cancer-associated myofibroblasts and present the first indication that curcumin can trigger DNA damage-independent and safe senescence in stromal fibroblasts.

MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner

International Nuclear Information System (INIS)

Miyamoto, Kana; Ninomiya, Ken; Sonoda, Koh-Hei; Miyauchi, Yoshiteru; Hoshi, Hiroko; Iwasaki, Ryotaro; Miyamoto, Hiroya

2009-01-01

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1, and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts.

Paracrine Maturation and Migration of SH-SY5Y Cells by Dental Pulp Stem Cells.

Science.gov (United States)

Gervois, P; Wolfs, E; Dillen, Y; Hilkens, P; Ratajczak, J; Driesen, R B; Vangansewinkel, T; Bronckaers, A; Brône, B; Struys, T; Lambrichts, I

2017-06-01

Neurological disorders are characterized by neurodegeneration and/or loss of neuronal function, which cannot be adequately repaired by the host. Therefore, there is need for novel treatment options such as cell-based therapies that aim to salvage or reconstitute the lost tissue or that stimulate host repair. The present study aimed to evaluate the paracrine effects of human dental pulp stem cells (hDPSCs) on the migration and neural maturation of human SH-SY5Y neuroblastoma cells. The hDPSC secretome had a significant chemoattractive effect on SH-SY5Y cells as shown by a transwell assay. To evaluate neural maturation, SH-SY5Y cells were first induced toward neuronal cells, after which they were exposed to the hDPSC secretome. In addition, SH-SY5Y cells subjected to the hDPSC secretome showed increased neuritogenesis compared with nonexposed cells. Maturated cells were shown to increase immune reactivity for neuronal markers compared with controls. Ultrastructurally, retinoic acid (RA) signaling and subsequent exposure to the hDPSC secretome induced a gradual rise in metabolic activity and neuronal features such as multivesicular bodies and cytoskeletal elements associated with cellular communication. In addition, electrophysiological recordings of differentiating cells demonstrated a transition toward a neuronal electrophysiological profile based on the maximum tetrodotoxin (TTX)-sensitive, Na + current. Moreover, conditioned medium (CM)-hDPSC-maturated SH-SY5Y cells developed distinct features including, Cd 2+ -sensitive currents, which suggests that CM-hDPSC-maturated SH-SY5Y acquired voltage-gated Ca 2+ channels. The results reported in this study demonstrate the potential of hDPSCs to support differentiation and recruitment of cells with neuronal precursor characteristics in a paracrine manner. Moreover, this in vitro experimental design showed that the widely used SH-SY5Y cell line can improve and simplify the preclinical in vitro research on the molecular

Do placebo expectations influence perceived exertion during physical exercise?

Directory of Open Access Journals (Sweden)

Hendrik Mothes

Full Text Available This study investigates the role of placebo expectations in individuals' perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a the effects of exercise and b the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting "scientific evidence" that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment would additionally enhance exercise benefits or would only be worn for control purposes. Participants' physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion.

Chemokine CXCL3 mediates prostate cancer cells proliferation, migration and gene expression changes in an autocrine/paracrine fashion.

Science.gov (United States)

Xin, Hua; Cao, Yu; Shao, Ming-Liang; Zhang, Wei; Zhang, Chun-Bin; Wang, Jing-Tao; Liang, Li-Chun; Shao, Wen-Wu; Qi, Ya-Ling; Li, Yue; Zhang, Ze-Yu; Yang, Zhe; Sun, Yu-Hong; Zhang, Peng-Xia; Jia, Lin-Lin; Wang, Wei-Qun

2018-05-01

We have previously indicated that CXCL3 was upregulated in the tissues of prostate cancer, and exogenous administration of CXCL3 played a predominant role in the tumorigenicity of prostate cancer cells. In the present study, we further explored the role and the underlying mechanism of CXCL3 overexpression in the oncogenic potential of prostate cancer in an autocrine/paracrine fashion. CXCL3-overexpressing prostate cancer cell line PC-3 and immortalized prostate stromal cell line WPMY-1 were established by gene transfection. CCK-8, transwell assays and growth of tumor xenografts were conducted to characterize the effects of CXCL3 on PC-3 cells' proliferation and migration. Western blotting was conducted to test whether CXCL3 could affect the expression of tumorigenesis-associated genes. The results showed that CXCL3 overexpression in PC-3 cells and the PC-3 cells treated with the supernatants of CXCL3-transfected WPMY-1 cells stimulated the proliferation and migration of PC-3 cells in vitro and in a nude mouse xenograft model. Western blotting revealed higher levels of p-ERK, Akt and Bcl-2 and lower levels of Bax in the tumor xenografts transplanted with CXCL3-transfected PC-3 cells. Moreover, the tumor xenografts derived from the PC-3 cells treated with supernatants of CXCL3-transfected WPMY-1 cells showed higher expression of ERK, Akt and Bcl-2 and lower expression of Bax. These findings suggest that CXCL3 autocrine/paracrine pathways are involved in the development of prostate cancer by regulating the expression of the target genes that are related to the progression of malignancies.

Evidence for autocrine and paracrine regulation of allergen-induced mast cell mediator release in the guinea pig airways.

Science.gov (United States)

Yu, Li; Liu, Qi; Canning, Brendan J

2018-03-05

Mast cells play an essential role in immediate type hypersensitivity reactions and in chronic allergic diseases of the airways, including asthma. Mast cell mediator release can be modulated by locally released autacoids and circulating hormones, but surprisingly little is known about the autocrine effects of mediators released upon mast cell activation. We thus set out to characterize the autocrine and paracrine effects of mast cell mediators on mast cell activation in the guinea pig airways. By direct measures of histamine, cysteinyl-leukotriene and thromboxane release and with studies of allergen-evoked contractions of airway smooth muscle, we describe a complex interplay amongst these autacoids. Notably, we observed an autocrine effect of the cysteinyl-leukotrienes acting through cysLT 1 receptors on mast cell leukotriene release. We confirmed the results of previous studies demonstrating a marked enhancement of mast cell mediator release following cyclooxygenase inhibition, but we have extended these results by showing that COX-2 derived eicosanoids inhibit cysteinyl-leukotriene release and yet are without effect on histamine release. Given the prominent role of COX-1 inhibition in aspirin-sensitive asthma, these data implicate preformed mediators stored in granules as the initial drivers of these adverse reactions. Finally, we describe the paracrine signaling cascade leading to thromboxane synthesis in the guinea pig airways following allergen challenge, which occurs indirectly, secondary to cysLT 1 receptor activation on structural cells and/ or leukocytes within the airway wall, and a COX-2 dependent synthesis of the eicosanoid. The results highlight the importance of cell-cell and autocrine interactions in regulating allergic responses in the airways. Copyright © 2017. Published by Elsevier B.V.

Physical Exertion and Immediate Classroom Mental Performance Among Elementary School Children.

Science.gov (United States)

Gabbard, Carl

This study was designed (1) to investigate the relationship between physical exertion and mental performance in elementary school children and (2) to determine if male or female mental performances are more affected by physical exertion. A total of 95 second graders participated in six treatments of induced physical exertion during their regularly…

Exertional heat stroke management strategies in United States high school football.

Science.gov (United States)

Kerr, Zachary Y; Marshall, Stephen W; Comstock, R Dawn; Casa, Douglas J

2014-01-01

The 5-year period of 2005-2009 saw more exertional heat stroke-related deaths in organized sports than any other 5-year period in the past 35 years. The risk of exertional heat stroke appears highest in football, particularly during the preseason. To estimate the incidence of exertional heat stroke events and assess the utilization of exertional heat stroke management strategies during the 2011 preseason in United States high school football programs. Cross-sectional study; Level of evidence, 3. A self-administered online questionnaire addressing the incidence of exertional heat stroke events and utilization of exertional heat stroke management strategies (eg, removing athlete's football equipment, calling Emergency Medical Services [EMS]) was completed in May to June 2012 by 1142 (18.0%) athletic trainers providing care to high school football athletes during the 2011 preseason. Among all respondents, 20.3% reported treating at least 1 exertional heat stroke event. An average of 0.50 ± 1.37 preseason exertional heat stroke events were treated per program. Athletic trainers responding to exertional heat stroke reported using an average of 6.6 ± 1.8 management strategies. The most common management strategies were low-level therapeutic interventions such as removing the athlete's football equipment (98.2%) and clothing (77.8%) and moving the athlete to a shaded area (91.6%). Few athletic trainers reported active management strategies such as calling EMS (29.3%) or using a rectal thermometer to check core body temperature (0.9%). Athletic trainers in states with mandated preseason heat acclimatization guidelines reported a higher utilization of management strategies such as cooling the athlete through air conditioning (90.1% vs 65.0%, respectively; P football programs. The standard of care is (and should be) to treat proactively; therefore, treatment is not a perfect proxy for incidence. Nevertheless, there is an urgent need for improved education and awareness of

Human Wharton's jelly mesenchymal stem cells promote skin wound healing through paracrine signaling.

Science.gov (United States)

Arno, Anna I; Amini-Nik, Saeid; Blit, Patrick H; Al-Shehab, Mohammed; Belo, Cassandra; Herer, Elaine; Tien, Col Homer; Jeschke, Marc G

2014-02-24

The prevalence of nonhealing wounds is predicted to increase due to the growing aging population. Despite the use of novel skin substitutes and wound dressings, poorly vascularized wound niches impair wound repair. Mesenchymal stem cells (MSCs) have been reported to provide paracrine signals to promote wound healing, but the effect of human Wharton's jelly-derived MSCs (WJ-MSCs) has not yet been described in human normal skin. Human WJ-MSCs and normal skin fibroblasts were isolated from donated umbilical cords and normal adult human skin. Fibroblasts were treated with WJ-MSC-conditioned medium (WJ-MSC-CM) or nonconditioned medium. Expression of genes involved in re-epithelialization (transforming growth factor-β2), neovascularization (hypoxia-inducible factor-1α) and fibroproliferation (plasminogen activator inhibitor-1) was upregulated in WJ-MSC-CM-treated fibroblasts (P≤0.05). WJ-MSC-CM enhanced normal skin fibroblast proliferation (P≤0.001) and migration (P≤0.05), and promoted wound healing in an excisional full-thickness skin murine model. Under our experimental conditions, WJ-MSCs enhanced skin wound healing in an in vivo mouse model.

Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

Directory of Open Access Journals (Sweden)

Tom J. Burdon

2011-01-01

Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

Factors associated with high physical exertion during manual lifting

DEFF Research Database (Denmark)

Andersen, Lars L.; Sundstrup, Emil; Brandt, Mikkel

2018-01-01

BACKGROUND: High physical exertion during work is a risk factor for back pain and long-term sickness absence. OBJECTIVE: To investigate which factors are associated with physical exertion during manual lifting. METHODS: From 14 workplaces across Denmark, 200 blue-collar workers reported perceived...... physical exertion (Borg-CR10) during manual lifting from floor to table height of 5, 10, 20 and 30 kg at the beginning and end of the working day. The workers also responded to a questionnaire and went through testing of isometric back muscle strength. Associations were modelled using logistic regression...... during manual lifting in blue-collar workers. These factors should be considered when planning work with manual lifting for individual workers....

Exertional Rhabdomyolysis after Spinning

OpenAIRE

Jeong, Youjin; Kweon, Hyuk-Jung; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

2016-01-01

Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24?48 hours after attending a spi...

Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2012-2016.

Science.gov (United States)

2017-03-01

Among active component service members in 2016, there were 525 incident diagnoses of rhabdomyolysis likely due to physical exertion and/or heat stress ("exertional rhabdomyolysis"). The crude incidence rate in 2016 was 40.7 cases per 100,000 person-years. Annual rates of incident diagnoses of exertional rhabdomyolysis increased 46.2% between 2013 and 2016, with the greatest percentage change occurring between 2014 and 2015. In 2016, relative to their respective counterparts, the highest incidence rates of exertional rhabdomyolysis affected service members who were male; younger than 20 years of age; and black, non-Hispanic. During the surveillance period, annual incidence rates were highest among service members of the Marine Corps, intermediate among those in the Army, and lowest among those in the Air Force and Navy. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or the Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain or swelling, limited range of motion, or the excretion of dark urine (possibly due to myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.

Autocrine-paracrine regulation of the mammary gland.

Science.gov (United States)

Weaver, S R; Hernandez, L L

2016-01-01

autocrine-paracrine regulation of the mammary gland, with an examination of both foundational work and the progress made within the last 10 to 20 yr of research. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Exertional headache and coronary ischemia despite normal electrocardiographic stress testing.

Science.gov (United States)

Cutrer, F Michael; Huerter, Karina

2006-01-01

Exertional headaches may under certain conditions reflect coronary ischemia. We report the case of a patient seen in a neurology referral practice whose exertional headaches, even in the face of two normal electrocardiographic stress tests and in the absence of underlying chest pain were the sole symptoms of coronary ischemia as detected by Tc-99m Sestamibi testing SPECT stress testing. Stent placement resulted in complete resolution of headaches. Exertional headache in the absence of chest pain may reflect underlying symptomatic coronary artery disease (CAD) even when conventional electrocardiographic stress testing does not indicate ischemia.

Attenuation of radiation-induced DNA damage due to paracrine interactions between normal human epithelial and stromal cells

International Nuclear Information System (INIS)

Saenko, V.A.; Nakazawa, Yu.; Rogounovitch, T.I.; Suzuki, K.; Mitsutake, N.; Matsuse, M.; Yamashita, S.

2007-01-01

Complete text of publication follows. Objective: Developmentally, every tissue accommodates different types of cells, such as epitheliocytes and stromal cells in parenchymal organs. To better understand the complexity of radiation response, it is necessary to evaluate possible cross-talk between different tissue components. This work was set out to investigate reciprocal influence of normal human epithelial cells and fibroblasts on the extent of radiation-induced DNA damage. Methods: Model cultures of primary human thyrocytes (PT), normal diploid fibroblasts (BJ), PT/BJ cell co-culture and conditioned medium transfer were used to examine DNA damage in terms of γ-H2AX foci number per cell or by Comet assay after exposure to different doses of γ-rays. Results: In co-cultures, the kinetics of γ-H2AX foci number change was dose-dependent and similar to that in individual PT and BJ cultures. The number of γ-H2AX foci in co-cultures was significantly lower (∼25%) in both types of cells comparing to individual cultures. Reciprocal conditioned medium transfer to individual counterpart cells prior to irradiation resulted in approximately 35% reduction in the number γ-H2AX foci at 1 Gy and lower doses in both PT and BJ demonstrating the role of paracrine soluble factors. Comet assay corroborated the results of γ-H2AX foci counting in conditioned medium transfer experiments. In contrast to medium conditioned on PT cells, conditioned medium collected from several human thyroid cancer cell lines failed to establish DNA-protected state in BJ fibroblasts. In its turn, medium conditioned on BJ cells did not change the extent of radiation-induced DNA damage in cancer cell lines tested. Conclusion: The results imply the existence of a network of soluble factor-mediated paracrine interactions between normal epithelial and stromal cells that could be a part of natural mechanism by which cells protect DNA from genotoxic stress.

Influence of permittivity on gradient force exerted on Mie spheres.

Science.gov (United States)

Chen, Jun; Li, Kaikai; Li, Xiao

2018-04-01

In optical trapping, whether a particle could be stably trapped into the focus region greatly depends on the strength of the gradient force. Individual theoretical study on gradient force exerted on a Mie particle is rare because the mathematical separation of the gradient force and the scattering force in the Mie regime is difficult. Based on the recent forces separation work by Du et al. [Sci. Rep.7, 18042 (2017)SRCEC32045-232210.1038/s41598-017-17874-1], we investigate the influence of permittivity (an important macroscopic physical quantity) on the gradient force exerted on a Mie particle by cooperating numerical calculation using fast Fourier transform and analytical analysis using multipole expansion. It is revealed that gradient forces exerted on small spheres are mainly determined by the electric dipole moment except for certain permittivity with which the real part of polarizability of the electric dipole approaches zero, and gradient forces exerted on larger spheres are complex because of the superposition of the multipole moments. The classification of permittivity corresponding to different varying tendencies of gradient forces exerted on small spheres or larger Mie particles are illustrated. Absorption of particles favors the trapping of small spheres by gradient force, while it is bad for the trapping of larger particles. Moreover, the absolute values of the maximal gradient forces exerted on larger Mie particles decline greatly versus the varied imaginary part of permittivity. This work provides elaborate investigation on the different varying tendencies of gradient forces versus permittivity, which favors more accurate and free optical trapping.

Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation.

Directory of Open Access Journals (Sweden)

Simon D Tran

Full Text Available BACKGROUND: There are reports that bone marrow cell (BM transplants repaired irradiated salivary glands (SGs and re-established saliva secretion. However, the mechanisms of action behind these reports have not been elucidated. METHODS: To test if a paracrine mechanism was the main effect behind this reported improvement in salivary organ function, whole BM cells were lysed and its soluble intracellular contents (termed as "BM Soup" injected into mice with irradiation-injured SGs. The hypothesis was that BM Soup would protect salivary cells, increase tissue neovascularization, function, and regeneration. Two minor aims were also tested a comparing two routes of delivering BM Soup, intravenous (I.V. versus intra-glandular injections, and b comparing the age of the BM Soup's donors. The treatment-comparison group consisted of irradiated mice receiving injections of living whole BM cells. Control mice received irradiation and injections of saline or sham-irradiation. All mice were followed for 8 weeks post-irradiation. RESULTS: BM Soup restored salivary flow rates to normal levels, protected salivary acinar, ductal, myoepithelial, and progenitor cells, increased cell proliferation and blood vessels, and up-regulated expression of tissue remodeling/repair/regenerative genes (MMP2, CyclinD1, BMP7, EGF, NGF. BM Soup was as an efficient therapeutic agent as injections of live BM cells. Both intra-glandular or I.V. injections of BM Soup, and from both young and older mouse donors were as effective in repairing irradiated SGs. The intra-glandular route reduced injection frequency/dosage by four-fold. CONCLUSION: BM Soup, which contains only the cell by-products, can be advantageously used to repair irradiation-damaged SGs rather than transplanting whole live BM cells which carry the risk of differentiating into unwanted/tumorigenic cell types in SGs.

Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation.

Science.gov (United States)

Tran, Simon D; Liu, Younan; Xia, Dengsheng; Maria, Ola M; Khalili, Saeed; Wang, Renee Wan-Jou; Quan, Vu-Hung; Hu, Shen; Seuntjens, Jan

2013-01-01

There are reports that bone marrow cell (BM) transplants repaired irradiated salivary glands (SGs) and re-established saliva secretion. However, the mechanisms of action behind these reports have not been elucidated. To test if a paracrine mechanism was the main effect behind this reported improvement in salivary organ function, whole BM cells were lysed and its soluble intracellular contents (termed as "BM Soup") injected into mice with irradiation-injured SGs. The hypothesis was that BM Soup would protect salivary cells, increase tissue neovascularization, function, and regeneration. Two minor aims were also tested a) comparing two routes of delivering BM Soup, intravenous (I.V.) versus intra-glandular injections, and b) comparing the age of the BM Soup's donors. The treatment-comparison group consisted of irradiated mice receiving injections of living whole BM cells. Control mice received irradiation and injections of saline or sham-irradiation. All mice were followed for 8 weeks post-irradiation. BM Soup restored salivary flow rates to normal levels, protected salivary acinar, ductal, myoepithelial, and progenitor cells, increased cell proliferation and blood vessels, and up-regulated expression of tissue remodeling/repair/regenerative genes (MMP2, CyclinD1, BMP7, EGF, NGF). BM Soup was as an efficient therapeutic agent as injections of live BM cells. Both intra-glandular or I.V. injections of BM Soup, and from both young and older mouse donors were as effective in repairing irradiated SGs. The intra-glandular route reduced injection frequency/dosage by four-fold. BM Soup, which contains only the cell by-products, can be advantageously used to repair irradiation-damaged SGs rather than transplanting whole live BM cells which carry the risk of differentiating into unwanted/tumorigenic cell types in SGs.

Regenerating medicine related to the stem-cells and its mechanisms of action from adults cells

International Nuclear Information System (INIS)

Hernandez Ramirez, Porfirio

2009-01-01

Regenerating medicine is a branch of Medicine very developed in past years. Advances in this field have been closely linked with the new knowledge achieved on stem-cells and its ability to become in cells of different tissues. This type of medicine is based on the behaviors adopted by organism to substitute those damaged cells by the healthy ones by different processes in specific tissues. Therapeutic measures used may include the stem-cell transplantation, the use of soluble molecules, genic therapy and tissues engineering. Nowadays, the more used method is the adult stem-cells. However, is not well known the mechanisms by which the transplanted cells could to improve or to promote the tissue regeneration. To explain these mechanisms some hypotheses has been proposed including the cellular trans-differentiation, cells fusion, and the effects secondaries to cells release by cells of different soluble molecules with specific actions; in addition to the autocrine and paracrine effects that may have these soluble factors, it is suggested too the existence of a telecrine action. It is probable that more than one of these mechanisms be executed

Photodynamic therapy potentiates the paracrine endothelial stimulation by colorectal cancer

Science.gov (United States)

Lamberti, María Julia; Florencia Pansa, María; Emanuel Vera, Renzo; Belén Rumie Vittar, Natalia; Rivarola, Viviana Alicia

2014-11-01

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death worldwide. Recurrence is a major problem and is often the ultimate cause of death. In this context, the tumor microenvironment influences tumor progression and is considered as a new essential feature that clearly impacts on treatment outcome, and must therefore be taken into consideration. Photodynamic therapy (PDT), oxygen, light and drug-dependent, is a novel treatment modality when CRC patients are inoperable. Tumor vasculature and parenchyma cells are both potential targets of PDT damage modulating tumor-stroma interactions. In biological activity assessment in photodynamic research, three-dimensional (3D) cultures are essential to integrate biomechanical, biochemical, and biophysical properties that better predict the outcome of oxygen- and drug-dependent medical therapies. Therefore, the objective of this study was to investigate the antitumor effect of methyl 5-aminolevulinic acid-PDT using a light emitting diode for the treatment of CRC cells in a scenario that mimics targeted tissue complexity, providing a potential bridge for the gap between 2D cultures and animal models. Since photodynamic intervention of the tumor microenvironment can effectively modulate the tumor-stroma interaction, it was proposed to characterize the endothelial response to CRC paracrine communication, if one of these two populations is photosensitized. In conclusion, we demonstrated that the dialogue between endothelial and tumor populations when subjected to lethal PDT conditions induces an increase in angiogenic phenotype, and we think that it should be carefully considered for the development of PDT therapeutic protocols.

Endothelial cells activate the cancer stem cell-associated NANOGP8 pathway in colorectal cancer cells in a paracrine fashion.

Science.gov (United States)

Wang, Rui; Bhattacharya, Rajat; Ye, Xiangcang; Fan, Fan; Boulbes, Delphine R; Xia, Ling; Ellis, Lee M

2017-08-01

In colorectal cancer (CRC), cancer stem cells (CSCs) have been hypothesized to mediate cell survival and chemoresistance. Previous studies from our laboratory described a role for liver parenchymal endothelial cells (LPECs) in mediating the CSC phenotype in CRC cells in a paracrine/angiocrine fashion. The objectives of this study were to determine whether endothelial cells (ECs) from different organs can induce the CSC phenotype in CRC cells and to elucidate the signaling pathways involved. We treated a newly developed CRC cell line (HCP-1) and established CRC cell lines (HT29 and SW480) with conditioned medium (CM) from primary ECs isolated from nonmalignant liver, lung, colon mucosa, and kidney. Our results showed that CM from ECs from all organs increased the number of CSCs, as determined by sphere formation, and protein levels of NANOG and OCT4 in CRC cells. With the focus of further elucidating the role of the liver vascular network in mediating the CSC phenotype, we demonstrated that CM from LPECs increased resistance to 5-fluorouracil in CRC cells. Moreover, we showed that LPEC CM specifically induced NANOGP8 expression in CRC cells by specific enzyme digestion and a luciferase reporter assay using a vector containing the NANOGP8 promoter. Lastly, we found that LPEC CM-induced NANOGP8 expression and sphere formation were mediated by AKT activation. Our studies demonstrated a paracrine role for ECs in regulating the CSC phenotype and chemoresistance in CRC cells by AKT-mediated induction of NANOGP8. These studies suggest a more specific approach to target CSCs by blocking the expression of NANOGP8 in cancer cells. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions.

Science.gov (United States)

Paquet, Joseph; Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

2015-07-01

: Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities. ©AlphaMed Press.

Exertional Rhabdomyolysis: What Is It and Why Should We Care?

Science.gov (United States)

Thomas, David Q.; Carlson, Kelli A.; Marzano, Amy; Garrahy, Deborah

2012-01-01

Exertional rhabdomyolysis gained increased attention recently when 13 football players from the University of Iowa developed this condition after an especially demanding practice session and were hospitalized. Exertional rhabdomyolysis may lead to severe kidney stress, kidney failure, and even sudden death. Anyone who does physical exercise at a…

Emotional reactions to success and failure of collective action as predictors of future action intentions: a longitudinal investigation in the context of student protests in Germany.

Science.gov (United States)

Tausch, Nicole; Becker, Julia C

2013-09-01

This research examined how emotional responses to success and failure of collective action relate to willingness to engage in collective action in the future. It was hypothesized that both pride (in relation to a success) and anger (in response to failure) would motivate future collective action. Findings are reported from a two-wave longitudinal study (N= 98) in the context of student protests against tuition fees in Germany, which was conducted before and after collective action had resulted in both a success and a failure. While anger positively predicted action intentions, over and above baseline action intentions, pride exerted a significant indirect effect on action intentions via increased efficacy perceptions, over and above baseline efficacy and action intentions. Politicized identification positively predicted the intensity of both pride and anger and baseline group efficacy positively predicted the intensity of anger. The theoretical and practical implications of these findings are discussed. © 2012 The British Psychological Society.

Cardiac hypertrophy and IGF-1 response to testosterone propionate treatment in trained male rats

Directory of Open Access Journals (Sweden)

Żebrowska Aleksandra

2017-04-01

Full Text Available Several studies have suggested that testosterone exerts a growth-promoting effect in the heart. Limited data are available regarding interactions between possible endocrine/paracrine effects in response to exercise training. Therefore, we examined supraphysiological testosterone-induced heart hypertrophy and cardiac insulin-like growth factor (IGF-1 content in sedentary and exercise-trained rats.

Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

DEFF Research Database (Denmark)

Corsino, P.; Davis, B.; Law, M.

2007-01-01

) promoter results in mammary gland hyperplasia and fibrosis, and mammary tumors. Cell lines isolated from MMTV-cyclin D1-Cdk2 (MMTV-D1K2) tumors exhibit Rb and p130 hyperphosphorylation and up-regulation of the protein products of E2F-dependent genes. These results suggest that cyclin D1/Cdk2 complexes may...... sites. Together, these results suggest that deregulation of the Cdk/Rb/E2F axis reprograms mammary epithelial cells to initiate a paracrine loop with tumor-associated fibroblasts involving TGF beta and HGF, resulting in desmoplasia. The MMTV-DIK2 mice should provide a useful model system...

Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

Science.gov (United States)

Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

2016-01-01

Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed.

Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

Science.gov (United States)

Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

2016-01-01

Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed. PMID:27900193

Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

Science.gov (United States)

Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

2013-12-01

Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital. Postnatal day (P)7 rats were treated with phenobarbital (0-40mg/kg) and/or melatonin (0-80mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive-compulsive disorder.

Science.gov (United States)

Zghoul, Tarek; Blier, Pierre

2003-03-01

Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

Exertional Heat Illness and Human Gene Expression

National Research Council Canada - National Science Library

Sonna, L.A; Sawka, M. N; Lilly, C. M

2007-01-01

Microarray analysis of gene expression at the level of RNA has generated new insights into the relationship between cellular responses to acute heat shock in vitro, exercise, and exertional heat illness...

Exertional heat illness: emerging concepts and advances in prehospital care.

Science.gov (United States)

Pryor, Riana R; Roth, Ronald N; Suyama, Joe; Hostler, David

2015-06-01

Exertional heat illness is a classification of disease with clinical presentations that are not always diagnosed easily. Exertional heat stroke is a significant cause of death in competitive sports, and the increasing popularity of marathons races and ultra-endurance competitions will make treating many heat illnesses more common for Emergency Medical Services (EMS) providers. Although evidence is available primarily from case series and healthy volunteer studies, the consensus for treating exertional heat illness, coupled with altered mental status, is whole body rapid cooling. Cold or ice water immersion remains the most effective treatment to achieve this goal. External thermometry is unreliable in the context of heat stress and direct internal temperature measurement by rectal or esophageal probes must be used when diagnosing heat illness and during cooling. With rapid recognition and implementation of effective cooling, most patients suffering from exertional heat stroke will recover quickly and can be discharged home with instructions to rest and to avoid heat stress and exercise for a minimum of 48 hours; although, further research pertaining to return to activity is warranted.

Binding Action and Emotion in Social Understanding

Science.gov (United States)

Ferri, Francesca; Ebisch, Sjoerd J. H.; Costantini, Marcello; Salone, Anatolia; Arciero, Giampiero; Mazzola, Viridiana; Ferro, Filippo Maria; Romani, Gian Luca; Gallese, Vittorio

2013-01-01

In social life actions are tightly linked with emotions. The integration of affective- and action-related information has to be considered as a fundamental component of appropriate social understanding. The present functional magnetic resonance imaging study aimed at investigating whether an emotion (Happiness, Anger or Neutral) dynamically expressed by an observed agent modulates brain activity underlying the perception of his grasping action. As control stimuli, participants observed the same agent either only expressing an emotion or only performing a grasping action. Our results showed that the observation of an action embedded in an emotional context (agent’s facial expression), compared with the observation of the same action embedded in a neutral context, elicits higher neural response at the level of motor frontal cortices, temporal and occipital cortices, bilaterally. Particularly, the dynamic facial expression of anger modulates the re-enactment of a motor representation of the observed action. This is supported by the evidence that observing actions embedded in the context of anger, but not happiness, compared with a neutral context, elicits stronger activity in the bilateral pre-central gyrus and inferior frontal gyrus, besides the pre-supplementary motor area, a region playing a central role in motor control. Angry faces not only seem to modulate the simulation of actions, but may also trigger motor reaction. These findings suggest that emotions exert a modulatory role on action observation in different cortical areas involved in action processing. PMID:23349792

Neuroprotective actions of the synthetic estrogen 17alpha-ethynylestradiol in the hippocampus.

Science.gov (United States)

Picazo, Ofir; Becerril-Montes, Adriana; Huidobro-Perez, Delia; Garcia-Segura, Luis M

2010-07-01

17alpha-ethynylestradiol (EE2), a major constituent of many oral contraceptives, is similar in structure to 17beta-estradiol, which has neuroprotective properties in several animal models. This study explored the potential neuroprotective actions of EE2 against kainic and quinolinic acid toxicity in the hippocampus of adult ovariectomized Wistar rats. A decrease in the number of Nissl-stained neurons and the induction of vimentin immunoreactivity in astrocytes was observed in the hilus of the dentate gyrus of the hippocampus after the administration of either kainic acid or quinolinic acid. EE2 prevented the neuronal loss and the induction of vimentin immunoreactivity induced by kainic acid at low (1 microg/rat) and high (10-100 microg/rat) doses and exerted a protection against quinolinic acid toxicity at a low dose (1 microg/rat) only. These observations demonstrate that EE2 exerts neuroprotective actions against excitotoxic insults. This finding is relevant for the design of new neuroprotective estrogenic compounds.

Impaired Player-Coach Perceptions of Exertion and Recovery During Match Congestion

NARCIS (Netherlands)

Doeven, Steven H.; Brink, Michel S.; Frencken, Wouter G. P.; Lemmink, Koen A. P. M.

2017-01-01

During intensified phases of competition, attunement of exertion and recovery is crucial to maintain performance. Although a mismatch between coach' and players' perceptions of training load is demonstrated, it is unknown if these discrepancies also exist for match exertion and recovery. PURPOSE:

Sevoflurane improves gaseous exchange and exerts protective ...

African Journals Online (AJOL)

Sevoflurane improves gaseous exchange and exerts protective effects in ... Lung water content and cell count were estimated by standard protocols. ... It reversed LPS-induced oxidative stress, as demonstrated by increase in total antioxidant ...

Exertional Tolerance Assessments After Mild Traumatic Brain Injury: A Systematic Review.

Science.gov (United States)

Quatman-Yates, Catherine; Bailes, Anna; Constand, Sara; Sroka, Mary Claire; Nissen, Katharine; Kurowski, Brad; Hugentobler, Jason

2018-05-01

To review the literature to identify and summarize strategies for evaluating responses to physical exertion after mild traumatic brain injury (mTBI) for clinical and research purposes. PubMed and EBSCOhost through December 31, 2016. Two independent reviewers selected studies based on the following criteria: (1) inclusion of participants with mTBI/concussion, (2) use of a measurement of physiological or psychosomatic response to exertion, (3) a repeatable description of the exertion protocol was provided, (4) a sample of at least 10 participants with a mean age between 8 and 65 years, and (5) the article was in English. The search process yielded 2685 articles, of which 14 studies met the eligibility requirements. A quality assessment using a checklist was conducted for each study by 2 independent study team members and verified by a third team member. Data were extracted by one team member and verified by a second team member. A qualitative synthesis of the studies revealed that most protocols used a treadmill or cycle ergometer as the exercise modality. Protocol methods varied across studies including differences in initial intensity determination, progression parameters, and exertion duration. Common outcome measures were self-reported symptoms, heart rate, and blood pressure. The strongest evidence indicates that exertional assessments can provide important insight about mTBI recovery and should be administered using symptoms as a guide. Additional studies are needed to verify optimal modes and protocols for post-mTBI exertional assessments. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

Science.gov (United States)

Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

2016-01-01

Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

IL1-and TGF beta-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine 'Bystander senescence'

Czech Academy of Sciences Publication Activity Database

Hubáčková, Soňa; Krejčíková, Kateřina; Bartek, Jiří; Hodný, Zdeněk

2012-01-01

Roč. 4, č. 12 (2012), 932-951 ISSN 1945-4589 R&D Projects: GA ČR GA204/08/1418; GA ČR GAP301/10/1525 Institutional support: RVO:68378050 Keywords : senescence-associated secretome * DNA damage response * cytokines * JAK/STAT3 * TGF beta * NF kappa B * IL6 * IL beta * Nox4 * autocrine and paracrine signaling * tumor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.696, year: 2012

1,4,2-Benzo/pyridodithiazine 1,1-dioxides structurally related to the ATP-sensitive potassium channel openers 1,2,4-Benzo/pyridothiadiazine 1,1-dioxides exert a myorelaxant activity linked to a distinct mechanism of action.

Science.gov (United States)

Pirotte, Bernard; de Tullio, Pascal; Florence, Xavier; Goffin, Eric; Somers, Fabian; Boverie, Stéphane; Lebrun, Philippe

2013-04-25

The synthesis of diversely substituted 3-alkyl/aralkyl/arylamino-1,4,2-benzodithiazine 1,1-dioxides and 3-alkylaminopyrido[4,3-e]-1,4,2-dithiazine 1,1-dioxides is described. Their biological activities on pancreatic β-cells and on smooth muscle cells were compared to those of the reference ATP-sensitive potassium channel (KATP channel) openers diazoxide and 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide. The aim was to assess the impact on biological activities of the replacement of the 1,2,4-thiadiazine ring by an isosteric 1,4,2-dithiazine ring. Most of the dithiazine analogues were found to be inactive on the pancreatic tissue, although some compounds bearing a 1-phenylethylamino side chain at the 3-position exerted a marked myorelaxant activity. Such an effect did not appear to be related to the opening of KATP channels but rather reflected a mechanism of action similar to that of calcium channel blockers. Tightly related 3-(1-phenylethyl)sulfanyl-4H-1,2,4-benzothiadiazine 1,1-dioxides were also found to exert a pronounced myorelaxant activity, resulting from both a KATP channel activation and a calcium channel blocker mechanism. The present work highlights the critical importance of an intracyclic NH group at the 4-position, as well as an exocyclic NH group linked to the 3-position of the benzo- and pyridothiadiazine dioxides, for activity on KATP channels.

Sevoflurane improves gaseous exchange and exerts protective ...

African Journals Online (AJOL)

mice, and exerted protective effects against acute LPS-induced lung injury. ... This is an Open Access article that uses a funding model which does not charge readers .... field microscope [20]. ... by Tukey's test were used for statistical analysis.

Exosomes and Their Therapeutic Potentials of Stem Cells

Directory of Open Access Journals (Sweden)

Chao Han

2016-01-01

Full Text Available Exosomes, a group of vesicles originating from the multivesicular bodies (MVBs, are released into the extracellular space when MVBs fuse with the plasma membrane. Numerous studies indicate that exosomes play important roles in cell-to-cell communication, and exosomes from specific cell types and conditions display multiple functions such as exerting positive effects on regeneration in many tissues. It is widely accepted that the therapeutic potential of stem cells may be mediated largely by the paracrine factors, so harnessing the paracrine effects of stem and progenitor cells without affecting these living, replicating, and potentially pluripotent cell populations is an advantage in terms of safety and complexity. Ascending evidence indicated that exosomes might be the main components of paracrine factors; thus, understanding the role of exosomes in each subtype of stem cells is far-reaching. In this review, we discuss the functions of exosomes from different types of stem cells and emphasize the therapeutic potentials of exosomes, providing an alternative way of developing strategies to cure diseases.

Chronic exertional compartment syndrome with medial tibial stress syndrome in twins.

Science.gov (United States)

Banerjee, Purnajyoti; McLean, Christopher

2011-06-14

Chronic exertional compartment syndrome and medial tibial stress syndrome are uncommon conditions that affect long-distance runners or players involved in team sports that require extensive running. We report 2 cases of bilateral chronic exertional compartment syndrome, with medial tibial stress syndrome in identical twins diagnosed with the use of a Kodiag monitor (B. Braun Medical, Sheffield, United Kingdom) fulfilling the modified diagnostic criteria for chronic exertional compartment syndrome as described by Pedowitz et al, which includes: (1) pre-exercise compartment pressure level >15 mm Hg; (2) 1 minute post-exercise pressure >30 mm Hg; and (3) 5 minutes post-exercise pressure >20 mm Hg in the presence of clinical features. Both patients were treated with bilateral anterior fasciotomies through minimal incision and deep posterior fasciotomies with tibial periosteal stripping performed through longer anteromedial incisions under direct vision followed by intensive physiotherapy resulting in complete symptomatic recovery. The etiology of chronic exertional compartment syndrome is not fully understood, but it is postulated abnormal increases in intramuscular pressure during exercise impair local perfusion, causing ischemic muscle pain. No familial predisposition has been reported to date. However, some authors have found that no significant difference exists in the relative perfusion, in patients, diagnosed with chronic exertional compartment syndrome. Magnetic resonance images of affected compartments have indicated that the pain is not due to ischemia, but rather from a disproportionate oxygen supply versus demand. We believe this is the first report of chronic exertional compartment syndrome with medial tibial stress syndrome in twins, raising the question of whether there is a genetic predisposition to the causation of these conditions. Copyright 2011, SLACK Incorporated.

Pulmonary antioxidants exert differential protective effects against ...

Indian Academy of Sciences (India)

Unknown

PM collections from both urban and industrial sites caused 50% oxidative degradation of DNA in vitro at concentrations as low ... chemical analysis in order that progress can be made in ... One popular hypothesis is that PM exerts toxic effects.

Pressure exerted by a vesicle on a surface

International Nuclear Information System (INIS)

Owczarek, A L; Prellberg, T

2014-01-01

Several recent works have considered the pressure exerted on a wall by a model polymer. We extend this consideration to vesicles attached to a wall, and hence include osmotic pressure. We do this by considering a two-dimensional directed model, namely that of area-weighted Dyck paths. Not surprisingly, the pressure exerted by the vesicle on the wall depends on the osmotic pressure inside, especially its sign. Here, we discuss the scaling of this pressure in the different regimes, paying particular attention to the crossover between positive and negative osmotic pressure. In our directed model, there exists an underlying Airy function scaling form, from which we extract the dependence of the bulk pressure on small osmotic pressures. (paper)

Dual effects exerted in vitro by micromolar concentrations of deoxynivalenol on undifferentiated caco-2 cells.

Science.gov (United States)

Manda, Gina; Mocanu, Mihaela Andreea; Marin, Daniela Eliza; Taranu, Ionelia

2015-02-16

Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37-1.50 μM), relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

Liver heterotopia in the head of a patient with osteosarcoma of the maxilla. A paracrine tumor-induced hepatogenesis?

Science.gov (United States)

Corsi, Alessandro; Riminucci, Mara

2017-02-01

Heterotopia of liver tissue is uncommon. It has been reported at various sites, more frequently near the orthotopic liver, including gallbladder, hepatic ligaments, omentum, and retroperitoneum, rarely within the diaphragm and the thoracic cavity, and never within the head. We report here a 22-year-old patient surgically treated for a maxillary osteosarcoma in which microscopic liver tissue islands were incidentally detected in the respiratory mucosa of the surgical margin. The islands comprised well-differentiated HepPar-1-positive hepatocytes and were surrounded by cytokeratin-7- and cytokeratin-19-positive bile duct-like structures. This case, which is unique in the medical literature, may suggest an inductive paracrine effect of the osteosarcoma cells by secretion of factors promoting hepatocyte specification of primitive endodermal progenitors and subsequent liver morphogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Subgroup-Elimination Transcriptomics Identifies Signaling Proteins that Define Subclasses of TRPV1-Positive Neurons and a Novel Paracrine Circuit

Science.gov (United States)

Isensee, Jörg; Wenzel, Carsten; Buschow, Rene; Weissmann, Robert; Kuss, Andreas W.; Hucho, Tim

2014-01-01

Normal and painful stimuli are detected by specialized subgroups of peripheral sensory neurons. The understanding of the functional differences of each neuronal subgroup would be strongly enhanced by knowledge of the respective subgroup transcriptome. The separation of the subgroup of interest, however, has proven challenging as they can hardly be enriched. Instead of enriching, we now rapidly eliminated the subgroup of neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia. Elimination was accomplished by brief treatment with TRPV1 agonists followed by the removal of compromised TRPV1(+) neurons using density centrifugation. By differential microarray and sequencing (RNA-Seq) based expression profiling we compared the transcriptome of all cells within sensory ganglia versus the same cells lacking TRPV1 expressing neurons, which revealed 240 differentially expressed genes (adj. p1.5). Corroborating the specificity of the approach, many of these genes have been reported to be involved in noxious heat or pain sensitization. Beyond the expected enrichment of ion channels, we found the TRPV1 transcriptome to be enriched for GPCRs and other signaling proteins involved in adenosine, calcium, and phosphatidylinositol signaling. Quantitative population analysis using a recent High Content Screening (HCS) microscopy approach identified substantial heterogeneity of expressed target proteins even within TRPV1-positive neurons. Signaling components defined distinct further subgroups within the population of TRPV1-positive neurons. Analysis of one such signaling system showed that the pain sensitizing prostaglandin PGD2 activates DP1 receptors expressed predominantly on TRPV1(+) neurons. In contrast, we found the PGD2 producing prostaglandin D synthase to be expressed exclusively in myelinated large-diameter neurons lacking TRPV1, which suggests a novel paracrine neuron-neuron communication. Thus, subgroup analysis based on the elimination

Thyroid hormone action: Astrocyte-neuron communication.

Directory of Open Access Journals (Sweden)

Beatriz eMorte

2014-05-01

Full Text Available Thyroid hormone action is exerted mainly through regulation of gene expression by binding of T3 to the nuclear receptors. T4 plays an important role as a source of intracellular T3 in the central nervous system via the action of the type 2 deiodinase, expressed in the astrocytes. A model of T3 availability to neural cells has been proposed and validated. The model contemplates that brain T3 has a double origin: a fraction is available directly from the circulation, and another is produced locally from T4 in the astrocytes by type 2 deiodinase. The fetal brain depends almost entirely on the T3 generated locally. The contribution of systemic T3 increases subsequently during development to account for approximately 50% of total brain T3 in the late postnatal and adult stages. In this article we review the experimental data in support of this model, and how the factors affecting T3 availability in the brain, such as deiodinases and transporters, play a decisive role in modulating local thyroid hormone action during development.

Does heavy physical exertion trigger myocardial infarction?

DEFF Research Database (Denmark)

Hallqvist, J; Möller, J; Ahlbom, A

2000-01-01

To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were...

Effects of fitness and self-confidence on time perception during exertion

Directory of Open Access Journals (Sweden)

2015-09-01

Full Text Available Aims: Human physical and psychological features influence perceptions of the environment during activity. If during exercise an individual over-estimates time, they may interpret this as spending longer than necessary under a potentially aversive state of exertion. This may in turn decrease one’s sense of exercise success and tendency to persevere with exercise. We tested if experimentally manipulating sense of exercise self-efficacy would affect time perception during standardised physical exertion. Method: Exercise Self-Efficacy (ESE of 18 -73 year olds (N=51 was measured before and after an exercise challenge of moderate intensity. Height, weight and body fat composition were measured before participants were randomly allocated to one of three groups. After a 4-minute treadmill fitness test, participants were presented with either bogus feedback about their performance (positive or negative or no feedback (control. Before and during exercise, participants estimated a prescribed 2-minute time interval. Ratings of perceived exertion were also measured periodically. Results: Feedback on performance had no significant effect on time perception, even when controlling for individual exertion level. Reported ESE was also unaffected by whether someone received positive, negative or no feedback. Age was again found to be significantly correlated with VO2max, r(51 = .62, p < .001, but in contrast to prior findings, estimates of general fitness such as VO2max, BMI and waist circumference were unrelated to changes in time perception due to exertion. Conclusions: These findings failed to support prior findings and anecdotal evidence suggesting that exertion might alter one’s perception of time. We also failed to find any support for effects on ESE when participants were given explicit performance feedback. Finally, participants’ physical characteristics appear to be unrelated to time perception whilst exercising at moderate intensity.

Physical exercise at the workplace reduces perceived physical exertion during healthcare work

DEFF Research Database (Denmark)

Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel

2015-01-01

BACKGROUND: High physical exertion during work is a risk factor for musculoskeletal pain and long-term sickness absence. Physical exertion (RPE) reflects the balance between physical work demands and physical capacity of the individual. Thus, increasing the physical capacity through physical......: 3.1 on a scale of 0 to 10, average WRPE: 3.6 on a scale of 0 to 10) from 18 departments at three participating hospitals. Participants were randomly allocated at the cluster level to 10 weeks of: (1) workplace physical exercise (WORK) performed in groups during working hours for 5×10 minutes per...... exercise may decrease physical exertion during work. This study investigates the effect of workplace-based versus home-based physical exercise on physical exertion during work (WRPE) among healthcare workers. METHODS: 200 female healthcare workers (age: 42.0, body mass index: 24.1, average pain intensity...

The Influence of a Bout of Exertion on Novice Barefoot Running Dynamics.

Science.gov (United States)

Hashish, Rami; Samarawickrame, Sachithra D; Baker, Lucinda; Salem, George J

2016-06-01

Barefoot, forefoot strike (FFS) running has recently risen in popularity. Relative to shod, rear-foot strike (RFS) running, employing a FFS is associated with heightened triceps surae muscle activation and ankle mechanical demand. Novice to this pattern, it is plausible that habitually shod RFS runners exhibit fatigue to the triceps surae when acutely transitioning to barefoot running, thereby limiting their ability to attenuate impact. Therefore, the purpose was to determine how habitually shod RFS runners respond to an exertion bout of barefoot running, operationally defined as a barefoot run 20% of mean daily running distance. Twenty-one RFS runners performed novice barefoot running, before and after exertion. Ankle peak torque, triceps surae EMG median frequency, foot-strike patterns, joint energy absorption, and loading rates were evaluated. Of the 21 runners, 6 maintained a RFS, 10 adopted a mid-foot strike (MFS), and 5 adopted a FFS during novice barefoot running. In-response to exertion, MFS and FFS runners demonstrated reductions in peak torque, median frequency, and ankle energy absorption, and an increase in loading rate. RFS runners demonstrated reductions in peak torque and loading rate. These results indicate that a short bout of running may elicit fatigue to novice barefoot runners, limiting their ability to attenuate impact. Key pointsIn response to exertion, novice barefoot runners demonstrate fatigue to their soleus.In response to exertion, novice barefoot runners demonstrate a reduction in ankle energy absorptionIn response to exertion, novice barefoot runners demonstrate an increase in loading rate.

20 CFR 220.132 - Physical exertion requirements.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Physical exertion requirements. 220.132 Section 220.132 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT... of walking and standing is often necessary in carrying out job duties. Jobs are sedentary if walking...

Motivational incentives lead to a strong increase in lateral prefrontal activity after self-control exertion.

Science.gov (United States)

Luethi, Matthias S; Friese, Malte; Binder, Julia; Boesiger, Peter; Luechinger, Roger; Rasch, Björn

2016-10-01

Self-control is key to success in life. Initial acts of self-control temporarily impair subsequent self-control performance. Why such self-control failures occur is unclear, with prominent models postulating a loss of a limited resource vs a loss of motivation, respectively. Here, we used functional magnetic resonance imaging to identify the neural correlates of motivation-induced benefits on self-control. Participants initially exerted or did not exert self-control. In a subsequent Stroop task, participants performed worse after exerting self-control, but not if they were motivated to perform well by monetary incentives. On the neural level, having exerted self-control resulted in decreased activation in the left inferior frontal gyrus. Increasing motivation resulted in a particularly strong activation of this area specifically after exerting self-control. Thus, after self-control exertion participants showed more prefrontal neural activity without improving performance beyond baseline level. These findings suggest that impaired performance after self-control exertion may not exclusively be due to a loss of motivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Adipose-derived stem cells enhance myogenic differentiation in the mdx mouse model of muscular dystrophy via paracrine signaling

Directory of Open Access Journals (Sweden)

Ji-qing Cao

2016-01-01

Full Text Available Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells (6 × 10 6 were injected into the gastrocnemius muscle of mdx mice at various sites. Dystrophin expression was found in the muscle fibers. Phosphorylation levels of Akt, mammalian target of rapamycin (mTOR, eIF-4E binding protein 1 and S6 kinase 1 were increased, and the Akt/mTOR pathway was activated. Simultaneously, myogenin levels were increased, whereas cleaved caspase 3 and vimentin levels were decreased. Necrosis and fibrosis were reduced in the muscle fibers. These findings suggest that adipose-derived stem cells promote the regeneration and survival of muscle cells by inhibiting apoptosis and fibrosis, thereby alleviating muscle damage in muscular dystrophy.

Comparison of the force exerted by hippocampal and DRG growth cones.

Science.gov (United States)

Amin, Ladan; Ercolini, Erika; Ban, Jelena; Torre, Vincent

2013-01-01

Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal neurons. Developing GCs from dissociated DRG and hippocampal neurons were obtained from P1-P2 and P10-P12 rats. Comparing their morphology, we observed that the area of GCs of hippocampal neurons was 8-10 µm(2) and did not vary between P1-P2 and P10-P12 rats, but GCs of DRG neurons were larger and their area increased from P1-P2 to P10-P12 by 2-4 times. The force exerted by DRG filopodia was in the order of 1-2 pN and never exceeded 5 pN, while hippocampal filopodia exerted a larger force, often in the order of 5 pN. Hippocampal and DRG lamellipodia exerted lateral forces up to 20 pN, but lamellipodia of DRG neurons could exert a vertical force larger than that of hippocampal neurons. Force-velocity relationships (Fv) in both types of neurons had the same qualitative behaviour, consistent with a common autocatalytic model of force generation. These results indicate that molecular mechanisms of force generation of GC from CNS and PNS neurons are similar but the amplitude of generated force is influenced by their cytoskeletal properties.

Muscles and their myokines.

Science.gov (United States)

Pedersen, Bente Klarlund

2011-01-15

In the past, the role of physical activity as a life-style modulating factor has been considered as that of a tool to balance energy intake. Although it is important to avoid obesity, physical inactivity should be discussed in a much broader context. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular diseases, cancer, dementia and even depression. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an 'exercise factor', which could be released from skeletal muscle during contraction and mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We have suggested that cytokines or other peptides that are produced, expressed and released by muscle fibres and exert autocrine, paracrine or endocrine effects should be classified as 'myokines'. Given that skeletal muscle is the largest organ in the human body, our discovery that contracting skeletal muscle secretes proteins sets a novel paradigm: skeletal muscle is an endocrine organ producing and releasing myokines, which work in a hormone-like fashion, exerting specific endocrine effects on other organs. Other myokines work via paracrine mechanisms, exerting local effects on signalling pathways involved in muscle metabolism. It has been suggested that myokines may contribute to exercise-induced protection against several chronic diseases.

Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system

Science.gov (United States)

Zhao, Xin; Wang, Chuang; Cui, Wu-Geng; Ma, Qing; Zhou, Wen-Hua

2015-01-01

Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain. PMID:25761874

[Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

Science.gov (United States)

Li, S N; Zhang, K Y

1992-11-01

Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration.

Science.gov (United States)

Glaser, Talita; Cappellari, Angélica Regina; Pillat, Micheli Mainardi; Iser, Isabele Cristiana; Wink, Márcia Rosângela; Battastini, Ana Maria Oliveira; Ulrich, Henning

2012-09-01

Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

Regulation of connexins expression levels by microRNAs, an update

Directory of Open Access Journals (Sweden)

Juan Francisco Calderon

2016-11-01

Full Text Available Control of cell-cell coordination and communication is regulated by several factors, including paracrine and autocrine release of biomolecules, and direct exchange of soluble factors between cells through gap junction channels. Additionally, hemichannels also participate in cell-cell coordination through the release of signaling molecules, such as ATP and glutamate. A family of transmembrane proteins named connexins forms both gap junction channels and hemichannels. Because of their importance in cell and tissue coordination, connexins are controlled both by post-translational and post-transcriptional modifications. In recent years, non-coding RNAs have garnered research interest due to their ability to exert post-transcriptional regulation of gene expression. One of the most recent, well-documented control mechanisms of protein synthesis is found through the action of small, single-stranded RNA, called micro RNAs (miRNAs or miRs. Put simply, miRNAs are negative regulators of the expression of a myriad proteins involved in many physiological and pathological processes. This mini review will briefly summarize what is currently known about the action of miRNAs over Cxs expression/function in different organs under some relevant physiological and pathological conditions

Dual Effects Exerted in Vitro by Micromolar Concentrations of Deoxynivalenol on Undifferentiated Caco-2 Cells

Directory of Open Access Journals (Sweden)

Gina Manda

2015-02-01

Full Text Available Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON, raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37–1.50 μM, relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

Melittin exerts an antitumor effect on non‑small cell lung cancer cells.

Science.gov (United States)

Zhang, Su-Fang; Chen, Zhe

2017-09-01

Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells. Subcutaneous injection of melittin at doses of 1 and 10 mg/kg significantly suppressed non‑small cell lung cancer tumor growth by 27 and 61%, respectively. In addition, melittin significantly inhibited the secretion of vascular endothelial growth factor (VEGF) in non‑small cell lung cancer cells. Furthermore, melittin decreased the protein expression of VEGF and hypoxia‑inducible factor 1‑α. Therefore, the antitumor activity of melittin may be associated with the anti‑angiogenic actions of inhibiting the VEGF and hypoxia‑inducible factor signaling pathways.

Exercise, physical activity, and exertion over the business cycle.

Science.gov (United States)

Colman, Gregory; Dave, Dhaval

2013-09-01

Shifts in time and income constraints over economic expansions and contractions would be expected to affect individuals' behaviors. We explore the impact of the business cycle on individuals' exercise, time use, and total physical exertion, utilizing information on 112,000 individual records from the 2003-2010 American Time Use Surveys. In doing so, we test a key causal link that has been hypothesized in the relation between unemployment and health, but not heretofore assessed. Using more precise measures of exercise (and other activities) than previous studies, we find that as work-time decreases during a recession, recreational exercise, TV-watching, sleeping, childcare, and housework increase. This, however, does not compensate for the decrease in work-related exertion due to job-loss, and total physical exertion declines. These effects are strongest among low-educated men, which is validating given that employment in the Great Recession has declined most within manufacturing, mining, and construction. We also find evidence of intra-household spillover effects, wherein individuals respond to shifts in spousal employment conditional on their own labor supply. The decrease in total physical activity during recessions is especially problematic for vulnerable populations concentrated in boom-and-bust industries, and may have longer-term effects on obesity and related health outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Stiffness and thickness of fascia do not explain chronic exertional compartment syndrome

DEFF Research Database (Denmark)

Dahl, Morten; Hansen, Philip; Stål, Per

2011-01-01

Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown.......Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown....

Action of apilite on radiosensitivity of mice

International Nuclear Information System (INIS)

Artemov, N.M.; Kon'kova, L.G.; Sergeyeva, L.I.

1975-01-01

A preparation of bee venom - apilite - has been administered to mice in different periods prior to and after the exposure to 600 and 500 r (6 and 10 μg/g, respectively). This preparation is freed from allergizating proteins and enzymes of the venom. Its basic active substance is polypeptid melittine. Apilite has been found to exert a protective effect: the survival of the experimental groups of mice is 27-44 per cent higher than that of the controls. It has also been revealed that apilite has a positive action on a number of indices of the peripheral blood of irradiated animals

Thrombin like activity of Asclepias curassavica L. latex: action of cysteine proteases.

Science.gov (United States)

Shivaprasad, H V; Rajesh, R; Nanda, B L; Dharmappa, K K; Vishwanath, B S

2009-05-04

To validate the scientific basis of plant latex to stop bleeding on fresh cuts. Cysteine protease(s) from Asclepias curassavica (Asclepiadaceae) plant latex was assessed for pro-coagulant and thrombin like activities. A waxy material from the latex of Asclepias curassavica latex was removed by freezing and thawing. The resulted latex enzyme fraction was assayed for proteolytic activity using denatured casein as substrate. Its coagulant activity and thrombin like activity were determined using citrated plasma and pure fibrinogen, respectively. Inhibition studies were performed using specific protease inhibitors to know the type of protease. The latex enzyme fraction exhibited strong proteolytic activity when compared to trypsin and exerted pro-coagulant action by reducing plasma clotting time from 195 to 58 s whereas trypsin reduced clotting time marginally from 195 to 155 s. The pro-coagulant activity of this enzyme fraction was exerted by selectively hydrolyzing A alpha and B beta subunits of fibrinogen to form fibrin clot when pure fibrinogen was used as substrate as assessed by fibrinogen-agarose plate method and fibrinogen polymerization assay. Trypsin failed to induce any fibrin clot under similar conditions. The electrophoretic pattern of latex enzyme fraction-induced fibrin clot was very much similar to that of thrombin-induced fibrin clot and mimic thrombin like action. The proteolytic activity including thrombin like activity of Asclepias curassavica latex enzyme fraction was completely inhibited by iodoaceticacid (IAA). Cysteine proteases from Asclepias curassavica latex exhibited strong pro-coagulant action and were found to be specific in its action (Thrombin like). This could be the basis for the use of plant latex in pharmacological applications that justify their use as folk medicine.

Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

Science.gov (United States)

Homberg, Judith R.; Olivier, Jocelien D. A.; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

2011-01-01

The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine

American football and fatal exertional heat stroke: a case study of Korey Stringer.

Science.gov (United States)

Grundstein, Andrew; Knox, John A; Vanos, Jennifer; Cooper, Earl R; Casa, Douglas J

2017-08-01

On August 1, 2001, Korey Stringer, a Pro Bowl offensive tackle for the Minnesota Vikings, became the first and to date the only professional American football player to die from exertional heat stroke (EHS). The death helped raise awareness of the dangers of exertional heat illnesses in athletes and prompted the development of heat safety policies at the professional, collegiate, and interscholastic levels. Despite the public awareness of this death, no published study has examined in detail the circumstances surrounding Stringer's fatal EHS. Using the well-documented details of the case, our study shows that Stringer's fatal EHS was the result of a combination of physiological limitations, organizational and treatment failings, and extreme environmental conditions. The COMfort FormulA (COMFA) energy budget model was used to assess the relative importance of several extrinsic factors on Stringer's EHS, including weather conditions, clothing insulation, and activity levels. We found that Stringer's high-intensity training in relation to the oppressive environmental conditions was the most prominent factor in producing dangerous, uncompensable heat stress conditions and that the full football uniform played a smaller role in influencing Stringer's energy budget. The extreme energy budget levels that led to the fatal EHS would have been avoided according to our modeling through a combination of reduced intensity and lower clothing insulation. Finally, a long delay in providing medical treatment made the EHS fatal. These results highlight the importance of modern heat safety guidelines that provide controls on extrinsic factors, such as the adjustment of duration and intensity of training along with protective equipment modifications based on environmental conditions and the presence of an emergency action plan focused on rapid recognition and immediate on-site aggressive cooling of EHS cases.

Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

Directory of Open Access Journals (Sweden)

Judith R Homberg

Full Text Available The selective serotonin reuptake inhibitor (SSRI Prozac® (fluoxetine is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg at postnatal day (PND 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (norfluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (norfluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential

American football and fatal exertional heat stroke: a case study of Korey Stringer

Science.gov (United States)

Grundstein, Andrew; Knox, John A.; Vanos, Jennifer; Cooper, Earl R.; Casa, Douglas J.

2017-08-01

On August 1, 2001, Korey Stringer, a Pro Bowl offensive tackle for the Minnesota Vikings, became the first and to date the only professional American football player to die from exertional heat stroke (EHS). The death helped raise awareness of the dangers of exertional heat illnesses in athletes and prompted the development of heat safety policies at the professional, collegiate, and interscholastic levels. Despite the public awareness of this death, no published study has examined in detail the circumstances surrounding Stringer's fatal EHS. Using the well-documented details of the case, our study shows that Stringer's fatal EHS was the result of a combination of physiological limitations, organizational and treatment failings, and extreme environmental conditions. The COMfort FormulA (COMFA) energy budget model was used to assess the relative importance of several extrinsic factors on Stringer's EHS, including weather conditions, clothing insulation, and activity levels. We found that Stringer's high-intensity training in relation to the oppressive environmental conditions was the most prominent factor in producing dangerous, uncompensable heat stress conditions and that the full football uniform played a smaller role in influencing Stringer's energy budget. The extreme energy budget levels that led to the fatal EHS would have been avoided according to our modeling through a combination of reduced intensity and lower clothing insulation. Finally, a long delay in providing medical treatment made the EHS fatal. These results highlight the importance of modern heat safety guidelines that provide controls on extrinsic factors, such as the adjustment of duration and intensity of training along with protective equipment modifications based on environmental conditions and the presence of an emergency action plan focused on rapid recognition and immediate on-site aggressive cooling of EHS cases.

Physiological Actions of Fibroblast Growth Factor-23

Directory of Open Access Journals (Sweden)

Reinhold G. Erben

2018-05-01

Full Text Available Fibroblast growth factor-23 (FGF23 is a bone-derived hormone suppressing phosphate reabsorption and vitamin D hormone synthesis in the kidney. At physiological concentrations of the hormone, the endocrine actions of FGF23 in the kidney are αKlotho-dependent, because high-affinity binding of FGF23 to FGF receptors requires the presence of the co-receptor αKlotho on target cells. It is well established that excessive concentrations of intact FGF23 in the blood lead to phosphate wasting in patients with normal kidney function. Based on the importance of diseases associated with gain of FGF23 function such as phosphate-wasting diseases and chronic kidney disease, a large body of literature has focused on the pathophysiological consequences of FGF23 excess. Less emphasis has been put on the role of FGF23 in normal physiology. Nevertheless, during recent years, lessons we have learned from loss-of-function models have shown that besides the paramount physiological roles of FGF23 in the control of 1α-hydroxylase expression and of apical membrane expression of sodium-phosphate co-transporters in proximal renal tubules, FGF23 also is an important stimulator of calcium and sodium reabsorption in distal renal tubules. In addition, there is an emerging role of FGF23 as an auto-/paracrine regulator of alkaline phosphatase expression and mineralization in bone. In contrast to the renal actions of FGF23, the FGF23-mediated suppression of alkaline phosphatase in bone is αKlotho-independent. Moreover, FGF23 may be a physiological suppressor of differentiation of hematopoietic stem cells into the erythroid lineage in the bone microenvironment. At present, there is little evidence for a physiological role of FGF23 in organs other than kidney and bone. The purpose of this mini-review is to highlight the current knowledge about the complex physiological functions of FGF23.

Lactate and pH evaluation in exhausted humans with prolonged TASER X26 exposure or continued exertion.

Science.gov (United States)

Ho, Jeffrey D; Dawes, Donald M; Cole, Jon B; Hottinger, Julie C; Overton, Kenneth G; Miner, James R

2009-09-10

Safety concerns about TASER Conducted Electrical Weapon (CEW) use and media reports of deaths after exposure have been expressed. CEWs are sometimes used on exhausted subjects to end resistance. The alternative is often a continued struggle. It is unclear if CEW use is metabolically different than allowing a continued struggle. We sought to determine if CEW exposure on exhausted humans caused worsening acidosis when compared with continued exertion. This was a prospective study of human volunteers recruited during a CEW training course. Volunteers were from several different occupations and represented a wide range of ages and body mass index characteristics. Medical histories, baseline pH and lactate values were obtained. Patients were assigned to one of four groups: 2 control groups consisting of Exertion only and CEW Exposure only, and the 2 experimental groups that were Exertion plus CEW Exposure and Exertion plus additional Exertion. Blood sampling occurred after Exertion and after any CEW exposure. This was repeated every 2-min until 20 min after protocol completion. Descriptive statistics were used to compare the four groups. The experimental groups and the control groups were compared individually at each time point using Wilcoxon rank sum tests. Lactate and pH association was assessed using multiple linear regression. Forty subjects were enrolled. There were no median pH or lactate differences between CEW Exposure groups at baseline, or between Exertion protocol groups immediately after completion. The CEW Exposure only group had higher pH and lower lactate values at all time points after exposure than the Exertion only group. After completing the Exertion protocol, there was no difference in the pH or lactate values between the continued Exertion group and the CEW Exposure group at any time points. Subjects who had CEW Exposure only had higher pH and lower lactate values than subjects who completed the Exertion protocol only. CEW exposure does not appear

In vitro antitumor actions of extracts from endemic plant Helichrysum zivojinii.

Science.gov (United States)

Matić, Ivana Z; Aljančić, Ivana; Žižak, Željko; Vajs, Vlatka; Jadranin, Milka; Milosavljević, Slobodan; Juranić, Zorica D

2013-02-18

The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Černjavski & Soška (family Asteraceae) against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC). The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Extracts obtained from the endemic plant Helichrysum zivojinii may represent an important source of novel potential

Relationships between recall of perceived exertion and blood lactate concentration in a judo competition.

Science.gov (United States)

Serrano, M A; Salvador, A; González-Bono, E G; Sanchís, C; Suay, F

2001-06-01

Relationships between perceived exertion and blood lactate have usually been studied in laboratory or training contexts but not in competition, the most important setting in which sports performance is evaluated. The purpose of this study was to examine the relationships between psychological and physiological indices of the physical effort in a competition setting, taking into account the duration of effort. For this, we employed two Ratings of Perceived Exertion (RPE and CR-10) and lactic acid plasma concentration as a biological marker of the effort performed. 13 male judo fighters who participated in a sports club competition provided capillary blood samples to assay lactate concentrations and indicated on scale their Recall of Perceived Exertion in the total competition and again in just the Last Fight to compare the usefulness of RPE and CR-10 in assessing discrete bouts of effort and a whole session. Analysis showed that perceived exertion or the effort made during the whole competition was positively and significantly related to maximal lactate concentration and lactate increase in competition, thus extending the validity of this scale to sports contests. The Recall of Perceived Exertion scores were not significantly correlated with the duration of effort.

Action of carbon monoxide on the affinity of hemoglobin for oxygen

Energy Technology Data Exchange (ETDEWEB)

Vanuxem, D.; Weiller, P.J.; Guillot, C.; Grimaud, C.

1982-01-01

The authors have studied the action of carbon monoxide on the affinity of hemoglobin for oxygen by measuring P50 in whole blood and in stripped hemoglobin before and after exposition of blood samples from heavy smokers and polycythemic patients with high levels of HbCO to hyperbaric oxygen (2.2 ata). The concentration of 2,3-diphosphoglycerate was normal although P50 was significantly lowered, not only in whole blood but also in stripped hemoglobin. Hyperbaric oxygen normalized P50 by removing CO radicals from stripped hemoglobin. This may indicate that CO radicals exert a direct action on the hemoglobin molecule, at least at the HbCO levels studied in this work.

Juglans regia Hexane Extract Exerts Antitumor Effect, Apoptosis ...

African Journals Online (AJOL)

Original Research Article. Juglans regia Hexane Extract Exerts Antitumor Effect,. Apoptosis Induction and Cell Circle Arrest in Prostate. Cancer Cells In vitro. Wei Li1, De-Yuan Li2*, ... composition of walnut is juglone (5-hydroxy-1, 4- naphthoquinone), the .... extract was confirmed by studying apoptotic body formation using ...

Additive phosphaturic action of parathyrin and calcitonin

International Nuclear Information System (INIS)

Oberleitner, H.; Lang, F.; Greger, P.; Sporer, H.; Deetjen, P.

1980-01-01

Parathyrin and calcitonin exert their effects on phosphate metabolism by influencing the functions of at least three organ systems, i.e. bone, gut and kidneys. To study the renal effects of these hormones under exclusion of systemic effects microinfusion studies were performed in anesthetised rats. After thyroparathyroidectomy radioactively labelled phosphate containing solutions were microinfused into single proximal convoluted tubules. The tracer recovery in the urine allowed calculation of phosphate reabsorption in the nephron segments beyond the micropuncture site. After a control period of 6 minutes the hormones were superfused to the nephron surface and tracer recovery measured during the following 36 minutes. Within few minutes both, parathyrin and calcitonin, clearly reduced phosphate reabsorption. Infusions of supramaximal doses of either hormone abolished the local action of this hormone but did not influence the effect of the other. Thus the phosphaturic actions of parathyrin and calcitonin are additive, indicating that the hormones involve different mechanisms and/or nephron sites. (author)

EMMPRIN regulates tumor growth and metastasis by recruiting bone marrow-derived cells through paracrine signaling of SDF-1 and VEGF.

Science.gov (United States)

Chen, Yanke; Gou, Xingchun; Kong, Derek Kai; Wang, Xiaofei; Wang, Jianhui; Chen, Zeming; Huang, Chen; Zhou, Jiangbing

2015-10-20

EMMPRIN, a cell adhesion molecule highly expressed in a variety of tumors, is associated with poor prognosis in cancer patients. Mechanistically, EMMPRIN has been characterized to contribute to tumor development and progression by controlling the expression of MMPs and VEGF. In the present study, by using fluorescently labeled bone marrow-derived cells (BMDCs), we found that the down-regulation of EMMPRIN expression in cancer cells reduces tumor growth and metastasis, and is associated with the reduced recruitment of BMDCs. Further protein profiling studies suggest that EMMPRIN controls BMDC recruitment through regulating the secretion of soluble factors, notably, VEGF and SDF-1. We demonstrate that the expression and secretion of SDF-1 in tumor cells are regulated by EMMPRIN. This study reveals a novel mechanism by which EMMPRIN promotes tumor growth and metastasis by recruitment of BMDCs through controlling secretion and paracrine signaling of SDF-1 and VEGF.

Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis.

Science.gov (United States)

Packer, Milton

2018-06-01

Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated neurohormonal activation appears to enhance the expression of SGLT2 in the renal tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular sites in a manner that can oppose the sodium retention produced by leptin. In addition, SGLT2 inhibitors reduce the accumulation and inflammation of perivisceral adipose tissue, thus minimizing the secretion of leptin and its paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis probably contributes to the impairment of cardiac distensibility and glomerular function that characterizes obesity-related HFpEF. Ongoing clinical trials with SGLT2 inhibitors in heart failure are positioned to confirm or refute the hypothesis that these drugs may favourably influence the course of obesity-related HFpEF by their ability to attenuate the secretion and actions of leptin. © 2018 John Wiley & Sons Ltd.

Overexpression of GDNF in the uninjured DRG exerts analgesic effects on neuropathic pain following segmental spinal nerve ligation in mice.

Science.gov (United States)

Takasu, Kumiko; Sakai, Atsushi; Hanawa, Hideki; Shimada, Takashi; Suzuki, Hidenori

2011-11-01

Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein (EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia in association with an increase in GDNF protein expression in each virus injection site, whereas injection into the injured L5 DRG or plantar skin had no effects. These results suggest that GDNF exerts its analgesic effects in the neuropathic pain state by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by the uninjured DRG neurons. This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by these neurons. Therefore, research focusing on these GDNF-dependent neurons in the uninjured DRG would provide a new strategy for treating neuropathic pain. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms

Energy Technology Data Exchange (ETDEWEB)

Qi, Xiaobao; Zhou, Chuncai; Li, Peng [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore); Xu, Weixin [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore (Singapore); Cao, Ye; Ling, Hua; Ning Chen, Wei; Ming Li, Chang; Xu, Rong [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore); Lamrani, Mouad [Menicon Co., Ltd. Immeuble Espace Cordeliers, 2, rue President Carnot, 69002 Lyon (France); Mu, Yuguang, E-mail: ygmu@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore (Singapore); Leong, Susanna Su Jan [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore); Wook Chang, Matthew, E-mail: matthewchang@ntu.edu.sg [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore); Chan-Park, Mary B., E-mail: mbechan@ntu.edu.sg [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore)

2010-07-30

Research highlights: {yields} Short antimicrobial peptides with nine and eleven residues were developed. {yields} These peptides show strong bactericidal activity against clinically important bacterial and fungal pathogens. {yields} These peptides exhibit high stability in the presence of salts, and low cytotoxicity. {yields} These peptides exert their action by disrupting membrane lipids. -- Abstract: Short antimicrobial peptides with nine and eleven residues were developed against several clinically important bacterial and fungal pathogens (specifically Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Fusarium solani). Twelve analogues of previously reported peptides BP76 (KKLFKKILKFL) and Pac-525 (KWRRWVRWI) were designed, synthesized, and tested for their antimicrobial activities. Two of our eleven amino acid peptides, P11-5 (GKLFKKILKIL) and P11-6 (KKLIKKILKIL), have very low MICs of 3.1-12.5 {mu}g ml{sup -1} against all five pathogens. The MICs of these two peptides against S. aureus, C. albicans and F. solani are four to ten times lower than the corresponding MICs of the reference peptide BP76. P9-4 (KWRRWIRWL), our newly designed nine-amino acid analogue, also has particularly low MICs of 3.1-6.2 {mu}g ml{sup -1} against four of the tested pathogens; these MICs are two to eight times lower than those reported for Pac-525 (6.2-50 {mu}g ml{sup -1}).These new peptides (P11-5, P11-6 and P9-4) also exhibit improved stability in the presence of salts, and have low cytotoxicity as shown by the hemolysis and MTT assays. From the results of field-emission scanning electron microscopy, membrane depolarization and dye-leakage assays, we propose that these peptides exert their action by disrupting membrane lipids. Molecular dynamics simulation studies confirm that P11-6 peptide maintains relatively stable helical structure and exerts more perturbation action on the order of acyl tail of lipid bilayer.

Forces exerted by jumping children: A pilot study

NARCIS (Netherlands)

Moes, C.C.M.; Bakker, H.E.

1998-01-01

This article reports on a pilot study of the loads exerted vertically by children when jumping. The subjects of the study were 17 children, aged from two to twelve years. Measurements were made using video recordings and a force-plate. The influence of the stiffness of the base and of jumping with

High self-perceived exercise exertion before bedtime is associated with greater objectively assessed sleep efficiency.

Science.gov (United States)

Brand, Serge; Kalak, Nadeem; Gerber, Markus; Kirov, Roumen; Pühse, Uwe; Holsboer-Trachsler, Edith

2014-09-01

To assess the association between self-perceived exercise exertion before bedtime and objectively measured sleep. Fifty-two regularly exercising young adults (mean age, 19.70 years; 54% females) underwent sleep electroencephalographic recordings 1.5 h after completing moderate to vigorous exercise in the evening. Before sleeping, participants answered questions regarding degree of exertion of the exercise undertaken. Greater self-perceived exertion before bedtime was associated with higher objectively assessed sleep efficiency (r = 0.69, P associated with more deep sleep, shortened sleep onset time, fewer awakenings after sleep onset, and shorter wake duration after sleep onset. Multiple linear regression analysis showed that objective sleep efficiency was predicted by increased exercise exertion, shortened sleep onset time, increased deep sleep, and decreased light sleep. Against expectations and general recommendations for sleep hygiene, high self-perceived exercise exertion before bedtime was associated with better sleep patterns in a sample of healthy young adults. Further studies should also focus on elderly adults and adults suffering from insomnia. Copyright © 2014 Elsevier B.V. All rights reserved.

Benign vascular sexual headache and exertional headache: interrelationships and long term prognosis.

OpenAIRE

Silbert, P L; Edis, R H; Stewart-Wynne, E G; Gubbay, S S

1991-01-01

There is a definite relationship between the vascular type of benign sexual headache and benign exertional headache. Forty five patients with benign vascular sexual headache were reviewed. Twenty seven (60%) experienced benign vascular sexual headache alone and eighteen (40%) had experienced both benign vascular sexual headache and benign exertional headache on at least one occasion. The mean age was 34.3 years with a male:female ratio of 5.4:1. Thirty patients with a history of benign vascul...

Exertional Rhabdomyolysis in a 21-Year-Old Healthy Woman: A Case Report.

Science.gov (United States)

McKay, Brianna D; Yeo, Noelle M; Jenkins, Nathaniel D M; Miramonti, Amelia A; Cramer, Joel T

2017-05-01

McKay, BD, Yeo, NM, Jenkins, NDM, Miramonti, AA, and Cramer, JT. Exertional rhabdomyolysis in a 21-year-old healthy woman: a case report. J Strength Cond Res 31(5): 1403-1410, 2017-The optimal resistance training program to elicit muscle hypertrophy has been recently debated and researched. Although 3 sets of 10 repetitions at 70-80% of the 1 repetition maximum (1RM) are widely recommended, recent studies have shown that low-load (∼30% 1RM) high-repetition (3 sets of 30-40 repetitions) resistance training can elicit similar muscular hypertrophy. Incidentally, this type of resistance training has gained popularity. In the process of testing this hypothesis in a research study in our laboratory, a subject was diagnosed with exertional rhabdomyolysis after completing a resistance training session that involved 3 sets to failure at 30% 1RM. Reviewed were the events leading up to and throughout the diagnosis of exertional rhabdomyolysis in a healthy recreationally-trained 21-year-old woman who was enrolled in a study that compared the acute effects of high-load low-repetition vs. low-load high-repetition resistance training. The subject completed a total of 143 repetitions of the bilateral dumbbell biceps curl exercise. Three days after exercise, she reported excessive muscle soreness and swelling and sought medical attention. She was briefly hospitalized and then discharged with instructions to take acetaminophen for soreness, drink plenty of water, rest, and monitor her creatine kinase (CK) concentrations. Changes in the subject's CK concentrations, ultrasound-determined muscle thickness, and echo intensity monitored over a 14-day period are reported. This case illustrates the potential risk of developing exertional rhabdomyolysis after a low-load high-repetition resistance training session in healthy, young, recreationally-trained women. The fact that exertional rhabdomyolysis is a possible outcome may warrant caution when prescribing this type of resistance

The role of SDF-1-CXCR4/CXCR7 axis in biological behaviors of adipose tissue-derived mesenchymal stem cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Li, Qiang; Zhang, Aijun; Tao, Changbo; Li, Xueyang; Jin, Peisheng, E-mail: jinps2006@163.com

2013-11-22

Highlights: •SDF-1 pretreating increased the levels of CXCR4, CXCR7 in ADSCs. •SDF-1 improved cells paracrine migration and proliferation abilities. •CXCR4 and CXCR7 could function in ADSCs paracrine, migration and proliferation. -- Abstract: Numerous studies have reported that CXCR4 and CXCR7 play an essential, but differential role in stromal cell-derived factor-1 (SDF-1)-inducing cell chemotaxis, viability and paracrine actions of BMSCs. Adipose tissue-derived mesenchymal stem cells (ADSCs) have been suggested to be potential seed cells for clinical application instead of bone marrow derived stroma cell (BMSCs). However, the function of SDF-1/CXCR4 and SDF-1/CXCR7 in ADSCs is not well understood. This study was designed to analyze the effect of SDF-1/CXCR4 and SDF-1/CXCR7 axis on ADSCs biological behaviors in vitro. Using Flow cytometry and Western blot methods, we found for the first time that CXCR4/CXCR7 expression was increased after treatment with SDF-1 in ADSCs. SDF-1 promoted ADSCs paracrine, proliferation and migration abilities. CXCR4 or CXCR7 antibody suppressed ADSCs paracrine action induced by SDF-1. The migration of ADSCs can be abolished by CXCR4 antibody, while the proliferation of ADSCs was only downregulated by CXCR7 antibody. Our study indicated that the angiogenesis of ADSCs is, at least partly, mediated by SDF-1/CXCR4 and SDF-1/CXCR7 axis. However, only binding of SDF-1/CXCR7 was required for proliferation of ADSCs, and CXCR7 was required for migration of ADSCs induced by SDF-1. Our studies provide evidence that the activation of either axis may be helpful to improve the effectiveness of ADSCs-based stem cell therapy.

Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium.

Science.gov (United States)

Nallasamy, Shanmugasundaram; Li, Quanxi; Bagchi, Milan K; Bagchi, Indrani C

2012-01-01

The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors that control organogenesis and tissue interactions during embryonic development. We observed overlapping expression of these factors in uterine epithelial and stromal compartments of pregnant mice prior to embryo implantation. Conditional ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due to a failure in implantation. In these mutant mice (Msx1/2(d/d)), the uterine epithelium exhibited persistent proliferative activity and failed to attach to the embryos. Gene expression profiling of uterine epithelium and stroma of Msx1/2(d/d) mice revealed an elevated expression of several members of the Wnt gene family in the preimplantation uterus. Increased canonical Wnt signaling in the stromal cells activated β-catenin, stimulating the production of a subset of fibroblast growth factors (FGFs) in these cells. The secreted FGFs acted in a paracrine manner via the FGF receptors in the epithelium to promote epithelial proliferation, thereby preventing differentiation of this tissue and creating a non-receptive uterus refractory to implantation. Collectively, these findings delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which operate in the uterus at the time of implantation to control the mesenchymal-epithelial dialogue critical for successful establishment of pregnancy.

Update: Exertional rhabdomyolysis, active component, U.S. Army, Navy, Air Force, and Marine Corps, 2011-2015.

Science.gov (United States)

Armed Forces Health Surveillance Branch

2016-03-01

Among active component members of the U.S. Army, Navy, Air Force, and Marine Corps in 2015, there were 456 incident episodes of rhabdomyolysis likely due to physical exertion or heat stress ("exertional rhabdomyolysis"). Annual rates of incident diagnoses of exertional rhabdomyolysis increased 17% between 2014 and 2015. In 2015, the highest incidence rates occurred in service members who were male; younger than 20 years of age; black, non-Hispanic; members of the Marine Corps and Army; recruit trainees; and in combat-specific occupations. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain and swelling, limited range of motion, or the excretion of dark urine (e.g., myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.

A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats

DEFF Research Database (Denmark)

Andreassen, Kim V; Feigh, Michael; Hjuler, Sara T

2014-01-01

-induced obese (DIO) and Zucker diabetic fatty (ZDF) rats. In vitro, KBP-042 demonstrated superior binding affinity and activation of amylin and calcitonin receptors, and ex vivo, KBP-042 exerted inhibitory action on stimulated insulin and glucagon release from isolated islets. In vivo, KBP-042 induced...... a superior and pronounced reduction in food intake in conjunction with a sustained pair-fed corrected weight loss in DIO rats. Concomitantly, KBP-042 improved glucose homeostasis and reduced hyperinsulinemia and hyperleptinemia in conjunction with enhanced insulin sensitivity. In ZDF rats, KBP-042 induced...... antiobesity and antidiabetic efficacy by dual modulation of insulin sensitivity and directly decelerating stress on the pancreatic α- and β-cells. These results could provide the basis for oral KBP-042 as a novel therapeutic agent in type 2 diabetes....

Immediate movement history influences reach-to-grasp action selection in children and adults.

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Kent, Samuel W; Wilson, Andrew D; Plumb, Mandy S; Williams, Justin H G; Mon-Williams, Mark

2009-01-01

Action selection is subject to many biases. Immediate movement history is one such bias seen in young infants. Is this bias strong enough to affect adult behavior? Adult participants reached and grasped a cylinder positioned to require either pronation or supination of the hand. Successive cylinder positions changed either randomly or systematically between trials. Random positioning led to optimized economy of movement. In contrast, systematic changes in position biased action selection toward previously selected actions at the expense of movement economy. Thus, one switches to a new movement only when the savings outweigh the costs of the switch. Immediate movement history had an even larger influence on children aged 7-15 years. This suggests that switching costs are greater in children, which is consistent with their reduced grasping experience. The presence of this effect in adults suggests that immediate movement history exerts a more widespread and pervasive influence on patterns of action selection than researchers had previously recognized.

[Poor tolerance of exertion during sports and bronchial hyperreactivity].

Science.gov (United States)

Potiron-Josse, M; Boutet, S; Ginet, J

1992-11-01

135 sportsmen and women, 55 girls, 80 boys, aged from 7 to 30 years, from various sports, who complained of bad tolerance of exertion were examined with an exercise test and isocapnic spontaneous hyperventilation. 61, about 45%, during a hyperventilation test had a fall of V.E.M.S. greater than or equal to 20%, showing bronchial hyperreactivity. After three tests, this fall index was greater than or equal to 50%. 68% of the positive responses were seen in boys and 2/3 of the subjects with a positive response were atopics. No other argument could be maintained from the questioning or clinical history to predict the positive or negative character of the hyperventilation (age, sporting level, symptoms, previous asthma or asthmatic, allergy). H.S.V.I. of the chests of a sporting population that complains of exertion intolerance, therefore allows verification of an H.R.B. assessment of its severity and to follow evolution after treatment.

Self-reported post-exertional fatigue in Gulf War veterans: roles of autonomic testing

Science.gov (United States)

Li, Mian; Xu, Changqing; Yao, Wenguo; Mahan, Clare M.; Kang, Han K.; Sandbrink, Friedhelm; Zhai, Ping; Karasik, Pamela A.

2014-01-01

To determine if objective evidence of autonomic dysfunction exists from a group of Gulf War veterans with self-reported post-exertional fatigue, we evaluated 16 Gulf War ill veterans and 12 Gulf War controls. Participants of the ill group had self- reported, unexplained chronic post-exertional fatigue and the illness symptoms had persisted for years until the current clinical study. The controls had no self-reported post-exertional fatigue either at the time of initial survey nor at the time of the current study. We intended to identify clinical autonomic disorders using autonomic and neurophysiologic testing in the clinical context. We compared the autonomic measures between the 2 groups on cardiovascular function at both baseline and head-up tilt, and sudomotor function. We identified 1 participant with orthostatic hypotension, 1 posture orthostatic tachycardia syndrome, 2 distal small fiber neuropathy, and 1 length dependent distal neuropathy affecting both large and small fiber in the ill group; whereas none of above definable diagnoses was noted in the controls. The ill group had a significantly higher baseline heart rate compared to controls. Compound autonomic scoring scale showed a significant higher score (95% CI of mean: 1.72–2.67) among ill group compared to controls (0.58–1.59). We conclude that objective autonomic testing is necessary for the evaluation of self-reported, unexplained post-exertional fatigue among some Gulf War veterans with multi-symptom illnesses. Our observation that ill veterans with self-reported post-exertional fatigue had objective autonomic measures that were worse than controls warrants validation in a larger clinical series. PMID:24431987

Frontoethmoidal Schwannoma with Exertional Cerebrospinal Fluid Rhinorrhea: Case Report and Review of Literature.

Science.gov (United States)

Yoneoka, Yuichiro; Akiyama, Katsuhiko; Seki, Yasuhiro; Hasegawa, Go; Kakita, Akiyoshi

2018-03-01

Frontoethmoidal schwannomas are rare. No case manifesting exertional cerebrospinal fluid (CSF) rhinorrhea has ever been reported to the best of our knowledge. In this report, we describe an extremely rare case of frontoethmoidal schwannoma extending through the olfactory groove with exertional CSF rhinorrhea as the initial symptom. A 50-year-old woman was presented to our clinic for frequent nasal discharge on exertion. A postcontrast computed tomographic scan demonstrated heterogeneously enhanced tumor from the anterior cranial fossa to the anterior ethmoid sinus. A gadolinium-enhanced T1-weighted magnetic resonance image revealed a well-defined heterogeneously enhanced tumor situated in the midline anterior cranial fossa and anterior ethmoid sinus. After the resection, the defect of the right anterior skull base was reconstructed with a fascia graft and adipose tissue taken from the abdomen, as well as a pedicle periosteum flap. A histologic examination revealed the tumor as schwannoma. Her rhinorrhea completely resolved. She regained her sense of smell and taste 1 month after the operation. According to previous reports, olfactory groove, and paraolfactory groove/periolfactory groove schwannomas can be divided into 4 types: subfrontal, nasoethmoidal, frontoethmoidal, and ethmofrontal. Among them, a frontoethmoidal schwannoma can manifest exertional CSF rhinorrhea as an initial symptom. Copyright © 2018 Elsevier Inc. All rights reserved.

NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

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Y. V. Gavrilov

2015-12-01

Full Text Available Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05. Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05 more effectively reduces the number of silent myocardial ischemia.Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

Performance monitoring in the medial frontal cortex and related neural networks: From monitoring self actions to understanding others' actions.

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Ninomiya, Taihei; Noritake, Atsushi; Ullsperger, Markus; Isoda, Masaki

2018-04-27

Action is a key channel for interacting with the outer world. As such, the ability to monitor actions and their consequences - regardless as to whether they are self-generated or other-generated - is of crucial importance for adaptive behavior. The medial frontal cortex (MFC) has long been studied as a critical node for performance monitoring in nonsocial contexts. Accumulating evidence suggests that the MFC is involved in a wide range of functions necessary for one's own performance monitoring, including error detection, and monitoring and resolving response conflicts. Recent studies, however, have also pointed to the importance of the MFC in performance monitoring under social conditions, ranging from monitoring and understanding others' actions to reading others' mental states, such as their beliefs and intentions (i.e., mentalizing). Here we review the functional roles of the MFC and related neural networks in performance monitoring in both nonsocial and social contexts, with an emphasis on the emerging field of a social systems neuroscience approach using macaque monkeys as a model system. Future work should determine the way in which the MFC exerts its monitoring function via interactions with other brain regions, such as the superior temporal sulcus in the mentalizing system and the ventral premotor cortex in the mirror system. Copyright © 2018. Published by Elsevier B.V.

The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells

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Hemmingsen, Mette; Vedel, Søren; Skafte-Pedersen, Peder; Sabourin, David; Collas, Philippe; Bruus, Henrik; Dufva, Martin

2013-01-01

Introduction High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. Methods and results Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. Conclusions Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process. PMID:23723991

The role of paracrine and autocrine signaling in the early phase of adipogenic differentiation of adipose-derived stem cells.

Directory of Open Access Journals (Sweden)

Mette Hemmingsen

Full Text Available INTRODUCTION: High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. METHODS AND RESULTS: Adipogenic differentiation of human adipose-derived stem cells (ASCs cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium. Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin. The positive effects of conditioned medium were observed early in the differentiation process. CONCLUSIONS: Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s were shown to act in the recruitment phase of the differentiation process.

In vitro antitumor actions of extracts from endemic plant Helichrysum zivojinii

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Matić Ivana Z

2013-02-01

Full Text Available Abstract Background The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Černjavski & Soška (family Asteraceae against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC. Methods The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. Results The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Conclusion Extracts obtained from the endemic plant Helichrysum

Two distinct and competitive pathways confer the cellcidal actions of artemisinins

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Chen Sun

2015-01-01

Full Text Available The biological actions of artemisinin (ART, an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. Besides potent antimalarial activity, some of artemisinin derivatives (together with artemisinin, hereafter referred to as ARTs, in particular dihydroartemisinin (DHA, are also associated with anticancer and other antiparasitic activities. In this study, we used baker’s yeast Saccharomyces cerevisiae as cellular and genetic model to investigate the molecular and cellular properties of ARTs. Two clearly separable pathways exist. While all ARTs exhibit potent anti-mitochondrial actions as shown before, DHA exerts an additional strong heme-dependent, likely mitochondria-independent inhibitory action. More importantly, heme antagonizes the mitochondria-dependent cellcidal action. Indeed, when heme synthesis was inhibited, the mitochondria-dependent cellcidal action of ARTs could be dramatically strengthened, and significant yeast growth inhibition at as low as 100 nM ART, an increase of about 25 folds in sensitivity, was observed. We conclude that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.

Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

NARCIS (Netherlands)

Scalco, R.S.; Snoeck, M.; Quinlivan, R.; Treves, S.; Laforet, P.; Jungbluth, H.; Voermans, N.C.

2016-01-01

Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild

ANTICONVULSANT AND ANTIEPILEPTIC ACTIONS OF 2-DEOXY-DGLUCOSE IN EPILEPSY MODELS

Science.gov (United States)

Stafstrom, Carl E.; Ockuly, Jeffrey C.; Murphree, Lauren; Valley, Matthew T.; Roopra, Avtar; Sutula, Thomas P.

2009-01-01

Objective Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Since carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. Methods Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K+]o, 4-aminopyridine (4-AP), or bicuculline and in vivo against seizures evoked by 6 Hz stimulation in mice, audiogenic stimulation in Fring’s mice, and maximal electroshock and subcutaneous Metrazol in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. Results 2DG (10mM) reduced interictal epileptiform bursts induced by high [K+]o, 4-AP and bicuculline, and electrographic seizures induced by high [K+]o in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation in mice (ED50 = 79.7 mg/kg) and audiogenic stimulation in Fring’s mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a 2-fold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. Interpretation The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis. PMID:19399874

Motor performance of tongue with a computer-integrated system under different levels of background physical exertion

Science.gov (United States)

Huo, Xueliang; Johnson-Long, Ashley N.; Ghovanloo, Maysam; Shinohara, Minoru

2015-01-01

The purpose of this study was to compare the motor performance of tongue, using Tongue Drive System, to hand operation for relatively complex tasks under different levels of background physical exertion. Thirteen young able-bodied adults performed tasks that tested the accuracy and variability in tracking a sinusoidal waveform, and the performance in playing two video games that require accurate and rapid movements with cognitive processing using tongue and hand under two levels of background physical exertion. Results show additional background physical activity did not influence rapid and accurate displacement motor performance, but compromised the slow waveform tracking and shooting performances in both hand and tongue. Slow waveform tracking performance by the tongue was compromised with an additional motor or cognitive task, but with an additional motor task only for the hand. Practitioner Summary We investigated the influence of task complexity and background physical exertion on the motor performance of tongue and hand. Results indicate the task performance degrades with an additional concurrent task or physical exertion due to the limited attentional resources available for handling both the motor task and background exertion. PMID:24003900

Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium.

Directory of Open Access Journals (Sweden)

Shanmugasundaram Nallasamy

Full Text Available The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors that control organogenesis and tissue interactions during embryonic development. We observed overlapping expression of these factors in uterine epithelial and stromal compartments of pregnant mice prior to embryo implantation. Conditional ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due to a failure in implantation. In these mutant mice (Msx1/2(d/d, the uterine epithelium exhibited persistent proliferative activity and failed to attach to the embryos. Gene expression profiling of uterine epithelium and stroma of Msx1/2(d/d mice revealed an elevated expression of several members of the Wnt gene family in the preimplantation uterus. Increased canonical Wnt signaling in the stromal cells activated β-catenin, stimulating the production of a subset of fibroblast growth factors (FGFs in these cells. The secreted FGFs acted in a paracrine manner via the FGF receptors in the epithelium to promote epithelial proliferation, thereby preventing differentiation of this tissue and creating a non-receptive uterus refractory to implantation. Collectively, these findings delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which operate in the uterus at the time of implantation to control the mesenchymal-epithelial dialogue critical for successful establishment of pregnancy.

Mechanochemistry Induced Using Force Exerted by a Functionalized Microscope Tip

DEFF Research Database (Denmark)

Zhang, Yajie; Wang, Yongfeng; Lü, Jing-Tao

2017-01-01

Atomic-scale mechanochemistry is realized from force exerted by a C60 -functionalized scanning tunneling microscope tip. Two conformers of tin phthalocyanine can be prepared on coinage-metal surfaces. A transition between these conformers is induced on Cu(111) and Ag(100). Density...

Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell responses via inducing cortistatin in the gut.

Science.gov (United States)

Yue, Mengfan; Xia, Yufeng; Shi, Can; Guan, Chunge; Li, Yunfan; Liu, Rui; Wei, Zhifeng; Dai, Yue

2017-09-01

Berberine, an isoquinoline alkaloid, has been reported to ameliorate various autoimmune diseases including rheumatoid arthritis by oral administration. However, its mechanism remains mysterious due to an extremely low bioavailability. The fact that berberine readily accumulates in the gut, the largest endocrine organ in the body, attracted us to explore its anti-arthritic mechanism in view of the induction of intestinal immunosuppressive neuropeptides. In this study, berberine (200 mg·kg -1 , i.g.) was shown to ameliorate collagen-induced arthritis in rats, which was manifested by the reduction of clinical signs and joint destruction, as well as marked down-regulation of Th17 cell frequency and interleukin-17 level in blood. In contrast, an intravenous injection of berberine failed to affect arthritis in rats, implying that its anti-arthritic effect was gut-dependent. Further studies revealed that oral berberine selectively elevated the levels of cortistatin, of five gut-derived neuropeptides tested, in the intestines and sera of arthrititic rats. Antagonists of ghrelin/growth hormone secretagogue receptor 1 (a subtype of cortistatin receptor) almost completely abolished the ameliorative effect of berberine on arthritis and Th17 cell responses in rats. In vitro, berberine showed a moderate ability to promote the expression of cortistatin in nerve cells, which was strengthened when the nerve cells were cocultured with enteroendocrine cells to induce an autocrine/paracrine environment. In summary, oral berberine exerted anti-arthritic effect through inhibiting the Th17 cell response, which was closely associated with the induction of cortistatin generation from gut through augmenting autocrine/paracrine action between enteric nerve cells and endocrine cells. © 2017 Federation of European Biochemical Societies.

Action of fluorine, lead, and zinc on soils, vegetation and animals in metal works

Energy Technology Data Exchange (ETDEWEB)

Paluch, J.; Karweta, S.; Szalonek, I.

Almost all the activities of industry exert an influence on the biosphere. In examining the complicated problems of the interaction of industry and the biosphere it is necessary to distinguish between three fundamental groups of factors which, without doubt, are destructive. They are: (1) sources which pollute surface and subterranean water thus polluting soils; (2) sources which pollute the atmosphere with solids, gases and, rarely, liquids; and (3) the installations and actions which cause changes in the shape of the land, often connected with the direct devastation of the soil, and influence the hydrology of the area. The authors study the actions of fluorine, lead and zinc in relation to these factors. 4 tables.

[Exercise laryngoscopy: a new method for the differential diagnosis of dyspnea on exertion].

Science.gov (United States)

Tervonen, Hanna; Iljukov, Sergei; Niskanen, Minna-Liisa; Vilkman, Erkki; Sovijärvi, Anssi; Aaltonen, Leena-Maija

2011-01-01

Exertional dyspnea originating from the laryngeal level can be established with certainty only if the paradoxical vocal cord adduction is observed during dyspnea. We have developed a novel diagnostic method, exercise laryngoscopy, which involves observation of the larynx with a flexible endoscope applied via the nose during a bicycle ergometry test. It has been our aim to improve the differential diagnosis of dyspnea on exertion and thus also reduce unnecessary antiasthmatic medication. Exercise laryngoscopy allows examination in the out-patient clinics because the method is well tolerated.

Measurements of the Exerted Pressure by Pelvic Circumferential Compression Devices

Science.gov (United States)

Knops, Simon P; van Riel, Marcel P.J.M; Goossens, Richard H.M; van Lieshout, Esther M.M; Patka, Peter; Schipper, Inger B

2010-01-01

Background: Data on the efficacy and safety of non-invasive Pelvic Circumferential Compression Devices (PCCDs) is limited. Tissue damage may occur if a continuous pressure on the skin exceeding 9.3 kPa is sustained for more than two or three hours. The aim of this study was to gain insight into the pressure build-up at the interface, by measuring the PCCD-induced pressure when applying pulling forces to three different PCCDs (Pelvic Binder® , SAM-Sling ® and T-POD® ) in a simplified model. Methods: The resulting exerted pressures were measured at four ‘anatomical’ locations (right, left, posterior and anterior) in a model using a pressure measurement system consisting of pressure cuffs. Results: The exerted pressure varied substantially between the locations as well as between the PCCDs. Maximum pressures ranged from 18.9-23.3 kPa and from 19.2-27.5 kPa at the right location and left location, respectively. Pressures at the posterior location stayed below 18 kPa. At the anterior location pressures varied markedly between the different PCCDs. Conclusion: The circumferential compression by the different PCCDs showed high pressures measured at the four locations using a simplified model. Difference in design and functional characteristics of the PCCDs resulted in different pressure build-up at the four locations. When following the manufacturer’s instructions, the exerted pressure of all three PCCDs tested exceeded the tissue damaging level (9.3 kPa). In case of prolonged use in a clinical situation this might put patients at risk for developing tissue damage. PMID:20361001

Traction forces exerted by epithelial cell sheets

International Nuclear Information System (INIS)

Saez, A; Anon, E; Ghibaudo, M; Di Meglio, J-M; Hersen, P; Ladoux, B; Du Roure, O; Silberzan, P; Buguin, A

2010-01-01

Whereas the adhesion and migration of individual cells have been well described in terms of physical forces, the mechanics of multicellular assemblies is still poorly understood. Here, we study the behavior of epithelial cells cultured on microfabricated substrates designed to measure cell-to-substrate interactions. These substrates are covered by a dense array of flexible micropillars whose deflection enables us to measure traction forces. They are obtained by lithography and soft replica molding. The pillar deflection is measured by video microscopy and images are analyzed with home-made multiple particle tracking software. First, we have characterized the temporal and spatial distributions of traction forces of cellular assemblies of various sizes. The mechanical force balance within epithelial cell sheets shows that the forces exerted by neighboring cells strongly depend on their relative position in the monolayer: the largest deformations are always localized at the edge of the islands of cells in the active areas of cell protrusions. The average traction stress rapidly decreases from its maximum value at the edge but remains much larger than the inherent noise due to the force resolution of our pillar tracking software, indicating an important mechanical activity inside epithelial cell islands. Moreover, these traction forces vary linearly with the rigidity of the substrate over about two decades, suggesting that cells exert a given amount of deformation rather than a force. Finally, we engineer micropatterned substrates supporting pillars with anisotropic stiffness. On such substrates cellular growth is aligned with respect to the stiffest direction in correlation with the magnitude of the applied traction forces.

Exertion of forces by children performing a free-style jump

NARCIS (Netherlands)

Moes, C.C.M.; Visser, R.J.

1998-01-01

This research project focuses on the force characteristics and force/time relationships of loads exerted by jumping children. The current study is an experimental research into children jumping on both hard and soft substrates. The hard substrate is obtained by using a force plate. For the soft

Systemic exertion intolerance disease/chronic fatigue syndrome is common in sleep centre patients with hypersomnolence: A retrospective pilot study.

Science.gov (United States)

Maness, Caroline; Saini, Prabhjyot; Bliwise, Donald L; Olvera, Victoria; Rye, David B; Trotti, Lynn M

2018-04-06

Symptoms of the central disorders of hypersomnolence extend beyond excessive daytime sleepiness to include non-restorative sleep, fatigue and cognitive dysfunction. They share much in common with myalgic encephalomyelitis/chronic fatigue syndrome, recently renamed systemic exertion intolerance disease, whose additional features include post-exertional malaise and orthostatic intolerance. We sought to determine the frequency and correlates of systemic exertion intolerance disease in a hypersomnolent population. One-hundred and eighty-seven hypersomnolent patients completed questionnaires regarding sleepiness and fatigue; questionnaires and clinical records were used to assess for systemic exertion intolerance disease. Sleep studies, hypocretin and cataplexy were additionally used to assign diagnoses of hypersomnolence disorders or sleep apnea. Included diagnoses were idiopathic hypersomnia (n = 63), narcolepsy type 2 (n = 25), persistent sleepiness after obstructive sleep apnea treatment (n = 25), short habitual sleep duration (n = 41), and sleepiness with normal sleep study (n = 33). Twenty-one percent met systemic exertion intolerance disease criteria, and the frequency of systemic exertion intolerance disease was not different across sleep diagnoses (p = .37). Patients with systemic exertion intolerance disease were no different from those without this diagnosis by gender, age, Epworth Sleepiness Scale, depressive symptoms, or sleep study parameters. The whole cohort reported substantial fatigue on questionnaires, but the systemic exertion intolerance disease group exhibited more profound fatigue and was less likely to respond to traditional wake-promoting agents (88.6% versus 67.7%, p = .01). Systemic exertion intolerance disease appears to be a common co-morbidity in patients with hypersomnolence, which is not specific to hypersomnolence subtype but may portend a poorer prognosis for treatment response. © 2018 European Sleep Research Society.

Being Active and Impulsive: The Role of Goals for Action and Inaction in Self-Control.

Science.gov (United States)

Hepler, Justin; Albarracin, Dolores; McCulloch, Kathleen C; Noguchi, Kenji

2012-12-01

Although self-control often requires behavioral inaction (i.e., not eating a piece of cake), the process of inhibiting impulsive behavior is commonly characterized as cognitively active (i.e., actively exerting self-control). Two experiments examined whether motivation for action or inaction facilitates self-control behavior in the presence of tempting stimuli. Experiment 1 used a delay discounting task to assess the ability to delay gratification with respect to money. Experiment 2 used a Go/No-Go task to assess the ability to inhibit a dominant but incorrect motor response to the words "condom" and "sex". The results demonstrate that goals for inaction promote self-control, whereas goals for action promote impulsive behavior. These findings are discussed in light of recent evidence suggesting that goals for action and inaction modulate physiological resources that promote behavioral execution.

Circulating Angiogenic Growth Factors in Diabetes Patients with Peripheral Arterial Disease and Exertional Leg Pain in Ghana

Directory of Open Access Journals (Sweden)

Kwame Yeboah

2017-01-01

Full Text Available Objective. Peripheral arterial disease (PAD is a common complication of diabetes, associated with impairment in angiogenesis. Angiogenesis is regulated by angiogenic growth factors such as angiopoietin 1 (Ang-1, Ang-2, and vascular endothelial growth factor (VEGF. We studied the association between angiogenic growth factors versus PAD and exertional leg symptoms in diabetes patients in Ghana. Method. In this cross-sectional study, ankle-brachial index was measured with oscillometrically and exertional leg symptoms were screened with Edinburgh claudication questionnaire in 140 diabetes patients and 110 nondiabetes individuals. Circulating levels of Ang-1, Ang-2, and VEGF were measured with immunosorbent assay. Results. The prevalence of PAD and exertional leg pain was 16.8% and 24.8%, respectively. Compared to non-PAD participants, PAD patients had higher VEGF levels [85.8 (37.5–154.5 versus 57.7 (16.6–161.1 p=0.032] and lower Ang-1 levels [31.3 (24.8–42.6 versus 40.9 (28.2–62.1, p=0.017]. In multivariable logistic regression, patients with exertional leg pain had increased the odds of plasma Ang-2 levels [OR (95% CI: 2.08 (1.08–6.41, p=0.036]. Conclusion. Diabetes patients with PAD and exertional leg pain have imbalance in angiogenic growth factors, indicating impaired angiogenesis. In patients with exertional leg pains, Ang-2 may be an important biomarker.

EXERT Yourself and Help in the Search for an Alzheimer's Cure

Science.gov (United States)

... Yourself and Help in the Search for an Alzheimer’s Cure Can exercise slow or prevent cognitive decline in older people who are at increased risk for Alzheimer’s disease? The EXERT Study: Building Memories Through Exercise ...

The Influence of a Bout of Exertion on Novice Barefoot Running Dynamics

Directory of Open Access Journals (Sweden)

Rami Hashish, Sachithra D. Samarawickrame, Lucinda Baker, George J. Salem

2016-06-01

Full Text Available Barefoot, forefoot strike (FFS running has recently risen in popularity. Relative to shod, rear-foot strike (RFS running, employing a FFS is associated with heightened triceps surae muscle activation and ankle mechanical demand. Novice to this pattern, it is plausible that habitually shod RFS runners exhibit fatigue to the triceps surae when acutely transitioning to barefoot running, thereby limiting their ability to attenuate impact. Therefore, the purpose was to determine how habitually shod RFS runners respond to an exertion bout of barefoot running, operationally defined as a barefoot run 20% of mean daily running distance. Twenty-one RFS runners performed novice barefoot running, before and after exertion. Ankle peak torque, triceps surae EMG median frequency, foot-strike patterns, joint energy absorption, and loading rates were evaluated. Of the 21 runners, 6 maintained a RFS, 10 adopted a mid-foot strike (MFS, and 5 adopted a FFS during novice barefoot running. In-response to exertion, MFS and FFS runners demonstrated reductions in peak torque, median frequency, and ankle energy absorption, and an increase in loading rate. RFS runners demonstrated reductions in peak torque and loading rate. These results indicate that a short bout of running may elicit fatigue to novice barefoot runners, limiting their ability to attenuate impact.

Paracrine Pathways in Uterine Leiomyoma Stem Cells Involve Insulinlike Growth Factor 2 and Insulin Receptor A.

Science.gov (United States)

Moravek, Molly B; Yin, Ping; Coon, John S; Ono, Masanori; Druschitz, Stacy A; Malpani, Saurabh S; Dyson, Matthew T; Rademaker, Alfred W; Robins, Jared C; Wei, Jian-Jun; Kim, J Julie; Bulun, Serdar E

2017-05-01

Uterine leiomyomas (fibroids) are the most common benign tumors in women. Recently, three populations of leiomyoma cells were discovered on the basis of CD34 and CD49b expression, but molecular differences between these populations remain unknown. To define differential gene expression and signaling pathways in leiomyoma cell populations. Cells from human leiomyoma tissue were sorted by flow cytometry into three populations: CD34+/CD49b+, CD34+/CD49b-, and CD34-/CD49b-. Microarray gene expression profiling and pathway analysis were performed. To investigate the insulinlike growth factor (IGF) pathway, real-time quantitative polymerase chain reaction, immunoblotting, and 5-ethynyl-2'-deoxyuridine incorporation studies were performed in cells isolated from fresh leiomyoma. Research laboratory. Eight African American women. None. Gene expression patterns, cell proliferation, and differentiation. A total of 1164 genes were differentially expressed in the three leiomyoma cell populations, suggesting a hierarchical differentiation order whereby CD34+/CD49b+ stem cells differentiate to CD34+/CD49b- intermediary cells, which then terminally differentiate to CD34-/CD49b- cells. Pathway analysis revealed differential expression of several IGF signaling pathway genes. IGF2 was overexpressed in CD34+/CD49b- vs CD34-/CD49b- cells (83-fold; P leiomyoma stem cell proliferation and may represent paracrine signaling between leiomyoma cell types. Therapies targeting the IGF pathway should be investigated for both treatment and prevention of leiomyomas. Copyright © 2017 by the Endocrine Society

Exertional Heat Illness among Secondary School Athletes: Statewide Policy Implications

Science.gov (United States)

Rodgers, Jill; Slota, Peggy; Zamboni, Beth

2018-01-01

Exertional heat illness (EHI) is a leading cause of preventable death among student athletes. While causes and preventative measures for EHI are known, school districts may not be implementing evidence-based practices. This descriptive, exploratory study explored school policies, resources, and practices of coaches in a mid-Atlantic state in the…

Mind the gap : probing exertion experience with experiential design landscapes

NARCIS (Netherlands)

Ren, X.; Lu, Y.; Brombacher, A.C.; Bogers, S.J.A.

2016-01-01

In this paper, we report our study on applying Experiential Design Landscapes as the basis of design process to support the design of exertion games. We approach this question by setting up an 8-day interaction design module with 7 groups of students. The methods of our module were developed based

Exertional Heat Stroke and American Football: What the Team Physician Needs to Know.

Science.gov (United States)

Sylvester, Jillian E; Belval, Luke N; Casa, Douglas J; O'Connor, Francis G

Football is recognized as a leading contributor to sports injury secondary to the contact collision nature of the endeavor. While direct deaths from head and spine injury remain a significant contributor to the number of catastrophic injuries, indirect deaths (systemic failure) predominate. Exertional heat stroke has emerged as one of the leading indirect causes of death in high school and collegiate football. This review details for the team physician the unique challenge of exercising in the heat to the football player, and the prevention, diagnosis, management, and return-to-play issues pertinent to exertional heat illnesses.

[Relationship between efficacy exertion of diuretic traditional Chinese medicines and aquaporin].

Science.gov (United States)

Wang, Peng-cheng; Zhao, Shan; Wang, Qiu-hong; Kuang, Hai-xue

2015-06-01

In recent years, the discovery and studies on aquaporin have made us have a more in-depth understanding about the physiological and pathological processes of water metabolism. Over years, however, there has been no quantitative study on the target sites of diuretic traditional Chinese medicines at the molecular level. In that case, aquaporin was found to been a new target molecule to explain the efficacy exertion of diuretic traditional Chinese medicines. By studying aquaporin, researchers can understand the implicit meaning of the diuretic effect of traditional Chinese medicines and conduct quantitative studies on the diuretic effect. So far, many scholars have conducted a series of studies in the traditional Chinese medicine field by using the findings on aquaporin and made certain advances. This article provides a summary about the efficacy exertion of diuretic traditional Chinese medicines through target molecule aquaporin.

Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

Energy Technology Data Exchange (ETDEWEB)

De Siena, Rocco; Balducci, Luigi; Blasi, Antonella; Montanaro, Manuela Gessica; Saldarelli, Marilisa [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Saponaro, Vittorio [Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Bari (Italy); Martino, Carmela [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Logrieco, Gaetano [Department of Surgery, Hospital ' F. Miulli' 70021 AcquaViva delle Fonti, Bari (Italy); Soleti, Antonio; Fiobellot, Simona [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Madeddu, Paolo [Experimental Cardiovascular Medicine, Bristol Heart Institute, Bristol BS2 8WH (United Kingdom); Rossi, Giacomo [Department of Pathology, University of Camerino, 63100 Ascoli Piceno (Italy); Ribatti, Domenico [Department of Human Anatomy, University of Bari, 70125 Bari (Italy); Crovace, Antonio [Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Bari (Italy); Cristini, Silvia; Invernici, Gloria; Parati, Eugenio Agostino [Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute ' Carlo Besta' , 20133 Milan (Italy); Alessandri, Giulio, E-mail: cisiamo2@yahoo.com [Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute ' Carlo Besta' , 20133 Milan (Italy)

2010-07-01

Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50 x 10{sup 6} of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.

Stiffness and thickness of fascia do not explain chronic exertional compartment syndrome

DEFF Research Database (Denmark)

Dahl, Morten; Hansen, Philip; Stål, Per

2011-01-01

Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown....

Team Size and Stretching-Exercise Effects on Simulated Chest Compression Performance and Exertion

Directory of Open Access Journals (Sweden)

Jessica C. Schoen

2017-09-01

Full Text Available Introduction: Investigators conducted a prospective experimental study to evaluate the effect of team size and recovery exercises on individual providers’ compression quality and exertion. Investigators hypothesized that 1 larger teams would perform higher quality compressions with less exertion per provider when compared to smaller teams; and 2 brief stretching and breathing exercises during rest periods would sustain compressor performance and mitigate fatigue. Methods: In Phase I, a volunteer cohort of pre-clinical medical students performed four minutes of continuous compressions on a Resusci-Anne manikin to gauge the spectrum of compressor performance in the subject population. Compression rate, depth, and chest recoil were measured. In Phase II, the highest-performing Phase I subjects were placed into 2-, 3-, and/or 4-compressor teams; 2-compressor teams were assigned either to control group (no recovery exercises or intervention group (recovery exercises during rest. All Phase II teams participated in 20-minute simulations with compressor rotation every two minutes. Investigators recorded compression quality and real-time heart rate data, and calculated caloric expenditure from contact heart rate monitor measurements using validated physiologic formulas. Results: Phase I subjects delivered compressions that were 24.9% (IQR1–3: [0.5%–74.1%] correct with a median rate of 112.0 (IQR1–3: [103.5–124.9] compressions per minute and depth of 47.2 (IQR1–3: [35.7–55.2] mm. In their first rotations, all Phase II subjects delivered compressions of similar quality and correctness (p=0.09. Bivariate analyses of 2-, 3-, and 4-compressor teams’ subject compression characteristics by subsequent rotation did not identify significant differences within or across teams. On multivariate analyses, only subjects in 2-compressor teams exhibited significantly lower compression rates (control subjects; p<0.01, diminished chest release (intervention

Catestatin exerts direct protective effects on rat cardiomyocytes undergoing ischemia/reperfusion by stimulating PI3K-Akt-GSK3β pathway and preserving mitochondrial membrane potential.

Directory of Open Access Journals (Sweden)

Eleonora Bassino

Full Text Available Catestatin (Cst is a 21-amino acid peptide deriving from Chromogranin A. Cst exerts an overall protective effect against an excessive sympathetic stimulation of cardiovascular system, being able to antagonize catecholamine secretion and to reduce their positive inotropic effect, by stimulating the release of nitric oxide (NO from endothelial cells. Moreover, Cst reduces ischemia/reperfusion (I/R injury, improving post-ischemic cardiac function and cardiomyocyte survival. To define the cardioprotective signaling pathways activated by Cst (5 nM we used isolated adult rat cardiomyocytes undergoing simulated I/R. We evaluated cell viability rate with propidium iodide labeling and mitochondrial membrane potential (MMP with the fluorescent probe JC-1. The involvement of Akt, GSK3β, eNOS and phospholamban (PLN cascade was studied by immunofluorescence. The role of PI3K-Akt/NO/cGMP pathway was also investigated by using the pharmacological blockers wortmannin (Wm, L-NMMA and ODQ. Our experiments revealed that Cst increased cell viability rate by 65% and reduced cell contracture in I/R cardiomyocytes. Wm, L-NMMA and ODQ limited the protective effect of Cst. The protective outcome of Cst was related to its ability to maintain MMP and to increase AktSer473, GSK3βSer9, PLNThr17 and eNOSSer1179 phosphorylation, while treatment with Wm abolished these effects. Thus, the present results show that Cst is able to exert a direct action on cardiomyocytes and give new insights into the molecular mechanisms involved in its protective effect, highlighting the PI3K/NO/cGMP pathway as the trigger and the MMP preservation as the end point of its action.

Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon.

Science.gov (United States)

Del Coso, Juan; Valero, Marjorie; Salinero, Juan José; Lara, Beatriz; Gallo-Salazar, César; Areces, Francisco

2017-01-01

Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A). Using Williams and Folland's model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.

The pressure exerted by a confined ideal gas

International Nuclear Information System (INIS)

Pang Hai; Dai Wusheng; Xie Mi

2011-01-01

In this paper, we study the pressure exerted by a confined ideal gas on the container boundary and we introduce a surface force in gases. First, the general expression for the local surface pressure tensor is obtained. We find, by examples, that the pressure vanishes at the edges of a box, peaks at the middle of the surface and its magnitude for different statistics satisfies p Fermi > p classical > p Bose on every boundary point. Then, the relation between the surface pressure tensor and generalized forces is studied. Based on the relation, we find that a confined ideal gas can exert forces whose effect is to reduce the total surface area of the boundary of an incompressible object. The force provides mechanisms for several mechanical effects. (1) The force contributes to the adhesion of two thin films in contact with each other. We derive an expression for the adhesion force between two square sheets, estimate its magnitude, and also give a method for distinguishing it from other adhesion forces. (2) The force can lead to the recoiling of a DNA-like column. We study the recoiling process using a simple model and find a deviation from the result given in the thermodynamic limit, which is in accordance with experiments. (3) An open container immersed in a gas can be compressed by this force like the Casimir effect. We discuss the effect for various geometries. (paper)

IGF-1 and insulin exert opposite actions on ClC-K2 activity in the cortical collecting ducts.

Science.gov (United States)

Zaika, Oleg; Mamenko, Mykola; Boukelmoune, Nabila; Pochynyuk, Oleh

2015-01-01

Despite similar stimulatory actions on the epithelial sodium channel (ENaC)-mediated sodium reabsorption in the distal tubule, insulin promotes kaliuresis, whereas insulin-like growth factor-1 (IGF-1) causes a reduction in urinary potassium levels. The factors contributing to this phenomenon remain elusive. Electrogenic distal nephron ENaC-mediated Na(+) transport establishes driving force for Cl(-) reabsorption and K(+) secretion. Using patch-clamp electrophysiology, we document that a Cl(-) channel is highly abundant on the basolateral plasma membrane of intercalated cells in freshly isolated mouse cortical collecting duct (CCD) cells. The channel has characteristics attributable to the ClC-K2: slow gating kinetics, conductance ∼10 pS, voltage independence, Cl(-)>NO3 (-) anion selectivity, and inhibition/activation by low/high pH, respectively. IGF-1 (100 and 500 nM) acutely stimulates ClC-K2 activity in a reversible manner. Inhibition of PI3-kinase (PI3-K) with LY294002 (20 μM) abrogates activation of ClC-K2 by IGF-1. Interestingly, insulin (100 nM) reversibly decreases ClC-K2 activity in CCD cells. This inhibitory action is independent of PI3-K and is mediated by stimulation of a mitogen-activated protein kinase-dependent cascade. We propose that IGF-1, by stimulating ClC-K2 channels, promotes net Na(+) and Cl(-) reabsorption, thus reducing driving force for potassium secretion by the CCD. In contrast, inhibition of ClC-K2 by insulin favors coupling of Na(+) reabsorption with K(+) secretion at the apical membrane contributing to kaliuresis. Copyright © 2015 the American Physiological Society.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis.

Science.gov (United States)

Valberg, S J; McKenzie, E C; Eyrich, L V; Shivers, J; Barnes, N E; Finno, C J

2016-09-01

Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). Prospective and retrospective histopathological description. Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann-Whitney U and Fisher's exact tests. Centrally located myonuclei in mature myofibres were found in significantly more (Prhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder. © 2015 EVJ Ltd.

STAT3 can be activated through paracrine signaling in breast epithelial cells

International Nuclear Information System (INIS)

Lieblein, Jacqueline C; Ball, Sarah; Hutzen, Brian; Sasser, A Kate; Lin, Huey-Jen; Huang, Tim HM; Hall, Brett M; Lin, Jiayuh

2008-01-01

Many cancers, including breast cancer, have been identified with increased levels of phosphorylated or the active form of Signal Transducers and Activators of Transcription 3 (STAT3) protein. However, whether the tumor microenvironment plays a role in this activation is still poorly understood. Conditioned media, which contains soluble factors from MDA-MB-231 and MDA-MB-468 breast cancer cells and breast cancer associated fibroblasts, was added to MCF-10A breast epithelial and MDA-MB-453 breast cancer cells. The stimulation of phosphorylated STAT3 (p-STAT3) levels by conditioned media was assayed by Western blot in the presence or absence of neutralized IL-6 antibody, or a JAK/STAT3 inhibitor, JSI-124. The stimulation of cell proliferation in MCF-10A cells by conditioned media in the presence or absence of JSI-124 was subjected to MTT analysis. IL-6, IL-10, and VEGF levels were determined by ELISA analysis. Our results demonstrated that conditioned media from cell lines with constitutively active STAT3 are sufficient to induce p-STAT3 levels in various recipients that do not possess elevated p-STAT3 levels. This signaling occurs through the JAK/STAT3 pathway, leading to STAT3 phosphorylation as early as 30 minutes and is persistent for at least 24 hours. ELISA analysis confirmed a correlation between elevated levels of IL-6 production and p-STAT3. Neutralization of the IL-6 ligand or gp130 was sufficient to block increased levels of p-STAT3 (Y705) in treated cells. Furthermore, soluble factors within the MDA-MB-231 conditioned media were also sufficient to stimulate an increase in IL-6 production from MCF-10A cells. These results demonstrate STAT3 phosphorylation in breast epithelial cells can be stimulated by paracrine signaling through soluble factors from both breast cancer cells and breast cancer associated fibroblasts with elevated STAT3 phosphorylation. The induction of STAT3 phosphorylation is through the IL-6/JAK pathway and appears to be associated with

Compensatory Paracrine Mechanisms That Define The Urothelial Response to Injury in Partial Bladder Outlet Obstruction

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Bassuk, James; Lendvay, Thomas S.; Sweet, Robert; Han, Chang-Hee; Soygur, Tarkan; Cheng, Jan-Fang; Plaire, J. Chadwick; Charleston, Jay S.; Charleston, Lynne B.; Bagai, Shelly; Cochrane, Kimberly; Rubio, Eric; Bassuk, James A.; Fuchs, Elaine

2007-06-21

Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.

Paul Valéry’s Theory of Poetic Action

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Anna Maria Brigante

2013-07-01

Full Text Available This article purports to show that Paul Valéry’s poetic art is, in the end, a theory of poeticaction in which the main concern revolves around the work in progress rather than in the final product. Todo so, we follow the poet’s critique (with deep wittgensteinian elements of classic aesthetics’ stance on beauty and taste. In our view, this reflection results in Valéry’s proposal of a poetics which can be explained in three moments: poiein of reception – the recipient as producer; poiein in its proper sense – the produceras creator of the work and him/herself; and artificialist poiein – the creator as opposed to natural creation.Valéry’s emphasis on poiesis and, therefore, on the action exerted upon what is being done, makes his proposal also an ethical assertion: the artist’s action, his/her discipline whilst producing, create both thework and the artist. Thus, the spirit will also be a never-ending work in progress.

Epidemiology of exertional rhabdomyolysis susceptibility in standardbred horses reveals associated risk factors and underlying enhanced performance.

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Cajsa M Isgren

Full Text Available BACKGROUND: Exertional rhabdomyolysis syndrome is recognised in many athletic horse breeds and in recent years specific forms of the syndrome have been identified. However, although Standardbred horses are used worldwide for racing, there is a paucity of information about the epidemiological and performance-related aspects of the syndrome in this breed. The objectives of this study therefore were to determine the incidence, risk factors and performance effects of exertional rhabdomyolysis syndrome in Standardbred trotters and to compare the epidemiology and genetics of the syndrome with that in other breeds. METHODOLOGY/PRINCIPAL FINDINGS: A questionnaire-based case-control study (with analysis of online race records was conducted following identification of horses that were determined susceptible to exertional rhabdomyolysis (based on serum biochemistry from a total of 683 horses in 22 yards. Thirty six exertional rhabdomyolysis-susceptible horses were subsequently genotyped for the skeletal muscle glycogen synthase (GYS1 mutation responsible for type 1 polysaccharide storage myopathy. A total of 44 susceptible horses was reported, resulting in an annual incidence of 6.4 (95% CI 4.6-8.2% per 100 horses. Female horses were at significantly greater risk than males (odds ratio 7.1; 95% CI 2.1-23.4; p = 0.001 and nervous horses were at a greater risk than horses with calm or average temperaments (odds ratio 7.9; 95% CI 2.3-27.0; p = 0.001. Rhabdomyolysis-susceptible cases performed better from standstill starts (p = 0.04 than controls and had a higher percentage of wins (p = 0.006. All exertional rhabdomyolysis-susceptible horses tested were negative for the R309H GYS1 mutation. CONCLUSIONS/SIGNIFICANCE: Exertional rhabdomyolysis syndrome in Standardbred horses has a similar incidence and risk factors to the syndrome in Thoroughbred horses. If the disorder has a genetic basis in Standardbreds, improved performance in susceptible animals may be

Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

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Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M.; Hao, Hongying

2016-01-01

The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. PMID:27063098

Muscles and their myokines

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Pedersen, Bente Klarlund

2011-01-01

In the past, the role of physical activity as a life-style modulating factor has been considered as that of a tool to balance energy intake. Although it is important to avoid obesity, physical inactivity should be discussed in a much broader context. There is accumulating epidemiological evidence...... or endocrine effects should be classified as 'myokines'. Given that skeletal muscle is the largest organ in the human body, our discovery that contracting skeletal muscle secretes proteins sets a novel paradigm: skeletal muscle is an endocrine organ producing and releasing myokines, which work in a hormone......-like fashion, exerting specific endocrine effects on other organs. Other myokines work via paracrine mechanisms, exerting local effects on signalling pathways involved in muscle metabolism. It has been suggested that myokines may contribute to exercise-induced protection against several chronic diseases....

Muscles, exercise and obesity

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Pedersen, Bente K; Febbraio, Mark A

2012-01-01

During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines....... The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within...... the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal...

Jurisprudential aspects regarding the action in annulment of the debtor’s patrimonial transfers, the debtor being in insolvency procedure

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Angela MIFF

2015-06-01

Full Text Available The study aims to present relevant aspects from the jurisprudential solutions of the High Court of Cassation and Justice in matters of the action in annulment of the patrimonial transfers of the debtor in insolvency procedure and of other judicial actions introduced by the procedure bodies or, by case, the participants to the procedure who are enabled to use the measures prescribed by the law for the purpose of restoring the debtor’s patrimony. The jurisprudential solutions adopted under the incidence of the former Law no.85/2006 on the insolvency procedure represent, in present, under diverse aspects, elements of continuity with the principles and rules established by the new law in this matter. Law no.85/2014 on the prevention insolvency procedures and of insolvency establishes the legal frame for the exertion of the measures having as purpose the restoration, in the debtor’s patrimony, of certain assets, transferred by the debtor to the fraud of the creditors’ interests, or of their value, in the scope of covering the passive part to satisfy the creditors’ interests. The new law continues the tradition of the former regulations in this matter but, also, brings some novelty elements such as the decrease or, in some cases, the increase of the duration of certain terms that the exertion of the mentioned judicial actions or their object refer to or the completion of the category of the persons entitled to introduce the mentioned judicial actions with the creditor who holds more than 50% of the value of the claims enlisted in the amount of claims.

Defining the Focus of Attention: Effects of Attention on Perceived Exertion and Fatigue.

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Keith eLohse

2011-11-01

Full Text Available This manuscript presents two experiments designed to explore the effects of attention on perceived exertion and time to failure in a fatiguing athletic task. There were two major motivating factors for these experiments. First, there are few studies evaluating attentional focus effects in endurance tasks and, second, there is a lack of integration between studies of attentional focus as external/internal (e.g., Wulf, 2007 compared to associative/dissociative (e.g., Stevenson & Biddle, 1998. In Experiment 1, we used a fatiguing wall-sit posture (essentially a complex, isometric task to compare two different types of external attention with an internal focus on the position of the legs. An external focus (regardless of type increased the time taken to failure and reduced perceived exertion. In Experiment 2, we manipulated subjects’ expectancy of fatigue to test the interaction of attention and expectancy (both top-down factors in this highly fatiguing task. Previous theories of attention during endurance tasks have suggested that as fatigue/pain increase, bottom-up factors begin to dominate subjects’ attention. While this may be true, Experiment 2 showed that even in a highly fatiguing task, attentional strategies and expectancies affected the time to failure and perceived exertion.

Massage therapy: understanding the mechanisms of action on blood pressure. A scoping review.

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Nelson, Nicole L

2015-10-01

Massage therapy (MT) has shown potential in reducing blood pressure (BP); however, the psychophysiological pathways and structures involved in this outcome are unclear. The aims of this scoping review were twofold. (1) To summarize the current knowledge of the mechanisms of action of MT on BP. (2) To highlight the research gaps and challenges that researchers must overcome to further elucidate how MT attenuates BP. A scoping review was conducted to examine the evidence regarding the mechanisms of action of MT on BP. This review included the thematic analysis of 27 publications that considered the influence of MT on BP. Based on this analysis, six potential BP mediating pathways were identified Current theories suggest that MT exerts sympatholytic effects through physiologic and psychological mechanisms, improves hypothalamus-pituitary-adrenocortical axis function, and increases in blood flow, which, in turn, may improve endothelial function. Future study is needed, using more scientifically rigorous methodology, to fully elucidate the mechanism of action of MT. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Effect of Complex Working Conditions on Nurses Who Exert Coercive Measures in Forensic Psychiatric Care.

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Gustafsson, Niclas; Salzmann-Erikson, Martin

2016-09-01

Nurses who exert coercive measures on patients within psychiatric care are emotionally affected. However, research on their working conditions and environment is limited. The purpose of the current study was to describe nurses' experiences and thoughts concerning the exertion of coercive measures in forensic psychiatric care. The investigation was a qualitative interview study using unstructured interviews; data were analyzed with inductive content analysis. Results described participants' thoughts and experiences of coercive measures from four main categories: (a) acting against the patients' will, (b) reasoning about ethical justifications, (c) feelings of compassion, and (d) the need for debriefing. The current study illuminates the working conditions of nurses who exert coercive measures in clinical practice with patients who have a long-term relationship with severe symptomatology. The findings are important to further discuss how nurses and leaders can promote a healthier working environment. [Journal of Psychosocial Nursing and Mental Health Services, 54(9), 37-43.]. Copyright 2016, SLACK Incorporated.

Effects of music and video on perceived exertion during high-intensity exercise

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Enoch C.Chow; Jennifer L.Etnier

2017-01-01

Background:Dissociative attentional stimuli (e.g.,music,video) are effective in decreasing ratings of perceived exertion (RPE) during low-to-moderate intensity exercise,but have inconsistent results during exercise at higher intensity.The purpose of this study was to assess attentional focus and RPE during high-intensity exercise as a function of being exposed to music,video,both (music and video),or a no-treatment control condition.Methods:During the first session,healthy men (n =15) completed a maximal fitness test to determine the workload necessary for high-intensity exercise (operationalized as 125％ ventilatory threshold) to be performed during subsequent sessions.On 4 subsequent days,they completed 20 min of high-intensity exercise in a no-treatment control condition or while listening to music,watching a video,or both.Attentional focus,RPE,heart rate,and distance covered were measured every 4 min during the exercise.Results:Music and video in combination resulted in significantly lower RPE across time (partial η2 =0.36) and the size of the effect increased over time (partial η2 =0.14).Additionally,music and video in combination resulted in a significantly more dissociative focus than the other conditions (partial η2 =0.29).Conclusion:Music and video in combination may result in lower perceived exertion during high-intensity exercise when compared to music or video in isolation.Future research will be necessary to test if reductions in perceived exertion in response to dissociative attentional stimuli have implications for exercise adherence.

Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii.

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Pothoulakis, C

2009-10-15

Saccharomyces boulardii, a well-studied probiotic, can be effective in inflammatory gastrointestinal diseases with diverse pathophysiology, such as inflammatory bowel disease (IBD), and bacterially mediated or enterotoxin-mediated diarrhoea and inflammation. To discuss the mechanisms of action involved in the intestinal anti-inflammatory action of S. boulardii. Review of the literature related to the anti-inflammatory effects of this probiotic. Several mechanisms of action have been identified directed against the host and pathogenic microorganisms. S. boulardii and S. boulardii secreted-protein(s) inhibit production of proinflammatory cytokines by interfering with the global mediator of inflammation nuclear factor kappaB, and modulating the activity of the mitogen-activated protein kinases ERK1/2 and p38. S. boulardii activates expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) that protects from gut inflammation and IBD. S. boulardii also suppresses 'bacteria overgrowth' and host cell adherence, releases a protease that cleaves C. difficile toxin A and its intestinal receptor and stimulates antibody production against toxin A. Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes. The multiple anti-inflammatory mechanisms exerted by S. boulardii provide molecular explanations supporting its effectiveness in intestinal inflammatory states.

Review article: Anti-inflammatory mechanisms of action of Saccharomyces boulardii

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Pothoulakis, C.

2009-01-01

SUMMARY Background Saccharomyces boulardii (S. boulardii), a well-studied probiotic, can be effective in inflammatory gastrointestinal diseases with diverse pathophysiology, such as Inflammatory Bowel Disease (IBD), and bacterially – or enterotoxin-mediated diarrhea and inflammation. Aim Discuss the mechanisms of action involved in the intestinal anti-inflammatory action of S. boulardii Methods Review of the literature related to the anti-inflammatory effects of this probiotic. Results Several mechanisms of action have been identified directed against the host and pathogenic microorganisms. S. boulardii and S. boulardii secreted protein(s) inhibit production of proinflammatory cytokines by interfering with the global mediator of inflammation nuclear factor κB, and modulating the activity of the mitogen-activated protein kinases ERK1/2 and p38. S. boulardii activates expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) that protects from gut inflammation and IBD. S. boulardii also suppresses “bacteria overgrowth” and host cell adherence, releases a protease that cleaves C. difficile toxin A and its intestinal receptor, and stimulates antibody production against toxin A. Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes. Conclusions The multiple anti-inflammatory mechanisms exerted by S. boulardii provide molecular explanations supporting its effectiveness in intestinal inflammatory states. PMID:19706150

Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

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Mauricio A. Retamal

2017-11-01

Full Text Available In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia. It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs. Recent evidence shows that connexin43 (Cx43 hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons. This communication may be exerted via the release of bioactive molecules from SGCs and their subsequent action on receptors located at the soma of sensory neurons. The glio-neuronal communication seems to be relevant for the establishment of chronic pain, hyperalgesia and pathologies associated with tissue inflammation. Based on the current literature, it is possible to propose that Cx43 hemichannels expressed in SGCs could be a novel pharmacological target for treating chronic pain, which need to be directly evaluated in future studies.

Coupling knowledge and action in the management context

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Mazza, Carmelo; Strandgaard Pedersen, Jesper; Alvarez, José Luis

2003-01-01

In the last decade, scholarly interest has been mainly attracted on the nature of knowledge,mechanisms of knowledge production and the transformation of the institutions diffusingknowledge. Most of these studies share the underlying hypotheses that management knowledge`travels', as a package, from...... on priorities and undertake specific courses of actions This supports theidea that the managerial role is intrinsically political.Second, management education cannot simply deals with managerial recipes and rules of thumb. Itis increasingly asked for providing non-technical knowledge to help managers exert...... their politicalrole. To mobilize constituencies and create consensus on controversial decisions, technicalitiescould be less relevant than business-unrelated knowledge. We hold that has a relevant impact onboth the institutional settings and the content of management education.The paper is structured in three parts...

Neuroprotective actions of ghrelin and growth hormone secretagogues

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Laura M. Frago

2011-09-01

Full Text Available The brain incorporates and coordinates information based on the hormonal environment, receiving information from peripheral tissues through the circulation. Although it was initially thought that hormones only acted on the hypothalamus to perform endocrine functions, it is now known that they in fact exert diverse actions on many different brain regions including the hypothalamus. Ghrelin is a gastric hormone that stimulates growth hormone (GH secretion and food intake to regulate energy homeostasis and body weight by binding to its receptor, GHS-R1a, which is most highly expressed in the pituitary and hypothalamus. In addition, ghrelin has effects on learning and memory, reward and motivation, anxiety and depression, and could be a potential therapeutic agent in neurodegenerative disorders where excitotoxic neuronal cell death and inflammatory processes are involved.

Neuroprotective Actions of Ghrelin and Growth Hormone Secretagogues

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Frago, Laura M.; Baquedano, Eva; Argente, Jesús; Chowen, Julie A.

2011-01-01

The brain incorporates and coordinates information based on the hormonal environment, receiving information from peripheral tissues through the circulation. Although it was initially thought that hormones only acted on the hypothalamus to perform endocrine functions, it is now known that they in fact exert diverse actions on many different brain regions including the hypothalamus. Ghrelin is a gastric hormone that stimulates growth hormone secretion and food intake to regulate energy homeostasis and body weight by binding to its receptor, growth hormone secretagogues–GH secretagogue-receptor, which is most highly expressed in the pituitary and hypothalamus. In addition, ghrelin has effects on learning and memory, reward and motivation, anxiety, and depression, and could be a potential therapeutic agent in neurodegenerative disorders where excitotoxic neuronal cell death and inflammatory processes are involved. PMID:21994488

Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon.

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Juan Del Coso

Full Text Available Exertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs to explain inter-individual variability of serum creatine kinase (CK concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A.Using Williams and Folland's model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK <400 U·L-1 vs. marathoners with a high CK response (n = 31; serum CK ≥400 U·L-1.At the end of the race, low CK responders had lower serum CK (290±65 vs. 733±405 U·L-1; P<0.01 and myoglobin concentrations (443±328 vs. 1009±971 ng·mL-1, P<0.01 than high CK responders. Although the groups were similar in age, anthropometric characteristics, running experience and training habits, total genotype score was higher in low CK responders than in high CK responders (5.2±1.4 vs. 4.4±1.7 point, P = 0.02.Marathoners with a lower CK response after the race had a more favorable polygenic profile than runners with high serum CK concentrations. This might suggest a significant role of genetic polymorphisms in the levels of exertional muscle damage and rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.

Differential action of glycoprotein hormones: significance in cancer progression.

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Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

2014-02-01

Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

Implicit theories about willpower predict the activation of a rest goal following self-control exertion.

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Job, Veronika; Bernecker, Katharina; Miketta, Stefanie; Friese, Malte

2015-10-01

Past research indicates that peoples' implicit theories about the nature of willpower moderate the ego-depletion effect. Only people who believe or were led to believe that willpower is a limited resource (limited-resource theory) showed lower self-control performance after an initial demanding task. As of yet, the underlying processes explaining this moderating effect by theories about willpower remain unknown. Here, we propose that the exertion of self-control activates the goal to preserve and replenish mental resources (rest goal) in people with a limited-resource theory. Five studies tested this hypothesis. In Study 1, individual differences in implicit theories about willpower predicted increased accessibility of a rest goal after self-control exertion. Furthermore, measured (Study 2) and manipulated (Study 3) willpower theories predicted an increased preference for rest-conducive objects. Finally, Studies 4 and 5 provide evidence that theories about willpower predict actual resting behavior: In Study 4, participants who held a limited-resource theory took a longer break following self-control exertion than participants with a nonlimited-resource theory. Longer resting time predicted decreased rest goal accessibility afterward. In Study 5, participants with an induced limited-resource theory sat longer on chairs in an ostensible product-testing task when they had engaged in a task requiring self-control beforehand. This research provides consistent support for a motivational shift toward rest after self-control exertion in people holding a limited-resource theory about willpower. (c) 2015 APA, all rights reserved).

Bone Marrow Mesenchymal Stromal Cells Stimulate Skeletal Myoblast Proliferation through the Paracrine Release of VEGF

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Chellini, Flaminia; Mazzanti, Benedetta; Nistri, Silvia; Nosi, Daniele; Saccardi, Riccardo; Quercioli, Franco; Zecchi-Orlandini, Sandra; Formigli, Lucia

2012-01-01

Mesenchymal stromal cells (MSCs) are the leading cell candidates in the field of regenerative medicine. These cells have also been successfully used to improve skeletal muscle repair/regeneration; however, the mechanisms responsible for their beneficial effects remain to be clarified. On this basis, in the present study, we evaluated in a co-culture system, the ability of bone-marrow MSCs to influence C2C12 myoblast behavior and analyzed the cross-talk between the two cell types at the cellular and molecular level. We found that myoblast proliferation was greatly enhanced in the co-culture as judged by time lapse videomicroscopy, cyclin A expression and EdU incorporation. Moreover, myoblasts immunomagnetically separated from MSCs after co-culture expressed higher mRNA and protein levels of Notch-1, a key determinant of myoblast activation and proliferation, as compared with the single culture. Notch-1 intracellular domain and nuclear localization of Hes-1, a Notch-1 target gene, were also increased in the co-culture. Interestingly, the myoblastic response was mainly dependent on the paracrine release of vascular endothelial growth factor (VEGF) by MSCs. Indeed, the addition of MSC-derived conditioned medium (CM) to C2C12 cells yielded similar results as those observed in the co-culture and increased the phosphorylation and expression levels of VEGFR. The treatment with the selective pharmacological VEGFR inhibitor, KRN633, resulted in a marked attenuation of the receptor activation and concomitantly inhibited the effects of MSC-CM on C2C12 cell growth and Notch-1 signaling. In conclusion, this study provides novel evidence for a role of MSCs in stimulating myoblast cell proliferation and suggests that the functional interaction between the two cell types may be exploited for the development of new and more efficient cell-based skeletal muscle repair strategies. PMID:22815682

Subject-specific increases in serum S-100B distinguish sports-related concussion from sports-related exertion.

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Kiechle, Karin; Bazarian, Jeffrey J; Merchant-Borna, Kian; Stoecklein, Veit; Rozen, Eric; Blyth, Brian; Huang, Jason H; Dayawansa, Samantha; Kanz, Karl; Biberthaler, Peter

2014-01-01

The on-field diagnosis of sports-related concussion (SRC) is complicated by the lack of an accurate and objective marker of brain injury. To compare subject-specific changes in the astroglial protein, S100B, before and after SRC among collegiate and semi-professional contact sport athletes, and compare these changes to differences in S100B before and after non-contact exertion. Longitudinal cohort study. From 2009-2011, we performed a prospective study of athletes from Munich, Germany, and Rochester, New York, USA. Serum S100B was measured in all SRC athletes at pre-season baseline, within 3 hours of injury, and at days 2, 3 and 7 post-SRC. Among a subset of athletes, S100B was measured after non-contact exertion but before injury. All samples were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels. Forty-six athletes (30 Munich, 16 Rochester) underwent baseline testing. Thirty underwent additional post-exertion S100B testing. Twenty-two athletes (16 Rochester, 6 Munich) sustained a SRC, and 17 had S100B testing within 3 hours post-injury. The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline (0.099±0.008 µg/L vs. 0.058±0.006 µg/L, p = 0.0002). Mean post-exertion S100B was not significantly different than the preseason baseline. S100B levels at post-injury days 2, 3 and 7 were significantly lower than the 3-hour level, and not different than baseline. Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC (AUC 0.772 and 0.904, respectively). A 3-hour post-concussion S100B >0.122 µg/L and a proportional S100B increase of >45.9% over baseline were both 96.7% specific for SRC. Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion, and may be a useful adjunct to the diagnosis of SRC.

Subject-specific increases in serum S-100B distinguish sports-related concussion from sports-related exertion.

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Karin Kiechle

Full Text Available The on-field diagnosis of sports-related concussion (SRC is complicated by the lack of an accurate and objective marker of brain injury.To compare subject-specific changes in the astroglial protein, S100B, before and after SRC among collegiate and semi-professional contact sport athletes, and compare these changes to differences in S100B before and after non-contact exertion.Longitudinal cohort study.From 2009-2011, we performed a prospective study of athletes from Munich, Germany, and Rochester, New York, USA. Serum S100B was measured in all SRC athletes at pre-season baseline, within 3 hours of injury, and at days 2, 3 and 7 post-SRC. Among a subset of athletes, S100B was measured after non-contact exertion but before injury. All samples were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels.Forty-six athletes (30 Munich, 16 Rochester underwent baseline testing. Thirty underwent additional post-exertion S100B testing. Twenty-two athletes (16 Rochester, 6 Munich sustained a SRC, and 17 had S100B testing within 3 hours post-injury. The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline (0.099±0.008 µg/L vs. 0.058±0.006 µg/L, p = 0.0002. Mean post-exertion S100B was not significantly different than the preseason baseline. S100B levels at post-injury days 2, 3 and 7 were significantly lower than the 3-hour level, and not different than baseline. Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC (AUC 0.772 and 0.904, respectively. A 3-hour post-concussion S100B >0.122 µg/L and a proportional S100B increase of >45.9% over baseline were both 96.7% specific for SRC.Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion, and may be a useful adjunct to the diagnosis of SRC.

Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis.

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Verónica García-Alonso

Full Text Available Obesity induces white adipose tissue (WAT dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES. IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1 in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16 in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of

Characteristics of patients with chronic exertional compartment syndrome.

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Davis, Daniel E; Raikin, Steven; Garras, David N; Vitanzo, Peter; Labrador, Hallie; Espandar, Ramin

2013-10-01

Chronic exertional compartment syndrome (CECS) is a condition that causes reversible ischemia and lower extremity pain during exercise. To date there are few large studies examining the characteristics of patients with CECS. This study aimed to present these characteristics by examining the largest published series of patients with a confirmed diagnosis of the disorder. An IRB-approved, retrospective review was undertaken of patients with a suspected diagnosis of CECS undergoing pre- and postexercise compartment pressure testing between 2000 and 2012. Patients were evaluated for gender, age, duration of symptoms, pain level, specific compartments involved, compartment pressure measurements, and participation and type of athletics. Two-hundred twenty-six patients (393 legs) underwent compartment pressure testing. A diagnosis of CECS was made in 153 (67.7%) patients and 250 (63.6%) legs with elevated compartment measurements; average age of the patients was 24 years (range, 13-69 years). Female patients accounted for 92 (60.1%) of those with elevated pressures. Anterior and lateral compartment pressures were elevated most frequently, with 200 (42.5%) and 167 (35.5%) compartments, respectively. One hundred forty-one (92.2%) patients reported participation in sports, with running being the most common individual sport and soccer being the most common team sport. Duration of pain prior to diagnosis averaged 28 months. Although there is ample literature pertaining to the diagnostic criteria and treatment algorithm of the condition, few papers have described the type of patient most likely to develop CECS. This is the largest study to date to evaluate the type of patient likely to present with chronic exertional compartment syndrome. Level III, retrospective review.

The effects of acclimatization on blood clotting parameters in exertional heat stress.

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Vesić, Zoran; Vukasinović-Vesić, Milica; Dincić, Dragan; Surbatović, Maja; Radaković, Sonja S

2013-07-01

Exertional heat stress is a common problem in military services. Considering the coagulation abnormalities are of major importance in development of severe heat stroke, we wanted to examine changes in hemostatic parameters in soldiers during exertional heat stress test as well as the effects of a 10-day passive or active acclimatization in a climatic chamber. A total of 40 male soldiers with high aerobic capacity performed exertional heat stress test (EHST) either in cool [20 degrees C, 16 degrees C wet bulb globe temperature (WBGT)], or hot (40 degrees C, 29 degrees C, (WBGT) environment, unacclimatized (U) or after 10 days of passive (P) or active (A) acclimatization. Physiological strain was measured by tympanic temperatures (Tty) and heart rates (HR). Platelet count (PC), antithrombin III (AT), and prothrombin time (PT) were assessed in blood samples collected before and immediately after the EHST. EHST in hot conditions induced physiological heat stress (increase in Tty and HR), with a significant increase in prothrombin time in the groups U and A. Platelet counts were significantly higher after the EHST compared to the basic levels in all the investigated groups, regardless environmental conditions and acclimatization state. Antithrombin levels were not affected by EHST whatsoever. In the trained soldiers, physiological heat stress caused mild changes in some serum parameters of blood clotting such as prothrombin time, while others such as antithrombin levels were not affected. Platelet counts were increased after EHST in all groups. A 10-day passive or active acclimatization in climatic chamber showed no effect on parameters investigated.

Examining Effects of Physical Exertion on the Dynamic Visual Acuity Test in Collegiate Athletes.

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Patterson, Jessie N; Murphy, Anna M; Honaker, Julie A

2017-01-01

Acute symptoms of dizziness and/or imbalance commonly experienced in athletes postconcussion are speculated to arise from dysfunction at multiple levels (i.e., inner ear or central vestibular system) to appropriately integrate afferent sensory information. Disruption along any pathway of the balance system can result in symptoms of dizziness, decreased postural control function (vestibulospinal reflex), and reduced vestibulo-ocular reflex function. This may also lead to decreased gaze stability with movements of the head and may account for symptoms of blurred vision or diplopia reported in almost half of athletes sustaining a concussion. Current concussion position statements include measures of postural control to examine changes to the balance system postconcussion. The Balance Error Scoring System (BESS) is a commonly used low-cost postural control measure for concussion assessment. Although this is a widely used measure for documenting balance function on both immediate (sideline) and recovery monitoring, the BESS has been shown to be affected by physical exertion. Therefore, the BESS may not be the most efficient means of examining functional changes to the balance system immediately after head injury. Dynamic Visual Acuity Test (DVAT) has been found to effectively evaluate and monitor changes to the gaze stability system postinjury. Thus, DVAT may be an additional measure in the concussion assessment battery, as well as an alternative for more immediate sideline assessment to help make objective return-to-play decisions. The aim of the study was to determine the effects of physical exertion on a clinical vestibular assessment, the DVAT, in collegiate athletes, as a first step in defining the role of this measure in the concussion assessment battery. Cross-sectional, repeated-measures design. Twenty-eight healthy collegiate athletes (20 males, 8 females; age = 20.25 ± 1.46 yr, range = 18-25 yr) volunteered to participate in the study. Participants were

Paracrine Mechanisms of Intravenous Bone Marrow-Derived Mononuclear Stem Cells in Chronic Ischemic Stroke

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Ashu Bhasin

2016-10-01

Full Text Available Background: The emerging role of stem cell technology and transplantation has helped scientists to study their potential role in neural repair and regeneration. The fate of stem cells is determined by their niche, consisting of surrounding cells and the secreted trophic growth factors. This interim report evaluates the safety, feasibility and efficacy (if any of bone marrow-derived mononuclear stem cells (BM-MNC in chronic ischemic stroke by studying the release of serum vascular endothelial growth factor (VEGF and brain-derived neurotrophic growth factor (BDNF. Methods: Twenty stroke patients and 20 age-matched healthy controls were recruited with the following inclusion criteria: 3 months to 1.5 years from the index event, Medical Research Council (MRC grade of hand muscles of at least 2, Brunnstrom stage 2-5, conscious, and comprehendible. They were randomized to one group receiving autologous BM-MNC (mean 60-70 million and to another group receiving saline infusion (placebo. All patients were administered a neuromotor rehabilitation regime for 8 weeks. Clinical assessments [Fugl Meyer scale (FM, modified Barthel index (mBI, MRC grade, Ashworth tone scale] were carried out and serum VEGF and BDNF levels were assessed at baseline and at 8 weeks. Results: No serious adverse events were observed during the study. There was no statistically significant clinical improvement between the groups (FM: 95% CI 15.2-5.35, p = 0.25; mBI: 95% CI 14.3-4.5, p = 0.31. VEGF and BDNF expression was found to be greater in group 1 compared to group 2 (VEGF: 442.1 vs. 400.3 pg/ml, p = 0.67; BDNF: 21.3 vs. 19.5 ng/ml without any statistically significant difference. Conclusion: Autologous mononuclear stem cell infusion is safe and tolerable by chronic ischemic stroke patients. The released growth factors (VEGF and BDNF in the microenvironment could be due to the paracrine hypothesis of stem cell niche and neurorehabilitation regime.

XIAP gene expression and function is regulated by autocrine and paracrine TGF-β signaling

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Van Themsche Céline

2010-08-01

Full Text Available Abstract Background X-linked inhibitor of apoptosis protein (XIAP is often overexpressed in cancer cells, where it plays a key role in survival and also promotes invasiveness. To date however, the extracellular signals and intracellular pathways regulating its expression and activity remain incompletely understood. We have previously showed that exposure to each of the three TGF-β (transforming growth factor beta isoforms upregulates XIAP protein content in endometrial carcinoma cells in vitro. In the present study, we have investigated the clinical relevance of TGF-β isoforms in endometrial tumours and the mechanisms through which TGF-β isoforms regulate XIAP content in uterine cancer cells. Methods TGF-β isoforms immunoreactivity in clinical samples from endometrial tumours was assessed using immunofluorescence. Two model cancer cell lines (KLE endometrial carcinoma cells and HeLa cervical cancer cells and pharmacological inhibitors were used to investigate the signalling pathways regulating XIAP expression and activity in response to autocrine and paracrine TGF-β in cancer cell. Results We have found immunoreactivity for each TGF-β isoform in clinical samples from endometrial tumours, localizing to both stromal and epithelial/cancer cells. Blockade of autocrine TGF-β signaling in KLE endometrial carcinoma cells and HeLa cervical cancer cells reduced endogenous XIAP mRNA and protein levels. In addition, each TGF-β isoform upregulated XIAP gene expression when given exogenously, in a Smad/NF-κB dependent manner. This resulted in increased polyubiquitination of PTEN (phosphatase and tensin homolog on chromosome ten, a newly identified substrate for XIAP E3 ligase activity, and in a XIAP-dependent decrease of PTEN protein levels. Although each TGF-β isoform decreased PTEN content in a XIAP- and a Smad-dependent manner, decrease of PTEN levels in response to only one isoform, TGF-β3, was blocked by PI3-K inhibitor LY294002. Conclusions

How transformational leadership appears in action with adverse events? A study for Finnish nurse manager.

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Liukka, Mari; Hupli, Markku; Turunen, Hannele

2017-12-26

The aim of this study was to determine whether elements of transformational leadership are present in nursing managers' actions following adverse events. Transformational leadership exerts a positive influence on organisational culture and patient safety. Eleven nursing managers were interviewed individually using a semi-structured format. Data were analysed using inductive content analysis. Four themes emerged relating to nursing managers' actions following adverse events: patient-centredness as a principle for common action, courage to reform operational models to prevent future adverse events, nursing staff's encouragement of open and blame-free discussion, and challenge to recognize adverse events. Nursing managers must understand their responsibilities and the importance of making it clear to staff that patient-centredness should be evident in all health care actions. Nursing managers must also recognize the need to ensure that staff treat patients' interests as the top priority. If an adverse event occurs, the situation should be discussed with the nursing staff and any unique aspects of the event must be accounted for. Nursing managers must have the skill to motivate and empower staff to find new ways to work, to prevent adverse events and to promote patient safety. © 2017 John Wiley & Sons Ltd.

Leg 201Tl-SPECT in chronic exertional compartment syndrome

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Elkadri, N.; Slim, I.; Blondet, C.; Choquet, Ph.; Constantinesco, A.; Lecocq, J.

2004-01-01

Leg 201 Tl-SPECT in chronic exertional compartment syndrome Background: The chronic exertional compartment syndrome is one of the most frequent origins regarding leg pain due to sport training. The diagnosis can be established by invasive compartment pressure measurement. The aim of this study is to evaluate the role that could have 201 Tl-SPECT for patients with suspicion of compartment syndrome. Patients and methods: 51 leg 201 Tl-SPECT exams were performed (exercise - and rest without reinjection) in 49 patients; 28 had compartment syndrome confirmed by pressure measurement. About 100 MBq of 201 Tl were injected during exercise, when pain appeared or at least after 25 minutes exercise. We studied mean percentages of level uptake for each compartment, referred to the maximal uptake of both legs. Results: 47 compartments were concerned by compartment syndrome and 361 compartments were not. Scintigraphic patterns in compartments are reversible ischaemia (45%), uptake stability (36%) or reverse redistribution (19%); these patterns are not linked to compartment syndrome. However, there is a significant difference of rest 201 Tl level uptake between compartments with and without compartment syndrome and a significant correlation between muscular pressure measurement and rest level uptake. Conclusion: 201 Tl-SPECT shows that only ischaemia does not explain compartment syndrome. Moreover, it allows to predict pressure variation during exercise but it does not offer any interest in order to select patients for muscular invasive pressure measurement. (author)

DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

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Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp

2015-05-15

Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

International Nuclear Information System (INIS)

Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

2015-01-01

Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action

Inhibin-B secretion and FSH isoform distribution may play an integral part of follicular selection in the natural menstrual cycle

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Andersen, C. Yding

2017-01-01

The aim of the present paper is to expand the concept on how follicular selection takes place in the follicular phase of the natural menstrual cycle. It is suggested that inhibin-B exerts a more intimate role in this process than previously understood. Inhibin-B shows a peak in the circulation...... around cycle day 7, simultaneous with selection of the dominant follicle, whereas levels of estradiol and inhibin-A only start to increase a few days later suggesting that inhibin-B is mainly responsible for downregulating pituitary FSH release. New data now demonstrate that the circulatory peak...... of inhibin-B is reflected by peak production of inhibin-B, in contrast to inhibin-A, in the selected follicle with a diameter of 10-12 mm, where concentrations are one thousand times higher than in the circulation. This high inhibin-B concentration also exerts paracrine effects, stimulating theca cell...

Action of the isolated canine diaphragm on the lower ribs at high lung volumes.

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De Troyer, André; Wilson, Theodore A

2014-10-15

The normal diaphragm has an inspiratory action on the lower ribs, but subjects with chronic obstructive pulmonary disease commonly have an inward displacement of the lateral portions of the lower rib cage during inspiration. This paradoxical displacement, conventionally called 'Hoover's sign', has traditionally been attributed to the direct action of radially oriented diaphragmatic muscle fibres. In the present study, the inspiratory intercostal muscles in all interspaces in anaesthetized dogs were severed so that the diaphragm was the only muscle active during inspiration. The displacements of the lower ribs along the craniocaudal and laterolateral axes and the changes in pleural pressure (∆Ppl) and transdiaphragmatic pressure were measured during occluded breaths and mechanical ventilation at different lung volumes between functional residual capacity (FRC) and total lung capacity. From these data, the separate effects on rib displacement of ∆Ppl and of the force exerted by the diaphragm on the ribs were determined. Isolated spontaneous diaphragm contraction at FRC displaced the lower ribs cranially and outward, but this motion was progressively reversed into a caudal and inward motion as lung volume increased. However, although the force exerted by the diaphragm on the ribs decreased with increasing volume, it continued to displace the ribs cranially and outward. These observations suggest that Hoover's sign is usually caused by the decrease in the zone of apposition and, thus, by the dominant effect of ∆Ppl on the lower ribs, rather than an inward pull from the diaphragm. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Vitamin D and the brain: Genomic and non-genomic actions.

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Cui, Xiaoying; Gooch, Helen; Petty, Alice; McGrath, John J; Eyles, Darryl

2017-09-15

1,25(OH) 2 D 3 (vitamin D) is well-recognized as a neurosteroid that modulates multiple brain functions. A growing body of evidence indicates that vitamin D plays a pivotal role in brain development, neurotransmission, neuroprotection and immunomodulation. However, the precise molecular mechanisms by which vitamin D exerts these functions in the brain are still unclear. Vitamin D signalling occurs via the vitamin D receptor (VDR), a zinc-finger protein in the nuclear receptor superfamily. Like other nuclear steroids, vitamin D has both genomic and non-genomic actions. The transcriptional activity of vitamin D occurs via the nuclear VDR. Its faster, non-genomic actions can occur when the VDR is distributed outside the nucleus. The VDR is present in the developing and adult brain where it mediates the effects of vitamin D on brain development and function. The purpose of this review is to summarise the in vitro and in vivo work that has been conducted to characterise the genomic and non-genomic actions of vitamin D in the brain. Additionally we link these processes to functional neurochemical and behavioural outcomes. Elucidation of the precise molecular mechanisms underpinning vitamin D signalling in the brain may prove useful in understanding the role this steroid plays in brain ontogeny and function. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences between novice and experienced caregivers in muscle activity and perceived exertion while repositioning bedridden patients.

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Daikoku, Rie; Saito, Yayoi

2008-11-01

The aim of this study was to investigate the impact of caregiver knowledge and experience on muscle activity and perceived exertion while repositioning bedridden patients. Subjects were 40- to 65-year-old female caregivers divided into novice and experienced groups. Subjects from both groups performed home-care repositioning techniques on bedridden patients while muscle activity was recorded via electromyogram. Recordings were made from four muscles on the subjects' dominant side: the latissimus dorsi, the biceps brachii, the erector spinae, and the rectus femoris. The subjective burden involved in repositioning was also assessed using the rate of perceived exertion (RPE) and visual analog scales (VAS). Rectus femoris percentage of maximum voluntary contraction (%MVC) values were significantly lower than latissimus dorsi, erector spinae, and biceps brachii values in the novice group. %MVC values from the latissimus dorsi and biceps brachii were significantly higher among the novice group compared to the experienced group. RPE ratings from the novice group were significantly higher than those of the experienced group, and there was a non-significant trend for higher VAS values for the low back, arms, and legs in the novice group compared to the experienced group. Novice caregivers tended to change the patient's position by pulling with the upper limbs without using the lower limbs. In contrast, experienced caregivers exerted less energy by communicating with the patient and utilizing the patient's own movements. They used large, distributed muscle groups that effectively harnessed body mechanics and prevented excess exertion.

Seed predators exert selection on the subindividual variation of seed size.

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Sobral, M; Guitián, J; Guitián, P; Larrinaga, A R

2014-07-01

Subindividual variation among repeated organs in plants constitutes an overlooked level of variation in phenotypic selection studies, despite being a major component of phenotypic variation. Animals that interact with plants could be selective agents on subindividual variation. This study examines selective pressures exerted during post-dispersal seed predation and germination on the subindividual variation of seed size in hawthorn (Crataegus monogyna). With a seed offering experiment and a germination test, we estimated phenotypic selection differentials for average and subindividual variation of seed size due to seed predation and germination. Seed size affects germination, growth rate and the probability of an individual seed of escaping predation. Longer seeds showed higher germination rates, but this did not result in significant selection on phenotypes of the maternal trees. On the other hand, seed predators avoided wider seeds, and by doing so exerted phenotypic selection on adult average and subindividual variation of seed size. The detected selection on subindividual variation suggests that the levels of phenotypic variation within individual plants may be, at least partly, the adaptive consequence of animal-mediated selection. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Frequent Exertion and Frequent Standing at Work, by Industry and Occupation Group - United States, 2015.

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Shockey, Taylor M; Luckhaupt, Sara E; Groenewold, Matthew R; Lu, Ming-Lun

2018-01-12

Repeated exposure to occupational ergonomic hazards, such as frequent exertion (repetitive bending or twisting) and frequent standing, can lead to injuries, most commonly musculoskeletal disorders (1). Work-related musculoskeletal disorders have been estimated to cost the United States approximately $2.6 billion in annual direct and indirect costs (2). A recent literature review provided evidence that prolonged standing at work also leads to adverse health outcomes, such as back pain, physical fatigue, and muscle pain (3). To determine which industry and occupation groups currently have the highest prevalence rates of frequent exertion at work and frequent standing at work, CDC analyzed data from the 2015 National Health Interview Survey (NHIS) Occupational Health Supplement (OHS) regarding currently employed adults in the United States. By industry, the highest prevalence of both frequent exertion and frequent standing at work was among those in the agriculture, forestry, fishing, and hunting industry group (70.9%); by occupation, the highest prevalence was among those in the construction and extraction occupation group (76.9%). Large differences among industry and occupation groups were found with regard to these ergonomic hazards, suggesting a need for targeted interventions designed to reduce workplace exposure.

INSTITUTIONAL AND CONJUNCTURAL FACTORS ACTION ON AUTONOMY IN LOCAL PUBLIC ADMINISTRATION MANAGEMENT

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SCUTARIU PETRONELA

2016-02-01

Full Text Available Component without which the function of local public administration management would be compromised, administrative autonomy manifests under the action of various factors. From such an angle, the space of this article is dedicated to identifying the factors affecting the autonomy in management of local public administration in order to show their actions on its manifestation. By developing the present approach, beyond the incompleteness of the existing explanations relative to this sphere of interest, we have identified and highlighted the action of two sets of factors - institutional and conjunctural. Ensign turned out to be the action that institutional factors exert on autonomy, the latter being the greater, as the local administrative structure is higher, as the number of local public services is higher, when there are legal regulations that warrant it, and vice versa. Then analyzing conjunctural factors, we found that the influence of the economic crisis is, as expected, adverse to autonomy manifestation. Regarding the local development factor, we showed that a local community with a high degree of development functions without the intervention of center, a situation that favors autonomy, as opposed to a less developed community that requires the support of the center, intervention which mitigates the autonomy. By examining the action of political factor, we noticed that, although politicians define public strategies and policies that will be implemented, which gives it a positive connotation, most often autonomy suffers under the politics influence. Finally, the social organization in local collectivities provides favorable ground to the manifestation and functioning of autonomy in the management of local public administration.

Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

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Sebastià, N., E-mail: natividad.sebastia@uv.es [Radiation Protection Service, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Montoro, A. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Hervás, D. [Biostatistics Unit, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Pantelias, G.; Hatzi, V.I. [Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research “Demokritos”, Aghia Paraskevi, Athens (Greece); Soriano, J.M. [Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia (Spain); Villaescusa, J.I. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); and others

2014-08-15

Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

International Nuclear Information System (INIS)

Sebastià, N.; Montoro, A.; Hervás, D.; Pantelias, G.; Hatzi, V.I.; Soriano, J.M.; Villaescusa, J.I.

2014-01-01

Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

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Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

2016-01-15

The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Metabolic actions of FGF21: molecular mechanisms and therapeutic implications

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Xuan Ge

2012-08-01

Full Text Available Fibroblast growth factor 21 (FGF21 is an atypical member of the FGF family that functions as an endocrine factor. In obese animals, elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight, decreases hyperglycemia and hyperlipidemia, alleviates fatty liver and increases insulin sensitivity. FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets, including adipose tissue, liver, brain and pancreas. The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma (PPARγ and peroxisome proliferator-activated receptor alpha (PPARα. A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21. In humans, plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes, but are reduced in patients with autoimmune diabetes. This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions, and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.

Basolateral amygdalar D2 receptor activation is required for the companions-exerted suppressive effect on the cocaine conditioning.

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Tzeng, Wen-Yu; Cherng, Chian-Fang G; Yu, Lung; Wang, Ching-Yi

2017-01-01

The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Three cage mates, serving as companions, were arranged to house with the experimental mice in the cocaine conditioning compartment throughout the cocaine conditioning sessions. Approximately 1week before the conditioning procedure, intracranial ibotenic acid infusions were done in an attempt to cause excitotoxic lesions targeting bilateral BLA, DH and DLS. Albeit their BLA, DH, and DLS lesions, the lesioned mice exhibited comparable cocaine-induced CPP magnitudes compared to the intact and sham lesion controls. Bilateral BLA, but not DH or DLS, lesions abolished the companions-exerted suppressive effect on the cocaine-induced CPP. Intact mice receiving intra-BLA infusion of raclopride, a selective D2 antagonist, 30min prior to the cocaine conditioning did not exhibit the companions-exerted suppressive effect on the cocaine-induced CPP. Intra-BLA infusion of Sch23390, a selective D1 antagonist, did not affect the companions-exerted suppressive effect on the CPP. These results, taken together, prompt us to conclude that the intactness of BLA is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Importantly, activation of D2 receptor in the BLA is required for such suppressive effect on the CPP. Copyright © 2016 Elsevier Inc. All rights reserved.

Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats

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Toshikatsu Okumura

2016-02-01

Subcutaneously (80 mg/rat or intracisternally (2.5 μg/rat administered levodopa significantly increased the threshold of colonic distension-induced AWR in conscious rats. The dose difference to induce the antinociceptive action suggests levodopa acts centrally to exert its antinociceptive action against colonic distension. While neither sulpiride, a D2 dopamine receptor antagonist, nor SCH23390, a D1 dopamine receptor antagonist by itself changed the threshold of colonic distension-induced AWR, the intracisternally injected levodopa-induced antinociceptive action was significantly blocked by pretreatment with subcutaneously administered sulpiride but not SCH23390. Treatment with intracisternal SB334867, an orexin 1 receptor antagonist, significantly blocked the subcutaneously administered levodopa-induced antinociceptive action. These results suggest that levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain.

A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells

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Yu, Shu-Han; Zheng, Qizhi; Esopi, David; Macgregor-Das, Anne; Luo, Jun; Antonarakis, Emmanuel S.; Drake, Charles G.; Vessella, Robert; Morrissey, Colm; De Marzo, Angelo M.; Sfanos, Karen S.

2015-01-01

Correlative human studies suggest that the pleiotropic cytokine interleukin-6 (IL6) contributes to the development and/or progression of prostate cancer. However, the source of IL6 production in the prostate microenvironment in patients has yet to be determined. The cellular origin of IL6 in primary and metastatic prostate cancer was examined in formalin-fixed, paraffin-embedded (FFPE) tissues using a highly sensitive and specific chromogenic in situ hybridization (CISH) assay that underwent extensive analytical validation. Quantitative RT-PCR (q-RT-PCR) showed that benign prostate tissues often had higher expression of IL6 mRNA than matched tumor specimens. CISH analysis further indicated that both primary and metastatic prostate adenocarcinoma cells do not express IL6 mRNA. IL6 expression was highly heterogeneous across specimens and was nearly exclusively restricted to the prostate stromal compartment – including endothelial cells and macrophages among other cell types. The number of IL6-expressing cells correlated positively with the presence of acute inflammation. In metastatic disease, tumor cells were negative in all lesions examined and IL6 expression was restricted to endothelial cells within the vasculature of bone metastases. Finally, IL6 was not detected in any cells in soft tissue metastases. These data suggest that, in prostate cancer patients, paracrine rather than autocrine IL6 production is likely associated with any role for the cytokine in disease progression. PMID:26048576

The impact of omega 3 fatty acids in atherosclerosis and arterial stiffness: An overview of their actions.

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Verveniotis, Alexios; Siasos, Gerasimos; Oikonomou, Evangelos; Tsigkou, Vasiliki; Papageorgiou, Nikolaos; Zaromitidou, Marina; Psaltopoulou, Theodora; Marinos, Georgios; Deftereos, Spyridon; Vavuranakis, Manolis; Stefanadis, Christodoulos; Papavassiliou, Athanasios G; Tousoulis, Dimitris

2018-03-20

Fatty acids are common dietary nutrients particularly in economically developed countries. Research has revealed that omega-3fatty acids exert beneficial effects in the progression of atherosclerosis and cardiovascular disease. Moreover, eicosapentaenoic acid and docosahexaenoic acid possess a number of biological actions which improve cardio-metabolic health. Omega-3 fatty acids display remarkable anti-oxidant, anti-inflammatory, anti-thrombotic and anti-arrythmogenic actions. Furthermore, they improve the levels of triglycerides, glucose metabolism and endothelial function. The aim of this review article is to present physical, biochemical and biological properties of omega-3 fatty acids and summarize the most important mechanisms of action on arterial wall properties and arterial stiffness in atherosclerosis. Omega-3 fatty acids may prevent the progression of atherosclerosis. Endothelial dysfunction and arterial stiffness can be regulated by the supplementation of omega-3 fatty acids. The mechanisms of action of omega-3 fatty acids on cardiovascular health and arterial stiffening have been established. However, further research is needed in order to translate the conflicting results among the studies and improve the therapeutic options of cardiovascular disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals

OpenAIRE

Shao, Jian-Su; Cheng, Su-Li; Pingsterhaus, Joyce M.; Charlton-Kachigian, Nichole; Loewy, Arleen P.; Towler, Dwight A.

2005-01-01

In diabetic LDLR–/– mice, an ectopic BMP2-Msx2 gene regulatory program is upregulated in association with vascular calcification. We verified the procalcific actions of aortic Msx2 expression in vivo. CMV-Msx2 transgenic (CMV-Msx2Tg+) mice expressed 3-fold higher levels of aortic Msx2 than nontransgenic littermates. On high-fat diets, CMV-Msx2Tg+ mice exhibited marked cardiovascular calcification involving aortic and coronary tunica media. This corresponded to regions of Msx2 immunoreactivity...

Exertional dyspnoea in COPD: the clinical utility of cardiopulmonary exercise testing

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Denis E. O'Donnell

2016-09-01

Full Text Available Activity-related dyspnoea is often the most distressing symptom experienced by patients with chronic obstructive pulmonary disease (COPD and can persist despite comprehensive medical management. It is now clear that dyspnoea during physical activity occurs across the spectrum of disease severity, even in those with mild airway obstruction. Our understanding of the nature and source of dyspnoea is incomplete, but current aetiological concepts emphasise the importance of increased central neural drive to breathe in the setting of a reduced ability of the respiratory system to appropriately respond. Since dyspnoea is provoked or aggravated by physical activity, its concurrent measurement during standardised laboratory exercise testing is clearly important. Combining measurement of perceptual and physiological responses during exercise can provide valuable insights into symptom severity and its pathophysiological underpinnings. This review summarises the abnormal physiological responses to exercise in COPD, as these form the basis for modern constructs of the neurobiology of exertional dyspnoea. The main objectives are: 1 to examine the role of cardiopulmonary exercise testing (CPET in uncovering the physiological mechanisms of exertional dyspnoea in patients with mild-to-moderate COPD; 2 to examine the escalating negative sensory consequences of progressive respiratory impairment with disease advancement; and 3 to build a physiological rationale for individualised treatment optimisation based on CPET.

Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action

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Griffin, Michael O.; Ceballos, Guillermo; Villarreal, Francisco

2010-01-01

Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The firstt of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline’s multiple mechanisms of action as a means to understand their beneficial effects. PMID:20951211

Concordance between VDU-users' ratings of comfort and perceived exertion with experts' observations of workplace layout and working postures.

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Lindegård, A; Karlberg, C; Wigaeus Tornqvist, E; Toomingas, A; Hagberg, M

2005-05-01

The aim of the present study was to evaluate the concordance (agreement) between VDU-users' ratings of comfort and ergonomists' observations of workplace layout, and the concordance between VDU-users' ratings of perceived exertion and ergonomists' observations of working postures during VDU-work. The study population consisted of 853 symptom free subjects. Data on perceived comfort in different dimensions and data regarding perceived exertion in different body locations were collected by means of a questionnaire. Data concerning workplace layout and working postures were collected with an observation protocol, by an ergonomist. Concordance between ratings of comfort and observations of workplace layout was reasonably good for the chair and the keyboard (0.60, 0.58) and good regarding the screen and the input device (0.72, 0.61). Concordance between ratings of perceived exertion and observations of working postures indicated good agreement (0.63-0.77) for all measured body locations (neck, shoulder, wrist and trunk). In conclusion ratings of comfort and perceived exertion could be used as cost-efficient and user-friendly methods for practitioners to identify high exposure to poor workplace layout and poor working postures.

Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect

OpenAIRE

Saruta, Juri; To, Masahiro; Sugimoto, Masahiro; Yamamoto, Yuko; Shimizu, Tomoko; Nakagawa, Yusuke; Inoue, Hiroko; Saito, Ichiro; Tsukinoki, Keiichi

2017-01-01

Brain-derived neurotrophic factor (BDNF) is abundant in the hippocampus and plays critical roles in memory and synapse formation, as well as exerting antidepressant-like effects in psychiatric disorders. We previously reported that BDNF is expressed in salivary glands and affects blood BDNF content. However, the function of salivary BDNF remains unclear. The aim of this study was to generate transgenic mice overexpressing BDNF in the salivary glands. Hence, we used the Lama construct (hemaggl...

A 68-Year-Old Man With Dyspnea on Exertion and Cough.

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Agrawal, Abhinav; Sikachi, Rutuja R; Koenig, Seth; Khanijo, Sameer

2018-06-01

A 68-year-old man with a history of chronic lymphocytic leukemia well controlled on ibrutinib, hypertension, obesity, and a remote history of smoking (10 pack-years) presented with increasing dyspnea on exertion and cough. He had previously finished two courses of oral antibiotics for his symptoms without significant improvement. On presentation, he had no fevers or sputum production. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Effects of perceived and exerted pain control on neural activity during pain relief in experimental heat hyperalgesia: a fMRI study.

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Mohr, C; Leyendecker, S; Petersen, D; Helmchen, C

2012-04-01

Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain control and emotional reappraisal irrespective of whether this control is exerted or only perceived. Self-initiated termination of pain elicits different expectations of subsequent pain relief as compared to perceived pain control. It is unknown whether and how this perceived vs. exerted control on pain differs and affects subsequent pain relief. Using fMRI, we studied two factors of pain control on pain relief: the (i) sense of control (perceived control but no execution) and (ii) the execution of control (exerted control). To account for the impact of factual execution of pain control on pain relief we applied bearable short and hardly bearable long contact-heat stimuli which were applied either controllable or not. Using controllability as factor, there was dissociable neural activity during pain relief: following the perceived control condition neural activity was found in the orbitofrontal and mediofrontal cortex and, following the exerted control condition, in the anterolateral and dorsolateral prefrontal cortex and posterior parietal cortex. We conclude that (i) pain controllability has an impact on pain relief and (ii) the prefrontal cortex shows dissociable neural activity during pain relief following exerted vs. perceived pain control. This might reflect the higher grade of uncertainty during pain relief following perceived pain control mediated by the orbitofrontal and medial prefrontal cortex and processes of working memory and updating expectations during pain relief following exerted control mediated by the lateral prefrontal cortex. © 2011 European Federation of International Association for the Study of Pain Chapters.

The Effect of Multimodal Feedback on Perceived Exertion on a VR Exercise Setting

DEFF Research Database (Denmark)

Bruun-Pedersen, Jon Ram; Andersen, Morten G.; Clemmesen, Mathias M.

2018-01-01

This paper seeks to determine if multimodal feedback, from auditory and haptic stimuli, can affect a user’s perceived exertion in a virtual reality setting. A simple virtual environment was created in the style of a desert to minimize the amount of visual distractions; a head mounted display was ...

Alcohol-paired contextual cues produce an immediate and selective loss of goal-directed action in rats

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Sean B Ostlund

2010-07-01

Full Text Available We assessed whether the presence of contextual cues paired with alcohol would disrupt rats’ capacity to express appropriate goal-directed action control. Rats were first given differential context conditioning such that one set of contextual cues was paired with the injection of ethanol and a second, distinctive set of cues was paired with the injection of saline. All rats were then trained in a third, neutral context to press one lever for grain pellets and another lever for sucrose pellets. They were then given two extinction tests to evaluate their ability to choose between the two actions in response to the devaluation of one of the two food outcomes with one test conducted in the alcohol-paired context and the other conducted in the control (saline-paired context. In the control context, rats exhibited goal-directed action control; i.e., they were able selectively to withhold the action that previously earned the now devalued outcome. However, these same rats were impaired when tested in the alcohol-paired context, performing both actions at the same rate regardless of the current value of their respective outcomes. Subsequent testing revealed that the rats were capable of overcoming this impairment if they were giving response-contingent feedback about the current value of the food outcomes. These results provide a clear demonstration of the disruptive influence that alcohol-paired cues can exert on decision-making in general and goal-directed action selection and choice in particular.

Hydrocortisone Infusion Exerts Dose- and Sex-Dependent Effects on Attention to Emotional Stimuli

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Breitberg, Alaina; Drevets, Wayne C.; Wood, Suzanne E.; Mah, Linda; Schulkin, Jay; Sahakian, Barbara J.; Erickson, Kristine

2013-01-01

Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to…

EEG signatures of arm isometric exertions in preparation, planning and execution.

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Nasseroleslami, Bahman; Lakany, Heba; Conway, Bernard A

2014-04-15

The electroencephalographic (EEG) activity patterns in humans during motor behaviour provide insight into normal motor control processes and for diagnostic and rehabilitation applications. While the patterns preceding brisk voluntary movements, and especially movement execution, are well described, there are few EEG studies that address the cortical activation patterns seen in isometric exertions and their planning. In this paper, we report on time and time-frequency EEG signatures in experiments in normal subjects (n=8), using multichannel EEG during motor preparation, planning and execution of directional centre-out arm isometric exertions performed at the wrist in the horizontal plane, in response to instruction-delay visual cues. Our observations suggest that isometric force exertions are accompanied by transient and sustained event-related potentials (ERP) and event-related (de-)synchronisations (ERD/ERS), comparable to those of a movement task. Furthermore, the ERPs and ERD/ERS are also observed during preparation and planning of the isometric task. Comparison of ear-lobe-referenced and surface Laplacian ERPs indicates the contribution of superficial sources in supplementary and pre-motor (FC(z)), parietal (CP(z)) and primary motor cortical areas (C₁ and FC₁) to ERPs (primarily negative peaks in frontal and positive peaks in parietal areas), but contribution of deep sources to sustained time-domain potentials (negativity in planning and positivity in execution). Transient and sustained ERD patterns in μ and β frequency bands of ear-lobe-referenced and surface Laplacian EEG indicate the contribution of both superficial and deep sources to ERD/ERS. As no physical displacement happens during the task, we can infer that the underlying mechanisms of motor-related ERPs and ERD/ERS patterns do not only depend on change in limb coordinate or muscle-length-dependent ascending sensory information and are primary generated by motor preparation, direction

Differential growth factor induction and modulation of human gastric epithelial regeneration

International Nuclear Information System (INIS)

Tetreault, Marie-Pier; Chailler, Pierre; Rivard, Nathalie; Menard, Daniel

2005-01-01

While several autocrine/paracrine growth factors (GFs) can all stimulate epithelial regeneration in experimentally wounded primary gastric cultures, clinical relevance for their non-redundant cooperative actions in human gastric ulcer healing is suggested by the sequential pattern of GF gene induction in vivo. Using new HGE cell lines able to form a coherent monolayer with tight junctions as well as using primary human gastric epithelial cultures, we show that EGF, TGFα, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGFβ pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGFα exerts strong effects (even more than EGF) on cytoplasmic spreading and non-oriented protruding activity of bordering cells whereas HGF preferentially coordinates single lamella formation, cell elongation and migration into the wound. IGF-I and IGF-II rather induce the alignment of bordering cells and maintain a compact monolayer front. The number of mitotic cells maximally increases with EGF, followed by TGFα and IGF-I,-II. The current study demonstrates that GFs differentially regulate the regeneration of human gastric epithelial cells through specific modulation of cell shape adaptation, migration and proliferation, further stressing that a coordination of GF activities would be necessary for the normal progression of post-wounding epithelial repair

Effects of the Visual Exercise Environments on Cognitive Directed Attention, Energy Expenditure and Perceived Exertion

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Mike Rogerson

2015-06-01

Full Text Available Green exercise research often reports psychological health outcomes without rigorously controlling exercise. This study examines effects of visual exercise environments on directed attention, perceived exertion and time to exhaustion, whilst measuring and controlling the exercise component. Participants completed three experimental conditions in a randomized counterbalanced order. Conditions varied by video content viewed (nature; built; control during two consistently-ordered exercise bouts (Exercise 1: 60% VO2peakInt for 15-mins; Exercise 2: 85% VO2peakInt to voluntary exhaustion. In each condition, participants completed modified Backwards Digit Span tests (a measure of directed attention pre- and post-Exercise 1. Energy expenditure, respiratory exchange ratio and perceived exertion were measured during both exercise bouts. Time to exhaustion in Exercise 2 was also recorded. There was a significant time by condition interaction for Backwards Digit Span scores (F2,22 = 6.267, p = 0.007. Scores significantly improved in the nature condition (p < 0.001 but did not in the built or control conditions. There were no significant differences between conditions for either perceived exertion or physiological measures during either Exercise 1 or Exercise 2, or for time to exhaustion in Exercise 2. This was the first study to demonstrate effects of controlled exercise conducted in different visual environments on post-exercise directed attention. Via psychological mechanisms alone, visual nature facilitates attention restoration during moderate-intensity exercise.

Prognostic factors of craniopharyngioma with special reference to autocrine/paracrine signaling: underestimated implication of growth hormone receptor.

Science.gov (United States)

Ogawa, Yoshikazu; Watanabe, Mika; Tominaga, Teiji

2015-10-01

Craniopharyngioma is a slow-growing tumor classified as benign, but tight adhesion and significant local infiltration to the vital structures are common. In spite of improvement of modern microsurgery techniques and precise anatomical understanding not few cases of this tumor recur, and long-term tumor control and maintenance of quality of life are sometimes difficult. However, very little is known about the effects of the molecular characters of craniopharyngioma on the prognosis. Ninety eight cases of craniopharyngioma surgically treated at the Department of Neurosurgery, Tohoku University Hospital and Kohnan Hospital from April 1996 to May 2014, 45 males and 53 females aged from 2 to 80 years (mean, 40.84 years) were retrospectively reviewed, and postoperative outcomes and the possible involvement of the autocrine/paracrine mechanism were investigated. The patients were followed up at intervals of 6 months to assess tumor recurrence, and clinical outcomes were correlated with the findings of immunohistochemical examinations used growth hormone receptor (GHR) and downstream hormones. The follow-up period ranged from 3 to 209 months. Hormone expression was examined in 88 patients, of which 46 specimens (52.3 %) showed high expression of GHR. The GHR high expression group had a significantly shorter duration of postoperative stable disease compared with the low expression group (logrank test, p = 0.007). Simultaneous high expression of growth hormone (GH) and GHR was found in 33 specimens (37.5 %), and the high expression group had a significantly shorter duration of postoperative stable disease compared with the low expression group (logrank test, p = 0.011). No other hormones showed statistically significant differences in outcomes. High expression of GHR is associated with shorter duration of postoperative stable disease in patients with craniopharyngioma. If the surgical specimens were craniopharyngiomas with high GHR expression, GH supplementation

Ace inhibitors and cardiovascular regulation : the importance of autocrine and paracrine mechanisms

NARCIS (Netherlands)

Wijngaarden, Jan van

1992-01-01

As demonstrated in a large number of clinical studies, angiotensin converting enzyme (ACE) inhibitors are of great value for the treatment of cardiovascular disorders. Although the clinical merits of these drugs are now well recognized, their mechanism of action is not yet completely understood. The

Traction Stresses Exerted by Adherent Cells: From Angiogenesis to Metastasis

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Reinhart-King, Cynthia

2010-03-01

Cells exert traction stresses against their substrate that mediate their ability to sense the mechanical properties of their microenvironment. These same forces mediate cell adhesion, migration and the formation of stable cell-cell contacts during tissue formation. In this talk, I will present our data on the traction stresses generated by endothelial cells and metastatic breast cancer cells focused on understanding the processes of angiogenesis and metastasis, respectively. In the context of capillary formation, our data indicate that the mechanics of the substrate play a critical role in establishing endothelial cell-cell contacts. On more compliant substrates, endothelial cell shape and traction stresses polarize and promote the formation of stable cell-cell contacts. On stiffer substrates, traction stresses are less polarized and cell connectivity is disrupted. These data indicate that the mechanical properties of the microenvironment may drive cell connectivity and the formation of stable cell-cell contacts through the reorientation of traction stresses. In our studies of metastatic cell migration, we have found that traction stresses increase with increasing metastatic potential. We investigated three lines of varying metastatic potential (MCF10A, MCF7 and MDAMB231). MDAMB231, which are the most invasive, exert the most significant forces as measured by Traction Force Microscopy. These data present the possibility that cellular traction stress generation aids in the ability of metastatic cells to migrate through the matrix-dense tumor microenvironment. Such measurements are integral to link the mechanical and chemical microenvironment with the resulting response of the cell in health and disease.

Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone (ACTH

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Amy ePerrin Ross

2013-03-01

Full Text Available Relapses in multiple sclerosis (MS are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the HPA axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides (ACTH and α-, β-, γ-melanocyte-stimulating hormones [MSH] and their receptors (MCRs exert multiple actions, including modulation of inflammatory and immune mediator production. Melanocortin receptors are widely distributed within the central nervous system and in peripheral tissues including immune cells (eg, macrophages. This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management.

An Emotion-Enriched Context Influences the Effect of Action Observation on Cortical Excitability

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Giovanna Lagravinese

2017-10-01

Full Text Available Observing other people in action activates the “mirror neuron system” that serves for action comprehension and prediction. Recent evidence suggests that this function requires a high level codification triggered not only by components of motor behavior, but also by the environment where the action is embedded. An overlooked component of action perceiving is the one related to the emotional information provided by the context where the observed action takes place. Indeed, whether valence and arousal associated to an emotion might exert an influence on motor system activation during action observation has not been assessed so far. Here, cortico-spinal excitability of the left motor cortex was recorded in three groups of subjects. In the first condition, motor-evoked potential (MEPs were recorded from a muscle involved in the grasping movement (i.e., abductor pollicis brevis, APB while participants were watching the same reach-to-grasp movement embedded in contexts with negative emotional valence, but different levels of arousal: sadness (low arousal, and disgust (high arousal (“Context plus Movement-APB” condition. In the second condition, MEPs were recorded from APB muscle while participants were observing static images representing the contexts in which the movement observed by participants in “Context plus Movement-APB” condition took place (“Context Only-APB” condition. Finally, in the third condition, MEPS were recorded from a muscle not involved in the grasping action, i.e., abductor digiti minimi, ADM, while participants were watching the same videos shown during the “Context plus Movement-APB” condition (“Context plus Movement-ADM” condition. Results showed a greater increase of cortical excitability only during the observation of the hand moving in the context eliciting disgust, and these changes were specific for the muscle involved in the observed action. Our findings show that the emotional context in which a

Incidental Finding of Inferior Vena Cava Atresia Presenting with Deep Venous Thrombosis following Physical Exertion

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Shalini Koppisetty

2015-01-01

Full Text Available Inferior vena cava atresia (IVCA is a rare but well described vascular anomaly. It is a rare risk factor for deep venous thrombosis (DVT, found in approximately 5% of cases of unprovoked lower extremity (LE DVT in patients <30 years of age. Affected population is in the early thirties, predominantly male, often with a history of major physical exertion and presents with extensive or bilateral DVTs. Patients with IVC anomalies usually develop compensatory circulation through the collateral veins with enlarged azygous/hemizygous veins. Despite the compensatory circulation, the venous drainage of the lower limbs is often insufficient leading to venous stasis and thrombosis. We describe a case of extensive and bilateral deep venous thrombosis following physical exertion in a thirty-six-year-old male patient with incidental finding of IVCA on imaging.

ATP-dependent paracrine communication between enteric neurons and glia in a primary cell culture derived from embryonic mice.

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Gomes, P; Chevalier, J; Boesmans, W; Roosen, L; van den Abbeel, V; Neunlist, M; Tack, J; Vanden Berghe, P

2009-08-01

The importance of dynamic interactions between glia and neurons is increasingly recognized, both in the central and enteric nervous system. However, apart from their protective role, little is known about enteric neuro-glia interaction. The aim was to investigate neuro-glia intercellular communication in a mouse culture model using optical techniques. Complete embryonic (E13) guts were enzymatically dissociated, seeded on coverslips and studied with immunohistochemistry and Ca(2+)-imaging. Putative progenitor-like cells (expressing both PGP9.5 and S-100) differentiated over approximately 5 days into glia or neurons expressing typical cell-specific markers. The glia-neuron ratio could be manipulated by specific supplements (N2, G5). Neurons and glia were functionally identified both by their Ca(2+)-response to either depolarization (high K(+)) or lysophosphatidic acid and by the expression of typical markers. Neurons responded to ACh, DMPP, 5-HT, ATP and electrical stimulation, while glia responded to ATP and ADPbetas. Inhibition of glial responses by MRS2179 suggests involvement of P2Y1 receptors. Neuronal stimulation also caused delayed glial responses, which were reduced by suramin and by exogenous apyrases that catalyse nucleotide breakdown. Conversely, glial responses were enhanced by ARL-67156, an ecto-ATPase inhibitor. In this mouse enteric co-culture, functional glia and neurons can be easily monitored using optical techniques. Glial cells can be activated directly by ATP or ADPbetas. Activation of neuronal cells (DMPP, K(+)) causes secondary responses in glial cells, which can be modulated by tuning ATP and ADP breakdown. This strongly supports the involvement of paracrine purinergic communication between enteric neurons and glia.

Influence of Exogenous β-Hydroxybutyrate on Walking Economy and Rating of Perceived Exertion.

Science.gov (United States)

James, Shaun; Kjerulf Greer, Beau

2018-06-28

This study investigates the effect of a supplementary ketone, β-hydroxybutyrate (BHB), on walking economy and ratings of perceived exertion in apparently healthy individuals. In a repeated-measures, crossover design, ten non-aerobically trained participants (three males; seven females) performed two stages of a duration-modified Bruce treadmill protocol. Participants blindly consumed either 1 ounce of an exogenous BHB solution (KETO) or a noncaloric placebo (CON) 30 minutes prior to exercise testing. Blood ketone and glucose concentrations were measured prior to supplementation (baseline), immediately before exercise, and after exercise. Oxygen consumption (VO 2 ), respiratory exchange ratio (RER), energy expenditure (EE), and rating of perceived exertion (RPE) were recorded during the last two minutes of each stage. Blood BHB concentrations were significantly elevated at the pre-exercise and postexercise time points as compared to the CON condition (p .05) were found for VO 2 , RER, EE, or RPE. The intervention of this study did not produce evidence of an ergogenic benefit from BHB supplementation in a healthy subject pool.

A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis.

Science.gov (United States)

Kubota, Kenta; Seno, Takeshi; Konishi, Yoshiyuki

2013-11-20

Cerebellar granule neuronal cultures have been used to study the molecular mechanisms underlying neuronal functions, including neuronal morphogenesis. However, a limitation of this system is the difficulty to analyze isolated neurons because these are required to be maintained at a high density. Therefore, in the present study, we aimed to develop a simple and cost-effective method for culturing low-density cerebellar granule neurons. Cerebellar granule cells at two different densities (low- and high-density) were co-cultivated in order for the low-density culture to be supported by the paracrine signals from the high-density culture. This method enabled morphology analysis of isolated cerebellar granule neurons without astrocytic feeder cultures or supplements such as B27. Using this method, we investigated the function of a polarity factor. Studies using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an essential regulator of neuronal polarity, and inhibition of GSK-3 results in the formation of multiple axons. Pharmacological inhibitors for GSK-3 (6-bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of multiple axons of cerebellar granule neurons but significantly reduced their length. Consistent results were obtained by introducing kinase-dead form of GSK-3 beta (K85A). These results indicated that GSK-3 is not directly involved in the control of neuronal polarity in cerebellar granule neurons. Overall, this study provides a simple method for culturing low-density cerebellar granule neurons and insights in to the neuronal-type dependent function of GSK-3 in neuronal morphogenesis. © 2013 Elsevier B.V. All rights reserved.

Exertional Myopathy in a Juvenile Green Sea Turtle (Chelonia mydas Entangled in a Large Mesh Gillnet

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Brianne E. Phillips

2015-01-01

Full Text Available A juvenile female green sea turtle (Chelonia mydas was found entangled in a large mesh gillnet in Pamlico Sound, NC, and was weak upon presentation for treatment. Blood gas analysis revealed severe metabolic acidosis and hyperlactatemia. Plasma biochemistry analysis showed elevated aspartate aminotransferase and creatine kinase, marked hypercalcemia, hyperphosphatemia, and hyperkalemia. Death occurred within 24 hours of presentation despite treatment with intravenous and subcutaneous fluids and sodium bicarbonate. Necropsy revealed multifocal to diffuse pallor of the superficial and deep pectoral muscles. Mild, multifocal, and acute myofiber necrosis was identified by histopathological examination. While histological changes in the examined muscle were modest, the acid-base, mineral, and electrolyte abnormalities were sufficiently severe to contribute to this animal’s mortality. Exertional myopathy in reptiles has not been well characterized. Sea turtle mortality resulting from forced submergence has been attributed to blood gas derangements and seawater aspiration; however, exertional myopathy may also be an important contributing factor. If possible, sea turtles subjected to incidental capture and entanglement that exhibit weakness or dull mentation should be clinically evaluated prior to release to minimize the risk of delayed mortality. Treatment with appropriate fluid therapy and supportive care may mitigate the effects of exertional myopathy in some cases.

Local Actions of Melatonin in Somatic Cells of the Testis.

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Frungieri, Mónica Beatriz; Calandra, Ricardo Saúl; Rossi, Soledad Paola

2017-05-31

The pineal hormone melatonin regulates testicular function through the hypothalamic-adenohypophyseal axis. In addition, direct actions of melatonin in somatic cells of the testis have been described. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular growth, proliferation, energy metabolism and the oxidation state, and consequently may regulate spermatogenesis. These data pinpoint melatonin as a key player in the regulation of testicular physiology (i.e., steroidogenesis, spermatogenesis) mostly in seasonal breeders. In patients with idiopathic infertility, melatonin exerts anti-proliferative and anti-inflammatory effects on testicular macrophages, and provides protective effects against oxidative stress in testicular mast cells. Consequently, melatonin is also involved in the modulation of inflammatory and oxidant/anti-oxidant states in testicular pathology. Overall, the literature data indicate that melatonin has important effects on testicular function and male reproduction.

The action of diazoxide and minoxidil sulphate on rat blood vessels: a comparison with cromakalim.

Science.gov (United States)

Newgreen, D. T.; Bray, K. M.; McHarg, A. D.; Weston, A. H.; Duty, S.; Brown, B. S.; Kay, P. B.; Edwards, G.; Longmore, J.; Southerton, J. S.

1990-01-01

1. The actions of diazoxide and minoxidil sulphate have been compared with those of cromakalim in rat aorta and portal vein. 2. Diazoxide and minoxidil sulphate hyperpolarized the rat portal vein in a similar manner to cromakalim. 3. Cromakalim, diazoxide and minoxidil sulphate increased 42K and 86Rb efflux from rat portal vein, although minoxidil sulphate had only a small effect on 86Rb efflux. 4. Cromakalim, diazoxide and minoxidil sulphate increased 42K efflux from rat aorta but only cromakalim and diazoxide increased 86Rb efflux from this tissue. 5. Glibenclamide inhibited the relaxant actions of cromakalim, diazoxide and minoxidil sulphate on rat aorta and the increase in 42K efflux produced by these agents in this tissue. 6. Diazoxide relaxed an 80 mM KCl-induced contraction of rat aorta, whilst cromakalim and minoxidil sulphate were without effect. 7. Cromakalim, diazoxide and minoxidil sulphate had no effect on cyclic AMP or cyclic GMP concentrations in rat aorta. 8. It is concluded that diazoxide and minoxidil sulphate like cromakalim exhibit K+ channel opening properties in vascular smooth muscle. Diazoxide exerts an additional inhibitory action not related to the production of cyclic AMP or cyclic GMP. The action of minoxidil sulphate may be primarily located at a K+ channel which is relatively impermeable to 86Rb. PMID:2167738

Comfort and exertion while using filtering facepiece respirators with exhalation valve and an active venting system among male military personnel.

Science.gov (United States)

Seng, Melvin; Wee, Liang En; Zhao, Xiahong; Cook, Alex R; Chia, Sin Eng; Lee, Vernon J

2017-07-06

This study aimed to determine if disposable filtering facepiece respirators (FFRs), with exhalation valve (EV) and a novel active venting system (AVS), provided greater perceived comfort and exertion when compared to standard N95 FFRs without these features among male military personnel performing prolonged essential outdoor duties. We used a randomised open-label controlled crossover study design to compare three FFR options: (a) standard FFR; (b) FFR with EV; and (c) FFR with EV+AVS. Male military personnel aged between 18 and 20 years completed a questionnaire at the beginning (baseline), after two hours of standardised non-strenuous outdoor duty and after 12 hours of duty divided into two-hour work-rest cycles. Participants rated the degree of discomfort, exertion and symptoms using a five-point Likert scale. The association between outcomes and the types of FFR was assessed using a multivariate ordered probit mixed-effects model. For a majority of the symptoms, study participants rated FFR with EV and FFR with EV+AVS with significantly better scores than standard FFR. Both FFR with EV and FFR with EV+AVS had significantly less discomfort (FFR with EV+AVS: 91.1%; FFR with EV: 57.6%) and exertion (FFR with EV+AVS: 83.5%; FFR with EV: 34.4%) than standard FFR. FFR with EV+AVS also had significantly better scores for exertion (53.4%) and comfort (39.4%) when compared to FFR with EV. Usage of FFR with EV+AVS resulted in significantly reduced symptoms, discomfort and exertion when compared to FFR with EV and standard FFR.

Immunoregulatory action of melatonin. The mechanism of action and the effect on inflammatory cells

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Sylwia Mańka

2016-10-01

Full Text Available Literature data indicate a significant immunoregulatory role of melatonin. Melatonin exerts an effect directly affecting leucocytes bearing specific melatonin receptors or indirectly by means of melatonin regulating other hormones, opioids or cytokines. Despite numerous experiments, the influence of the hormone on the immune system is still controversial. Melatonin affects the immune response acting as both an activator and an inhibitor of the inflammatory process. The hormone acts as an “immunological buffer” activating impaired immunity in immunosuppression, chronic stress or old age as well as suppressing overreaction of the immune system. Melatonin mediates between neurohormonal and immune systems by means of the immune-pineal axis acting as a negative feedback mechanism. The axis connects development of the immune reaction with pineal activity and melatonin secretion induced by inflammatory mediators. The seasonal and circadian fluctuation of the melatonin level and the fluctuation related changes of the immune parameters can be responsible for some autoimmune and infectious diseases. In spite of that, there is a growing number of papers suggesting considerable therapeutic potential of melatonin in inflammatory disease treatment. This paper presents well-systematized information on the mechanism of melatonin action and its influence on cells involved in the inflammatory process – neutrophils and monocytes.

Mechanical effects of strong measurement: back-action noise and cooling

Science.gov (United States)

Schwab, Keith

2007-03-01

Our recent experiments show that it is now possible to prepare and measure mechanical systems with thermal occupation factors of N˜25 and perform continuous position measurements close to the limits required by the Heisenberg Uncertainty Principle (1). I will discuss our back-action measurements with nanomechanical structures strongly coupled to single electron transistors. We have been able to observe the stochastic back-action forces exerted by the SET as well as a cooling effect which has analogies to cooling in optical cavities. Furthermore, I will discuss progress using optical fields coupled to mechanical modes which show substantial cooling using the pondermotive effects of the photons impacting a flexible dielectric mirror (2). Both of these techniques pave the way to demonstrating the true quantum properties of a mechanical device: squeezed states, superposition states, and entangled states. (1) ``Quantum Measurement Backaction and Cooling Observed with a Nanomechanical Resonator,'' A. Naik, O. Buu, M.D. LaHaye, M.P. Blencowe, A.D. Armour, A.A. Clerk, K.C. Schwab, Nature 443, 193 (2006). (2) ``Self-cooling of a micro-mirror by radiation pressure,'' S. Gigan, H.R. Boehm, M. Patemostro, F. Blaser, G. Langer, J. Hertzberg, K. Schwab, D. Baeuerle, M. Aspelmeyer, A. Zeilinger, Nature 444, 67 (2006).

Short-range intercellular calcium signaling in bone

DEFF Research Database (Denmark)

Jørgensen, Niklas Rye

2005-01-01

different mechanisms for this propagation. One mechanism involves the secretion of a nucleotide, possibly ATP, acting in an autocrine action to purinergic P2Y2 receptors on the neighboring cells, leading to intracellular IP3 generation and subsequent release of calcium from intracellular stores. The other...... to osteoclasts as well. We demonstrated that paracrine action of ATP was responsible for the wave propagation, but now the purinergic P2X7 receptor was involved. Thus, the studies demonstrate that calcium signals can be propagated not only among osteoblasts, but also between osteoblasts and osteoclasts...

Perceived exertion during muscle fatigue as reflected in movement-related cortical potentials: an event-related potential study.

Science.gov (United States)

Guo, Feng; Sun, Yong-Jun; Zhang, Ri-Hui

2017-02-08

The aim of this study was to explore the mechanism on perceived exertion during muscle fatigue. A total of 15 individuals in the fatigue group and 13 individuals in the nonfatigue group were recruited into this study, performing 200 intermittent handgrip contractions with 30% maximal voluntary contraction. The force, surface electromyography (sEMG), movement-related cortical potentials (MRCPs), and rating perception of effort (RPE) were combined to evaluate the perceived exertion during muscle fatigue. The maximal handgrip force significantly decreased (Pfatigue. The RPE scores reported by the individuals and the motor potential amplitude of MRCPs in the fatigue group significantly increased (Pfatigue but could also reflect the peripheral local muscle fatigue.

Angina and exertional myocardial ischemia in diabetic and nondiabetic patients: assessment by exercise thallium scintigraphy

International Nuclear Information System (INIS)

Nesto, R.W.; Phillips, R.T.; Kett, K.G.; Hill, T.; Perper, E.; Young, E.; Leland, O.S. Jr.

1988-01-01

Patients with diabetes mellitus and coronary artery disease are thought to have painless myocardial ischemia more often than patients without diabetes. We studied 50 consecutive patients with diabetes and 50 consecutive patients without diabetes, all with ischemia, on exercise thallium scintigraphy to show the reliability of angina as a marker for exertional ischemia. The two groups had similar clinical characteristics, treadmill test results, and extent of infarction and ischemia, but only 7 patients with diabetes compared with 17 patients without diabetes had angina during exertional ischemia. In diabetic patients the extent of retinopathy, nephropathy, or peripheral neuropathy was similar in patients with and without angina. Angina is an unreliable index of myocardial ischemia in diabetic patients with coronary artery disease. Given the increased cardiac morbidity and mortality in such patients, periodic objective assessments of the extent of ischemia are warranted

Immunohistochemical evidence for an endocrine/paracrine role for ghrelin in the reproductive tissues of sheep

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Brown Yvonne A

2005-10-01

tissues of the adult and fetal sheep. In addition, the data indicate that testicular expression of ghrelin and its receptor is physiologically regulated in the adult and developmentally regulated in the fetus. Therefore, the ghrelin ligand/receptor system may have a role (endocrine and/or paracrine in the development (cellular proliferation and function of the reproductive axis of the sheep.

Tourette Syndrome and Consciousness of Action

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Andrea E. Cavanna

2013-09-01

Full Text Available Background: Tourette syndrome (TS is a neuropsychiatric disorder characterized by the chronic presence of multiple motor tics and at least one vocal/phonic tic since childhood. Tics typically change and vary in both intensity and severity over time, with remission and exacerbation common. In the vast majority of patients, tic expression is characteristically accompanied by discomforting bodily sensations, known as sensory phenomena or premonitory urges.Methods: We reviewed the existing literature on premonitory urges associated with the sense of voluntariness of action in TS.Results: Although the wish to move is perceived by the patient as involuntary, the decision to release the tic is often perceived by the patient as a voluntary capitulation to the subjective urge. Most patients with TS can exert a degree of control over the urge and constantly try to inhibit the movement. Based on these features, it has been suggested that tics performed in response to an urge to move should be classified as ‘unvoluntary’, as opposed to voluntary or involuntary acts. However, recent experimental data suggest that the brain areas involved in the generation of the wish to act show considerable overlap between healthy subjects and patients with TS.Discussion: The simultaneous presence of both voluntary and involuntary aspects in the expression of tic symptoms by patients with TS is consistent with the hypothesis that tics can have the same neurophysiologic substrate as voluntary acts, even though they are misperceived as being involuntary. This reinforces the view of TS as a hyperkinetic movement disorder primarily affecting the conscious experience of action.

Forces exerted during exercises by patients with adolescent idiopathic scoliosis wearing fiberglass braces

OpenAIRE

Romano Michele; Carabalona Roberta; Petrilli Silvia; Sibilla Paolo; Negrini Stefano

2006-01-01

Abstract Objective To quantify and compare the forces exerted by scoliosis patients in fiberglass braces during exercises usually prescribed in departments where casts are made. The exercises are intended to increase corrective forces, activate muscles, stimulate ventilation and help the patient psychologically. Setting Outpatient care. Patients 17 consecutive adolescent patients wearing fiberglass brace for idiopathic scoliosis. Interventions Exercises (kyphotization, rotation, "escape from ...

Post-match Perceived Exertion, Feeling and Wellness in Professional Soccer Players.

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Fessi, Mohamed Saifeddin; Moalla, Wassim

2018-01-18

The aim of this study was to assess post-match perceived exertion, feeling and wellness according to the match outcome (winning, drawing or losing) in professional soccer players. Twelve outfield players were followed during 52 official matches where the outcomes (win, draw or lose) were noted. Following each match players completed both a 10-point scale rating of perceived exertion (RPE) and an 11-point scale rating of perceived feeling. Rating of perceived sleep quality, stress, fatigue and muscle soreness were collected separately on a 7-point scale the day following each match. Player RPE was higher by a very largely magnitude following a loss compared to a draw or a win and higher by a small magnitude after a draw compared to a win. Players felt more pleasure after a win compared to a draw or loss and more displeasure after a loss compared to draw. The players reported a largely and moderately better-perceived sleep quality, less stress and fatigue following a win compared to draw or a loss, and a moderately bad-perceived sleep quality, higher stress and fatigue following a draw compared to a loss. In contrast, only a trivial-small change was observed in perceived muscle soreness between all outcomes. Matches outcomes moderately to largely affect RPE, perceived feeling, sleep quality, stress and fatigue whereas perceived muscle soreness remains high regardless of the match outcome. However, winning a match decreases the strain and improves both pleasure and wellness in professional soccer players.

Action Learning: Avoiding Conflict or Enabling Action

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Corley, Aileen; Thorne, Ann

2006-01-01

Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

Nongenomic actions of cortisol in the teleost lactotroph model

DEFF Research Database (Denmark)

Borski, Russell J; Tipsmark, Christian Kølbæk; Mita, M

2006-01-01

of the present study was to investigate the role of phospholipase C (PLC)-IP3 in mediating cortisol's actions. During 30 min and 4-hour incubation, chicken GnRH-II induces a 2-4 fold increase in PRL release from the tilapia pituitary. The stimulatory effect of cGnRH-II was reduced by cortisol, cortisol-21......-hemisuccinate (HEF) and its membrane impermeant analog, HEF-BSA. Since GnRH induces PRL release, in part, via activation of PLC this suggests that cortisol may rapidly inhibit GnRH-induced PRL release by suppressing PLC activity. We also found that cortisol rapidly inhibits IP3 accumulation in tilapia RPD under...... stimulation by angiotensin II, a factor known to exert its cellular effects through stimulation of the PLC-IP3 pathway. Further studies demonstrate that cortisol reduces PLC activity (measured by the hydrolysis of 3H-PIP2) in a dose dependent manner from crude tilapia lactotroph membrane preparations. SRIF...

Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways.

Science.gov (United States)

Yang, Lichao; Guo, Han; Li, Ying; Meng, Xianglan; Yan, Lu; Dan Zhang; Wu, Sangang; Zhou, Hao; Peng, Lu; Xie, Qiang; Jin, Xin

2016-10-10

The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1990-05-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1989-06-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

[Visits of patients with exertional rhabdomyolysis to the Emergency Department at Landspítali, The National University Hospital of Iceland in the years 2008-2012].

Science.gov (United States)

Halldorsson, Arnljotur Bjorn; Benedikz, Elisabet; Olafsson, Isleifur; Mogensen, Brynjolfur

2016-03-01

Overexertion and too much training are among the -multiple etiologies of rhabdomyolysis. Creatine kinase (CK) and myo-globine, released from skeletal muscle cells, are useful for diagnosis and follow-up. Acute kidney injury is a serious complication of myoglobinemia. Literature on exertional rhabdomyolysis in the general population is scarce. The aim of this study was to investigate the epidemiology of exertional rhabdomyolysis among patients diagnosed at Landspítali The National University Hospital of Iceland in 2008-2012. The study was retrospective and observational. All patients presenting with muscle pain after exertion and elevated creatine kinase >1000 IU/L, during the period from 1 January 2008 to 31 December 2012, were included. Patients with CK elevations secondary to causes other than exertion were excluded. Variables included: patient number and gender, CK-levels, date of hospital admission, cause of rhabdomyolysis, location of injured muscle groups, length of hospital stay, complications and means of fluid replacement. Population figures of the capital region were gathered from Statistics Iceland and information on sport practice in the capital region from The National Olympic and Sports Association of Iceland. Exertional rhabdomyolysis was diagnosed in 54 patients, 18 females (33,3%) and 36 males (66,7%), or 8,3% of rhabdomyolysis cases from all causes in the study period (648 cases). Incidence in the capital region was 5,0/100.000 inhabitants per year in the study period. Median age was 28 years and median CK-level was 24.132 IU/L. CK-levels were higher among females but the difference between genders was not significant. Muscle groups of the upper and lower extremities were most frequently affected (89%). Thirty patients received intravenous fluids. They had significantly higher CK values than other patients. One patient developed acute kidney injury. Information on sport practice and physical training in the capital region was not available

Neural basis of exertional fatigue in the heat: A review of magnetic resonance imaging methods.

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Tan, X R; Low, I C C; Stephenson, M C; Soong, T W; Lee, J K W

2018-03-01

The central nervous system, specifically the brain, is implicated in the development of exertional fatigue under a hot environment. Diverse neuroimaging techniques have been used to visualize the brain activity during or after exercise. Notably, the use of magnetic resonance imaging (MRI) has become prevalent due to its excellent spatial resolution and versatility. This review evaluates the significance and limitations of various brain MRI techniques in exercise studies-brain volumetric analysis, functional MRI, functional connectivity MRI, and arterial spin labeling. The review aims to provide a summary on the neural basis of exertional fatigue and proposes future directions for brain MRI studies. A systematic literature search was performed where a total of thirty-seven brain MRI studies associated with exercise, fatigue, or related physiological factors were reviewed. The findings suggest that with moderate dehydration, there is a decrease in total brain volume accompanied with expansion of ventricular volume. With exercise fatigue, there is increased activation of sensorimotor and cognitive brain areas, increased thalamo-insular activation and decreased interhemispheric connectivity in motor cortex. Under passive hyperthermia, there are regional changes in cerebral perfusion, a reduction in local connectivity in functional brain networks and an impairment to executive function. Current literature suggests that the brain structure and function are influenced by exercise, fatigue, and related physiological perturbations. However, there is still a dearth of knowledge and it is hoped that through understanding of MRI advantages and limitations, future studies will shed light on the central origin of exertional fatigue in the heat. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts

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Miguel Tofiño-Vian

2017-01-01

Full Text Available Osteoarthritis (OA affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin- (IL- 1β indicate that conditioned medium, microvesicles, and exosomes from ASC downregulate senescence-associated β-galactosidase activity and the accumulation of γH2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E2. The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects.

Chronic Exposure to Subtherapeutic Antibiotics Aggravates Ischemic Stroke Outcome in Mice

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Xiao-Hui Dong

2017-10-01

Full Text Available Subtherapeutic antibiotics have been widely used in agriculture since the 1950s, which can be accumulated in human body through various approaches and may have long-term consequences. However, there is limited information about the link between chronic subtherapeutic antibiotic exposure and the outcome of ischemic brain injury. Here we showed that long-term treatment with subtherapeutic chlortetracycline, penicillin or vancomycin, which were widely used in agriculture approved by US Food and Drug Administration (FDA, could impair EPC functions, reduce ischemic brain angiogenesis and aggravate cerebral ischemic injury and long-term stroke outcomes in mice. In addition, transplantated EPCs from chronic antibiotic-treated mice showed a lower therapeutic effect on cerebral ischemic injury reduction and local angiogenesis promotion compared to those from control mice, and EPCs from the donor animals could integrate into the recipient ischemic brain in mice. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury reduction in mice, which could be impaired by chronic antibiotic exposure. In conclusion, chronic subtherapeutic antibiotic exposure aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of both EPC-mediated angiogenesis and EPCs' paracrine effects. These findings reveal a previously unrecognized impact of chronic subtherapeutic antibiotic exposure on ischemic injury.

Underlying mechanism of regulatory actions of diclofenac, a nonsteroidal anti-inflammatory agent, on neuronal potassium channels and firing: an experimental and theoretical study.

Science.gov (United States)

Huang, C W; Hung, T Y; Liao, Y K; Hsu, M C; Wu, S N

2013-06-01

Diclofenac (DIC), a nonsteroidal anti-inflammatory drug, is known to exert anti-nociceptive and anti-convulsant actions; however, its effects on ion currents, in neurons remain debatable. We aimed to investigate (1) potential effects of diclofenac on membrane potential and potassium currents in differentiated NSC-34 neuronal cells and dorsal root ganglion (DRG) neurons with whole-cell patch-clamp technology, and (2) firing of action potentials (APs), using a simulation model from hippocampal CA1 pyramidal neurons based on diclofenac's effects on potassium currents. In the NSC-34 cells, diclofenac exerted an inhibitory effect on delayed-rectifier K⁺ current (I(KDR)) with an IC₅₀ value of 73 μM. Diclofenac not merely inhibited the I(KDR) amplitude in response to membrane depolarization, but also accelerated the process of current inactivation. The inhibition by diclofenac of IK(DR) was not reversed by subsequent application of either naloxone. Importantly, diclofenac (300 μM) increased the amplitude of M-type K⁺ current (I)(KM)), while flupirtine (10 μM) or meclofenamic acid (10 μM) enhanced it effectively. Consistently, diclofenac (100 μM) increased the amplitude of I(KM) and diminished the I(KDR) amplitude, with a shortening of inactivation time constant in DRG neurons. Furthermore, by using the simulation modeling, we demonstrated the potential electrophysiological mechanisms underlying changes in AP firing caused by diclofenac. During the exposure to diclofenac, the actions on both I(KM) and I(KDR) could be potential mechanism through which it influences the excitability of fast-spiking neurons. Caution needs to be made in attributing the effects of diclofenac primarily to those produced by the activation of I(KM).

Cytotoxic action of Brazilian propolis in vitro on canine osteosarcoma cells.

Science.gov (United States)

Cinegaglia, N C; Bersano, P R O; Búfalo, M C; Sforcin, J M

2013-09-01

Osteosarcoma (OSA) is a primary bone neoplasm frequently diagnosed in dogs. The biology of OSA in pet dogs is identical to that of pediatric patients, and it has been considered an excellent model in vivo to study human OSA. Since the individual response to chemotherapy is unpredictable and considering that propolis is a natural product with several biological properties, this work evaluated the cytotoxic action of propolis on canine OSA cells. The primary cell culture of canine OSA was obtained from the tumor of a dog with OSA. Cell viability was assessed after incubation with propolis, 70% ethanol (propolis solvent), and carboplatin after 6, 24, 48, and 72 h. Cell viability was analyzed by the crystal violet method. Data showed that canine OSA cells were sensitive to propolis in a dose- and time-dependent manner and had a distinct morphology compared to control. Its solvent (70% ethanol) had no effect on cell viability, suggesting that the cytotoxic action was exclusively due to propolis. Our propolis sample exerted a cytotoxic effect on canine OSA cells, and its introduction as a possible therapeutic agent in vivo could be investigated, providing a new contribution to OSA treatment. Copyright © 2012 John Wiley & Sons, Ltd.

Direct action of aldosterone on transmembrane 22Na efflux from arterial smooth muscle. Rapid and delayed effects

International Nuclear Information System (INIS)

Moura, A.M.; Worcel, M.

1984-01-01

Acute subcutaneous (s.c.) administration of aldosterone increases ex vivo 22 Na efflux from rat tail artery smooth muscle, which appears to be due to a specific action on mineralocorticoid receptors. Indeed, this effect is blocked by the antimineralocorticoid compounds RU 28318 [17 beta-hydroxy-3-oxo,7 alpha-propyl(17 alpha)-pregn 4-ene, 21 potassium carboxylate] and spironolactone. The specific glucocorticoid receptor agonist RU 26988 does not modify 22 Na efflux. The authors show here that aldosterone has, at physiological concentrations, a mineralocorticoid specific stimulating effect on passive and sodium pump dependent transmembrane movements of sodium from the rat tail artery smooth muscle. Aldosterone exerts two types of action on sodium transport: 1) a delayed stimulation of ouabain-dependent 22 Na efflux and ouabain-independent 22 Na efflux, which are completely blocked by actinomycin D; and 2) a very rapid increase of passive 22 Na efflux, which is insensitive to actinomycin D and therefore does not seem to depend on transcription of genomic information

Controlling Attention through Action: Observing Actions Primes Action-Related Stimulus Dimensions

Science.gov (United States)

Fagioli, Sabrina; Ferlazzo, Fabio; Hommel, Bernhard

2007-01-01

Previous findings suggest that planning an action "backward-primes" perceptual dimension related to this action: planning a grasp facilitates the processing of visual size information, while planning a reach facilitates the processing of location information. Here we show that dimensional priming of perception through action occurs even in the…

Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection.

Science.gov (United States)

Nakamura, A; Hayashi, K; Fujiwara, K; Ozawa, Y; Honda, M; Saruta, T

2000-06-01

Aranidipine, a newly developed calcium antagonist, possesses unique pharmacologic characteristics in that its metabolite (M-1) still has antihypertensive action. We examined the effects of both agents on renal microcirculation using the isolated perfused hydronephrotic rat kidney. During norepinephrine-induced constriction, the addition of aranidipine dilated both afferent and efferent arterioles in a dose-dependent manner; at 10(-6) M, 83 +/- 6% and 90 +/- 6% reversal, respectively. In contrast, its active metabolite exerted dilator action predominantly on the afferent arteriole (79 +/- 4% vs. 44 +/- 17% at 10(-6) M for afferent and efferent arterioles, respectively). We further examined the long-term (8 weeks) effect of these agents on the development of renal injury in salt-loaded subtotally nephrectomized spontaneously hypertensive rats. Both aranidipine and M-1 reduced blood pressure by a similar magnitude. The decreases in proteinuria were observed in the aranidipine-treated group at weeks 6, 8, and 10, whereas in the M-1 group, significant reduction was attained only at week 6. Histopathologic examination revealed that both treatments improved glomerular and arteriolar sclerosis. Glomerular sclerosis, however, was less pronounced in the aranidipine-treated group than in the M-1 group. In conclusion, aranidipine has dilator action on both arterioles, whereas M-1 caused predominant dilation of afferent arterioles. Such metabolic changes may constitute a determinant of efferent arteriolar action of the calcium antagonist.

The Effects of Initial Self-Control Exertion and Subsequent Glucose Consumption on Search Accuracy by Dogs

Directory of Open Access Journals (Sweden)

Miller, Holly C.

2013-07-01

Full Text Available Previous reports have suggested that canine self-control is sensitive to fatigue and that an initial act of behavioral inhibition (sit-stay 10 min relative to a control condition (cage 10 min can deplete self-control, increase risk-taking, and reduce subsequent persistence on a puzzle task. Glucose, but not a calorie-free placebo drink has been shown to replenish this depletion. The current study sought to complement and extend these findings by examining whether initial exertion of self-control would also affect canine working memory as measured by search accuracy on a subsequently administered invisible displacement rotation task. The results evidenced that initial self-control exertion (relative to the control condition resulted in poorer search accuracy. The consumption of glucose did not have a replenishing effect. If anything, glucose was associated with poorer search accuracy.

Psychological stress exerts an adjuvant effect on skin dendritic cell functions in vivo.

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Saint-Mezard, Pierre; Chavagnac, Cyril; Bosset, Sophie; Ionescu, Marius; Peyron, Eric; Kaiserlian, Dominique; Nicolas, Jean-Francois; Bérard, Frédéric

2003-10-15

Psychological stress affects the pathophysiology of infectious, inflammatory, and autoimmune diseases. However, the mechanisms by which stress could modulate immune responses in vivo are poorly understood. In this study, we report that application of a psychological stress before immunization exerts an adjuvant effect on dendritic cell (DC), resulting in increased primary and memory Ag-specific T cell immune responses. Acute stress dramatically enhanced the skin delayed-type hypersensitivity reaction to haptens, which is mediated by CD8(+) CTLs. This effect was due to increased migration of skin DCs, resulting in augmented CD8(+) T cell priming in draining lymph nodes and enhanced recruitment of CD8(+) T cell effectors in the skin upon challenge. This adjuvant effect of stress was mediated by norepinephrine (NE), but not corticosteroids, as demonstrated by normalization of the skin delayed-type hypersensitivity reaction and DC migratory properties following selective depletion of NE. These results suggest that release of NE by sympathetic nerve termini during a psychological stress exerts an adjuvant effect on DC by promoting enhanced migration to lymph nodes, resulting in increased Ag-specific T cell responses. Our findings may open new ways in the treatment of inflammatory diseases, e.g., psoriasis, allergic contact dermatitis, and atopic dermatitis.

Evaluation of the anti-inflammatory actions of various functional food materials including glucosamine on synovial cells.

Science.gov (United States)

Yamagishi, Yoshie; Someya, Akimasa; Imai, Kensuke; Nagao, Junji; Nagaoka, Isao

2017-08-01

The anti-inflammatory actions of glucosamine (GlcN) on arthritic disorders involve the suppression of inflammatory mediator production from synovial cells. GlcN has also been reported to inhibit the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The present study aimed to determine the cooperative and anti‑inflammatory actions of functional food materials and evaluated the production of interleukin (IL)‑8 and phosphorylation of p38 MAPK in IL-1β-activated synovial cells, incubated with the combination of GlcN and various functional food materials containing L‑methionine (Met), undenatured type II collagen (UC‑II), chondroitin sulfate (CS), methylsulfonylmethane (MSM) and agaro-oligosaccharide (AO). The results indicated that Met, UC‑II, CS, MSM and AO slightly or moderately suppressed the IL-1β-stimulated IL‑8 production by human synovial MH7A cells. The same compounds further decreased the IL‑8 level lowered by GlcN. Similarly, they slightly suppressed the phosphorylation level of p38 MAPK and further reduced the phosphorylation level lowered by GlcN. These observations suggest a possibility that these functional food materials exert an anti‑inflammatory action (inhibition of IL‑8 production) in combination with GlcN by cooperatively suppressing the p38 MAPK signaling (phosphorylation).

Grasshopper Lazarillo, a GPI-anchored Lipocalin, increases Drosophila longevity and stress resistance, and functionally replaces its secreted homolog NLaz.

Science.gov (United States)

Ruiz, Mario; Wicker-Thomas, Claude; Sanchez, Diego; Ganfornina, Maria D

2012-10-01

Lazarillo (Laz) is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein first characterized in the developing nervous system of the grasshopper Schistocerca americana. It belongs to the Lipocalins, a functionally diverse family of mostly secreted proteins. In this work we test whether the protective capacity known for Laz homologs in flies and vertebrates (NLaz, GLaz and ApoD) is evolutionarily conserved in grasshopper Laz, and can be exerted from the plasma membrane in a cell-autonomous manner. First we demonstrate that extracellular forms of Laz have autocrine and paracrine protecting effects for oxidative stress-challenged Drosophila S2 cells. Then we assay the effects of overexpressing GPI-linked Laz in adult Drosophila and whether it rescues both known and novel phenotypes of NLaz null mutants. Local effects of GPI-linked Laz inside and outside the nervous system promote survival upon different stress forms, and extend lifespan and healthspan of the flies in a cell-type dependent manner. Outside the nervous system, expression in fat body cells but not in hemocytes results in protection. Within the nervous system, glial cell expression is more effective than neuronal expression. Laz actions are sexually dimorphic in some expression domains. Fat storage promotion and not modifications in hydrocarbon profiles or quantities explain the starvation-desiccation resistance caused by Laz overexpression. This effect is exerted when Laz is expressed ubiquitously or in dopaminergic cells, but not in hemocytes. Grasshopper Laz functionally restores the loss of NLaz, rescuing stress-sensitivity as well as premature accumulation of aging-related damage, monitored by advanced glycation end products (AGEs). However Laz does not rescue NLaz courtship behavioral defects. Finally, the presence of two new Lipocalins with predicted GPI-anchors in mosquitoes shows that the functional advantages of GPI-linkage have been commonly exploited by Lipocalins in the arthropodan lineage

Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism.

Science.gov (United States)

Rajan, Ravi Kumar; M, Siva Selva Kumar; Balaji, Bhaskar

2017-12-01

Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions. The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model. PCOS was induced in Sprague-Dawley rats with of 1 mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100 mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied. Soy isoflavones (100 mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary. Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood. Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.

Anti-inflammatory and anti-chemotactic effects of dietary flaxseed oil on CD8(+) T cell/adipocyte-mediated cross-talk.

Science.gov (United States)

Monk, Jennifer M; Liddle, Danyelle M; Brown, Morgan J; Zarepoor, Leila; De Boer, Anna A; Ma, David W L; Power, Krista A; Robinson, Lindsay E

2016-03-01

CD8(+) T cell/adipocyte paracrine interactions represent a critical step in the development of the obese inflammatory phenotype that is disrupted by long-chain n-3 PUFA. Our objective was to determine the effect of flaxseed-derived n-3 PUFA (α-linolenic acid) on these paracrine interactions. C57BL/6 mice were fed 3.5% flaxseed oil (FX) + 3.5% corn oil diet w/w or an isocaloric 7% corn oil w/w control diet (CON) for 3 wk. 3T3-L1 adipocytes and purified primary splenic CD8(+) T cells were cocultured at an obese cellular ratio (10% CD8(+) T cells) and LPS-stimulated (10 ng/mL mimicking obese circulating endotoxin levels) for 24 h. FX cocultures reduced (i) secreted IL-6, tumor necrosis factor α (TNF-α), macrophage chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), and RANTES (regulated on activation, normal T cell expressed and secreted) levels; (ii) activation of inflammatory transcription factors NFκB (nuclear factor kappa-light-chain-enhancer of activated B cell) p65 and signal transducer and activator of transcription-3 (STAT3); and (iii) RAW264.7 macrophage chemotaxis versus CON (p ≤ 0.05). Coculture of pre-inflamed adipocytes (10 ng/mL LPS, 24 h prior to CD8(+) T-cell addition) resulted in reduced secretion of IL-6, IL-1β, MCP-1, MCP-3, MIP-1β, and RANTES in FX cocultures versus CON (p ≤ 0.05). FX exerts an anti-chemotactic and anti-inflammatory effect on CD8(+) T cell/adipocyte paracrine interactions (cross-talk), which has the potential to mitigate macrophage chemotaxis which drives components of the obese phenotype. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair.

Directory of Open Access Journals (Sweden)

Dezhong Yang

Full Text Available BACKGROUND: Recent studies have demonstrated that transplantation of adipose-derived stem cell (ADSC can improve cardiac function in animal models of myocardial infarction (MI. However, the mechanisms underlying the beneficial effect are not fully understood. In this study, we characterized the paracrine effect of transplanted ADSC and investigated its relative importance versus direct differentiation in ADSC transplantation mediated cardiac repair. METHODOLOGY/PRINCIPAL FINDINGS: MI was experimentally induced in mice by ligation of the left anterior descending coronary artery. Either human ADSC, conditioned medium (CM collected from the same amount of ADSC or control medium was injected into the peri-infarct region immediately after MI. Compared with the control group, both ADSC and ADSC-CM significantly reduced myocardial infarct size and improved cardiac function. The therapeutic efficacy of ADSC was moderately superior to ADSC-CM. ADSC-CM significantly reduced cardiomyocyte apoptosis in the infarct border zone, to a similar degree with ADSC treatment. ADSC enhanced angiogenesis in the infarct border zone, but to a stronger degree than that seen in the ADSC-CM treatment. ADSC was able to differentiate to endothelial cell and smooth muscle cell in post-MI heart; these ADSC-derived vascular cells amount to about 9% of the enhanced angiogenesis. No cardiomyocyte differentiated from ADSC was found. CONCLUSIONS: ADSC-CM is sufficient to improve cardiac function of infarcted hearts. The therapeutic function of ADSC transplantation is mainly induced by paracrine-mediated cardioprotection and angiogenesis, while ADSC differentiation contributes a minor benefit by being involved in angiogenesis. Highlights 1 ADSC-CM is sufficient to exert a therapeutic potential. 2. ADSC was able to differentiate to vascular cells but not cardiomyocyte. 3. ADSC derived vascular cells amount to about 9% of the enhanced angiogenesis. 4. Paracrine effect is the major

The Effects of Direction of Exertion, Path, and Load Placement in Nursing Cart Pushing and Pulling Tasks: An Electromyographical Study.

Science.gov (United States)

Kao, Huei Chu; Lin, Chiuhsiang Joe; Lee, Yung Hui; Chen, Su Huang

2015-01-01

The purpose of this study was to explore the effects of direction of exertion (DOE) (pushing, pulling), path (walking in a straight line, turning left, walking uphill), and load placement (LP) (the 18 blocks were indicated by X, Y and Z axis; there were 3 levels on the X axis, 2 levels on the Y axis, and 3 levels on the Z axis) on muscle activity and ratings of perceived exertion in nursing cart pushing and pulling tasks. Ten participants who were female students and not experienced nurses were recruited to participate in the experiment. Each participant performed 108 experimental trials in the study, consisting of 2 directions of exertion (push and pull), 3 paths, and 18 load placements (indicated by X, Y and Z axes). A 23kg load was placed into one load placement. The dependent variables were electromyographic (EMG) data of four muscles collected bilaterally as follows: Left (L) and right (R) trapezius (TR), flexor digitorum superficialis (FDS), extensor digitorum (ED), and erector spinae (ES) and subjective ratings of perceived exertion (RPE). Split-split-plot ANOVA was conducted to analyze significant differences between DOE, path, and LP in the EMG and RPE data. Pulling cart tasks produced a significantly higher activation of the muscles (RTR:54.4%, LTR:50.3%, LFDS:57.0%, LED:63.4%, RES:40.7%, LES:36.7%) than pushing cart tasks (RTR:42.4%, LTR:35.1%, LFDS:32.3%, LED:55.1%, RES:33.3%, LES:32.1%). A significantly greater perceived exertion was found in pulling cart tasks than pushing cart tasks. Significantly higher activation of all muscles and perceived exertion were observed for walking uphill than walking in a straight line and turning left. Significantly lower muscle activity of all muscles and subject ratings were observed for the central position on the X axis, the bottom position on the Y axis, and the posterior position on the Z axis. These findings suggest that nursing staff should adopt forward pushing when moving a nursing cart, instead of backward

Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

Directory of Open Access Journals (Sweden)

Hany H Arab

Full Text Available Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o. attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO and tumor necrosis factor-α (TNF-α levels along with nuclear factor kappa B (NF-κB p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10 levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH, glutathione peroxidase (GPx and the total antioxidant capacity (TAC. With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2 in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2 and nitric oxide (NO. Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

Assessing potential targets of calcium action in light-modulated gravitropism

Science.gov (United States)

Roux, S. J.

1995-01-01

Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

A Functional Return-to-Play Progression After Exertional Heat Stroke in a High School Football Player.

Science.gov (United States)

Lopez, Rebecca M; Tanner, Patrick; Irani, Sarah; Mularoni, P Patrick

2018-03-01

  To present a functional return-to-play (RTP) progression after exertional heat stroke (EHS) in a 17-year-old high school football defensive end (height = 185 cm, mass = 145.5 kg).   The patient had no pertinent medical history but moved to a warm climate several days before the EHS occurred. After completing an off-season conditioning test (14- × 110-yd [12.6- × 99.0-m] sprints) on a warm afternoon (temperature = approximately 34°C [93°F], relative humidity = 53%), the patient collapsed. An athletic trainer (AT) was called to the field, where he found the patient conscious but exhibiting central nervous system dysfunction. Emergency medical services were summoned and immediately transported the patient to the hospital.   Exertional heat stroke, heat exhaustion, exertional sickling, rhabdomyolysis, and cardiac arrhythmia.   The patient was immediately transported to a hospital, where his oral temperature was 39.6°C (103.3°F). He was transferred to a children's hospital and treated for rhabdomyolysis, transaminitis, and renal failure. He was hospitalized for 11 days. After a physician's clearance once the laboratory results normalized, an RTP progression was completed. The protocol began with light activity and progressed over 3 weeks to full football practice. During activity, an AT monitored the patient's gastrointestinal temperature, heart rate, rating of perceived exertion, fluid consumption, and sweat losses.   Documentation of RTP guidelines for young athletes is lacking. We used a protocol intended for the football setting to ensure the athlete was heat tolerant, had adequate physical fitness, and could safely RTP. Despite his EHS, he recovered fully, with no lasting effects, and successfully returned to compete in the final 5 games of the season.   Using a gradual RTP progression and close monitoring, a high school defensive end successfully returned to football practice and games after EHS. This case demonstrates the feasibility of

Anti-Inflammatory and Immune Regulatory Actions of Naja naja atra Venom

Directory of Open Access Journals (Sweden)

Shu-Zhi Wang

2018-02-01

Full Text Available Naja naja atra venom (NNAV is composed of various proteins, peptides, and enzymes with different biological and pharmacological functions. A number of previous studies have reported that NNAV exerts potent analgesic effects on various animal models of pain. The clinical studies using whole venom or active components have confirmed that NNAV is an effective and safe medicine for treatment of chronic pain. Furthermore, recent studies have demonstrated that NNAV has anti-inflammatory and immune regulatory actions in vitro and in vivo. In this review article, we summarize recent studies of NNAV and its components on inflammation and immunity. The main new findings in NNAV research show that it may enhance innate and humoral immune responses while suppressing T lymphocytes-mediated cellular immunity, thus suggesting that NNAV and its active components may have therapeutic values in the treatment of inflammatory and autoimmune diseases.

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1990-09-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1994-03-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1991-05-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1993-09-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1990-11-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1992-08-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1991-02-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1993-06-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1990-03-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1991-07-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1992-05-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1993-12-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1993-03-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1991-11-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1992-03-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1992-11-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July - September 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1989-12-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio embryos

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Tsai Tzu-Chun

2012-07-01

Full Text Available Abstract Background Dysmorphogenesis and multiple organ defects are well known in zebrafish (Danio rerio embryos with T-box transcription factor 5 (tbx5 deficiencies, mimicking human Holt-Oram syndrome. Methods Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with tbx5-morpholino (MO antisense RNA and mismatched antisense RNA in the 1-cell stage served as controls, while zebrafish embryos co-injected with exogenous growth hormone (GH concomitant with tbx5-MO comprised the treatment group. Results The attenuating effects of GH in tbx5-MO knockdown embryos were quantified and observed at 24, 30, 48, 72, and 96 h post-fertilization. Though the understanding of mechanisms involving GH in the tbx5 functioning complex is limited, exogenous GH supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF-1 pathway, including igf1, ghra, and ghrb, and signal transductors (erk1, akt2, and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. Supplementary GH also reduced apoptosis as determined by a TUNEL assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (p27 and cdk2 and cardiomyogenetic genes (amhc, vmhc, and cmlc2. Conclusions Based on our results, tbx5 knockdown causes a pseudo GH deficiency in zebrafish during early embryonic stages, and supplementation of exogenous GH can partially restore dysmorphogenesis, apoptosis, cell growth inhibition, and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner.

Action of methotrexate and tofacitinib on directly stimulated and bystander-activated lymphocytes.

Science.gov (United States)

Piscianz, Elisa; Candilera, Vanessa; Valencic, Erica; Loganes, Claudia; Paron, Greta; De Iudicibus, Sara; Decorti, Giuliana; Tommasini, Alberto

2016-07-01

Chronic inflammation associated with autoimmune activation is characteristic of rheumatic diseases from childhood to adulthood. In recent decades, significant improvements in the treatment of these types of disease have been achieved using disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and, more recently, using biologic inhibitors. The recent introduction of kinase inhibitors (for example, tofacitinib; Tofa) further increases the available ARDs. However, there are patients that do not respond to any treatment strategies, for whom combination therapies are proposed. The data regarding the combined action of different drugs is lacking and the knowledge of the mechanisms of ARDs and their actions upon pathogenic lymphocytes, which are hypothesized to sustain disease, is poor. An in vitro model of inflammation was developed in the current study, in which stimulated and unstimulated lymphocytes were cultured together, but tracked separately, to investigate the action of MTX and Tofa on the two populations. By analysing lymphocyte proliferation and activation, and cytokine secretion in the culture supernatants, it was established that, due to the presence of activated cells, unstimulated cells underwent a bystander activation that was modulated by the ARDs. Additionally, varying administration schedules were demonstrated to affect lymphocytes differently in vitro, either directly or via bystander activation. Furthermore, MTX and Tofa exerted different effects; while MTX showed an antiproliferative effect, Tofa marginally effected activation, although only a slight antiproliferative action, which could be potentiated by sequential treatment with MTX. Thus, it was hypothesized that these differences may be exploited in sequential therapeutic strategies, to maximize the anti‑rheumatic effect. These findings are notable and must be accounted for, as bystander‑activated cells in vivo could contribute to the spread of autoimmune activation

The mechanism of action of MF59 - an innately attractive adjuvant formulation.

Science.gov (United States)

O'Hagan, D T; Ott, G S; De Gregorio, E; Seubert, A

2012-06-19

MF59 is a safe and effective vaccine adjuvant which was originally approved to be included in a licensed influenza vaccine to be used in the elderly in Europe in 1997. The MF59 adjuvanted influenza vaccine (Fluad™) is now licensed in more than 20 countries worldwide and more than 85 million doses have been administered. More recently the vaccine adjuvant has also been shown to be safe and effective in young children and resulted in a significant increase in influenza vaccine efficacy in a controlled clinical trial in Europe. Since the early days of its discovery we have explored the mechanism of action of MF59, using a variety of available techniques. In recent years we have explored more thoroughly the mechanism of action using new and more sophisticated techniques. It is remarkable how consistent the data has been, using a variety of different approaches both in several small animal models and also using human immune cells in vitro. Here we present a summary of all the work performed to date on the mechanism of action of MF59 and we present a unified theory based on the accumulated data of how it exerts its adjuvant effects. A key element of the mechanism of action appears to be the creation of a transient 'immunocompetent' local environment at the injection site, resulting in the recruitment of key immune cells, which are able to take up antigen and adjuvant and transport them to the local lymph nodes, where the immune response is induced. This recruitment appears to be triggered by the induction of a chemokine driven gradient by the impact of MF59 on local cells, which are activated to secrete further chemokines, which are recruitment factors for more immune cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

A review on alcohol: from the central action mechanism to chemical dependency

Directory of Open Access Journals (Sweden)

João Victor Vezali Costardi

2015-08-01

Full Text Available SummaryIntroduction:alcohol is a psychotropic depressant of the central nervous system (CNS that promotes simultaneous changes in several neuronal pathways, exerting a profound neurological impact that leads to various behavioral and biological alterations.Objectives:to describe the effects of alcohol on the CNS, identifying the signaling pathways that are modified and the biological effects resulting from its consumption.Methods:a literature review was conducted and articles published in different languages over the last 15 years were retrieved.Results:the studies reviewed describe the direct effect of alcohol on several neurotransmitter receptors (gamma-aminobutyric acid [GABA], glutamate, endocannabinoids AEA and 2-AG, among others, the indirect effect of alcohol on the limbic and opioid systems, and the effect on calcium and potassium channels and on proteins regulated by GABA in the hippocampus.Discussion and conclusion:the multiple actions of alcohol on the CNS result in a general effect of psychomotor depression, difficulties in information storage and logical reasoning and motor incoordination, in addition to stimulating the reward system, a fact that may explain the development of addiction. Knowledge on the neuronal signaling pathways that are altered by alcohol allows the identification of effectors which could reduce its central action, thus, offering new therapeutic perspectives for the rehabilitation of alcohol addicts.

A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment.

Science.gov (United States)

Zuo, Li; Tozawa, Keiichi; Okada, Atsushi; Yasui, Takahiro; Taguchi, Kazumi; Ito, Yasuhiko; Hirose, Yasuhiko; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Ando, Ryosuke; Itoh, Yasunori; Zou, Jiangang; Kohri, Kenjiro

2014-06-01

We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation. Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells. Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Action preferences and the anticipation of action outcomes

NARCIS (Netherlands)

Mann, D.L.; Schaefers, T.; Canal Bruland, R.

2014-01-01

Skilled performers of time-constrained motor actions acquire information about the action preferences of their opponents in an effort to better anticipate the outcome of that opponent's actions. However, there is reason to doubt that knowledge of an opponent's action preferences would unequivocally

The endoplasmic reticulum exerts control over organelle streaming during cell expansion.

Science.gov (United States)

Stefano, Giovanni; Renna, Luciana; Brandizzi, Federica

2014-03-01

Cytoplasmic streaming is crucial for cell homeostasis and expansion but the precise driving forces are largely unknown. In plants, partial loss of cytoplasmic streaming due to chemical and genetic ablation of myosins supports the existence of yet-unknown motors for organelle movement. Here we tested a role of the endoplasmic reticulum (ER) as propelling force for cytoplasmic streaming during cell expansion. Through quantitative live-cell analyses in wild-type Arabidopsis thaliana cells and mutants with compromised ER structure and streaming, we demonstrate that cytoplasmic streaming undergoes profound changes during cell expansion and that it depends on motor forces co-exerted by the ER and the cytoskeleton.

Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

Energy Technology Data Exchange (ETDEWEB)

Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

2013-11-15

Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment. �

Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

International Nuclear Information System (INIS)

Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra

2013-01-01

Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment. �

The Effect of Lysophosphatidic Acid during In Vitro Maturation of Bovine Oocytes: Embryonic Development and mRNA Abundances of Genes Involved in Apoptosis and Oocyte Competence

Directory of Open Access Journals (Sweden)

Dorota Boruszewska

2014-01-01

Full Text Available In the present study we examined whether LPA can be synthesized and act during in vitro maturation of bovine cumulus oocyte complexes (COCs. We found transcription of genes coding for enzymes of LPA synthesis pathway (ATX and PLA2 and of LPA receptors (LPAR 1–4 in bovine oocytes and cumulus cells, following in vitro maturation. COCs were matured in vitro in presence or absence of LPA (10−5 M for 24 h. Supplementation of maturation medium with LPA increased mRNA abundance of FST and GDF9 in oocytes and decreased mRNA abundance of CTSs in cumulus cells. Additionally, oocytes stimulated with LPA had higher transcription levels of BCL2 and lower transcription levels of BAX resulting in the significantly lower BAX/BCL2 ratio. Blastocyst rates on day 7 were similar in the control and the LPA-stimulated COCs. Our study demonstrates for the first time that bovine COCs are a potential source and target of LPA action. We postulate that LPA exerts an autocrine and/or paracrine signaling, through several LPARs, between the oocyte and cumulus cells. LPA supplementation of maturation medium improves COC quality, and although this was not translated into an enhanced in vitro development until the blastocyst stage, improved oocyte competence may be relevant for subsequent in vivo survival.

11β-Hydroxysteroid Dehydrogenases and Hypertension in the Metabolic Syndrome.

Science.gov (United States)

Bailey, Matthew A

2017-11-14

The metabolic syndrome describes a clustering of risk factors-visceral obesity, dyslipidaemia, insulin resistance, and salt-sensitive hypertension-that increases mortality related to cardiovascular disease, type 2 diabetes, cancer, and non-alcoholic fatty liver disease. The prevalence of these concurrent comorbidities is ~ 25-30% worldwide, and metabolic syndrome therefore presents a significant global public health burden. Evidence from clinical and preclinical studies indicates that glucocorticoid excess is a key causal feature of metabolic syndrome. This is not increased systemic in circulating cortisol, rather increased bioavailability of active glucocorticoids within tissues. This review examines the role of covert glucocorticoid excess on the hypertension of the metabolic syndrome. Here, the role of the 11β-hydroxysteroid dehydrogenase enzymes, which exert intracrine and paracrine control over glucocorticoid signalling, is examined. 11βHSD1 amplifies glucocorticoid action in cells and contributes to hypertension through direct and indirect effects on the kidney and vasculature. The deactivation of glucocorticoid by 11βHSD2 controls ligand access to glucocorticoid and mineralocorticoid receptors: loss of function promotes salt retention and hypertension. As for hypertension in general, high blood pressure in the metabolic syndrome reflects a complex interaction between multiple systems. The clear association between high dietary salt, glucocorticoid production, and metabolic disorders has major relevance for human health and warrants systematic evaluation.

Vitamin D endocrine system involvement in autoimmune rheumatic diseases.

Science.gov (United States)

Cutolo, Maurizio; Pizzorni, Carmen; Sulli, Alberto

2011-12-01

Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels. Copyright © 2011 Elsevier B.V. All rights reserved.

Self-selected music-induced reduction of perceived exertion during moderate-intensity exercise does not interfere with post-exercise improvements in inhibitory control.

Science.gov (United States)

Tanaka, Daichi; Tsukamoto, Hayato; Suga, Tadashi; Takenaka, Saki; Hamaoka, Takafumi; Hashimoto, Takeshi; Isaka, Tadao

2018-05-26

Acute aerobic exercise improves inhibitory control (IC). This improvement is often associated with increases in perceived exertion during exercise. However, listening to music during aerobic exercise mitigates an exercise-induced increase in perceived exertion. Thus, it is hypothesized that such effects of music may interfere with exercise-induced improvements in IC. To test this hypothesis, we examined the effect of music on post-exercise IC improvements that were induced by moderate-intensity exercise. Fifteen healthy young men performed cycle ergometer exercise with music or non-music. The exercise was performed using a moderate-intensity of 60% of VO 2 peak for 30 min. The music condition was performed while listening to self-selected music. The non-music condition involved no music. To evaluate IC, the Stroop task was administered before exercise, immediately after exercise, and during the 30-min post-exercise recovery period. The rate of perceived exertion immediately before moderate-intensity exercise completed was significantly lower in music condition than in non-music condition. The IC significantly improved immediately after exercise and during the post-exercise recovery period compared to before exercise in both music and non-music conditions. The post-exercise IC improvements did not significantly differ between the two conditions. These findings indicate that self-selected music-induced mitigation of the increase in perceived exertion during moderate-intensity exercise dose not interfere with exercise-induced improvements in IC. Therefore, we suggest that listening to music may be a beneficial strategy in mitigating the increase in perceived exertion during aerobic exercise without decreasing the positive effects on IC. Copyright © 2018 Elsevier Inc. All rights reserved.

Antimicrobial compounds targeting Gram-negative bacteria in food: Their mode of action and combinational effects

DEFF Research Database (Denmark)

Hyldgaard, Morten

2015-01-01

compromising food shelf-life or safety. Natural antimicrobial compounds have therefore gained increased interest as a label-friendly alternative that can be added directly to food products. Although natural antimicrobials constitute an interesting source of compounds, it is often not understood how...... they interact with bacterial cells to exert their mechanism of inhibition or killing. Furthermore, natural antimicrobials are often not potent enough as single compounds, and may cause unwanted sensory side-effects, which limit the quantities that can be applied to food. These problems might be circumvented...... by combining antimicrobials to decrease the concentrations needed without compromising their antimicrobial activity. The work described in this dissertation presents two projects concerning the mechanism of action of selected natural antimicrobial compounds primarily against Gram-negative bacteria, and two...

Effects of the Visual Exercise Environments on Cognitive Directed Attention, Energy Expenditure and Perceived Exertion.

Science.gov (United States)

Rogerson, Mike; Barton, Jo

2015-06-30

Green exercise research often reports psychological health outcomes without rigorously controlling exercise. This study examines effects of visual exercise environments on directed attention, perceived exertion and time to exhaustion, whilst measuring and controlling the exercise component. Participants completed three experimental conditions in a randomized counterbalanced order. Conditions varied by video content viewed (nature; built; control) during two consistently-ordered exercise bouts (Exercise 1: 60% VO2peakInt for 15-mins; Exercise 2: 85% VO2peakInt to voluntary exhaustion). In each condition, participants completed modified Backwards Digit Span tests (a measure of directed attention) pre- and post-Exercise 1. Energy expenditure, respiratory exchange ratio and perceived exertion were measured during both exercise bouts. Time to exhaustion in Exercise 2 was also recorded. There was a significant time by condition interaction for Backwards Digit Span scores (F2,22 = 6.267, p = 0.007). Scores significantly improved in the nature condition (p visual environments on post-exercise directed attention. Via psychological mechanisms alone, visual nature facilitates attention restoration during moderate-intensity exercise.

DAPs: Deep Action Proposals for Action Understanding

KAUST Repository

Escorcia, Victor

2016-09-17

Object proposals have contributed significantly to recent advances in object understanding in images. Inspired by the success of this approach, we introduce Deep Action Proposals (DAPs), an effective and efficient algorithm for generating temporal action proposals from long videos. We show how to take advantage of the vast capacity of deep learning models and memory cells to retrieve from untrimmed videos temporal segments, which are likely to contain actions. A comprehensive evaluation indicates that our approach outperforms previous work on a large scale action benchmark, runs at 134 FPS making it practical for large-scale scenarios, and exhibits an appealing ability to generalize, i.e. to retrieve good quality temporal proposals of actions unseen in training.

Effect of Stimulant Medication Use by Children with ADHD on Heart Rate and Perceived Exertion

Science.gov (United States)

Mahon, Anthony D.; Woodruff, Megan E.; Horn, Mary P.; Marjerrison, Andrea D.; Cole, Andrew S.

2012-01-01

The effect of stimulant medication use by children with attention deficit/hyperactivity disorder (ADHD) on the rating of perceived exertion (RPE)--heart rate (HR) relationship was examined. Children with ADHD (n = 20; 11.3 [plus or minus] 1.8 yrs) and children without ADHD (n = 25; 11.2 [plus or minus] 2.1 yrs) were studied. Children with ADHD…

Effects of rest interval length on Smith machine bench press performance and perceived exertion in trained men.

Science.gov (United States)

Tibana, Ramires A; Vieira, Denis C L; Tajra, Vitor; Bottaro, Martim; de Salles, Belmiro F; Willardson, Jeffrey M; Prestes, Jonato

2013-12-01

This study compared two different rest intervals (RI) between sets of resistance exercise. Ten resistance-trained men (M age = 24.3, SD = 3.5 yr.; M weigh t= 80.0 kg, SD = 15.3; M height = 1.75 m, SD = 0.04) performed five sets of Smith machine bench presses at 60% of one repetition maximum, either with 1.5 min. or 3 min. RI between sets. Their repetition performance, total training volume, velocity, fatigue, rating of perceived exertion, and muscular power were measured. All of these measures indicated that performance was significantly better and fatigue was significantly lower in the 3 min. RI as compared with the 1.5 min. RI, except the rating of perceived exertion which did not show a significant difference. A longer RI between sets promotes superior performance for the bench press.

Evidence for paracrine/autocrine regulation of GLP-1-producing cells

DEFF Research Database (Denmark)

Kappe, Camilla; Zhang, Qimin; Holst, Jens Juul

2013-01-01

Glucagon-like peptide-1 (GLP-1), secreted from gut L cells upon nutrient intake, forms the basis for novel drugs against type 2 diabetes (T2D). Secretion of GLP-1 has been suggested to be impaired in T2D and in conditions associated with hyperlipidemia and insulin resistance. Further, recent...... studies support lipotoxicity of GLP-1-producing cells in vitro. However, little is known about the regulation of L-cell viability/function, the effects of insulin signaling, or the potential effects of stable GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors. We determined effects of insulin...... as well as possible autocrine action of GLP-1 on viability/apoptosis of GLP-1-secreting cells in the presence/absence of palmitate, while also assessing direct effects on function. The studies were performed using the GLP-1-secreting cell line GLUTag, and palmitate was used to simulate hyperlipidemia. Our...

Givental action and trivialisation of circle action

NARCIS (Netherlands)

Dotsenko, V.; Shadrin, S.; Vallette, B.

2015-01-01

In this paper, we show that the Givental group action on genus zero cohomological field theories, also known as formal Frobenius manifolds or hypercommutative algebras, naturally arises in the deformation theory of Batalin-Vilkovisky algebras. We prove that the Givental action is equal to an action

Tricholin, a new antifungal agent from Trichoderma viride, and its action in biological control of Rhizoctonia solani.

Science.gov (United States)

Lin, A; Lee, T M; Rern, J C

1994-07-01

Tricholin, a ribosome-inactivating protein isolated from the culture broth of Trichoderma viride, has been shown to exert fungicidal effects on Rhizoctonia solani through a multi-hit kinetic interaction. Tricholin causes a parallel cessation of growth, uptake of amino acids, and protein biosynthesis. The in vivo mode of action of tricholin on protein synthesis and cell growth appears to be attributed to the diminishing of the polysome formation in R. solani through damage to large ribosomal subunits. These results concur with previous data and prove that tricholin is an effective inhibitor of protein synthesis. The efficacy of tricholin as an antibiotic agent was estimated to have a duration of approximately 42 hours.

Is credit for early action credible early action?

International Nuclear Information System (INIS)

Rolfe, C.; Michaelowa, A.; Dutschke, M.

1999-12-01

Credit for early action as a tool for greenhouse gas emissions reduction is compared with various market instruments as a means of narrowing the gap between projected emissions and those of the Kyoto Protocol. Market instruments work by creating a market price for emissions and use the market to encourage reductions at the lowest price, which is done by placing limits on greenhouse gas emissions and allowing the market to decide where reductions occur, or by imposing a carbon tax or emissions charge. While they can be applied within a sector, they are usually used to encourage reductions throughout the economy or across large sectors. Credit for early action also creates an incentive for emissions reductions throughout the economy or at least across many sectors. Credit for early action tools do not work by either imposing a carbon tax or emissions charge or placing limits on emissions, rather they promise that entities that take action against greenhouse gases prior to the imposition of a carbon tax or emissions limits will receive a credit against future taxes or limits. An overview is provided of the Kyoto Protocol and the rationale for taking early action, and a review is included of the theory and specific proposals for market instruments and credit for early action. A comparative analysis is provided of these approaches by examining their relative efficiency, environmental effectiveness, and impacts on the redistribution of wealth. Credit for early action is viewed as problematic on a number of counts and is seen as an interim strategy for imposition while political support for market instruments develop. The environmental effectiveness of credit for early action is very difficult to predict, and credit for early action programs do not yield the lowest cost emissions reductions. Credit for early action programs will not achieve compliance with the Kyoto Protocol at the lowest cost, and credits for early action will increase the compliance costs for those who

Human occipital cortices differentially exert saccadic suppression: intracranial recording in children

Science.gov (United States)

Uematsu, Mitsugu; Matsuzaki, Naoyuki; Brown, Erik C.; Kojima, Katsuaki; Asano, Eishi

2013-01-01

By repeating saccades unconsciously, humans explore the surrounding world every day. Saccades inevitably move external visual images across the retina at high velocity; nonetheless, healthy humans don’t perceive transient blurring of the visual scene during saccades. This perceptual stability is referred to as saccadic suppression. Functional suppression is believed to take place transiently in the visual systems, but it remains unknown how commonly or differentially the human occipital lobe activities are suppressed at the large-scale cortical network level. We determined the spatial-temporal dynamics of intracranially-recorded gamma activity at 80–150 Hz around spontaneous saccades under no-task conditions during wakefulness and those in darkness during REM sleep. Regardless of wakefulness or REM sleep, a small degree of attenuation of gamma activity was noted in the occipital regions during saccades, most extensively in the polar and least in the medial portions. Longer saccades were associated with more intense gamma-attenuation. Gamma-attenuation was subsequently followed by gamma-augmentation most extensively involving the medial and least involving the polar occipital region. Such gamma-augmentation was more intense during wakefulness and temporally locked to the offset of saccades. The polarities of initial peaks of perisaccadic event-related potentials (ERPs) were frequently positive in the medial and negative in the polar occipital regions. The present study, for the first time, provided the electrophysiological evidence that human occipital cortices differentially exert peri-saccadic modulation. Transiently suppressed sensitivity of the primary visual cortex in the polar region may be an important neural basis for saccadic suppression. Presence of occipital gamma-attenuation even during REM sleep suggests that saccadic suppression might be exerted even without external visual inputs. The primary visual cortex in the medial region, compared to the

Combination of Tramadol with Minocycline Exerted Synergistic Effects on a Rat Model of Nerve Injury-Induced Neuropathic Pain

Directory of Open Access Journals (Sweden)

Xiao-Peng Mei

2012-09-01

Full Text Available Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.

Equivalent anticancer activities of dietary vitamin D and calcitriol in an animal model of breast cancer: importance of mammary CYP27B1 for treatment and prevention.

Science.gov (United States)

Krishnan, Aruna V; Swami, Srilatha; Feldman, David

2013-07-01

Calcitriol [1,25(OH)2D3], the hormonally active form of vitamin D exerts anti-proliferative, pro-apoptotic, anti-inflammatory effects and other anticancer actions in breast cancer (BCa) cell cultures and animal models of BCa. Our research is focused on investigating the potential beneficial effects of dietary vitamin D3 compared to calcitriol and the underlying mechanisms in BCa treatment and chemoprevention. We recently found that dietary vitamin D3 exhibits significant tumor inhibitory effects in xenograft models of BCa that are equivalent to those elicited by the administration of the active hormone calcitriol. At the easily achievable dose tested in our studies, dietary vitamin D3 exhibited substantial tumor inhibitory activity and, unlike calcitriol, did not cause hypercalcemia demonstrating its relative safety. We found elevations in circulating calcitriol as well as increased CYP27B1 expression in the tumor and the intestine in tumor-bearing mice ingesting a vitamin D3-supplemented diet. We hypothesize that the elevation in circulating 25(OH)D induced by dietary vitamin D3 supplements stimulates local synthesis of calcitriol in the mammary tumor microenvironment and the ensuing paracrine/autocrine actions play a major role in the anticancer activity of dietary vitamin D3. Our findings suggest that the endocrine activity of calcitriol derived from tumor and other extra-renal sources such as the intestine, probably also plays a role in mediating the anticancer effects of dietary vitamin D3. Thus it appears that multiple sites of 1α-hydroxylation contribute to the anticancer effects of dietary vitamin D3. Our data strongly suggest that dietary vitamin D will be useful in the chemoprevention and treatment of BCa since it is a safe, economical and easily available nutritional agent that is equivalent to calcitriol in exerting anticancer effects, at least in mouse models. Furthermore, adequate vitamin D nutrition and avoidance of vitamin D deficiency appear to be

Action-based flood forecasting for triggering humanitarian action

Science.gov (United States)

Coughlan de Perez, Erin; van den Hurk, Bart; van Aalst, Maarten K.; Amuron, Irene; Bamanya, Deus; Hauser, Tristan; Jongma, Brenden; Lopez, Ana; Mason, Simon; Mendler de Suarez, Janot; Pappenberger, Florian; Rueth, Alexandra; Stephens, Elisabeth; Suarez, Pablo; Wagemaker, Jurjen; Zsoter, Ervin

2016-09-01

Too often, credible scientific early warning information of increased disaster risk does not result in humanitarian action. With financial resources tilted heavily towards response after a disaster, disaster managers have limited incentive and ability to process complex scientific data, including uncertainties. These incentives are beginning to change, with the advent of several new forecast-based financing systems that provide funding based on a forecast of an extreme event. Given the changing landscape, here we demonstrate a method to select and use appropriate forecasts for specific humanitarian disaster prevention actions, even in a data-scarce location. This action-based forecasting methodology takes into account the parameters of each action, such as action lifetime, when verifying a forecast. Forecasts are linked with action based on an understanding of (1) the magnitude of previous flooding events and (2) the willingness to act "in vain" for specific actions. This is applied in the context of the Uganda Red Cross Society forecast-based financing pilot project, with forecasts from the Global Flood Awareness System (GloFAS). Using this method, we define the "danger level" of flooding, and we select the probabilistic forecast triggers that are appropriate for specific actions. Results from this methodology can be applied globally across hazards and fed into a financing system that ensures that automatic, pre-funded early action will be triggered by forecasts.

Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Systemic Exertion Intolerance Disease: Three Distinct Clinical Entities

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Frank N.M. Twisk

2018-04-01

Full Text Available Many researchers consider chronic fatigue syndrome (CFS to be a synonym of Myalgic Encephalomyelitis (ME. However, the case criteria of ME and CFS define two distinct clinical entities. Although some patients will meet both case criteria, other patients can meet the diagnosis of ME and not fulfil the case criteria for CFS, while the diagnosis of CFS is largely insufficient to be qualified as a ME patient. ME is a neuromuscular disease with distinctive muscular symptoms, including prolonged muscle weakness after exertion, and neurological signs implicating cerebral dysfunction, including cognitive impairment and sensory symptoms. The only mandatory symptom of CFS is chronic fatigue. Chronic fatigue must be accompanied by at least four out of eight nonspecific symptoms: substantial impairment in short-term memory or concentration, a sore throat, tender lymph nodes, muscle pain, multijoint pain, a new type of headaches, unrefreshing sleep, and postexertional “malaise” lasting more than 24 h. So, regardless whether the name ME is appropriate or not, ME is not synonymous to CFS. That is not a matter of opinion, but a matter of definition. Due to the definitions of ME and CFS, “ME/CFS” does not exist and cannot be replaced by a new clinical entity (SEID: Systemic Exertion Intolerance Disease, as recently suggested.

Everyday robotic action: Lessons from human action control

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Roy eDe Kleijn

2014-03-01

Full Text Available Robots are increasingly capable of performing everyday human activities such as cooking, cleaning, and doing the laundry. This requires the real-time planning and execution of complex, temporally-extended sequential actions under high degrees of uncertainty, which provides many challenges to traditional approaches to robot action control. We argue that important lessons in this respect can be learned from research on human action control. We provide a brief overview of available psychological insights into this issue and focus on four principles that we think could be particularly beneficial for robot control: the integration of symbolic and subsymbolic planning of action sequences, the integration of feedforward and feedback control, the clustering of complex actions into subcomponents, and the contextualization of action-control structures through goal representations.

Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue

International Nuclear Information System (INIS)

Santander, Ana M.; Lopez-Ocejo, Omar; Casas, Olivia; Agostini, Thais; Sanchez, Lidia; Lamas-Basulto, Eduardo; Carrio, Roberto; Cleary, Margot P.; Gonzalez-Perez, Ruben R.; Torroella-Kouri, Marta

2015-01-01

The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity

Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue

Energy Technology Data Exchange (ETDEWEB)

Santander, Ana M.; Lopez-Ocejo, Omar; Casas, Olivia; Agostini, Thais; Sanchez, Lidia; Lamas-Basulto, Eduardo; Carrio, Roberto [Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136 (United States); Cleary, Margot P. [Hormel Institute, University of Minnesota, Austin, MN 55912 (United States); Gonzalez-Perez, Ruben R. [Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30314 (United States); Torroella-Kouri, Marta, E-mail: mtorroella@med.miami.edu [Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136 (United States); Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1475 NW 12th Ave, Miami, FL 33136 (United States)

2015-01-15

The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.

ACTION OF SYNTHETIC DETERGENTS ON THE METABOLISM OF BACTERIA.

Science.gov (United States)

Baker, Z; Harrison, R W; Miller, B F

1941-01-31

A study of the effects of synthetic detergents and wetting agents on respiration and glycolysis of Gram-positive and Gram-negative microorganisms has led to the following conclusions. 1. All the cationic detergents studied are very effective inhibitors of bacterial metabolism at 1:3000 concentration, and several are equally active at 1:30,000. Few of the anionic detergents inhibit as effectively as the cationic compounds. 2. Gram-positive and Gram-negative microorganisms are equally sensitive to the action of the cationic detergents. On the other hand, all the anionic detergents included in our studies selectively inhibit the metabolism of Gram-positive microorganisms. 3. The inhibitory action of both types of detergents is influenced markedly by hydrogen ion concentration. Cationic detergents exhibit their maximum activity in the alkaline pH range, and the anionic, in the acid range. 4. Studies of homologous series of straight chain alkyl sulfates and sulfoacetates (C(8) to C(18)) demonstrate that maximum inhibition is exerted by the 12, 14, and 16 carbon compounds (lauryl, myristyl, and cetyl). 5. It has been observed that three lauryl esters of amino acids are powerful inhibitors of bacterial metabolism. To our knowledge, the effects on bacterial metabolism of such cationic detergents (without the quaternary ammonium structure) have not been studied previously. Our results demonstrate that other cationic detergents can exhibit an inhibitory activity comparable to quaternary ammonium compounds. 6. Certain detergents stimulate bacterial metabolism at concentrations lower than the inhibiting values. This effect has been found more frequently among the anionic detergents.

Metallic nanomaterials formed by exerting large plastic strains

International Nuclear Information System (INIS)

Richert, M; Richert, J.; Zasadzinski, J.; Hawrylkiewicz, S.

2002-01-01

The investigations included pure Al and Cu single crystals, AlMg5 alloy and AlCuZr alloy have been presented. The materials were deformed by the cyclic extrusion compression method (CEC) within the range of true strains φ = 0.4-59.8 (1 to 67 deformation cycles by the CEC method). In all examined materials a strong tendency to form banded was observed. Within the range of very large plastic strains there was observed intensive rebuilding of the banded microstructure into subgrains, at first of rhombic shape, and next into equiaxial subgrains. A characteristic feature of the newly formed subgrains, not encountered in the range of conventional deformations, was the occurrence of large misorientation angles between the newly formed subgrains. The proportion of large misorientation angles in the microstructure varied, and it increased with increasing deformation. Reduction of the recovery process in AlMg5 and AlCuZr alloys preserved the growth of the newly formed nanograins, favoring the retaining of the nanomeric dimensions. This results show that there is the effective possibility of production of metallic nanomaterials by exerting of very large nonconventional plastic strains. (author)

Response of a NPP reactor building under seismic action with regard to different soil properties

International Nuclear Information System (INIS)

Wagenknecht, E.

1987-01-01

The object of this investigation is the response of a reactor building on seismic action with systematic variation of the soil stiffness. A thin-walled orthotropic containment shell on varying heavy and rigid foundations is regarded as calculation model. The soil stiffness is simulated by meand of spring elements for horizontal translation and for rocking motions of the building. By the response spectra method the loads of the containment shell are calculated for a horizontal seismic excitation. The investigation is aimed at determining the influence of differentiated soil stiffnesses on the containment action effects and at recognizing the causes for the occuring effects. The results are thoroughly represented by selected quantities of the building's response, the effects from the soil-structure interaction are discussed and the causes of the effects cleary explained. Apossibility is provided for determining critical soil stiffnesses which cause a siginificat intensification effect. The results of the investigations show that both the soil stiffness and structural configuration of the reactor building particulary in case of the substructure being heavy and rigid, exert a decisive on the loading of the superstructure. (orig.)

Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome.

Science.gov (United States)

Fuller, Scott; Stephens, Jacqueline M

2015-03-01

Metabolic syndrome and its complications continue to rise in prevalence and show no signs of abating in the immediate future. Therefore, the search for effective treatments is a high priority in biomedical research. Products derived from botanicals have a time-honored history of use in the treatment of metabolic diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as fenugreek, is an annual herbaceous plant that has been a staple of traditional herbal medicine in many cultures. Although fenugreek has been studied in both clinical and basic research settings, questions remain about its efficacy and biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber component of the plant are the most intensively studied bioactive constituents present in fenugreek. These compounds have been demonstrated to exert beneficial effects on several physiologic markers including glucose tolerance, inflammation, insulin action, liver function, blood lipids, and cardiovascular health. Although insights into the molecular mechanisms underlying the favorable effects of fenugreek have been gained, we still do not have definitive evidence establishing its role as a therapeutic agent in metabolic disease. This review aims to summarize the currently available evidence on the physiologic effects of the 3 best-characterized bioactive compounds of fenugreek, with particular emphasis on biologic mechanisms of action relevant in the context of metabolic syndrome. © 2015 American Society for Nutrition.

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

Science.gov (United States)

Locri, Filippo; Amato, Rosario; Marsili, Stefania; Rusciano, Dario; Bagnoli, Paola

2018-01-01

Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG), were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM), a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®), a balanced mixture of fatty acids (FAs), counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role. PMID:29517994

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Massimo Dal Monte

2018-03-01

Full Text Available Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON and is an initial symptom of multiple sclerosis (MS. Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE mouse model of MS, a well-established model also for optic neuritis. In this model, C57BL6 mice, intraperitoneally injected with a fragment of the myelin oligodendrocyte glycoprotein (MOG, were found to develop inflammation, Müller cell gliosis, and infiltration of macrophages with increased production of oncomodulin (OCM, a calcium binding protein that acts as an atypical trophic factor for neurons enabling RGC axon regeneration. Immunolabeling of retinal whole mounts with a Brn3a antibody demonstrated drastic RGC loss. Dietary supplementation with Neuro-FAG (nFAG®, a balanced mixture of fatty acids (FAs, counteracted inflammatory and gliotic processes in the retina. In contrast, infiltration of macrophages and their production of OCM remained at elevated levels thus eventually preserving OCM trophic activity. In addition, the diet supplement with nFAG exerted a neuroprotective effect preventing MOG-induced RGC death. In conclusion, these data suggest that the balanced mixture of FAs may represent a useful form of diet supplementation to limit inflammatory events and death of RGCs associated to optic neuritis. This would occur without affecting macrophage infiltration and the release of OCM thus favoring the maintenance of OCM neuroprotective role.

The effectiveness of fish oil supplementation in asthmatic rats is limited by an inefficient action on ASM function.

Science.gov (United States)

Miranda, D T S Z; Zanatta, A L; Dias, B C L; Fogaça, R T H; Maurer, J B B; Donatti, L; Calder, P C; Nishiyama, A

2013-09-01

Episodes of acute exacerbation are the major clinical feature of asthma and therefore represent an important focus for developing novel therapies for this disease. There are many reports that the n-3 fatty acids found in fish oil exert anti-inflammatory effects, but there are few studies of the action of fish oil on airway smooth muscle (ASM) function. In the present investigation, we evaluated the effect of fish oil supplementation on smooth muscle force of contraction in ovalbumin-induced asthmatic Wistar rats, and its consequences on static lung compliance, mucus production, leukocyte chemotaxis and production of proinflammatory cytokines. Fish oil supplementation suppressed the infiltration of inflammatory cells into the lung in asthmatic animals (2.04 ± 0.19 × 10(6) cells vs. 3.33 ± 0.43 × 10(6) cells in the control asthmatic group; P < 0.05). Static lung compliance increased with fish oil supplementation in asthmatic rats (0.640 ± 0.053 mL/cm H2O vs. 0.399 ± 0.043 mL/cm H2O; P < 0.05). However, fish oil did not prevent asthma-associated lung eosinophilia and did not affect the concentrations of tumor necrosis factor-α and interleukin-1β in lung tissue or the proportion of the airways obliterated with mucus. Fish oil had no effect on the force of contraction in asthmatic rats in response to acetylcholine (3.026 ± 0.274 mN vs. 2.813 ± 0.364 mN in the control asthmatic group). In conclusion, although fish oil exerts some benefits in this model of asthma, its effectiveness appears to be limited by an inefficient action on airway smooth muscle function.

The stem cell secretome and its role in brain repair.

Science.gov (United States)

Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

2013-12-01

Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Challenges and opportunities for stem cell therapy in patients with chronic kidney disease.

Science.gov (United States)

Hickson, LaTonya J; Eirin, Alfonso; Lerman, Lilach O

2016-04-01

Chronic kidney disease (CKD) is a global health care burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including proangiogenic, anti-inflammatory, and antifibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This Review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Forsythoside A exerts antipyretic effect on yeast-induced pyrexia mice via inhibiting transient receptor potential vanilloid 1 function

Science.gov (United States)

Liu, Cuiling; Su, Hongchang; Wan, Hongye; Qin, Qingxia; Wu, Xuan; Kong, Xiangying; Lin, Na

2017-01-01

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel gated by noxious heat, playing major roles in thermoregulation. Forsythoside A (FT-A) is the most abundant phenylethanoid glycosides in Fructus Forsythiae, which has been prescribed as a medicinal herb for treating fever in China for a long history. However, how FT-A affects pyrexia and what is the underlying molecular mechanism remain largely unknown. Here we found that FT-A exerted apparent antipyretic effect through decreasing the levels of prostaglandin E2 (PGE2) and interleukin 8 (IL-8) in a dose-dependent fashion on the yeast induced pyrexia mice. Interestingly, FT-A significantly downregulated TRPV1 expression in the hypothalamus and dorsal root ganglion (DRG) of the yeast induced pyrexia mice. Moreover, FT-A inhibited IL-8 and PGE2 secretions, and calcium influx in the HEK 293T-TRPV1 cells after stimulated with capsaicin, the specific TRPV1 agonist. Further investigation of the molecular mechanisms revealed that FT-A treatment rapidly inhibited phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 in both yeast induced pyrexia mice and HEK 293T-TRPV1 cells. These results suggest that FT-A may serve as a potential antipyretic agent and the therapeutic action of Fructus Forsythiae on pyretic related disease is, in part, due to the FT-A activities. PMID:28123347

Fascaplysin Exerts Anti-Cancer Effects through the Downregulation of Survivin and HIF-1α and Inhibition of VEGFR2 and TRKA

Directory of Open Access Journals (Sweden)

Taek-In Oh

2017-09-01

Full Text Available Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4; however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB, indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues. In addition, survivin and HIF-1α were downregulated in vitro and in vivo by suppressing 4EBP1-p70S6K1 axis-mediated de novo protein synthesis. Kinase screening assays and drug-protein docking simulation studies demonstrated that fascaplysin strongly inhibited vascular endothelial growth factor receptor 2 (VEGFR2 and tropomyosin-related kinase A (TRKA via DFG-out non-competitive inhibition. Overall, these results suggest that fascaplysin inhibits TRKA and VEGFR2 and downregulates survivin and HIF-1α, resulting in suppression of tumor growth. Fascaplysin, therefore, represents a potential therapeutic approach for the treatment of multiple types of solid cancer.

Effects of 12 months aerobic exercise intervention on work ability, need for recovery, productivity and rating of exertion among cleaners

DEFF Research Database (Denmark)

Lidegaard, Mark; Søgaard, Karen; Krustrup, Peter

2018-01-01

PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster-randomised (w......PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster......-randomised (work location; sex; age; length of service) to aerobic exercise [N = 57, 44.9 years, 75.4% female, body mass index (BMI) 26.2], receiving 2 weekly aerobic exercise sessions during 12 months, or a reference group (N = 59, 45.7 years, 76.3% female, BMI 27.1), receiving health-promoting lectures. Self.......2) in the aerobic exercise group compared to the reference group. Productivity and rating of exertion were unaltered. Analysis stratified on age showed significant effects only among the participants aged ≤ 45 years. CONCLUSIONS: After 12 months work ability improved and need for recovery decreased. A period of 4...

Hearing sounds, understanding actions: action representation in mirror neurons.

Science.gov (United States)

Kohler, Evelyne; Keysers, Christian; Umiltà, M Alessandra; Fogassi, Leonardo; Gallese, Vittorio; Rizzolatti, Giacomo

2002-08-02

Many object-related actions can be recognized by their sound. We found neurons in monkey premotor cortex that discharge when the animal performs a specific action and when it hears the related sound. Most of the neurons also discharge when the monkey observes the same action. These audiovisual mirror neurons code actions independently of whether these actions are performed, heard, or seen. This discovery in the monkey homolog of Broca's area might shed light on the origin of language: audiovisual mirror neurons code abstract contents-the meaning of actions-and have the auditory access typical of human language to these contents.

Evaluation of Interhandle Distance During Pushing and Pulling of a Four-Caster Cart for Upper Limb Exertion.

Science.gov (United States)

Ohnishi, Akihiro; Takanokura, Masato; Sugama, Atsushi

2016-09-01

This study examined the relationship between interhandle distances and upper limb exertion during simply pushing and pulling of a cart with four swivel wheels, defined by a roll box pallet (RBP) in a Japanese industrial standard. Six healthy young male participants were asked to push and pull an RBP at a distance of 5.2 m under six conditions corresponding to different interhandle distances (40 cm, 60 cm, and 80 cm) and weights (130 kg and 250 kg). The upper limb exertion was studied by shoulder abduction and flexion, and elbow flexion, as well as surface electromyogram (EMG) in shoulder extensor, and elbow flexor and extensor. Participants were required to provide subjective evaluations on operability after each trial. Subjective operability indicated that a narrower interhandle distance had a better operability for pushing. Interhandle distance was also related to upper limb exertion especially for pushing. A narrow interhandle distance caused smaller shoulder adduction but larger elbow flexion. The normalized EMG data revealed that muscular activity became smaller with a narrow interhandle distance in shoulder extensor. During the pulling task, elbow flexion was smaller at a narrow interhandle distance, although subjective operability and normalized EMG were not significantly varied. A wider interhandle distance, such as 80 cm, was not suitable in the forwardbackward movement of the RBP. Therefore, this study concluded that an interhandle distance of 40 cm would be suitable for pushing and pulling an RBP to protect the workers' hands against the risk of injury by installing inner handles.

Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats.

Directory of Open Access Journals (Sweden)

Luciana A Reis

Full Text Available This study evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs or their conditioned medium (CM on the repair and prevention of Acute Kidney Injury (AKI induced by gentamicin (G. Animals received daily injections of G up to 20 days. On the 10(th day, injections of BMSCs, CM, CM+trypsin, CM+RNase or exosome-like microvesicles extracted from the CM were administered. In the prevention groups, the animals received the BMSCs 24 h before or on the 5(th day of G treatment. Creatinine (Cr, urea (U, FENa and cytokines were quantified. The kidneys were evaluated using hematoxylin/eosin staining and immunohystochemistry. The levels of Cr, U and FENa increased during all the periods of G treatment. The BMSC transplantation, its CM or exosome injections inhibited the increase in Cr, U, FENa, necrosis, apoptosis and also increased cell proliferation. The pro-inflammatory cytokines decreased while the anti-inflammatory cytokines increased compared to G. When the CM or its exosomes were incubated with RNase (but not trypsin, these effects were blunted. The Y chromosome was not observed in the 24-h prevention group, but it persisted in the kidney for all of the periods analyzed, suggesting that the injury is necessary for the docking and maintenance of BMSCs in the kidney. In conclusion, the BMSCs and CM minimized the G-induced renal damage through paracrine effects, most likely through the RNA carried by the exosome-like microvesicles. The use of the CM from BMSCs can be a potential therapeutic tool for this type of nephrotoxicity, allowing for the avoidance of cell transplantations.

Fitness Assessment Comparison Between the "Jackie Chan Action Run" Videogame, 1-Mile Run/Walk, and the PACER.

Science.gov (United States)

Haddock, Bryan; Siegel, Shannon; Costa, Pablo; Jarvis, Sarah; Klug, Nicholas; Medina, Ernie; Wilkin, Linda

2012-06-01

The purpose of this study was to examine whether a correlation existed among the scores of the "Jackie Chan Studio Fitness(™) Action Run" active videogame (XaviX(®), SSD Company, Ltd., Kusatsu, Japan), the 1-mile run/walk, and Progressive Aerobic Cardiovascular Endurance Run (PACER) aerobic fitness tests of the FITNESSGRAM(®) (The Cooper Institute, Dallas, TX) in order to provide a potential alternative testing method for days that are not environmentally desirable for outdoor testing. Participants were a convenience sample from physical education classes of students between the ages of 10 and 15 years. Participants (n=108) were randomly assigned to one of three groups with the only difference being the order of testing. The tests included the "Jackie Chan Action Run" active videogame, the 1-mile run/walk, and the PACER. Testing occurred on three different days during the physical education class. Rating of perceived exertion (RPE) was reported. Significant correlations (r=-0.598 to 0.312) were found among the three aerobic fitness tests administered (P<0.05). The RPE for the "Jackie Chan Action Run" was lower than the RPE for the 1-mile run/walk and the PACER (3.81±1.89, 5.93±1.77, and 5.71±2.14, respectively). The results suggest that the "Jackie Chan Action Run" test could be an alternative to the 1-mile run/walk and PACER, allowing physical education teachers to perform aerobic fitness testing in an indoor setting that requires less space. Also, children may be more willing to participate in the "Jackie Chan Action Run" based on the lower RPE.

Regulation of ghrelin secretion and action.

Science.gov (United States)

Camiña, Jesus P; Carreira, Marcos C; Micic, Dragan; Pombo, Manuel; Kelestimur, Fahrettin; Dieguez, Carlos; Casanueva, Felipe F

2003-10-01

The pulsatile release of growth hormone (GH) from anterior pituitary gland is regulated by the interplay of at least two hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin, via their engagement with specific cell surface receptors on the anterior pituitary somatotroph. Furthermore, release of GH in vivo may also be controlled by a third type of receptor, the growth hormone secretagogue receptor, a G-protein-coupled receptor, called GHS receptor type 1a (GHSR1a), which was identified in the pituitary and the hypothalamus in humans using a nonpeptidyl growth hormone secretagogue (MK-0677). Ghrelin, the endogenous ligand for the GHS-R1a, is a 28-amino-acid peptide isolated from human stomach that is modified by a straight chain octanoyl group covalently linked to Ser3, which is essential for its endocrine activity. This hormone, predominantly expressed and secreted by the stomach, has a dual action on GH secretion and food intake, showing interdependency between these actions. The finding that fasting and food intake, respectively, increase and decrease the secretion of ghrelin suggests that this hormone may be the bridge connecting somatic growth and body composition with energy metabolism, and appears to play a role in the alteration of energy homeostasis and body weight in pathophysiological states such as hypothyroidism and hyperthyroidism. Despite this, little is known about the intracellular signaling through which ghrelin exerts its regulatory actions. Activation of intracellular calcium mobilization is one of the earliest known cellular signals elicited by ghrelin. In HEK- 293 cells expressing the GHS-R1a, ghrelin induces a biphasic cytosolic calcium elevation characterized by a spike phase of the response, which reflects Ins(1,4,5)P3- dependent calcium mobilization of intracellular stores, and a sustained phase of the response, which is due to calcium influx across the plasma membrane triggered by aperture of capacitative calcium channels

Enhancing excitability of dopamine neurons promotes motivational behaviour through increased action initiation.

Science.gov (United States)

Boekhoudt, Linde; Wijbrans, Ellen C; Man, Jodie H K; Luijendijk, Mieneke C M; de Jong, Johannes W; van der Plasse, Geoffrey; Vanderschuren, Louk J M J; Adan, Roger A H

2018-01-01

Motivational deficits are a key symptom in multiple psychiatric disorders, including major depressive disorder, schizophrenia and addiction. A likely neural substrate for these motivational deficits is the brain dopamine (DA) system. In particular, DA signalling in the nucleus accumbens, which originates from DA neurons in the ventral tegmental area (VTA), has been identified as a crucial substrate for effort-related and activational aspects of motivation. Unravelling how VTA DA neuronal activity relates to motivational behaviours is required to understand how motivational deficits in psychiatry can be specifically targeted. In this study, we therefore used designer receptors exclusively activated by designer drugs (DREADD) in TH:Cre rats, in order to determine the effects of chemogenetic DA neuron activation on different aspects of motivational behaviour. We found that chemogenetic activation of DA neurons in the VTA, but not substantia nigra, significantly increased responding for sucrose under a progressive ratio schedule of reinforcement. More specifically, high effort exertion was characterized by increased initiations of reward-seeking actions. This effect was dependent on effort requirements and instrumental contingencies, but was not affected by sucrose pre-feeding. Together, these findings indicate that VTA DA neuronal activation drives motivational behaviour by facilitating action initiation. With this study, we show that enhancing excitability of VTA DA neurons is a viable strategy to improve motivational behaviour. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Finding minimal action sequences with a simple evaluation of actions

Science.gov (United States)

Shah, Ashvin; Gurney, Kevin N.

2014-01-01

Animals are able to discover the minimal number of actions that achieves an outcome (the minimal action sequence). In most accounts of this, actions are associated with a measure of behavior that is higher for actions that lead to the outcome with a shorter action sequence, and learning mechanisms find the actions associated with the highest measure. In this sense, previous accounts focus on more than the simple binary signal of “was the outcome achieved?”; they focus on “how well was the outcome achieved?” However, such mechanisms may not govern all types of behavioral development. In particular, in the process of action discovery (Redgrave and Gurney, 2006), actions are reinforced if they simply lead to a salient outcome because biological reinforcement signals occur too quickly to evaluate the consequences of an action beyond an indication of the outcome's occurrence. Thus, action discovery mechanisms focus on the simple evaluation of “was the outcome achieved?” and not “how well was the outcome achieved?” Notwithstanding this impoverishment of information, can the process of action discovery find the minimal action sequence? We address this question by implementing computational mechanisms, referred to in this paper as no-cost learning rules, in which each action that leads to the outcome is associated with the same measure of behavior. No-cost rules focus on “was the outcome achieved?” and are consistent with action discovery. No-cost rules discover the minimal action sequence in simulated tasks and execute it for a substantial amount of time. Extensive training, however, results in extraneous actions, suggesting that a separate process (which has been proposed in action discovery) must attenuate learning if no-cost rules participate in behavioral development. We describe how no-cost rules develop behavior, what happens when attenuation is disrupted, and relate the new mechanisms to wider computational and biological context. PMID:25506326

Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles against Escherichia coli correlated with molecular chain conformation

Energy Technology Data Exchange (ETDEWEB)

Wen, Yan [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); School of Science, Tianjin University of Commerce, Tianjin 300134 (China); Yao, Fanglian, E-mail: yaofanglian@tju.edu.cn [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Sun, Fang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tan, Zhilei [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300222 (China); Tian, Liang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Xie, Lei; Song, Qingchao [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300222 (China)

2015-03-01

The action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles (CM-HTCC/PAMAM) against Escherichia coli (E. coli) was investigated via a combination of approaches including measurements of cell membrane integrity, outer membrane (OM) and inner membrane (IM) permeability, and scanning electron microscopy (SEM). CM-HTCC/PAMAM dendrimer nanoparticles likely acted in a sequent event-driven mechanism, beginning with the binding of positively charged groups from nanoparticle surface with negative cell surface, thereby causing the disorganization of cell membrane, and subsequent leakage of intracellular components which might ultimately lead to cell death. Moreover, the chain conformation of polymers was taken into account for a better understanding of the antibacterial action mode by means of viscosity and GPC measurements. High utilization ratio of positive charge and large specific surface area generated from a compacted conformation of CM-HTCC/PAMAM, significantly different from the extended conformation of HTCC, were proposed to be involved in the antibacterial action. - Highlights: • The nanoparticles exerted antibacterial activity in a sequent event-driven manner. • Electrostatic interaction and surface adsorption shared roles in antibacterial mode. • The two factors were controlled by the compacted conformation of nanoparticles.

Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles against Escherichia coli correlated with molecular chain conformation

International Nuclear Information System (INIS)

Wen, Yan; Yao, Fanglian; Sun, Fang; Tan, Zhilei; Tian, Liang; Xie, Lei; Song, Qingchao

2015-01-01

The action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles (CM-HTCC/PAMAM) against Escherichia coli (E. coli) was investigated via a combination of approaches including measurements of cell membrane integrity, outer membrane (OM) and inner membrane (IM) permeability, and scanning electron microscopy (SEM). CM-HTCC/PAMAM dendrimer nanoparticles likely acted in a sequent event-driven mechanism, beginning with the binding of positively charged groups from nanoparticle surface with negative cell surface, thereby causing the disorganization of cell membrane, and subsequent leakage of intracellular components which might ultimately lead to cell death. Moreover, the chain conformation of polymers was taken into account for a better understanding of the antibacterial action mode by means of viscosity and GPC measurements. High utilization ratio of positive charge and large specific surface area generated from a compacted conformation of CM-HTCC/PAMAM, significantly different from the extended conformation of HTCC, were proposed to be involved in the antibacterial action. - Highlights: • The nanoparticles exerted antibacterial activity in a sequent event-driven manner. • Electrostatic interaction and surface adsorption shared roles in antibacterial mode. • The two factors were controlled by the compacted conformation of nanoparticles

Hybrid Action Systems

DEFF Research Database (Denmark)

Rönnkö, M.; Ravn, Anders Peter; Sere, K.

2003-01-01

In this paper we investigate the use of action systems with differential actions in the specifcation of hybrid systems. As the main contribution we generalize the definition of a differential action, allowing the use of arbitrary relations over model variables and their time......-derivatives in modelling continuous-time dynamics. The generalized differential action has an intuitively appealing predicate transformer semantics, which we show to be both conjunctive and monotonic. In addition, we show that differential actions blend smoothly with conventional actions in action systems, even under...... parallel composition. Moreover, as the strength of the action system formalism is the support for stepwise development by refinement, we investigate refinement involving a differential action. We show that, due to the predicate transformer semantics, standard action refinement techniques apply also...

Impact Exerted by Nutritional Risk Screening on Clinical Outcome of Patients with Esophageal Cancer

OpenAIRE

Rui Wang; Hongfei Cai; Yang Li; Caiwen Chen; Youbin Cui

2018-01-01

Objective. Preoperative nutritional status of patients is closely associated with their recovery after the surgery. This study aims to ascertain the impact exerted by the nutritional risk screening on clinical outcome of patients with esophageal cancer. Methods. 160 patients with esophageal cancer aged over 60, having got therapy at the First Hospital of Jilin University from Jun 2016 to Feb 2017 were evaluated by adopting the NRS2002. 80 cases of patients got active therapy of nutritional su...

Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review

Directory of Open Access Journals (Sweden)

Sin-Yeang Teow

2016-01-01

Full Text Available Curcumin, the major constituent of Curcuma longa L. (Zingiberaceae family or turmeric, commonly used for cooking in Asian cuisine, is known to possess a broad range of pharmacological properties at relatively nontoxic doses. Curcumin is found to be effective against Staphylococcus aureus (S. aureus. As demonstrated by in vitro experiment, curcumin exerts even more potent effects when used in combination with various other antibacterial agents. Hence, curcumin which is a natural product derived from plant is believed to have profound medicinal benefits and could be potentially developed into a naturally derived antibiotic in the future. However, there are several noteworthy challenges in the development of curcumin as a medicine. S. aureus infections, particularly those caused by the multidrug-resistant strains, have emerged as a global health issue and urgent action is needed. This review focuses on the antibacterial activities of curcumin against both methicillin-sensitive S. aureus (MSSA and methicillin-resistant S. aureus (MRSA. We also attempt to highlight the potential challenges in the effort of developing curcumin into a therapeutic antibacterial agent.

A UNIFIED THEORY ON THE ACTION OF POLITICAL PRESCRIBERS. A RESEARCH PROPOSAL.

Directory of Open Access Journals (Sweden)

Constantin SASU

2018-06-01

Full Text Available The decision of an individual to vote or not and to choose one of the candidates participating in the competition on the electoral market is the result of a cumulus of factors that act directly or indirectly in this process. Most of the papers address the role of opinion formers in the process of forming the voting option by choosing one of the following two ways: (1 either the Opinion Leadership Model (Katz, 1957, Keller & Berry, 2003 (2 or Celebrity Political Endorsement (Henneberg S., Chen Y., 2007 as a primary source of information for voters, delivered to them through marketing strategies similar to those of supporting credible personalities in front of consumers, general prescriptors. The development of the model to be studied also departs from the need to unify, in a single model, the action that people with special characteristics exert on voters, in order for them to shape their voting option.

Our actions in my mind: Motor imagery of joint action

DEFF Research Database (Denmark)

Vesper, Cordula; Knoblich, Günther; Sebanz, Natalie

2014-01-01

How do people imagine performing actions together? The present study investigated motor imagery of joint actions that requires integrating one's own and another's part of an action. In two experiments, individual participants imagined jumping alone or jointly next to an imagined partner. The joint...... condition required coordinating one's own imagined actions with an imagined partner's actions to synchronize landing times. We investigated whether the timing of participants' own imagined jumps would reflect the difference in jump distance to their imagined partner's jumps. The results showed...... of joint jumping. These findings link research on motor imagery and joint action, demonstrating that individuals are able to integrate simulations of different parts of a joint action....

THE EFFECTS OF DIFFERENT TRUNK INCLINATIONS ON BILATERAL TRUNK MUSCULAR ACTIVITIES, CENTRE OF PRESSURE AND FORCE EXERTIONS IN STATIC PUSHING POSTURES.

Science.gov (United States)

Sanjaya, Kadek Heri; Lee, Soomin; Sriwarno, Andar Bagus; Shimomura, Yoshihito; Katsuura, Tetsuo

2014-06-01

In order to reconcile contradictory results from previous studies on manual pushing, a study was conducted to examine the effect of trunk inclination on muscular activities, centre of pressure (COP) and force exertion during static pushing. Ten subjects pushed at 0 degrees, 15 degrees, 30 degrees, and 45 degrees body inclinations in parallel and staggered feet stances. Wall and ground force plates measured pushing force, wall COP, vertical ground reaction force (GRF) and ground COP. Electromyogram data were recorded at 10 trunk muscle sites. Pushing force was found to increase with body inclination. GRF peaked at 15 degrees and reached its lowest level at the 45 degrees inclination. The lowest wall force plate standard deviation of COP displacement was found at the 30 degrees inclination. The lowest low back muscular activity was found at the 15 degrees and 30 degrees inclinations. Based on force exertion, muscular load, and stability, the 30 degrees body inclination was found to be the best posture for static pushing. This study also showed asymmetry in muscular activity and force exertion which has been received less attention in manual pushing studies. These findings will require further study.

Validation of the Omni Scale of Perceived Exertion in a sample of Spanish-speaking youth from the USA.

Science.gov (United States)

Suminski, Richard R; Robertson, Robert J; Goss, Fredric L; Olvera, Norma

2008-08-01

Whether the translation of verbal descriptors from English to Spanish affects the validity of the Children's OMNI Scale of Perceived Exertion is not known, so the validity of a Spanish version of the OMNI was examined with 32 boys and 36 girls (9 to 12 years old) for whom Spanish was the primary language. Oxygen consumption, ventilation, respiratory rate, respiratory exchange ratio, heart rate, and ratings of perceived exertion for the overall body (RPE-O) were measured during an incremental treadmill test. All response values displayed significant linear increases across test stages. The linear regression analyses indicated RPE-O values were distributed as positive linear functions of oxygen consumption, ventilation, respiratory rate, respiratory exchange ratio, heart rate, and percent of maximal oxygen consumption. All regression models were statistically significant. The Spanish OMNI Scale is valid for estimating exercise effort during walking and running amongst Hispanic youth whose primary language is Spanish.

Bisphenol A Modifies the Regulation Exerted by Testosterone on 5α-Reductase Isozymes in Ventral Prostate of Adult Rats

Directory of Open Access Journals (Sweden)

Pilar Sánchez

2013-01-01

Full Text Available The development, growth, and function of the prostate gland depend on androgen stimulation. The primary androgen in prostate is 5-dihydrotestosterone (DHT which is synthesized from circulating testosterone (T through the action of 5-reductase (5-R. Although 5-R occurs as five isozymes, only 5-R1 and 5-R2 are physiologically involved in steroidogenesis. The endocrine disruptor bisphenol A (BPA alters sexual organs, including the prostate. Our previous findings indicated that BPA decreased the expression of 5-R1 and 5-R2 in rat prostate but also circulating T. Thus, it is unclear whether BPA exerts this effect on 5-R isozymes by reducing circulating T or by any other mechanism. In this study, we examine the effects of short-term exposure to BPA at doses below 25 g/Kg/d and above 300 g/Kg/d of the TDI on mRNA levels of 5-R1 and 5-R2 in prostate of adult castrated rats supplemented with T to achieve constant circulating T levels. mRNA levels were measured by absolute quantitative RT-PCR, T levels by RIA, and DHT levels by ELISA. Our results indicated that in castrated rats treated with T BPA at the two doses studied significantly decreased the mRNA levels of both 5-R isozymes in a dose-dependent manner without modifications in circulating T.

Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome.

Science.gov (United States)

Keech, Andrew; Sandler, Carolina X; Vollmer-Conna, Ute; Cvejic, Erin; Lloyd, Andrew R; Barry, Benjamin K

2015-12-01

To design and validate an instrument to capture the characteristic post-exertional exacerbation of fatigue in patients with chronic fatigue syndrome (CFS). Firstly, patients with CFS (N=19) participated in five focus group discussions to jointly explore the nature of fatigue and dynamic changes after activity, and inform development of a self-report instrument - the Fatigue and Energy Scale (FES). The psychometric properties of the FES were then examined in two case-control challenge studies: a physically-demanding challenge (moderate-intensity aerobic exercise; N=10 patients), and a cognitively-demanding challenge (simulated driving; N=11 patients). Finally, ecological validity was evaluated by recording in association with tasks of daily living (N=9). Common descriptors for fatigue included 'exhaustion', 'tiredness', 'drained of energy', 'heaviness in the limbs', and 'foggy in the head'. Based on the qualitative data, fatigue was conceptualised as consisting of 'physical' and 'cognitive' dimensions. Analysis of the psychometric properties of the FES showed good sensitivity to the changing symptoms during a post-exertional exacerbation of fatigue following both physical exercise and driving simulation challenges, as well as tasks of daily living. The 'fatigue' experienced by patients with CFS covers both physical and cognitive components. The FES captured the phenomenon of a post-exertional exacerbation of fatigue commonly reported by patients with CFS. The characteristics of the symptom response to physical and cognitive challenges were similar. Both the FES and the challenge paradigms offer key tools to reliably investigate biological correlates of the dynamic changes in fatigue. Copyright © 2015 Elsevier Inc. All rights reserved.

Cysteamine induces cholecystokinin release from the duodenum. Evidence for somatostatin as an inhibitory paracrine regulator of cholecystokinin secretion in the rat

International Nuclear Information System (INIS)

Abucham, J.; Reichlin, S.

1990-01-01

To determine whether cholecystokinin secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced in vivo with cysteamine (250 mg/kg body wt, IV) or anti-somatostatin antiserum in anaesthetized rats and in vitro with cysteamine (30 micrograms/mL) in a rat duodenum-incubation system. Cholecystokinin secretion was assessed in vivo by measuring amylase in duodenal perfusates collected at 10-minute intervals for 1 hour and in vitro by a carboxy-terminal radioimmunoassay. Cysteamine induced a marked decrease in duodenal immunoreactive somatostatin both in vivo (50%) and in vitro (60%). The rate of amylase secretion increased from 9.7 +/- 2.1 U (mean +/- SE) to 28.0 +/- 4.8 U at 20 minutes (P less than 0.001). The cholecystokinin-receptor antagonist CR-1392 abolished amylase response for 30 minutes, whereas the more potent antagonists Asperlicin (18.0 mg/kg body wt, IV) and L-364,718 (0.25 mg/kg body wt, IV) caused prolonged blockade. The rate of amylase secretion in gastrectomized animals increased from 7.2 +/- 2.0 U to 15.0 +/- 2.2 U 20 minutes after cysteamine administration (P less than 0.01), indicating that the effect was not due to the presence of gastrin. In vitro, cysteamine caused a nearly fourfold increase in cholecystokinin secretion compared with controls (63.1 +/- 4.9 vs. 15.2 +/- 3.7, respectively; P less than 0.001). In vivo immunoneutralization of circulating somatostatin with a high-affinity and high-capacity antiserum produced no significant change in the rate of amylase secretion. These results suggest that cholecystokinin secretion is tonically inhibited by somatostatin and that this effect is mediated by locally secreted (paracrine) but not by circulating somatostatin

Locked-in syndrome caused by the pressure exerted by the sound gun

Directory of Open Access Journals (Sweden)

Ayse Belin Ozer

2014-01-01

Full Text Available A 19-year-old male patient who wounded himself with a gun in the cranial region had a Glasgow coma scale of 3E. At posttraumatic day 7, locked-in syndrome was considered upon detection of vertical eye movements, meaningful winks, and quadriplegia. Apart from the classical view, computed tomography (CT and postmortem examination of the brain showed an infarct area in the cerebellum. However, vertebrobasilar artery system was normal. In this case report, we would like to present that unlike cases with ischemia, specific CT findings may not be evident in posttraumatic cases and ischemia may occur in the cerebellum as a result of the pressure exerted by a sound gun.

Gender differences in exerted forces and physiological load during pushing and pulling of wheeled cages by postal workers

NARCIS (Netherlands)

Van Der Beek, Allard J.; Kluver, B.D.R.; Frings-Dresen, M. H. W.; Hoozemans, M. J M

The aim was to determine gender differences regarding exerted forces and physiological load during push/pull tasks simulating the daily working practice of postal workers. Eight female and four male workers handled four-wheeled cages under eight conditions corresponding to the cage weight (130, 250,

Effect of Music Tempo on Attentional Focus and Perceived Exertion during Self-selected Paced Walking

OpenAIRE

SILVA, ALDO COELHO; DOS SANTOS FERREIRA, SANDRO; ALVES, RAGAMI CHAVES; FOLLADOR, LUCIO; DA SILVA, SERGIO GREGORIO

2016-01-01

This study investigated the influence of music on the rating of perceived exertion (RPE) and attentional focus during walking at a self-selected pace. Fifteen overweight and obese women volunteered to participate in the study. They underwent four sessions: the first for incremental maximal test and anthropometric measurement followed by three experimental sessions. After the first session, they were exposed to three 30-minute walking sessions at a self-selected pace in a counterbalanced order...

Magnetic tweezers optimized to exert high forces over extended distances from the magnet in multicellular systems

Science.gov (United States)

Selvaggi, L.; Pasakarnis, L.; Brunner, D.; Aegerter, C. M.

2018-04-01

Magnetic tweezers are mainly divided into two classes depending on the ability of applying torque or forces to the magnetic probe. We focused on the second category and designed a device composed by a single electromagnet equipped with a core having a special asymmetric profile to exert forces as large as 230 pN-2.8 μm Dynabeads at distances in excess of 100 μm from the magnetic tip. Compared to existing solutions our magnetic tweezers overcome important limitations, opening new experimental paths for the study of a wide range of materials in a variety of biophysical research settings. We discuss the benefits and drawbacks of different magnet core characteristics, which led us to design the current core profile. To demonstrate the usefulness of our magnetic tweezers, we determined the microrheological properties inside embryos of Drosophila melanogaster during the syncytial stage. Measurements in different locations along the dorsal-ventral axis of the embryos showed little variation, with a slight increase in cytoplasm viscosity at the periphery of the embryos. The mean cytoplasm viscosity we obtain by active force exertion inside the embryos is comparable to that determined passively using high-speed video microrheology.

The time between intention and action affect the experience of action

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Mikkel C. Vinding

2015-06-01

Full Text Available We present a study investigating how the delay between the intention to act and the following action, influenced the experience of action. In experiments investigating sense of agency and experience of action, the contrast is most often between voluntary and involuntary actions. It is rarely asked whether different types of intentions influence the experience of action differently. To investigate this we distinguished between proximal intentions (i.e. intentions for immediate actions and delayed intentions (i.e. intentions with a temporal delay between intention and action. The distinction was implemented in an intentional binding paradigm, by varying the delay between the time where participants formed the intention to act and the time at which they performed the action. The results showed that delayed intentions were followed by a stronger binding effect for the tone following the action compared to proximal intentions. The actions were reported to have occurred earlier for delayed intentions than for proximal intentions. This effect was independent of the binding effect usually found in intentional binding experiments. This suggests that two perceptual shifts occurred in the contrast between delayed intentions and proximal intentions: The first being the binding effect, the second a general shift in the perceived time of action. Neither the stronger binding effect for tone, nor the earlier reports of action, differed across delays for delayed intentions. The results imply that delayed intentions and proximal intentions have a different impact on the experience of action.

The emergence of neurotransmitters as immune modulators.

Science.gov (United States)

Franco, Rafael; Pacheco, Rodrigo; Lluis, Carmen; Ahern, Gerard P; O'Connell, Peta J

2007-09-01

Initially, the idea that neurotransmitters could serve as immunomodulators emerged with the discovery that their release and diffusion from nervous tissue could lead to signaling through lymphocyte cell-surface receptors and the modulation of immune function. It is now evident that neurotransmitters can also be released from leukocytes and act as autocrine or paracrine modulators. Here, we review the data indicating that leukocytes synthesize and release 'neurotransmitters' and we also discuss the diverse effects that these compounds exert in a variety of immune cells. The role of neurotransmitters in immune-related diseases is also reviewed succinctly. Current and future developments in understanding the cross-talk between the immune and nervous systems will probably identify new avenues for treating immune-mediated diseases using agonists or antagonists of neurotransmitter receptors.

Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation

Directory of Open Access Journals (Sweden)

Miguel Angel Burguillos

2015-03-01

Full Text Available Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4 in microglia’s inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3 released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.

S100ß and fibroblast growth factor-2 are present in cultured Schwann cells and may exert paracrine actions on the peripheral nerve injury S100ß e fator de crescimento de fibroblasto-2 estão presentes nas células de Schwann cultivadas e exercem ações parácrinas na lesão do nervo

Directory of Open Access Journals (Sweden)

Tatiana Duobles

2008-12-01

Full Text Available PURPOSE: The neurotrophic factor fibroblast growth factor-2 (FGF-2, bFGF and Ca++ binding protein S100ß are expressed by the Schwann cells of the peripheral nerves and by the satellite cells of the dorsal root ganglia (DRG. Recent studies have pointed out the importance of the molecules in the paracrine mechanisms related to neuronal maintenance and plasticity of lesioned motor and sensory peripheral neurons. Moreover, cultured Schwann cells have been employed experimentally in the treatment of central nervous system lesions, in special the spinal cord injury, a procedure that triggers an enhanced sensorymotor function. Those cells have been proposed to repair long gap nerve injury. METHODS: Here we used double labeling immunohistochemistry and Western blot to better characterize in vitro and in vivo the presence of the proteins in the Schwann cells and in the satellite cells of the DRG as well as their regulation in those cells after a crush of the rat sciatic nerve. RESULTS: FGF-2 and S100ß are present in the Schwann cells of the sciatic nerve and in the satellite cells of the DRG. S100ß positive satellite cells showed increased size of the axotomized DRG and possessed elevated amount of FGF-2 immunoreactivity. Reactive satellite cells with increased FGF-2 labeling formed a ring-like structure surrounding DRG neuronal cell bodies.Reactive S100ß positive Schwann cells of proximal stump of axotomized sciatic nerve also expressed higher amounts of FGF-2. CONCLUSION: Reactive peripheral glial cells synthesizing FGF-2 and S100ß may be important in wound repair and restorative events in the lesioned peripheral nerves.OBJETIVO: O fator neurotrófico fator de crescimento de fibroblastos-2 (FGF-2, bFGF e a proteína ligante de Ca++ S100ß são expressos pelas células de Schwann dos nervos e por células satélites do gânglio da raiz dorsal (GRD. Estudos recentes indicam a importância das moléculas nos mecanismos parácrinos relacionados �

Perceived exertion is as effective as the perceptual strain index in predicting physiological strain when wearing personal protective clothing.

Science.gov (United States)

Borg, David N; Costello, Joseph T; Bach, Aaron J; Stewart, Ian B

2017-02-01

The perceptual strain index (PeSI) has been shown to overcome the limitations associated with the assessment of the physiological strain index (PSI), primarily the need to obtain a core body temperature measurement. The PeSI uses the subjective scales of thermal sensation and perceived exertion (RPE) to provide surrogate measures of core temperature and heart rate, respectively. Unfortunately, thermal sensation has shown large variability in providing an estimation of core body temperature. Therefore, the primary aim of this study was to determine if thermal comfort improved the ability of the PeSI to predict the PSI during exertional-heat stress. Eighteen healthy males (age: 23.5years; body mass: 79.4kg; maximal aerobic capacity: 57.2ml·kg -1 ·min -1 ) wore four different chemical/biological protective garments while walking on treadmill at a low (temperatures 21, 30 or 37°C. Trials were terminated when heart rate exceeded 90% of maximum, when core body temperature reached 39°C, at 120min or due to volitional fatigue. Core body temperature, heart rate, thermal sensation, thermal comfort and RPE were recorded at 15min intervals and at termination. Multiple statistical methods were used to determine the most accurate perceptual predictor. Significant moderate relationships were observed between the PeSI (r=0.74; pestimate physiological strain during exertional-heat stress under these work conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

DAPs: Deep Action Proposals for Action Understanding

KAUST Repository

Escorcia, Victor; Caba Heilbron, Fabian; Niebles, Juan Carlos; Ghanem, Bernard

2016-01-01

action proposals from long videos. We show how to take advantage of the vast capacity of deep learning models and memory cells to retrieve from untrimmed videos temporal segments, which are likely to contain actions. A comprehensive evaluation indicates

The effect of working position on trunk posture and exertion for routine nursing tasks: an experimental study.

Science.gov (United States)

Freitag, Sonja; Seddouki, Rachida; Dulon, Madeleine; Kersten, Jan Felix; Larsson, Tore J; Nienhaus, Albert

2014-04-01

To examine the influence of the two following factors on the proportion of time that nurses spend in a forward-bending trunk posture: (i) the bed height during basic care activities at the bedside and (ii) the work method during basic care activities in the bathroom. A further aim was to examine the connection between the proportion of time spent in a forward-bending posture and the perceived exertion. Twelve nurses in a geriatric nursing home each performed a standardized care routine at the bedside and in the bathroom. The CUELA (German abbreviation for 'computer-assisted recording and long-term analysis of musculoskeletal loads') measuring system was used to record all trunk inclinations. Each participant conducted three tests with the bed at different heights (knee height, thigh height, and hip height) and in the bathroom, three tests were performed with different work methods (standing, kneeling, and sitting). After each test, participants rated their perceived exertion on the 15-point Borg scale (6 = no exertion at all and 20 = exhaustion). If the bed was raised from knee to thigh level, the proportion of time spent in an upright position increased by 8.2% points. However, the effect was not significant (P = 0.193). Only when the bed was raised to hip height, there was a significant increase of 19.8% points (reference: thigh level; P = 0.003) and 28.0% points (reference: knee height; P nursing personnel work in an upright position, the less strenuous they perceive the work to be. Raising the bed to hip height and using a stool in the bathroom significantly increase the proportion of time that nursing personnel work in an upright position. Nursing staff can spend a considerably greater proportion of their time in an ergonomic posture if stools and height-adjustable beds are provided in healthcare institutions.

Progressive metabolic impairment underlies the novel nematicidal action of fluensulfone on the potato cyst nematode Globodera pallida.

Science.gov (United States)

Kearn, James; Lilley, Catherine; Urwin, Peter; O'Connor, Vincent; Holden-Dye, Lindy

2017-10-01

Fluensulfone is a new nematicide with an excellent profile of selective toxicity against plant parasitic nematodes. Here, its effects on the physiology and biochemistry of the potato cyst nematode Globodera pallida have been investigated and comparisons made with its effect on the life-span of the free-living nematode Caenorhabditis elegans to provide insight into its mode of action and its selective toxicity. Fluensulfone exerts acute effects (≤1h; ≥100μM) on stylet thrusting and motility of hatched second stage G. pallida juveniles (J2s). Chronic exposure to lower concentrations of fluensulfone (≥3days; ≤30μM), reveals a slowly developing metabolic insult in which G. pallida J2s sequentially exhibit a reduction in motility, loss of a metabolic marker for cell viability, high lipid content and tissue degeneration prior to death. These effects are absent in adults and dauers of the model genetic nematode Caenorhabditis elegans. The nematicidal action of fluensulfone follows a time-course which progresses from an early impact on motility through to an accumulating metabolic impairment, an inability to access lipid stores and death. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity.

Science.gov (United States)

Mueller, Michaela; Thorell, Anders; Claudel, Thierry; Jha, Pooja; Koefeler, Harald; Lackner, Carolin; Hoesel, Bastian; Fauler, Guenter; Stojakovic, Tatjana; Einarsson, Curt; Marschall, Hanns-Ulrich; Trauner, Michael

2015-06-01

Bile acids (BAs) are major regulators of hepatic BA and lipid metabolism but their mechanisms of action in non-alcoholic fatty liver disease (NAFLD) are still poorly understood. Here we aimed to explore the molecular and biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross-talk between liver and visceral white adipose tissue (vWAT) regarding BA and cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD patients. In this randomized controlled pharmacodynamic study, we analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese patients receiving UDCA (20 mg/kg/day) or no treatment three weeks prior to bariatric surgery. Short term UDCA administration stimulated BA synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X receptor (FXR) activation, resulting in cholesterol 7α-hydroxylase induction mirrored by elevated C4 and 7α-hydroxycholesterol. Enhanced BA formation depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the liver, thereby increasing hepatic triglyceride content. In addition, induced SCD activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic and more lipogenic monounsaturated fatty acids such as oleic acid. These data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces neutral lipid accumulation in both liver and vWAT. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Ept7 influences estrogen action in the pituitary gland and body weight of rats.

Science.gov (United States)

Kurz, Scott G; Dennison, Kirsten L; Samanas, Nyssa Becker; Hickman, Maureen Peters; Eckert, Quincy A; Walker, Tiffany L; Cupp, Andrea S; Shull, James D

2014-06-01

Estrogens control many aspects of pituitary gland biology, including regulation of lactotroph homeostasis and synthesis and secretion of prolactin. In rat models, these actions are strain specific and heritable, and multiple quantitative trait loci (QTL) have been mapped that impact the responsiveness of the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female progeny generated in an intercross between BN rats, in which the lactotroph population is insensitive to estrogens, and ACI rats, which develop lactotroph hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen treatment. The primary objective of this study was to confirm the existence of Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary gland of female and male rats to 17β-estradiol (E2) and diethylstilbestrol (DES), respectively. Secondary objectives were to determine if Ept7 influences the responsiveness of the male reproductive tract to DES and to identify other discernible phenotypes influenced by Ept7. To achieve these objectives, a congenic rat strain that harbors BN alleles across the Ept7 interval on the genetic background of the ACI strain was generated and characterized to define the effect of administered estrogens on the anterior pituitary gland and male reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect on development of lactotroph hyperplasia in response to estrogen treatment, but does not affect atrophy of the male reproductive tissues in response to hormone treatment. Ept7 was also observed to exert gender specific effects on body weight in young adult rats.

Interhemispheric inhibition during mental actions of different complexity.

Directory of Open Access Journals (Sweden)

Nicolas Gueugneau

Full Text Available Several investigations suggest that actual and mental actions trigger similar neural substrates. Yet, neurophysiological evidences on the nature of interhemispheric interactions during mental movements are still meagre. Here, we asked whether the content of mental images, investigated by task complexity, is finely represented in the inhibitory interactions between the two primary motor cortices (M1s. Subjects' left M1 was stimulated by means of transcranial magnetic stimulation (TMS while they were performing actual or mental movements of increasing complexity with their right hand and exerting a maximum isometric force with their left thumb and index. Thus, we simultaneously assessed the corticospinal excitability in the right opponent pollicis muscle (OP and the ipsilateral silent period (iSP in the left OP during actual and mental movements. Corticospinal excitability in right OP increased during actual and mental movements, but task complexity-dependent changes were only observed during actual movements. Interhemispheric motor inhibition in the left OP was similarly modulated by task complexity in both mental and actual movements. Precisely, the duration and the area of the iSP increased with task complexity in both movement conditions. Our findings suggest that mental and actual movements share similar inhibitory neural circuits between the two homologous primary motor cortex areas.

Influence of fatigue, stress, muscle soreness and sleep on perceived exertion during submaximal effort.

Science.gov (United States)

Haddad, Monoem; Chaouachi, Anis; Wong, Del P; Castagna, Carlo; Hambli, Mourad; Hue, Olivier; Chamari, Karim

2013-07-02

The aim of this study was to assess the effects of the Hooper's Index variations (i.e., self-ratings of fatigue, stress, delayed onset muscle soreness (DOMS), and sleep) on rating of perceived exertion during a 10 min submaximal exercise training session (RPE-10 min) and then check the stability and the internal consistency of RPE-10 min. Seventeen junior soccer players took part in this study. The individual Hooper's indices taken before each training session were correlated with RPE-10 min during a constant intensity and duration effort (10 min) using Pearson product moment correlation. Intraclass correlation (ICC) was used to assess the internal consistency of the RPE-10 min. All individual correlations between RPE-10 min and quality of sleep and quantity of fatigue, stress, and DOMS were non-significant (p>0.05). No significant correlations were resulted between RPE-10 min and Hooper's Index in all athletes. The ICC of RPE-10 min was 0.77 thus demonstrating internal consistency. The results of the present study demonstrated the objectivity and utility of RPE as a psychological tool for monitoring training during traditional soccer training. Therefore, the results of the present study suggest that fatigue, stress, DOMS and sleep are not major contributors of perceived exertion during traditional soccer training without excessive training loads. It seems that psychobiological factors other than fatigue, stress, DOMS and sleep may have mediated the 10 min exercise perceptual intensity. © 2013.

Selective algicidal action of peptides against harmful algal bloom species.

Directory of Open Access Journals (Sweden)

Seong-Cheol Park

Full Text Available Recently, harmful algal bloom (HAB, also termed "red tide", has been recognized as a serious problem in marine environments according to climate changes worldwide. Many novel materials or methods to prevent HAB have not yet been employed except for clay dispersion, in which can the resulting sedimentation on the seafloor can also cause alteration in marine ecology or secondary environmental pollution. In the current study, we investigated that antimicrobial peptide have a potential in controlling HAB without cytotoxicity to harmless marine organisms. Here, antimicrobial peptides are proposed as new algicidal compounds in combating HAB cells. HPA3 and HPA3NT3 peptides which exert potent antimicrobial activity via pore forming action in plasma membrane showed that HPA3NT3 reduced the motility of algal cells, disrupted their plasma membrane, and induced the efflux of intracellular components. Against raphidoflagellate such as Heterosigma akashiwo, Chattonella sp., and C. marina, it displayed a rapid lysing action in cell membranes at 1~4 µM within 2 min. Comparatively, its lysing effects occurred at 8 µM within 1 h in dinoflagellate such as Cochlodium polykrikoides, Prorocentrum micans, and P. minimum. Moreover, its lysing action induced the lysis of chloroplasts and loss of chlorophyll a. In the contrary, this peptide was not effective against Skeletonema costatum, harmless algal cell, even at 256 µM, moreover, it killed only H. akashiwo or C. marina in co-cultivation with S. costatum, indicating to its selective algicidal activity between harmful and harmless algal cells. The peptide was non-hemolytic against red blood cells of Sebastes schlegeli, the black rockfish, at 120 µM. HAB cells were quickly and selectively lysed following treatment of antimicrobial peptides without cytotoxicity to harmless marine organisms. Thus, the antibiotic peptides examined in our study appear to have much potential in effectively controlling HAB with minimal

Hybrid Action Systems

DEFF Research Database (Denmark)

Ronkko, Mauno; Ravn, Anders P.

1997-01-01

a differential action, which allows differential equations as primitive actions. The extension allows us to model hybrid systems with both continuous and discrete behaviour. The main result of this paper is an extension of such a hybrid action system with parallel composition. The extension does not change...... the original meaning of the parallel composition, and therefore also the ordinary action systems can be composed in parallel with the hybrid action systems....

Climate Action Team

Science.gov (United States)

Science Partnerships Contact Us Climate Action Team & Climate Action Initiative The Climate Action programs and the state's Climate Adaptation Strategy. The CAT members are state agency secretaries and the . See CAT reports Climate Action Team Pages CAT Home Members Working Groups Reports Back to Top

Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine

Science.gov (United States)

Covey, Dan P.; Juliano, Steven A.; Garris, Paul A.

2013-01-01

Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties. PMID:23671560

Action Rules Mining

CERN Document Server

Dardzinska, Agnieszka

2013-01-01

We are surrounded by data, numerical, categorical and otherwise, which must to be analyzed and processed to convert it into information that instructs, answers or aids understanding and decision making. Data analysts in many disciplines such as business, education or medicine, are frequently asked to analyze new data sets which are often composed of numerous tables possessing different properties. They try to find completely new correlations between attributes and show new possibilities for users.   Action rules mining discusses some of data mining and knowledge discovery principles and then describe representative concepts, methods and algorithms connected with action. The author introduces the formal definition of action rule, notion of a simple association action rule and a representative action rule, the cost of association action rule, and gives a strategy how to construct simple association action rules of a lowest cost. A new approach for generating action rules from datasets with numerical attributes...

Impulsive action and motivation.

Science.gov (United States)

Frijda, Nico H

2010-07-01

This paper explores the way in which emotions are causal determinants of action. It argues that emotional events, as appraised by the individual, elicit changes in motive states (called states of action readiness), which in turn may (or may not) cause action. Actions can be elicited automatically, without prior intention (called impulsive actions), or intentionally. Impulsive actions reflect the simplest and biologically most general form in which emotions can cause action, since they require no reflection, no foresight, and no planning. Impulsive actions are determined conjointly by the nature of action readiness, the affordances perceived in the eliciting event as appraised, and the individual's action repertoire. Those actions from one's repertoire are performed that both match the perceived affordances and the aim of the state of action readiness. Copyright © 2010 Elsevier B.V. All rights reserved.

Grass Carp Follisatin: Molecular Cloning, Functional Characterization, Dopamine D1 Regulation at Pituitary Level, and Implication in Growth Hormone Regulation

Directory of Open Access Journals (Sweden)

Roger S. K. Fung

2017-08-01

Full Text Available Activin is involved in pituitary hormone regulation and its pituitary actions can be nullified by local production of its binding protein follistatin. In our recent study with grass carp, local release of growth hormone (GH was shown to induce activin expression at pituitary level, which in turn could exert an intrapituitary feedback to inhibit GH synthesis and secretion. To further examine the activin/follistatin system in the carp pituitary, grass carp follistatin was cloned and confirmed to be single-copy gene widely expressed at tissue level. At the pituitary level, follistatin signals could be located in carp somatotrophs, gonadotrophs, and lactotrophs. Functional expression also revealed that carp follistatin was effective in neutralizing activin’s action in stimulating target promoter with activin-responsive elements. In grass carp pituitary cells, follistatin co-treatment was found to revert activin inhibition on GH mRNA expression. Meanwhile, follistatin mRNA levels could be up-regulated by local production of activin but the opposite was true for dopaminergic activation with dopamine (DA or its agonist apomorphine. Since GH stimulation by DA via pituitary D1 receptor is well-documented in fish models, the receptor specificity for follistatin regulation by DA was also investigated. Using a pharmacological approach, the inhibitory effect of DA on follistatin gene expression was confirmed to be mediated by pituitary D1 but not D2 receptor. Furthermore, activation of D1 receptor by the D1-specific agonist SKF77434 was also effective in blocking follistatin mRNA expression induced by activin and GH treatment both in carp pituitary cells as well as in carp somatotrophs enriched by density gradient centrifugation. These results, as a whole, suggest that activin can interact with dopaminergic input from the hypothalamus to regulate follistatin expression in carp pituitary, which may contribute to GH regulation by activin/follistatin system

Acute kidney injury mediated by oxidative stress in Egyptian horses with exertional rhabdomyolysis.

Science.gov (United States)

el-Ashker, Maged R

2011-06-01

The present study was carried out to evaluate the role of oxidative stress in the pathophysiologic process of acute renal failure associated with exertional rhabdomyolysis (ER) in Egyptian horses. ER was tentatively diagnosed in 31 Baladi horses based on case history, physical examination findings and confirmed by elevation of plasma creatine kinase (CK) and urine myoglobin concentrations. According to severity of the condition, the diseased horses were categorized into two main groups; the first group included 18 horses with minimal clinical signs and plasma CK 100 000 IU/L). It was found that plasma creatol (CTL) was positively correlated (p Baladi horses with severe rhabdomyolysis.

Estimation of the flow resistances exerted in coronary arteries using a vessel length-based method.

Science.gov (United States)

Lee, Kyung Eun; Kwon, Soon-Sung; Ji, Yoon Cheol; Shin, Eun-Seok; Choi, Jin-Ho; Kim, Sung Joon; Shim, Eun Bo

2016-08-01

Flow resistances exerted in the coronary arteries are the key parameters for the image-based computer simulation of coronary hemodynamics. The resistances depend on the anatomical characteristics of the coronary system. A simple and reliable estimation of the resistances is a compulsory procedure to compute the fractional flow reserve (FFR) of stenosed coronary arteries, an important clinical index of coronary artery disease. The cardiac muscle volume reconstructed from computed tomography (CT) images has been used to assess the resistance of the feeding coronary artery (muscle volume-based method). In this study, we estimate the flow resistances exerted in coronary arteries by using a novel method. Based on a physiological observation that longer coronary arteries have more daughter branches feeding a larger mass of cardiac muscle, the method measures the vessel lengths from coronary angiogram or CT images (vessel length-based method) and predicts the coronary flow resistances. The underlying equations are derived from the physiological relation among flow rate, resistance, and vessel length. To validate the present estimation method, we calculate the coronary flow division over coronary major arteries for 50 patients using the vessel length-based method as well as the muscle volume-based one. These results are compared with the direct measurements in a clinical study. Further proving the usefulness of the present method, we compute the coronary FFR from the images of optical coherence tomography.

Freedom and enforcement in action a study in formal action theory

CERN Document Server

Czelakowski, Janusz

2015-01-01

Action theory is the object of growing attention in a variety of scientific disciplines, and this is the first volume to offer a synthetic view of the range of approaches possible in the topic. The volume focuses on the nexus of formal action theory with a startlingly diverse set of subjects, which range from logic, linguistics, artificial intelligence, and automata theory to jurisprudence, deontology, and economics. It covers semantic, mathematical and logical aspects of action, showing how the problem of action breaks the boundaries of traditional branches of logic located in syntactics and semantics and now lies on lies on the borderline between logical pragmatics and praxeology.   The chapters here focus on specialized tasks in formal action theory, beginning with a thorough description and formalization of the language of action, and moving through material on the differing models of action theory to focus on probabilistic models, the relations of formal action theory to deontic logic, and its key appl...

Learning about goals : development of action perception and action control

NARCIS (Netherlands)

Verschoor, Stephan Alexander

2014-01-01

By using innovative paradigms, the present thesis provides convincing evidence that action-effect learning, and sensorimotor processes in general play a crucial role in the development of action- perception and production in infancy. This finding was further generalized to sequential action.

Ultrasound-Guided Fasciotomy for Chronic Exertional Compartment Syndrome: A Cadaveric Investigation.

Science.gov (United States)

Lueders, Daniel R; Sellon, Jacob L; Smith, Jay; Finnoff, Jonathan T

2017-07-01

Chronic exertional compartment syndrome (CECS) is a common cause of exertional leg pain. It is commonly treated with a surgical fasciotomy, which has a surgical complication rate of up to 16% and takes approximately 6-12 weeks to return to preprocedure activity levels. Therefore, the development of a less invasive, effective outpatient intervention to treat CECS is desirable. To describe and validate an ultrasound-guided (USG) fasciotomy technique for the anterior and lateral compartments of the lower limb in an unembalmed cadaveric model. Prospective, cadaveric laboratory investigation. Academic institution procedural skills laboratory. Ten unembalmed cadaveric knee-ankle-foot specimens from 1 female (2 specimens) and 7 male donors aged 62-91 years (mean 78.6 years) with body mass indices of 18.9-35.3 kg/m 2 (mean 27.1 kg/m 2 ). Two experienced operators each performed USG anterior and lateral compartment fasciotomies on 5 unembalmed cadaveric legs. A third physician subsequently dissected the legs to assess the continuity of the fasciotomies and to identify any neurovascular damage related to the procedures. Fasciotomy length (in centimeters) and classification by completeness (achieved target length or did not achieve target length) and continuity (continuous or discontinuous) based on predetermined criteria. Muscles, retinaculae, and neurovascular structures were assessed for damage. No neurovascular injuries occurred in any of the 20 USG fasciotomies. The average fasciotomy length was 22.5 cm. All 20 of the fasciotomies achieved the target length. A continuous cephalocaudal fasciotomy was accomplished in 13 of 20 fasciotomies. When a fasciotomy was not continuous, the average length and number of intact fascial bands was 1.52 cm and 2.3, respectively. USG fasciotomy of the anterior and lateral leg compartments can be safely performed in a cadaveric model and can achieve a fasciotomy length comparable to surgical fasciotomy. Most procedures successfully

An antiinflammatory actions of exenatide

Directory of Open Access Journals (Sweden)

S Yu Vorotnikova

2012-12-01

Full Text Available Реферат по статье: Chaudhuri A, Ghanim H, Vora M, Sia CL, Korzeniewski K, Dhindsa S, Makdissi A, Dandona P. Exenatide exerts a potent antiinflammatory effect. J Clin Endocrinol Metab. 2012 Jan; 97(1: 198-207.

Non-conscious visual cues related to affect and action alter perception of effort and endurance performance

Directory of Open Access Journals (Sweden)

Anthony William Blanchfield

2014-12-01

Full Text Available The psychobiological model of endurance performance proposes that endurance performance is determined by a decision-making process based on perception of effort and potential motivation. Recent research has reported that effort-based decision-making during cognitive tasks can be altered by non-conscious visual cues relating to affect and action. The effect of these non-conscious visual cues on effort and performance during physical tasks is however unknown. We report two experiments investigating the effect of subliminal priming with visual cues related to affect and action on perception of effort and endurance performance. In Experiment 1 thirteen individuals were subliminally primed with happy or sad faces as they cycled to exhaustion in a counterbalanced and randomized crossover design. A paired t-test (happy vs. sad faces revealed that individuals cycled for significantly longer (178 s, p = .04 when subliminally primed with happy faces. A 2 x 5 (condition x iso-time ANOVA also revealed a significant main effect of condition on rating of perceived exertion (RPE during the time to exhaustion (TTE test with lower RPE when subjects were subliminally primed with happy faces (p = .04. In Experiment 2, a single-subject randomization tests design found that subliminal priming with action words facilitated a significantly longer (399 s, p = .04 TTE in comparison to inaction words (p = .04. Like Experiment 1, this greater TTE was accompanied by a significantly lower RPE (p = .03. These experiments are the first to show that subliminal visual cues relating to affect and action can alter perception of effort and endurance performance. Non-conscious visual cues may therefore influence the effort-based decision-making process that is proposed to determine endurance performance. Accordingly, the findings raise notable implications for individuals who may encounter such visual cues during endurance competitions, training, or health related exercise.

Enforcement actions: Significant actions resolved individual actions. Semiannual progress report, January 1996--June 1996

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-08-01

This document summarizes significant enforcement actions that have been resolved during the period of January-June 1996. The report includes copies of Orders and Notices of Violations sent by the Nuclear Regulatory Commission to individuals with respect to the enforcement actions.

Enforcement actions: Significant actions resolved individual actions. Semiannual progress report, January 1996--June 1996

International Nuclear Information System (INIS)

1996-08-01

This document summarizes significant enforcement actions that have been resolved during the period of January-June 1996. The report includes copies of Orders and Notices of Violations sent by the Nuclear Regulatory Commission to individuals with respect to the enforcement actions

Creativity as action

DEFF Research Database (Denmark)

Glaveanu, Vlad Petre; Lubart, Todd; Bonnardel, Nathalie

2013-01-01

The present paper outlines an action theory of creativity and substantiates this approach by investigating creative expression in five different domains. We propose an action framework for the analysis of creative acts built on the assumption that creativity is a relational, inter......, science, scriptwriting, and music. Results point to complex models of action and inter-action specific for each domain and also to interesting patterns of similarity and differences between domains. These findings highlight the fact that creative action takes place not “inside” individual creators but “in...

Nootkatone confers hepatoprotective and anti-fibrotic actions in a murine model of liver fibrosis by suppressing oxidative stress, inflammation, and apoptosis.

Science.gov (United States)

Kurdi, Amani; Hassan, Kamal; Venkataraman, Balaji; Rajesh, Mohanraj

2018-02-01

In this study, the hepatoprotective and anti-fibrotic actions of nootkatone (NTK) were investigated using carbon tetrachloride (CCl 4 )-induced liver fibrosis in mice. CCl 4 administration elevated serum aspartate and alanine transaminases levels, respectively. In addition, CCl 4 produced hepatic oxidative and nitrative stress, characterized by diminished hemeoxygenase-1 expression, antioxidant defenses, and accumulation of 4-hydroxynonenal and 3-nitrotyrosine. Furthermore, CCl 4 administration evoked profound expression of pro-inflammatory cytokine expressions such as tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-1β in hepatic tissues, which corroborated with nuclear factor κB activation. Additionally, CCl 4 -treated animals exhibited higher apoptosis, characterized by increased caspase 3 activity, DNA fragmentation, and poly (ADP-ribose) polymerase activation. Moreover, histological and biochemical investigations revealed marked fibrosis in the livers of CCl 4 -administered animals. However, NTK treatment mitigated CCl 4 -induced phenotypic changes. In conclusion, our findings suggest that NTK exerts hepatoprotective and anti-fibrotic actions by suppressing oxidative stress, inflammation, and apoptosis. © 2017 Wiley Periodicals, Inc.

The effective action

International Nuclear Information System (INIS)

DeWitt, B.

1987-01-01

The concept of the effective action in quantum field theory was introduced into physics by Julian Schwinger in 1954. The effective action summarizes, in a single functional, all the quantum properties of the fields under consideration. The functional derivative of the effective action yields the effective field equations, which replace the classical field equations as descriptors of the dynamical behavior of quantized fields. Solutions of these equations are 'in-out' matrix elements of the field operators and, when substituted back into the effective action itself, yield logarithms of the corresponding 'in-out' amplitudes. The classical field equations are gauge covariant, a fact that derives from the gauge invariance of the classical action. One has learned how to construct effective actions that are similarly gauge invariant (in each order of perturbation theory) and that yield effective field equations having the covariance properties of their classical analogs. Despite this advance, problems remain, stemming from the fact that there is not one but an infinite number of gauge invariant effective actions, one for every background-covariant choice of supplementary conditions and ghost fields. Vilkovisky (1984) has argued persuasively that by requiring additionally that the effective action be invariant under local invertible changes in the choice of basic field variables, one can construct a natural unique gauge invariant effective action. This lecture will examine Vilkovisky's ideas. 3 refs

Self-rating level of perceived exertion for guiding exercise intensity during a 12-week cardiac rehabilitation programme and the influence of heart rate reducing medication

DEFF Research Database (Denmark)

Tang, Lars H.; Zwisler, Ann-Dorthe; Taylor, Rod S

2016-01-01

OBJECTIVES: To investigate whether self-rating level of perceived exertion can adequately guide exercise intensity during a 12-week cardiac rehabilitation programme. DESIGN: Linear regression analysis using rehabilitation data from two randomised controlled trials. METHODS: Patients undergoing ra......-led and self-regulated model using rating of perceived exertion can help guide exercise intensity in everyday clinical practice among patients with heart disease, irrespective if they are taking heart rate-reducing medication....... radiofrequency ablation for atrial fibrillation or following heart valve surgery and participating in exercise-based rehabilitation were included. The 12-week rehabilitation outpatient programme comprised three weekly training sessions, each consisting of 20min aerobic exercise divided into three steps. Patients...... were asked to base their exercise intensity for each step on a predefined rating of perceived exertion specified in a training diary. Exercise intensity was objectively measured by heart rate during the last 2min for each exercise step. Comparative analysis and linear regression of the rating...

Heart rate variability during exertional heat stress: effects of heat production and treatment.

Science.gov (United States)

Flouris, Andreas D; Bravi, Andrea; Wright-Beatty, Heather E; Green, Geoffrey; Seely, Andrew J; Kenny, Glen P

2014-04-01

We assessed the efficacy of different treatments (i.e., treatment with ice water immersion vs. natural recovery) and the effect of exercise intensities (i.e., low vs. high) for restoring heart rate variability (HRV) indices during recovery from exertional heat stress (EHS). Nine healthy adults (26 ± 3 years, 174.2 ± 3.8 cm, 74.6 ± 4.3 kg, 17.9 ± 2.8 % body fat, 57 ± 2 mL·kg·(-1) min(-1) peak oxygen uptake) completed four EHS sessions incorporating either walking (4.0-4.5 km·h(-1), 2 % incline) or jogging (~7.0 km·h(-1), 2 % incline) on a treadmill in a hot-dry environment (40 °C, 20-30 % relative humidity) while wearing a non-permeable rain poncho for a slow or fast rate of rectal temperature (T re) increase, respectively. Upon reaching a T re of 39.5 °C, participants recovered until T re returned to 38 °C either passively or with whole-body immersion in 2 °C water. A comprehensive panel of 93 HRV measures were computed from the time, frequency, time-frequency, scale-invariant, entropy and non-linear domains. Exertional heat stress significantly affected 60/93 HRV measures analysed. Analyses during recovery demonstrated that there were no significant differences between HRV measures that had been influenced by EHS at the end of passive recovery vs. whole-body cooling treatment (p > 0.05). Nevertheless, the cooling treatment required statistically significantly less time to reduce T re (p whole-body immersion in 2 °C water results in faster cooling, there were no observed differences in restoration of autonomic heart rate modulation as measured by HRV indices with whole-body cold-water immersion compared to passive recovery in thermoneutral conditions.

ACTION OF CHEMICALLY DIFFERENT PROSTAGLANDIN BLOCKERS ON THE ADRENAL HORMONES IN PIGEONS DURING STRESS.

Science.gov (United States)

Sarkar, S; Ghosh, S; Sengupta, S; Dasadhikari, S; Ghosh, A

1999-01-01

The effect of prostaglandin (PG) inhibitors differing in their chemical nature, viz. Aspirin (acetylsalicylic acid), Mefenamic acid (fenamates), Diclofenac (phenylacetic acid derivative) and Piroxicam (oxicam derivative) on the adrenal hormones was studied in acutely stressed pigeons. None of these PG blockers exerted any significant effect on the catecholamine and corticosterone content of the control, i.e. unstressed pigeon adrenal gland excepting mefenamic acid which caused a release of epinephrine. Aspirin, diclofenac and piroxicam did not modulate the catecholamine or corticosterone secretion whereas mefenamic acid caused a released of both epinephrine and norepinephrine and increased the adrenal corticosterone content in the acutely stressed pigeons. These results were compared with those obtained from studies on the effects of other chemically different PG blockers, indomethacin (a methylated indole derivative) and ibuprofen (a propionic acid derivative). It is suggested that chemically and structurally different PG inhibitors show diverse action in the same species under similar stress conditions.

Effects of dietary salt on adrenomedullin and its receptor mRNAs in rat kidney

DEFF Research Database (Denmark)

Jensen, B L; Gambaryan, S; Schmaus, E

1998-01-01

There is accumulating evidence that adrenomedullin (ADM) is involved in the control of salt and water homeostasis. ADM is considered to act primarily in a paracrine fashion, and since the kidneys are target organs for ADM, we investigated the localization and regulation of ADM and ADM receptor (ADM...... and a preferential action of ADM in the papilla. Ten days of feeding a low-salt (0.02%) or a high-salt diet (4%) did not change ADM mRNA or ADM-R mRNA in any kidney zone....

Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability.

Directory of Open Access Journals (Sweden)

Ori Nov

Full Text Available The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers, Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4 that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin

Experiencing Action Evaluation's Cyclic Process: Partnering Conflict, Reflection, and Action

Science.gov (United States)

Burrows, Andrea C.; Harkness, Shelly Sheats

2016-01-01

In this article, the authors describe experiences in and offer suggestions from a course entitled "Educational Innovation for Excellence Through Action Research, Conflict Resolution, and Organizational Learning"--an action evaluation (AE). The class was taught using the principles of action research and AE. The authors explore the impact…

An in vitro quantification of pressures exerted by earlobe pulse oximeter probes following reports of device-related pressure ulcers in ICU patients .

Science.gov (United States)

Goodell, Teresa T

2012-11-01

The earlobe often is used to monitor perfusion when pulse oximeter signal quality is impaired in the fingers and toes. Prompted by intermittent occurrences of roughly circular earlobe pressure ulcers among patients in intensive care units, a convenience sample of seven calibrated pulse oximeter probes was used to quantify earlobe pressure exerted by these devices in vitro. All were tested twice with an electronic load cell, a strain gauge with a transducer that transforms the measured force into a readable numerical signal. The probe was clipped to the load cell just as it is clipped to the earlobe in the clinical setting. The probes exerted an average of 0.24 lb (SD 0.6) of force over an area of 0.3 square inches, equal to an average of 20.7 mm Hg (SD 0.6) pressure on tissue. This value exceeds some empirically derived values of capillary perfusion pressure. The occurrence of device-related pressure ulcers, as well pressure ulcers on the ears, has been documented, but little is known about device-related earlobe pressure ulcers or the actual pressure exerted by these devices. Additional in vitro studies are needed to quantify the pressures exerted by these and other probes, and future prevalence and incidence studies should include more detailed pressure ulcer location and device use documentation. Until more is known about the possible role of these devices in the development of pressure ulcers, clinicians should be cognizant of their potential for causing pressure ulcers, particularly in patients whose conditions can compromise skin integrity.

Diclofenac: an update on its mechanism of action and safety profile.

Science.gov (United States)

Gan, Tong J

2010-07-01

Diclofenac is a proven, commonly prescribed nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic properties, and has been shown to be effective in treating a variety of acute and chronic pain and inflammatory conditions. As with all NSAIDs, diclofenac exerts its action via inhibition of prostaglandin synthesis by inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) with relative equipotency. However, extensive research shows the pharmacologic activity of diclofenac goes beyond COX inhibition, and includes multimodal and, in some instances, novel mechanisms of action (MOA). Literature retrieval was performed through PubMed/MEDLINE (through May 2009) using combinations of the terms diclofenac, NSAID, mechanism of action, COX-1, COX-2, and pharmacology. Reference citations resulting from publications identified in the literature search were reviewed when appropriate. This article reviews the established, putative, and emerging MOAs of diclofenac; compares the drug's pharmacologic and pharmacodynamic properties with other NSAIDs to delineate its potentially unique qualities; hypothesizes why it has been chosen for further recent formulation enhancement; and evaluates the potential effect of its MOA characteristics on safety. Research suggests diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel MOAs may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARgamma), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. The review was not designed to compare MOAs of diclofenac with other NSAIDs. Additionally, as the highlighted putative and emerging MOAs do not have clinical data to demonstrate that these models are

3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects.

Science.gov (United States)

El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Chung, S P; Diem, T H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

2012-02-01

Oxidative stress-energy depletion therapy using oxidative stress induced by D-amino acid oxidase (DAO) and energy depletion induced by 3-bromopyruvate (3BP) was reported recently (El Sayed et al., Cancer Gene Ther., 19, 1-18, 2012). Even in the presence of oxygen, cancer cells oxidize glucose preferentially to produce lactate (Warburg effect) which seems vital for cancer microenvironment and progression. 3BP is a closely related structure to lactate and pyruvate and may antagonize their effects as a novel mechanism of its action. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP. Lactate and pyruvate enhanced migratory power of C6 glioma which was blocked by 3BP. Pyruvate and lactate did not protect against C6 glioma cell death induced by other glycolytic inhibitors e.g. citrate (inhibitor of phosphofructokinase) and sodium fluoride (inhibitor of enolase). Serial doses of 3BP were synergistic with citrate in decreasing viability of C6 glioma cells and spheroids. Glycolysis subjected to double inhibition using 3BP with citrate depleted ATP, clonogenic power and migratory power of C6 glioma cells. 3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time-dependent manner.

A 29-Year-Old Man With Nonproductive Cough, Exertional Dyspnea, and Chest Discomfort.

Science.gov (United States)

Halpenny, Darragh; Suh, James; Garofano, Suzette; Alpert, Jeffrey

2015-09-01

A 29-year-old man presented with a 5-month history of worsening dry cough, exertional dyspnea, chest tightness, and palpitations. He had been treated by his primary care physician with trials of guaifenesin/codeine, azithromycin, albuterol, and omeprazole without improvement. He denied wheezing, fever, sweats, anorexia, joint pain, swelling, or rash. He had no past medical history. He denied a history of tobacco smoking or IV drug use. He kept no pets, worked as a manager in an office environment, and had no history of occupational inhalational exposure. He reported using aerosolized insect spray to eradicate bed bugs in his house shortly before the cough began but did not report any acute symptoms when using the spray.

Age and Sex Differences in Controlled Force Exertion Measured by a Computing Bar Chart Target-Pursuit System

Science.gov (United States)

Nagasawa, Yoshinori; Demura, Shinichi

2009-01-01

This study aimed to examine the age and sex differences in controlled force exertion measured by the bar chart display in 207 males (age 42.1 [plus or minus] 19.8 years) and 249 females (age 41.7 [plus or minus] 19.1 years) aged 15 to 86 years. The subjects matched their submaximal grip strength to changing demand values, which appeared as a…

Action simulation plays a critical role in deceptive action recognition.

Science.gov (United States)

Tidoni, Emmanuele; Borgomaneri, Sara; di Pellegrino, Giuseppe; Avenanti, Alessio

2013-01-09

The ability to infer deceptive intents from nonverbal behavior is critical for social interactions. By combining single-pulse and repetitive transcranial magnetic stimulation (TMS) in healthy humans, we provide both correlational and causative evidence that action simulation is actively involved in the ability to recognize deceptive body movements. We recorded motor-evoked potentials during a faked-action discrimination (FAD) task: participants watched videos of actors lifting a cube and judged whether the actors were trying to deceive them concerning the real weight of the cube. Seeing faked actions facilitated the observers' motor system more than truthful actions in a body-part-specific manner, suggesting that motor resonance was sensitive to deceptive movements. Furthermore, we found that TMS virtual lesion to the anterior node of the action observation network, namely the left inferior frontal cortex (IFC), reduced perceptual sensitivity in the FAD task. In contrast, no change in FAD task performance was found after virtual lesions to the left temporoparietal junction (control site). Moreover, virtual lesion to the IFC failed to affect performance in a difficulty-matched spatial-control task that did not require processing of spatiotemporal (acceleration) and configurational (limb displacement) features of seen actions, which are critical to detecting deceptive intent in the actions of others. These findings indicate that the human IFC is critical for recognizing deceptive body movements and suggest that FAD relies on the simulation of subtle changes in action kinematics within the motor system.

Antinociceptive action and redox properties of citronellal, an essential oil present in lemongrass.

Science.gov (United States)

Quintans-Júnior, Lucindo; da Rocha, Ricardo Fagundes; Caregnato, Fernanda Freitas; Moreira, José Claudio Fonseca; da Silva, Francilene Amaral; Araújo, Adriano Antunes de Souza; dos Santos, João Paulo Almeida; Melo, Mônica Santos; de Sousa, Damião Pergentino; Bonjardim, Leonardo Rigoldi; Gelain, Daniel Pens

2011-06-01

Citronellal (CT) is a monoterpenoid and the major constituent of the mixture of terpenoids that give the citronella oil its lemon scent. Citronella oil is widely used around the world for various purposes and is mainly obtained from plants of the Cymbopogon genus, which are known as "lemongrass." Considering these plants have been used worldwide for various medicinal purposes, the interest of researchers to understand the biological activities of monoterpenoids related to the Cymbopogon genus has been increasing. In the present work, we investigated the antinociceptive action and the redox properties of CT. Our results indicate that intraperitoneal injection of CT was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CT also evoked antinociceptive response in the capsaicin and glutamate tests. The total radical-trapping antioxidant parameter and total antioxidant reactivity assays indicate that CT at doses of 0.1 and 1 mg/mL exerts a significant antioxidant activity, which is probably related to its ability to scavenge superoxide and nitric oxide, but not H(2)O(2) or hydroxyl radicals, as evaluated separately by specific in vitro tests. These results show for the first time the antinociceptive potential of CT and indicate that the antioxidant properties of this compound may rely on its mechanism of biological actions because CT-containing natural products are used to treat various diseases related to oxidative stress and reactive species.

Habits as action sequences: hierarchical action control and changes in outcome value.

Science.gov (United States)

Dezfouli, Amir; Lingawi, Nura W; Balleine, Bernard W

2014-11-05

Goal-directed action involves making high-level choices that are implemented using previously acquired action sequences to attain desired goals. Such a hierarchical schema is necessary for goal-directed actions to be scalable to real-life situations, but results in decision-making that is less flexible than when action sequences are unfolded and the decision-maker deliberates step-by-step over the outcome of each individual action. In particular, from this perspective, the offline revaluation of any outcomes that fall within action sequence boundaries will be invisible to the high-level planner resulting in decisions that are insensitive to such changes. Here, within the context of a two-stage decision-making task, we demonstrate that this property can explain the emergence of habits. Next, we show how this hierarchical account explains the insensitivity of over-trained actions to changes in outcome value. Finally, we provide new data that show that, under extended extinction conditions, habitual behaviour can revert to goal-directed control, presumably as a consequence of decomposing action sequences into single actions. This hierarchical view suggests that the development of action sequences and the insensitivity of actions to changes in outcome value are essentially two sides of the same coin, explaining why these two aspects of automatic behaviour involve a shared neural structure. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Petiveria alliacea exerts mnemonic and learning effects on rats.

Science.gov (United States)

Silva, Mallone Lopes; Luz, Diandra Araújo; Paixão, Thiago Portal da; Silva, João Paulo Bastos; Belém-Filho, Ivaldo Jesus Almeida; Fernandes, Luanna Melo Pereira; Gonçalves, Ana Cristina Baetas; Fontes-Júnior, Enéas Andrade; de Andrade, Marciene Ataíde; Maia, Cristiane Socorro Ferraz

2015-07-01

Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub native to the Amazon region and other tropical areas such as Central America and the Caribbean. Popularly known as mucuracaá, P. alliacea is used in the folk medicine for a broad variety of therapeutic purpose and also in religious ceremonies by slaves as a sedative, which highlights its properties on the Central Nervous System (CNS). The present study evaluated the effects of the P. alliacea leaves hydroalcoholic extract (PaLHE) on the cognition, including learning and memory. Three-month-old male and female Wistar rats (n=8-10/group) were administered with 900mg/kg of PaLHE. The behavioral assays included Step-down Inhibitory avoidance (IA) and Morris Water Maze (MWM) tests. Consistent with our previous reports, P. alliacea improved long-term memory. It also exerted previously unreported effects on short-term and spatial memory improvement, and increased learning in the tasks. The P. alliacea extract elicited mnemonic effects and improved the learning process in both IA and MWM tests. Our results highlight the importance of further studies in order to identify the active substances of the PaLHE and investigate the pharmacological mechanisms that underlies the reported effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Multimodal responsive action

DEFF Research Database (Denmark)

Oshima, Sae

; Raymond 2003; Schegloff and Lerner 2009), including those with multimodal actions (e.g. Olsher 2004; Fasulo & Monzoni 2009). Some responsive actions can also be completed with bodily behavior alone, such as: when an agreement display is achieved by using only nonvocal actions (Jarmon 1996), when...... the recipient’s gaze shift becomes a significant part of the speaker’s turn construction (Goodwin 1980), and when head nods show the recipient’s affiliation with the speaker’s stance (Stivers 2008). Still, much room remains for extending our current understanding of responding actions that necessarily involve...... a hairstylist and a client negotiate the quality of the service that has been provided. Here, the first action is usually the stylist’s question and/or explanation of the new cut that invites the client’s assessment/(dis)agreement, accompanied with embodied actions that project an imminent self...

The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

Energy Technology Data Exchange (ETDEWEB)

Liu, Tong; Yu, Rong [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Jin, Shao-Bo [Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Han, Liwei [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Lendahl, Urban [Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Zhao, Jian, E-mail: Jian.Zhao@ki.se [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Nistér, Monica [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden)

2013-11-01

Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion

The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

International Nuclear Information System (INIS)

Liu, Tong; Yu, Rong; Jin, Shao-Bo; Han, Liwei; Lendahl, Urban; Zhao, Jian; Nistér, Monica

2013-01-01

Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion

The effect of vocal and instrumental music on cardio respiratory variables, energy expenditure and exertion levels during sub maximal treadmill exercise.

Science.gov (United States)

Savitha, D; Sejil, T V; Rao, Shwetha; Roshan, C J; Roshan, C J

2013-01-01

The purpose of the study was to investigate the effect of vocal and instrumental music on various physiological parameters during submaximal exercise. Each subject underwent three sessions of exercise protocol without music, with vocal music, and instrumental versions of same piece of music. The protocol consisted of 10 min treadmill exercise at 70% HR(max) and 20 min of recovery. Minute to minute heart rate and breath by breath recording of respiratory parameters, rate of energy expenditure and perceived exertion levels were measured. Music, irrespective of the presence or absence of lyrics, enabled the subjects to exercise at a significantly lower heart rate and oxygen consumption, reduced the metabolic cost and perceived exertion levels of exercise (P Music having a relaxant effect could have probably increased the parasympathetic activation leading to these effects.

Oxytocin--its role in male reproduction and new potential therapeutic uses.

Science.gov (United States)

Thackare, Hemlata; Nicholson, Helen D; Whittington, Kate

2006-01-01

Oxytocin (OT) is traditionally thought of as a "female" neurohypophysis hormone due to its role in parturition and milk ejection. However, OT is recognized as having endocrine and paracrine roles in male reproduction. At ejaculation, a burst of OT is released from the neurohypophysis into the systemic circulation and stimulates contractions of the reproductive tract aiding sperm release. There is conclusive evidence that OT is synthesized within the mammalian testis, epididymis and prostate and the presence of OT receptors (OTRs) through the reproductive tract supports a local action for this peptide. OT has a paracrine role in stimulating contractility of the seminiferous tubules, epididymis and the prostate gland. Interestingly, OT has also been shown to modulate androgen levels in these tissues via stimulation of the conversion of testosterone to dihydrotestostone (DHT) by 5alpha-reductase. The elucidation of OT's role in male reproduction has suggested a number of potential therapeutic uses for this hormone. Exogenous administration of OT has, in some cases, been shown to increase the numbers of ejaculated sperm, possibly by stimulating contractions of the reproductive tract and thus aiding sperm passage. Within the prostate, OT has been shown to affect gland growth both directly and via its interaction with androgen metabolism. Prostate pathologies due to unregulated cell proliferation/growth, such as benign prostatic hyperplasia and cancer, are unfortunately very common and few effective treatments are available. Greater understanding of paracrine growth mediators, such as OT, is likely to provide new mechanisms for treating such pathologies.

Ocular Nerve Growth Factor (NGF) and NGF Eye Drop Application as Paradigms to Investigate NGF Neuroprotective and Reparative Actions.

Science.gov (United States)

Tirassa, Paola; Rosso, Pamela; Iannitelli, Angela

2018-01-01

The eye is a central nervous system structure that is uniquely accessible to local treatment. Through the ocular surface, it is possible to access the retina, optic nerve, and brain. Animal models of retina degeneration or optic nerve crush could thus serve as tools to investigate whether and how factors, which are anterogradely or retrogradely transported through the optic nerve, might contribute to activate neuroprotection and eventually regeneration. Among these factors, nerve growth factor (NGF) plays a crucial role during development of the visual system, as well as during the entire life span, and in pathological conditions. The ability of NGF to exert survival and trophic actions on the retina and brain cells when applied intraocularly and topically as eye drops is critically reviewed here, together with the effects of ocular neurotrophins on neuronal pathways influencing body rhythm, cognitions, and behavioral functions. The latest data from animal models and humans are presented, and the mechanism of action of ocularly administered NGF is discussed. NGF eye drops are proposed as an experimental strategy to investigate the role and cellular targets of neurotrophins in the mechanism(s) underlying neurodegeneration/regeneration and their involvement in the regulation of neurological and behavioral dysfunctions.

Inferring Action Structure and Causal Relationships in Continuous Sequences of Human Action

Science.gov (United States)

2014-01-01

and MySQL . However, all participants participated from in-lab computers. Results Figure 6 shows the distribution of participants’ raw key presses... Java program to present video of action sequences and collect ratings. The program presented all 12 actions, non-actions, and part-actions

RCRA corrective action determination of no further action

International Nuclear Information System (INIS)

1996-06-01

On July 27, 1990, the U.S. Environmental Protection Agency (EPA) proposed a regulatory framework (55 FR 30798) for responding to releases of hazardous waste and hazardous constituents from solid waste management units (SWMUs) at facilities seeking permits or permitted under the Resource Conservation and Recovery Act (RCRA). The proposed rule, 'Corrective Action for Solid Waste Management Units at Hazardous Waste Facilities', would create a new Subpart S under the 40 CFR 264 regulations, and outlines requirements for conducting RCRA Facility Investigations, evaluating potential remedies, and selecting and implementing remedies (i.e., corrective measures) at RCRA facilities. EPA anticipates instances where releases or suspected releases of hazardous wastes or constituents from SWMUs identified in a RCRA Facility Assessment, and subsequently addressed as part of required RCRA Facility Investigations, will be found to be non-existent or non-threatening to human health or the environment. Such releases may require no further action. For such situations, EPA proposed a mechanism for making a determination that no further corrective action is needed. This mechanism is known as a Determination of No Further Action (DNFA) (55 FR 30875). This information Brief describes what a DNFA is and discusses the mechanism for making a DNFA. This is one of a series of Information Briefs on RCRA corrective action

Experimental therapy of ovarian cancer with synthetic makaluvamine analog: in vitro and in vivo anticancer activity and molecular mechanisms of action.

Directory of Open Access Journals (Sweden)

Tao Chen

Full Text Available The present study was designed to determine the biological effects of novel marine alkaloid analog 7-(4-fluorobenzylamino-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H-one (FBA-TPQ on human ovarian cancer cells for its anti-tumor potential and the underlying mechanisms as a novel chemotherapeutic agent. Human ovarian cancer cells (A2780 and OVCAR-3, and Immortalized non-tumorigenic human Ovarian Surface Epithelial cells (IOSE-144, were exposed to FBA-TPQ for initial cytotoxicity evaluation (via MTS assay kit, Promega. The detailed in-vitro (cell level and in-vivo (animal model studies on the antitumor effects and possible underlying mechanisms of action of the compounds were then performed. FBA-TPQ exerted potent cytotoxicity against human ovarian cancer A2780 and OVCAR-3 cells as an effective inhibitor of cell growth and proliferation, while exerting lesser effects on non-tumorigenic IOSE-144 cells. Further study in the more sensitive OVCAR-3 cell line showed that it could potently induce cell apoptosis (Annexin V-FITC assay, G2/M cell cycle arrest (PI staining analysis and also dose-dependently inhibit OVCAR-3 xenograft tumors' growth on female athymic nude mice (BALB/c, nu/nu. Mechanistic studies (both in vitro and in vivo revealed that FBA-TPQ might exert its activity through Reactive Oxygen Species (ROS-associated activation of the death receptor, p53-MDM2, and PI3K-Akt pathways in OVCAR-3 cells, which is in accordance with in vitro microarray (Human genome microarrays, Agilent data analysis (GEO accession number: GSE25317. In conclusion, FBA-TPQ exhibits significant anticancer activity against ovarian cancer cells, with minimal toxicity to non-tumorigenic human IOSE-144 cells, indicating that it may be a potential therapeutic agent for ovarian cancer.

Egocentric Temporal Action Proposals.

Science.gov (United States)

Shao Huang; Weiqiang Wang; Shengfeng He; Lau, Rynson W H

2018-02-01

We present an approach to localize generic actions in egocentric videos, called temporal action proposals (TAPs), for accelerating the action recognition step. An egocentric TAP refers to a sequence of frames that may contain a generic action performed by the wearer of a head-mounted camera, e.g., taking a knife, spreading jam, pouring milk, or cutting carrots. Inspired by object proposals, this paper aims at generating a small number of TAPs, thereby replacing the popular sliding window strategy, for localizing all action events in the input video. To this end, we first propose to temporally segment the input video into action atoms, which are the smallest units that may contain an action. We then apply a hierarchical clustering algorithm with several egocentric cues to generate TAPs. Finally, we propose two actionness networks to score the likelihood of each TAP containing an action. The top ranked candidates are returned as output TAPs. Experimental results show that the proposed TAP detection framework performs significantly better than relevant approaches for egocentric action detection.

Normative Action Research

DEFF Research Database (Denmark)

Baboroglu, Oguz; Ravn, Ib

1992-01-01

This paper presents an argument for an enrichment of action research methodology. To the current state of action research, we add a constructivist epistemological argument, as well as a crucial inspiration from some futures-oriented planning approaches. Within the domain of social....... They are generated jointly by the stakeholders of a system and the involved action researchers and are tested every time that the prescriptions for action contained in them are followed by a system's stakeholders....

Evaluation of the antifungal activity and mode of action of Lafoensia pacari A. St.-Hil., Lythraceae, stem-bark extracts, fractions and ellagic acid

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Iberê F. Silva Junior

Full Text Available Stem-bark extracts, fractions and the isolated constituent, ellagic acid of Lafoensia pacari St. Hil. (Lythraceae were in vitro assayed for antifungal activity against a panel of yeasts, hialohyphomycetes as well as dermatophytes with the microbroth dilution method. The EtOH extract and its fractions and ellagic acid exhibited activity against Candida spp and Saccharomyces cerevisiae with MIC values between 250-1000 µg/mL, but they showed no action against filamentous fungi and dermatophytes (MIC>1000 µg/mL. Active extracts were evaluated in Neurospora crassa hyphal growth inhibition and sorbitol assays and then the effect of ergosterol on the MIC of ellagic acid was studied. The active extracts and its fractions and ellagic acid showed a blotchy zone around the paper disk and induced malformations of the hypha. Besides, MIC of the ellagic acid against the Saccharomyces cerevisiae was raised from 62 to 250 µg/mL in the presence of sorbitol 0.8 M, suggesting that the ellagic acid would probably exert its action on fungal cell wall. These results indicate that ellagic acid might be the main active antifungal compound of Lafoensia pacari and further suggest that the mode of antifungal action of these extracts and ellagic acid could be associated with the inhibition of fungal cell wall.

Aging, Atherosclerosis, and IGF-1

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Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung

2012-01-01

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1–induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging. PMID:22491965

Sex Steroid Actions in Male Bone

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Laurent, Michaël R.; Claessens, Frank; Gielen, Evelien; Lagerquist, Marie K.; Vandenput, Liesbeth; Börjesson, Anna E.; Ohlsson, Claes

2014-01-01

Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority. PMID:25202834

In vivo xenoestrogenic actions of cadmium and arsenic in anterior pituitary and uterus.

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Ronchetti, Sonia A; Novack, Gisela V; Bianchi, María S; Crocco, Melisa C; Duvilanski, Beatriz H; Cabilla, Jimena P

2016-07-01

Cadmium (Cd) and arsenic (iAs) are toxic metals ubiquitously present in the environment. Both pollutants exert nonmonotonic dose responses, being mostly cytotoxic at high concentrations but mimicking estrogen (E2) effects at low doses. Xenoestrogenic activity of Cd and iAs has been demonstrated in different hormone-dependent tumor cell lines; however, their actions in vivo remain largely unknown. Here, we investigated whether in vivo administration of low doses of Cd and iAs through drinking water would display xenoestrogenic effects in the anterior pituitary gland and uterus of ovariectomized rats. Cd (1ppm) and iAs (0.1ppm) exposure increased the wet weight of anterior pituitary gland and uterus and induced proestrus- and estrus-like vaginal smears. Both metals stimulate cell proliferation of these tissues as they increased the expression of proliferation markers. More importantly, they augmented soluble guanylyl cyclase α1 subunit expression, which has been linked to hormone-dependent tumor progression. Also, Cd and iAs modified protein levels of full-length estrogen receptor α and its truncated variants in an E2-like manner. Anterior pituitary hormone secretion was differentially affected by both metals. Luteinizing hormone synthesis and release were strongly diminished after Cd exposure and only mildly reduced by iAs. Both metals were able to increase prolactin synthesis, although only iAs augmented serum prolactin levels. This study shows for the first time that Cd and iAs exert strong xenoestrogenic effects on anterior pituitary gland at low doses. The differences between Cd and iAs E2-like behavior indicate that other Cd- and iAs-specific mechanisms could be involved. Altogether, these results contribute to the knowledge of reproductive disorders associated with Cd and iAs environmental contamination. © 2016 Society for Reproduction and Fertility.

Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep.

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Manikkam, Mohan; Thompson, Robert C; Herkimer, Carol; Welch, Kathleen B; Flak, Jonathan; Karsch, Fred J; Padmanabhan, Vasantha

2008-04-01

The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH) secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol (E2) receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis. We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release. Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release.

Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

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Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2013-07-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

Emotions and action

NARCIS (Netherlands)

Frijda, N.H.; Manstead, A.S.R.; Frijda, N.H.; Fischer, A.H.

2004-01-01

This chapter discusses the relationships between emotion and action. Emotion, by its very nature, is change in action readiness to maintain or change one's relationship to an object or event. Motivation, or motivational change, is one of the key aspects of emotions. Even so, action follows only

Additive Routes to Action Learning: Layering Experience Shapes Engagement of the Action Observation Network.

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Kirsch, Louise P; Cross, Emily S

2015-12-01

The way in which we perceive others in action is biased by one's prior experience with an observed action. For example, we can have auditory, visual, or motor experience with actions we observe others perform. How action experience via 1, 2, or all 3 of these modalities shapes action perception remains unclear. Here, we combine pre- and post-training functional magnetic resonance imaging measures with a dance training manipulation to address how building experience (from auditory to audiovisual to audiovisual plus motor) with a complex action shapes subsequent action perception. Results indicate that layering experience across these 3 modalities activates a number of sensorimotor cortical regions associated with the action observation network (AON) in such a way that the more modalities through which one experiences an action, the greater the response is within these AON regions during action perception. Moreover, a correlation between left premotor activity and participants' scores for reproducing an action suggests that the better an observer can perform an observed action, the stronger the neural response is. The findings suggest that the number of modalities through which an observer experiences an action impacts AON activity additively, and that premotor cortical activity might serve as an index of embodiment during action observation. © The Author 2015. Published by Oxford University Press.

Inhibition of Hypoxia Inducible Factor Alpha and Astrocyte-Elevated Gene-1 Mediates Cryptotanshinone Exerted Antitumor Activity in Hypoxic PC-3 Cells

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Hyo-Jeong Lee

2012-01-01

Full Text Available Although cryptotanshinone (CT was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1α in CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1α accumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1α siRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1α during hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1α to VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1α, AEG1, and VEGF as a potent chemotherapeutic agent.

Scalability of the muscular action in a parametric 3D model of the index finger.

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Sancho-Bru, Joaquín L; Vergara, Margarita; Rodríguez-Cervantes, Pablo-Jesús; Giurintano, David J; Pérez-González, Antonio

2008-01-01

A method for scaling the muscle action is proposed and used to achieve a 3D inverse dynamic model of the human finger with all its components scalable. This method is based on scaling the physiological cross-sectional area (PCSA) in a Hill muscle model. Different anthropometric parameters and maximal grip force data have been measured and their correlations have been analyzed and used for scaling the PCSA of each muscle. A linear relationship between the normalized PCSA and the product of the length and breadth of the hand has been finally used for scaling, with a slope of 0.01315 cm(-2), with the length and breadth of the hand expressed in centimeters. The parametric muscle model has been included in a parametric finger model previously developed by the authors, and it has been validated reproducing the results of an experiment in which subjects from different population groups exerted maximal voluntary forces with their index finger in a controlled posture.

The Impact of Leadership Styles and Knowledge Sharing on Police Officers' Willingness to Exert Extra Effort to Provide Better Security: A Study in the Riot Unit of the Turkish National Police

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Tombul, Fatih

2011-01-01

The motivation for this study is to understand the factors affecting police officers' willingness to exert extra effort for providing better service through knowledge sharing in different working environments such as riots. Since managers' leadership styles may be important factors affecting subordinates' willingness to exert extra effort, this…

Exertional Rhabdomyolysis after an Extreme Conditioning Competition: A Case Report

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Ramires Alsamir Tibana

2018-04-01

Full Text Available This case report describes an instance of exercise-induced rhabdomyolysis caused by an extreme conditioning program (ECP competition. A 35-year-old female presented with abdominal pain and soreness, which began one day after she completed two days of ECPcompetition composed of five workouts. Three days after competition, creatine kinase (CK was 77,590 U/L accompanied by myalgia and abnormal liver function tests, while renal function was normal and this resulted in a diagnosis of rhabdomyolysis. A follow-up examination revealed that her serum level of CK was still elevated to 3034 U/L on day 10 and 1257 U/L on day 25 following the ECP competition. The subject reported myalgia even up to 25 days after the ECP competition. Exertional rhabdomyolysis can be observed in ECP athletes following competition and highlights a dangerous condition, which may be increasing in recent years due to the massive expansion of ECP popularity and a growing number of competitions. Future research should investigate the causes of rhabdomyolysis that occur as a result of ECP, especially training methods and/or tasks developed specifically for these competitions.

The pro-apoptotic action of the peptide hormone Neb-colloostatin on insect haemocytes.

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Czarniewska, E; Mrówczynska, L; Kuczer, M; Rosinski, G

2012-12-15

The gonadoinhibitory peptide hormone Neb-colloostatin was first isolated from ovaries of the flesh fly Neobellieria bullata. This 19-mer peptide is thought to be a cleaved product of a collagen-like precursor molecule that is formed during remodelling of the extracellular matrix. In this study, we report that upon injection of picomolar and nanomolar doses, this peptide exerts a pro-apoptotic action on haemocytes of Tenebrio molitor adults, as visualized by changes in morphology and viability. The F-actin cytoskeleton was found to aggregate into distinctive patches. This may be responsible for the observed inhibition of adhesion of haemocytes and for the stimulation of filopodia formation. However, Neb-colloostatin injection did not induce the formation of autophagic vacuoles. Our results suggest that physiological concentrations of Neb-colloostatin play an important role in controlling the quantity and activity of haemocytes in insect haemolymph. They also suggest that during periods in which Neb-colloostatin is released, this peptide may cause a weakening of the insects' immune system. This is the first report that exposure to a peptide hormone causes apoptosis in insect haemocytes.

Impulsive action and motivation

NARCIS (Netherlands)

Frijda, N.H.

2010-01-01

This paper explores the way in which emotions are causal determinants of action. It argues that emotional events, as appraised by the individual, elicit changes in motive states (called states of action readiness), which in turn may (or may not) cause action. Actions can be elicited automatically,

Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC).

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Hombach-Klonisch, Sabine; Pocar, Paola; Kauffold, Johannes; Klonisch, Thomas

2006-04-01

Oviduct epithelial cells are important for the nourishment and survival of ovulated oocytes and early embryos, and they respond to the steroid hormones estrogen and progesterone. Endocrine-disrupting polyhalogenated aromatic hydrocarbons (PHAH) are environmental toxins that act in part through the ligand-activated transcription factor arylhydrocarbon receptor (AhR; dioxin receptor), and exposure to PHAH has been shown to decrease fertility. To investigate effects of PHAHs on the oviduct epithelium as a potential target tissue of dioxin-type endocrine disruptors, we have established a novel telomerase-immortalized oviduct porcine epithelial cell line (TERT-OPEC). TERT-OPEC exhibited active telomerase and the immunoreactive epithelial marker cytokeratin but lacked the stromal marker vimentin. TERT-OPEC contained functional estrogen receptor (ER)-alpha and AhR, as determined by the detection of ER-alpha- and AhR-specific target molecules. Treatment of TERT-OPEC with the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant increase in the production of the cytochrome P-450 microsomal enzyme CYP1A1. Activated AhR caused a downregulation of ER nuclear protein fraction and significantly decreased ER-signaling in TERT-OPEC as determined by ERE-luciferase transient transfection assays. In summary, the TCDD-induced and AhR-mediated anti-estrogenic responses by TERT-OPEC suggest that PHAH affect the predominantly estrogen-dependent differentiation of the oviduct epithelium within the fallopian tube. This action then alters the local endocrine milieu, potentially resulting in a largely unexplored cause of impaired embryonic development and female infertility.

From entrepreneurial intentions to actions: Self-control and action-related doubt, fear, and aversion

NARCIS (Netherlands)

Gelderen, van Marco; Kautonen, Teemu; Fink, Matthias

2015-01-01

This study draws on the Rubicon model of action phases to study the actions or lack of actions that follow the formation of entrepreneurial intentions. Concurrently, it examines the roles of selfcontrol and action-related emotions in explaining the intention–action gap using longitudinal

Negotiating action

Science.gov (United States)

2017-12-01

After years of working towards a climate accord, the Paris Agreement of 2015 marked the shift from negotiating to reach consensus on climate action to implementation of such action. The challenge now is to ensure transparency in the processes and identify the details of what is required.

Actions and Decisions

DEFF Research Database (Denmark)

Monthoux, Pierre Guillet de

2017-01-01

as Aristotelian syllogistic reasoning. Her constant analytical care to defend a philosophy of action against metaphysical assumptions and taken-for-granted “psychologisms” shows that an action-perspective is as analytic as ever one of decision-making. What differs is that the latter seems constantly attracted......How management philosophy is conceived depends on if pragmatism is acknowledged or not! After having been under the main domination of management science both research and education has until recently widened its scope from a decision-making to an action-perspective. It seems to be a recent...... reconnection to pragmatism that makes the 2011 Carnegie report propose to rethink management in liberal arts terms, whilst the vastly influential 1959 Carnegie Pierson report distanced itself from American pragmatism thus focusing on decisions and forgetting actions. Actions may contain decisions and choices...

The Action Observation System when Observing Hand Actions in Autism and Typical Development.

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Pokorny, Jennifer J; Hatt, Naomi V; Colombi, Costanza; Vivanti, Giacomo; Rogers, Sally J; Rivera, Susan M

2015-06-01

Social impairments in individuals with autism spectrum disorders (ASD) may be in part due to difficulty perceiving and recognizing the actions of others. Evidence from imitation studies, which involves both observation and execution of an action, suggests differences, in individuals with ASD, between the ability to imitate goal-directed actions involving objects (transitive actions) and the ability to imitate actions that do not involve objects (intransitive actions). In the present study, we examined whether there were differences in how ASD adolescents encoded transitive and intransitive actions compared to typically developing (TD) adolescents, by having participants view videos of a hand reaching across a screen toward an object or to where an object would be while functional magnetic resonance images were collected. Analyses focused on areas within the action observation network (AON), which is activated during the observation of actions performed by others. We hypothesized that the AON would differentiate transitive from intransitive actions only in the ASD group. However, results revealed that object presence modulated activity in the right inferior frontal gyrus and supramarginal gyrus of the TD group, a differentiation that was not seen in the ASD group. Furthermore, there were no significant group differences between the TD and ASD groups in any of the conditions. This suggests that there is not a global deficit of the AON in individuals with ASD while observing transitive and intransitive actions. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Enforcement actions: Significant actions resolved individuals actions. Semiannual progress report, July--December 1996

International Nuclear Information System (INIS)

1997-04-01

This compilation summarizes significant enforcement actions that have been resolved during the period (July - December 1996) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to-these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions

Enforcement actions: Significant actions resolved individuals actions. Semiannual progress report, July--December 1996

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-04-01

This compilation summarizes significant enforcement actions that have been resolved during the period (July - December 1996) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to-these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions.

Body posture modulates action perception.

Science.gov (United States)

Zimmermann, Marius; Toni, Ivan; de Lange, Floris P

2013-04-03

Recent studies have highlighted cognitive and neural similarities between planning and perceiving actions. Given that action planning involves a simulation of potential action plans that depends on the actor's body posture, we reasoned that perceiving actions may also be influenced by one's body posture. Here, we test whether and how this influence occurs by measuring behavioral and cerebral (fMRI) responses in human participants predicting goals of observed actions, while manipulating postural congruency between their own body posture and postures of the observed agents. Behaviorally, predicting action goals is facilitated when the body posture of the observer matches the posture achieved by the observed agent at the end of his action (action's goal posture). Cerebrally, this perceptual postural congruency effect modulates activity in a portion of the left intraparietal sulcus that has previously been shown to be involved in updating neural representations of one's own limb posture during action planning. This intraparietal area showed stronger responses when the goal posture of the observed action did not match the current body posture of the observer. These results add two novel elements to the notion that perceiving actions relies on the same predictive mechanism as planning actions. First, the predictions implemented by this mechanism are based on the current physical configuration of the body. Second, during both action planning and action observation, these predictions pertain to the goal state of the action.

Social variables exert selective pressures in the evolution and form of primate mimetic musculature.

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Burrows, Anne M; Li, Ly; Waller, Bridget M; Micheletta, Jerome

2016-04-01

Mammals use their faces in social interactions more so than any other vertebrates. Primates are an extreme among most mammals in their complex, direct, lifelong social interactions and their frequent use of facial displays is a means of proximate visual communication with conspecifics. The available repertoire of facial displays is primarily controlled by mimetic musculature, the muscles that move the face. The form of these muscles is, in turn, limited by and influenced by phylogenetic inertia but here we use examples, both morphological and physiological, to illustrate the influence that social variables may exert on the evolution and form of mimetic musculature among primates. Ecomorphology is concerned with the adaptive responses of morphology to various ecological variables such as diet, foliage density, predation pressures, and time of day activity. We present evidence that social variables also exert selective pressures on morphology, specifically using mimetic muscles among primates as an example. Social variables include group size, dominance 'style', and mating systems. We present two case studies to illustrate the potential influence of social behavior on adaptive morphology of mimetic musculature in primates: (1) gross morphology of the mimetic muscles around the external ear in closely related species of macaque (Macaca mulatta and Macaca nigra) characterized by varying dominance styles and (2) comparative physiology of the orbicularis oris muscle among select ape species. This muscle is used in both facial displays/expressions and in vocalizations/human speech. We present qualitative observations of myosin fiber-type distribution in this muscle of siamang (Symphalangus syndactylus), chimpanzee (Pan troglodytes), and human to demonstrate the potential influence of visual and auditory communication on muscle physiology. In sum, ecomorphologists should be aware of social selective pressures as well as ecological ones, and that observed morphology might

Exertional myopathy in a grizzly bear (Ursus arctos) captured by leghold snare.

Science.gov (United States)

Cattet, Marc; Stenhouse, Gordon; Bollinger, Trent

2008-10-01

We diagnosed exertional myopathy (EM) in a grizzly bear (Ursus arctos) that died approximately 10 days after capture by leghold snare in west-central Alberta, Canada, in June 2003. The diagnosis was based on history, post-capture movement data, gross necropsy, histopathology, and serum enzyme levels. We were unable to determine whether EM was the primary cause of death because autolysis precluded accurate evaluation of all tissues. Nevertheless, comparison of serum aspartate aminotransferase and creatine kinase concentrations and survival between the affected bear and other grizzly bears captured by leghold snare in the same research project suggests EM also occurred in other bears, but that it is not generally a cause of mortality. We propose, however, occurrence of nonfatal EM in grizzly bears after capture by leghold snare has potential implications for use of this capture method, including negative effects on wildlife welfare and research data.

Historiografia wobec Action Francaise

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Marek Kornat

2009-06-01

Full Text Available Action Franęaise in HistoriographyFrench radical right movement, Action Franęaise belongs to those political phe- nomenon in history which are differently interpreted by historiography. Principally we have eight interpretations. First ofthem is Action Franęaise own image and identity as royalist and anti-liberal "party of order”. One of the most important historical interpretation of this movement is French historian Rene Remond’s one. In his Les Droites aujourdhui Remond argued that Action Franęaise was model example of anti-liberal Right in France and in Europe of the first half of the XX century. The most popular interpretation of Action Franęaise are two: (1 Action Franęaise as an incarnation of conservative revolution (Carl Schmitt and (2 as the ideology of "integral nationalism” (Hans Konh, Carlton Hayes. Very original concept was developed by well known German historian Ernst Nolte, who considered Action Franęaise as pro- to-fascistmovement. British thinker Isaiah Berlin and Israeli historian Zeev Sternhell interpreted Action Franęaise as revolution of "anti-Enlightment” (les anti-Lumieres. Polish philosopher Stanisław Brzozowski argued that Action Franęaise was a con- seąuence of conflict between romanticism and positivism and was sure that Action Franęaise inherited much from positivistphilosophy. Non less controversial problem is forthehistorians the excommunication of Action Franęaise by Pope Pius XI in 1926. To our days there are many opposite attempts to reconstruct of this event and its origins. For many historians Pius XI tried to defend the doctrine of the Church which seemed to him intoxicated by the "nationalist and racialist heresy”. For some other writers the Vatican policy was under German influence and this caused papai action. In 1939 another Pope Pius XII decided to abolish the condemnation from 1926.

Nurses in action: An introduction to action research in nursing

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E. C. McKibbin

1996-03-01

Full Text Available Action Research is one of the new generation of qualitative research methods in the social sciences which has special significance for nurses in South Africa. The collaborative, participative and reflective qualities of Action Research appeal to practitioners, and lend themselves to joint problem solving activities in local contexts. This paper sets out a rationale for Action Research, then describes its features, strengths, and limitations. Ways of overcoming the latter are suggested. The paper concludes that Action Research has potential application in the field of nursing, not only for the purposes of practical problem solving, but also for improving the personal and professional practice of nurses, and for emancipating nurses from their subordinate position in the hierarchy of health science.

Opioidergic mechanisms underlying the actions of Vitex agnus-castus L.

Science.gov (United States)

Webster, Donna E; He, Ying; Chen, Shao-Nong; Pauli, Guido F; Farnsworth, Norman R; Wang, Zaijie Jim

2011-01-01

Vitex agnus-castus (VAC) has been used since ancient Greek times and has been shown clinically to be effective for the treatment of pre-menstrual syndrome. However, its mechanism of action has only been partially determined. Compounds, fractions, and extracts isolated from VAC were used in this study to thoroughly investigate possible opioidergic activity. First, an extract of VAC was found to bind and activate μ- and δ-, but not κ-opioid receptor subtypes (MOR, DOR, and KOR respectively). The extract was then resuspended in 10% methanol and partitioned sequentially with petroleum ether, CHCl(3), and EtOAc to form four fractions including a water fraction. The highest affinity for MOR was concentrated in the CHCl(3) fraction, whereas the highest affinity for DOR was found in the CHCl(3) and EtOAc fractions. The petroleum ether fraction had the highest agonist activity at MOR and DOR. Several flavonoids from VAC were found to bind to both MOR and DOR in a dose-dependent manner; however only casticin, a marker compound for genus Vitex, was found to have agonist activity selective for DOR at high concentrations. These results suggest VAC may exert its therapeutic effects through the activation of MOR, DOR, but not KOR. Copyright © 2010 Elsevier Inc. All rights reserved.

Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice.

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Wiśniewska, Anna; Olszanecki, Rafał; Totoń-Żurańska, Justyna; Kuś, Katarzyna; Stachowicz, Aneta; Suski, Maciej; Gębska, Anna; Gajda, Mariusz; Jawień, Jacek; Korbut, Ryszard

2017-08-04

Atherosclerosis is an inflammatory disease in which dysfunction of mitochondria play an important role, and disorders of lipid management intensify this process. Agmatine, an endogenous polyamine formed by decarboxylation of arginine, exerts a protective effect on mitochondria and modulates fatty acid metabolism. We investigated the effect of exogenous agmatine on the development of atherosclerosis and changes in lipid profile in apolipoprotein E knockout (apoE-/-) mice. Agmatine caused an approximate 40% decrease of atherosclerotic lesions, as estimated by en face and cross-section methods with an influence on macrophage but not on smooth muscle content in the plaques. Agmatine treatment did not changed gelatinase activity within the plaque area. What is more, the action of agmatine was associated with an increase in the number of high density lipoproteins (HDL) in blood. Real-Time PCR analysis showed that agmatine modulates liver mRNA levels of many factors involved in oxidation of fatty acid and cholesterol biosynthesis. Two-dimensional electrophoresis coupled with mass spectrometry identified 27 differentially expressed mitochondrial proteins upon agmatine treatment in the liver of apoE-/- mice, mostly proteins related to metabolism and apoptosis. In conclusion, prolonged administration of agmatine inhibits atherosclerosis in apoE-/- mice; however, the exact mechanisms linking observed changes and elevations of HDL plasma require further investigation.

Action Intentions: Action Influences Both On-Line Perception and Off-Line Representation

Directory of Open Access Journals (Sweden)

C Kirtley

2014-08-01

Full Text Available Given that one role of vision is to gather information for upcoming tasks, previous studies have investigated whether the preparation for action affects visual behaviour. The current studies aimed to determine if such influences on visual selection would also influence the formation of subsequent memory representations. Two experiments were conducted- in the first, participants' action intentions towards a scene were manipulated by the performance of different grasping postures as they observed the scene. This was followed by a memory test for the objects presented. Participants' eye movements were affected by their action intention, so that performing a power grip led to significantly longer fixation durations on power grip compatible objects. In contrast, memory for the objects and their properties was not affected by the action. Our second study required participants to make the action posture during the recall phase. No effect on eye movements was found, but recall was affected, with a particular advantage for recall of the position of grip-compatible objects. Previous studies have shown that action intentions can affect the on-line perception of objects. The current study suggests this may not extend to off-line representations if they are accessed after the action has been completed or abandoned. However, the recall of information may be affected if gestures are formed during retrieval. Memory representations may not be tailored specifically to an action, but actions can still affect the recall of information.

Prevalence of exertional rhabdomyolysis in endurance horses in the Pacific Northwestern United States.

Science.gov (United States)

Wilberger, M S; McKenzie, E C; Payton, M E; Rigas, J D; Valberg, S J

2015-03-01

Exertional rhabdomyolysis (ER) is a reported syndrome in competing endurance horses; however, the prevalence and cause of ER in this population have not been defined. To determine the prevalence of ER in a sample of endurance racing horses and investigate factors, including relevant genetic defects, contributing to the occurrence of rhabdomyolysis in this group. Prospective clinical study. Riders of 101 horses participating in one of four 50-mile (80.5 km) distance races completed a comprehensive questionnaire regarding the medical history, management and performance of their horse. Serum creatine kinase activity (CK) was measured before and 4 h after completion of exercise. Hair samples were analysed by PCR for the R309H mutation in the glycogen synthase gene (GYS1) responsible for type 1 polysaccharide storage myopathy (PSSM) and the C7360G mutation in the ryanodine receptor 1 (RYR1) gene causing malignant hyperthermia (MH). Samples were obtained from 68 Arabians, 20 half-Arabians and 13 horses of other breeds. Serum CK was above the resting reference interval (145-633 u/l) in 38 horses after racing (median 883 u/l, range 658-3739) but was compatible with values previously reported in apparently healthy endurance horses. Pathological ER was suspected to occur in 4 horses with serum CK activities exceeding 10,000 u/l 4 h after racing (median 84,825 u/l; range 10,846-381,790) including 3 Arabians and one half-Arabian horse. GYS1 and RYR1 mutations were not present in hair samples from any horses. Exertional rhabdomyolysis occurred at a prevalence of 4.0% in a sample of horses participating in 50 mile distance events and all affected horses were Arabian or half-Arabian. The cause of ER in the endurance horse population remains unknown; however, ER in competing Arabian endurance horses is unlikely to be due to type 1 PSSM or MH. © 2014 EVJ Ltd.

The Prose of Action

DEFF Research Database (Denmark)

Christiansen, Ulrik; Thrane, Sof

2014-01-01

risks changes over time in response to a lack of action on reported risks. In these processes Frontline Managers take on new responsibilities to make General Managers take action on reported risk. The reporting practice changes from the mere identification of risk to risk assessment and, finally......, to incorporating the possible response into the risk report. These findings add to extant literature by illustrating that actions do not automatically flow from the identification of risk. Rather, risk and action are dynamically interrelated in the sense that the prose in the risk report is a variable input...... to generate action and that a lack of action encourages managers to change their approach to reporting....

Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

International Nuclear Information System (INIS)

Kampa, Marilena; Boskou, Dimitrios; Gravanis, Achille; Castanas, Elias; Alexaki, Vassilia-Ismini; Notas, George; Nifli, Artemissia-Phoebe; Nistikaki, Anastassia; Hatzoglou, Anastassia; Bakogeorgou, Efstathia; Kouimtzoglou, Elena; Blekas, George

2004-01-01

The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production). The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system. Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action

Action research: Scandinavian Experiences

DEFF Research Database (Denmark)

Rasmussen, Lauge Baungaard

2004-01-01

The article focus on paradigms, methods and ethics of action research in the Scandinavian countries. The special features of the action research paradigm is identified. A historical overview follows of some main action research projects in Norway, Sweden and Denmark. The tendency towards upsclae...... action research projects from organisational or small community projects yo large-scale, regional based network apporaches are also outlined and discussed. Finally, a synthesised approach of the classical, socio-technical action research approach and the large-scale network and holistic approaches...

Joint action modulates motor system involvement during action observation in 3-year-olds

NARCIS (Netherlands)

Meyer, M.; Hunnius, S.; Elk, M. van; Ede, F.L. van; Bekkering, H.

2011-01-01

When we are engaged in a joint action, we need to integrate our partner's actions with our own actions. Previous research has shown that in adults the involvement of one's own motor system is enhanced during observation of an action partner as compared to during observation of an individual actor.

Does an Exercise Intervention Improving Aerobic Capacity Among Construction Workers Also Improve Musculoskeletal Pain, Work Ability, Productivity, Perceived Physical Exertion, and Sick Leave?

DEFF Research Database (Denmark)

Gram, Bibi; Holtermann, Andreas; Bültmann, Ute

2012-01-01

OBJECTIVE:: To investigate whether an exercise intervention shown to increase aerobic capacity, would also lead to less musculoskeletal pain; improved work ability, productivity, and perceived physical exertion; and less sick leave. METHODS:: Sixty-seven construction workers were randomized...... into an exercise group training 3 × 20 minutes per week and a control group. Questionnaires and text messages were completed before and after the 12-week intervention. RESULTS:: No significant changes were found in musculoskeletal pain, work ability, productivity, perceived physical exertion, and sick leave...... with the intervention. Questionnaires and text messages provided similar results of pain and work ability. CONCLUSIONS:: Although the intervention improved aerobic capacity, it was not successful in improving musculoskeletal pain and other work-related factors. A detectable improvement presumably requires a more...

Stereoscopically Observing Manipulative Actions.

Science.gov (United States)

Ferri, S; Pauwels, K; Rizzolatti, G; Orban, G A

2016-08-01

The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors "stimulus type" (action, static control, and dynamic control), "stereopsis" (present, absent) and "viewpoint" (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior. © The Author 2016. Published by Oxford University Press.