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  1. Pirfenidone exerts antifibrotic effects through inhibition of GLI transcription factors.

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    Didiasova, Miroslava; Singh, Rajeev; Wilhelm, Jochen; Kwapiszewska, Grazyna; Wujak, Lukasz; Zakrzewicz, Dariusz; Schaefer, Liliana; Markart, Philipp; Seeger, Werner; Lauth, Matthias; Wygrecka, Malgorzata

    2017-02-01

    Pirfenidone is an antifibrotic drug, recently approved for the treatment of patients suffering from idiopathic pulmonary fibrosis (IPF). Although pirfenidone exhibits anti-inflammatory, antioxidant, and antifibrotic properties, the molecular mechanism underlying its protective effects remains unknown. Here, we link pirfenidone action with the regulation of the profibrotic hedgehog (Hh) signaling pathway. We demonstrate that pirfenidone selectively destabilizes the glioma-associated oncogene homolog (GLI)2 protein, the primary activator of Hh-mediated gene transcription. Consequently, pirfenidone decreases overall Hh pathway activity in patients with IPF and in patient-derived primary lung fibroblasts and leads to diminished levels of Hh target genes such as GLI1, Hh receptor Patched-1, α-smooth muscle actin, and fibronectin and to reduced cell migration and proliferation. Interestingly, Hh-triggered TGF-β1 expression potentiated Hh responsiveness of primary lung fibroblasts by elevating the available pool of glioma-associated oncogene homolog (GLI)1/GLI2, thus creating a vicious cycle of amplifying fibrotic processes. Because GLI transcription factors are not only crucial for Hh-mediated changes but are also required as mediators of TGF-β signaling, our findings suggest that pirfenidone exerts its clinically beneficial effects through dual Hh/TGF-β inhibition by targeting the GLI2 protein.-Didiasova, M., Singh, R., Wilhelm, J., Kwapiszewska, G., Wujak, L., Zakrzewicz, D., Schaefer, L., Markart, P., Seeger, W., Lauth, M., Wygrecka, M. Pirfenidone exerts antifibrotic effects through inhibition of GLI transcription factors.

  2. Investigating the role of the ventromedial prefrontal cortex (vmPFC in the assessment of brands

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    Jose Paulo eSantos

    2011-06-01

    Full Text Available The ventromedial prefrontal cortex (vmPFC is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI study where 18 subjects assessed positive, indifferent and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

  3. Dipeptidyl peptidase IV inhibition exerts renoprotective effects in rats with established heart failure

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    Daniel Francisco De Arruda Junior

    2016-07-01

    Full Text Available Circulating dipeptidyl peptidase IV (DPPIV activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for four weeks with vildagliptin (120 mg/kg/day or vehicle by oral gavage. Echocardiography was performed before (pretreatment and at the end of treatment (post-treatment to evaluate cardiac function. The fractional area change increased (34±5 vs. 45±3%, p<0.05, and the isovolumic relaxation time decreased (33±2 vs. 27±1 ms; p<0.05 in HF rats treated with vildagliptin (post-treatment vs. pretreatment. On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1 serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with

  4. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

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    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  5. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

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    Pushpa Hegde

    Full Text Available Viscum album (VA preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2 and prostaglandin E2 (PGE2 play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

  6. Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters.

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    Ren, Huiwen; Wang, Yanhua; Xing, Yongning; Ran, Jianhua; Liu, Ming; Lei, Tianluo; Zhou, Hong; Li, Runtao; Sands, Jeff M; Yang, Baoxue

    2014-12-15

    Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl(-) levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics.

  7. Imatinib mesylate inhibits proliferation and exerts an antifibrotic effect in human breast stroma fibroblasts.

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    Gioni, Vassiliki; Karampinas, Theodoros; Voutsinas, Gerassimos; Roussidis, Andreas E; Papadopoulos, Savvas; Karamanos, Nikos K; Kletsas, Dimitris

    2008-05-01

    Tumor stroma plays an important role in cancer development. In a variety of tumors, such as breast carcinomas, a desmoplastic response, characterized by stromal fibroblast and collagen accumulation, is observed having synergistic effects on tumor progression. However, the effect of known anticancer drugs on stromal cells has not been thoroughly investigated. Imatinib mesylate is a selective inhibitor of several protein tyrosine kinases, including the receptor of platelet-derived growth factor, an important mediator of desmoplasia. Recently, we have shown that imatinib inhibits the growth and invasiveness of human epithelial breast cancer cells. Here, we studied the effect of imatinib on the proliferation and collagen accumulation in breast stromal fibroblasts. We have shown that it blocks the activation of the extracellular signal-regulated kinase and Akt signaling pathways and up-regulates cyclin-dependent kinase inhibitor p21(WAF1), leading to the inhibition of fibroblast proliferation, by arresting them at the G(0)/G(1) phase of the cell cycle. Imatinib inhibits more potently the platelet-derived growth factor-mediated stimulation of breast fibroblast proliferation. By using specific inhibitors, we have found that this is due to the inhibition of the Akt pathway. In addition, imatinib inhibits fibroblast-mediated collagen accumulation. Conventional and quantitative PCR analysis, as well as gelatin zymography, indicates that this is due to the down-regulation of mRNA synthesis of collagen I and collagen III-the main collagen types in breast stroma-and not to the up-regulation or activation of collagenases matrix metalloproteinase 2 and matrix metalloproteinase 9. These data indicate that imatinib has an antifibrotic effect on human breast stromal fibroblasts that may inhibit desmoplastic reaction and thus tumor progression.

  8. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation

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    Cuadrado, Irene [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Cidre, Florencia; Herranz, Sandra [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain); Estevez-Braun, Ana [Instituto Universitario de Bio-Orgánica “Antonio González”. Universidad de La Laguna. Avda. Astrofísico Fco. Sánchez 2. 38206. La Laguna, Tenerife (Spain); Instituto Canario de Investigaciones del Cáncer (ICIC) (Spain); Heras, Beatriz de las, E-mail: lasheras@farm.ucm.es [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Hortelano, Sonsoles, E-mail: shortelano@isciii.es [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain)

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE{sub 2} production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).

  9. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation.

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    Cuadrado, Irene; Cidre, Florencia; Herranz, Sandra; Estevez-Braun, Ana; de las Heras, Beatriz; Hortelano, Sonsoles

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE(2) production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE(2) in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. SODIUM POLYPRENYL PHOSPHATE (PHOSPRENYL EXERTS AN IL-2-DEPENDENT RESTORATIVE EFFECT UPON IN VIVO DTH INHIBITION

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    S. M. Sobolev

    2012-01-01

    Full Text Available Abstract. We have shown that polyprenyl phosphate (phosprenyl competes with interleukin 2 for binding with serum γ-globulin. It was also demonstrated that phosprenyl restores delayed type hypersensitivity induced by Listeria monocytogenes, after its inhibition with a γ-globulin which binds to IL-2 and blocks its activity. A role of serum γ-globulin and Phosprenyl in regulation of IL-2-dependent processes is discussed.

  11. Cholecystokinin exerts an effect via the endocannabinoid system to inhibit GABAergic transmission in midbrain periaqueductal gray.

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    Mitchell, Vanessa A; Jeong, Hyo-Jin; Drew, Geoffrey M; Vaughan, Christopher W

    2011-08-01

    Cholecystokinin modulates pain and anxiety via its functions within brain regions such as the midbrain periaqueductal gray (PAG). The aim of this study was to examine the cellular actions of cholecystokinin on PAG neurons. Whole-cell patch clamp recordings were made from rat midbrain PAG slices in vitro to examine the postsynaptic effects of cholecystokinin and its effects on synaptic transmission. Sulfated cholecystokinin-(26-33) (CCK-S, 100-300 nM), but not non-sulfated cholecystokinin-(26-33) (CCK-NS, 100-300 nM) produced an inward current in a sub-population of opioid sensitive and insensitive PAG neurons, which did not reverse over a range of membrane potentials. The CCK-S-induced current was abolished by the CCK1 selective antagonist devazepide (100 nM), but not by the CCK2 selective antagonists CI988 (100 nM, 1 μM) and LY225910 (1 μM). CCK-S, but not CCK-NS produced a reduction in the amplitude of evoked GABA(A)-mediated inhibitory postsynaptic currents (IPSCs) and an increase in the evoked IPSC paired-pulse ratio. By contrast, CCK-S had little effect on the rate and amplitude of TTX-resistant miniature IPSCs under basal conditions and when external K(+) was elevated. The CCK-S-induced inhibition of evoked IPSCs was abolished by the cannabinoid CB1 receptor antagonist AM251 (3 μM), the mGluR5 antagonist MPEP (10 μM) and the 1, 2-diacylglycerol lipase (DAGLα) inhibitor tetrahydrolipstatin (10 μM). In addition, CCK-S produced an increase in the rate of spontaneous non-NMDA-mediated, TTX-dependent excitatory postsynaptic currents (EPSCs). These results suggest that cholecystokinin produces direct neuronal depolarisation via CCK1 receptors and inhibits GABAergic synaptic transmission via action potential-dependent release of glutamate and mGluR5-induced endocannabinoid signaling. Thus, cholecystokinin has cellular actions within the PAG that can both oppose and reinforce opioid and cannabinoid modulation of pain and anxiety within this

  12. Pseudomonas aeruginosa auto inducer3-oxo-C12-HSL exerts bacteriostatic effect and inhibits Staphylococcus epidermidis biofilm.

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    Singh, Pradeep Kumar; Yadav, Vivek Kumar; Kalia, Manmohit; Dohare, Suhaga; Sharma, Deepmala; Agarwal, Vishnu

    2017-09-01

    Pseudomonas aeruginosa has evolved the 3-oxo-C12-HSL and C4-HSL based quorum sensing system which is responsible for the regulation of various virulence factors and helps to dominates over other bacterial species. Staphylococcus epidermidis has frequently been reported with P. aeruginosa while the role of C4-HSL and 3-oxo-C12-HSL on the S. epidermidis had widely been unexplored, and as per our knowledge, this is the first report on the impact of C4-HSL and 3-oxo-C12-HSL overS. epidermidis growth and biofilm. We found that among the two AHL molecules; only 3-oxo-C12-HSL was able to exert a significant effect in all the experiments including growth and biofilm of S. epidermidis. 3-oxo-C12-HSL at 100 μM and 200 μM concentrations were able to initiate the apparent transient type of planktonic growth inhibition in S. epidermidis. Microscopic analysis and biofilm quantification assay showed the inhibitory effect of 3-oxo-C12-HSL against S. epidermidis biofilm, initial attachment, and EPS production. The study concludes that P. aeruginosa associated 3-oxo-C12-HSL exerts the inhibitory effect on S. epidermidis growth and biofilms and thus it may also help Pseudomonasto dominate under the co-infection conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Inhibition of mitotic clonal expansion mediates fisetin-exerted prevention of adipocyte differentiation in 3T3-L1 cells.

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    Lee, Youngyi; Bae, Eun Ju

    2013-11-01

    Adipocytes are the key player in adipose tissue inflammation and subsequent systemic insulin resistance and its development involves complex process of proliferation and differentiation of preadipocytes. Fistein, a polyphenol flavonoid, is known to exert anti-inflammatory, anti-carcinogenic and anti-diabetic effects. In this study, we aimed to investigate the effect of fisetin on adipocyte proliferation and differentiation in 3T3-L1 preadipocyte cell line and its mechanism of action. We found that fisetin inhibits adipocyte differentiation in a concentration dependent manner, which were evidenced by Oil Red O staining and the protein expression of mature adipocyte marker genes fatty acid synthase and peroxisome proliferator-activated receptor γ. Moreover, the proliferation of preadipocytes was also markedly suppressed by treatment of fisetin for 24 and 48 h in the differentiation medium. We also found that fisetin inhibition of adipocyte differentiation was largely due to the effect on mitotic clonal expansion. Fisetin suppression of preadipocyte proliferation at early stage of differentiation was accompanied by the changes of expression of a series of cell cycle regulatory proteins. Altogether, our results suggest that the inhibition of adipocyte differentiation by fisetin may be at least in part mediated by cell cycle arrest during adipogenesis.

  14. Guanxinkang Decoction Exerts Its Antiatherosclerotic Effect Partly through Inhibiting the Endoplasmic Reticulum Stress

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    Hao Wang

    2014-01-01

    Full Text Available Purpose. To investigate the antiatherosclerotic effect of Guanxinkang (GXK decoction on the apoptosis, mitochondrial membrane potential (MMP, and endoplasmic reticulum stress (ERS of human umbilical vein endothelial cells (HUVEC pretreated with homocysteinemia (HCY. Materials and Methods. HUVEC were randomly divided into 5 groups: (1 blank control group (control, (2 model control group (model, (3 GXK low dose group, (4 GXK medium dose group, and (5 GXK high dose group. For the three GXK groups, HCY was given to reach the concentration of 3.0 mmol/L after HUVEC had been incubated with rabbit serum containing GXK for two hours. At 3, 6, 12, and 24 h after HCY had been incubated with the cells, the HUVEC were collected for test of the apoptosis rate, MMP, and GRP78 protein (reflecting ERS. Results. In the model control group, the apoptosis rate and GRP 78 protein expression of HUVEC significantly increased (P<0.05, while MMP significantly decreased (P<0.05 compared with the blank control group. After GXK treatment of medium and high doses, the apoptosis rate and the GRP 78 protein expression significantly (P<0.05 decreased, while MMP significantly increased (P<0.05 in a time-dependent manner compared with the model control group. Conclusion. GXK can antagonize the injury of HUVEC caused by HCY and the antagonism effect increases with the concentration and treatment duration of GXK, with the possible mechanism of GXK antagonism being through inhibiting ERS caused by HCY.

  15. Inhibition of Sirtuin 2 exerts neuroprotection in aging rats with increased neonatal iron intake

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    Xijin Wang; Meihua Wang; Liu Yang; Jie Bai; Zhiqiang Yan; Yuhong Zhang; Zhenguo Liu

    2014-01-01

    Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in signiifcant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake (120 μg/g per day) during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 (a selective Sirtuin 2 inhibitor) was injected into the substantia nigra at postnatal 540 days and 570 days (5 μg/side per day), striatal dopamine depletion was signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.

  16. Human thioredoxin exerts cardioprotective effect and attenuates reperfusion injury in rats partially via inhibiting apoptosis

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    WU Xiao-wei; TENG Zong-yan; JIANG Li-hong; FAN Ying; ZHANG Yu-hua; LI Xiu-rong; ZHANG Yi-na

    2008-01-01

    Background Thioredoxin is one of the most important redox regulating proteins. Although thioredoxin has been shown to protect cells against different kinds of oxidative stress, the role of thioredoxin in myocardial ischemia and reperfusion injury has not been fully understood. This study was conducted to explore the protective role of human thioredoxin on myocardial ischemia and reperfusion injury and its potential mechanisms.Methods Purified human thioredoxin was injected into adult Wister rats, which were subjected to 30 minutes of myocardial ischemia followed by 2 or 24 hours of reperfusion. We detected 1) the infarct size; 2) the level of malondisldehyde (MDA) in serum; 3) the expression of caspase-9, and cytochrome c in/out of mitochondia by Western blotting; 4) apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling ('rUNEL) assay and caspase-3 and its protein by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting; 5) the expression of bcl-2 and bax in cardium by immunohistochemical (IHC) assay.Results Human thioredoxin reduced myocardial ischemia/reperfusion injury as evidenced by significant decrease of myocardial infarct size (P<0.01), notable reduction of myocyte apoptosis (P <0.01), lower systemic oxidative stress level (P <0.01) after reperfusion for 2 hours, and few inflammatory cell infiltration after reperfusion for 24 hours in rats. Furthermore, treatment with human thioredoxin significantly reduced the release of mitochondrial cytochrome C (P<0.05),and inhibited the activity of caspase-9 (P <0.05) and caspase-3 (P <0.01 in mRNA and P <0.05 at protein level).Meanwhile, human thioredoxin markedly increased bcl-2 expression (P <0.05).Conclusions These results strongly suggest that human thioredoxin has cardioprotective effects on myocardial ischemia/reperfusion and its anti-apoptotic role may be mediated by modulating bcl-2 and the mitochondria-dependent apoptotic signaling pathway.

  17. Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity

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    Sheng-Teng Huang

    2011-01-01

    Full Text Available This study aimed to assess the potential anti-angiogenic mechanism of Phyllanthus urinaria (P. urinaria and characterize the major compound in P. urinaria that exerts anti-angiogenic effect. The water extract of P. urinaria and Ellagic Acid were used to evaluate the anti-angiogenic effect in chorioallantoic membrane (CAM in chicken embryo and human vascular endothelial cells (HUVECs. The matrix metalloproteinase-2 (MMP-2 activity was determined by gelatin zymography. The mRNA expressions of MMP-2, MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2 were analyzed by reverse transcription polymerase chain reaction (RT-PCR. Level of MMP-2 proteins in conditioned medium or cytosol was determined by western blot analysis. We confirmed that P. urinaria's in vivo anti-angiogenic effect was associated with a reduction in MMP-2 activity. Ellagic acid, one of the major polyphenolic components as identified in P. urinaria by high performance liquid chromatography mass spectrometry (HPLC/MS, exhibited the same anti-angiogenic effect in vivo. Both P. urinaria and Ellagic Acid inhibited MMP-2 activity in HUVECs with unchanged mRNA level. The mRNA expression levels of MMP-14 and TIMP-2 were not altered either. Results from comparing the change of MMP-2 protein levels in conditioned medium and cytosol of HUVECs after the P. urinaria or Ellagic Acid treatment revealed an inhibitory effect on the secretion of MMP-2 protein. This study concluded that Ellagic Acid is the active compound in P. urinaria to exhibit anti-angiogenic activity and to inhibit the secretion of MMP-2 protein from HUVECs.

  18. Phenolic acids isolated from the fungus Schizophyllum commune exert analgesic activity by inhibiting voltage-gated sodium channels.

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    Yao, Hui-Min; Wang, Gan; Liu, Ya-Ping; Rong, Ming-Qiang; Shen, Chuan-Bin; Yan, Xiu-Wen; Luo, Xiao-Dong; Lai, Ren

    2016-09-01

    The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune (SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography (TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance (NMR). The effects of these compounds on voltage-gated sodium (NaV) channels were evaluated using patch clamp. The analgesic activity of these compounds was tested in two types of mouse pain models induced by noxious chemicals. Five phenolic acids identified from SC extracts in the present study included vanillic acid, m-hydroxybenzoic acid, o-hydroxybenzeneacetic acid, 3-hydroxy-5-methybenzoic acid, and p-hydroxybenzoic acid. They inhibited the activity of both tetrodotoxin-resistant (TTX-r) and tetrodotoxin-sensitive (TTX-s) NaV channels. All the compounds showed low selectivity on NaV channel subtypes. After intraperitoneal injection, three compounds of these compounds exerted analgesic activity in mice. In conclusion, phenolic acids identified in SC demonstrated analgesic activity, facilitating the mechanistic studies of SC in the treatment of neurasthenia.

  19. Taurine exerts anti-osteoclastogenesis activity via inhibiting ROS generation, JNK phosphorylation and COX-2 expression in RAW264.7 cells.

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    Jang, Hae Jin; Kim, Sung-Jin

    2013-12-01

    Taurine is one of the abundant amino acids present in mammalian cells. It exerts various physiological actions such as wound healing, radioprotection, neuroprotection and anti-anxiety. In the present study, we sought to determine if taurine could inhibit osteoclastogenesis and explore the potential role of cyclooxygenase-2 (COX-2) and Jun N-terminal kinase (JNK) with reactive oxygen species (ROS). The level of intracellular ROS generated by lipopolysaccharide (LPS) was measured with DCFH-DA staining and fluorescence microscopic analysis was also performed in response to taurine in RAW264.7 cells. The expression of COX-2 and phosphorylation status of JNK by LPS was analyzed by Western blot analysis in the presence of taurine. Osteoclastogenesis was induced by LPS in the absence or presence of taurine and TRAP assay was performed to confirm the formation of osteoclast cells. ROS production was significantly enhanced by LPS and taurine treatment inhibited the ROS generation in a dose-dependent manner. The fluorescence microscopic analysis clearly showed the inhibition of ROS staining by taurine. Western blot analysis indicated that taurine significantly inhibited LPS induced COX-2 protein expression and it also inhibited phosphorylation of JNK. Taurine at the same concentration inhibited osteoclastogenesis induced by LPS, suggesting that taurine prevent osteoclast differentiation by inhibiting ROS generation. Inhibition of COX-2 expression and JNK phoshorylation could be an important mechanism by which taurine exerts anti-osteoclastogeneis.

  20. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Seong-Il [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Ko, Hee-Chul [Jeju Sasa Industry Development Agency, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Shin, Hye-Sun; Kim, Hyo-Min; Hong, Youn-Suk [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Lee, Nam-Ho [Department of Chemistry, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Kim, Se-Jae, E-mail: sjkim@jejunu.ac.kr [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Jeju Sasa Industry Development Agency, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of)

    2011-06-17

    Highlights: {yields} Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. {yields} Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. {yields} Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. {yields} Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), CCAAT/enhancer-binding protein {alpha} (C/EBP{alpha}), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPAR{gamma}, C/EBP{alpha}, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

  1. Erucin Exerts Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin: Possible Mediation through the Inhibition of NFκB Signaling

    Directory of Open Access Journals (Sweden)

    Ki Won Lee

    2013-10-01

    Full Text Available Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL-6, IL-1β, inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling.

  2. Erucin exerts anti-inflammatory properties in murine macrophages and mouse skin: possible mediation through the inhibition of NFκB signaling.

    Science.gov (United States)

    Cho, Han Jin; Lee, Ki Won; Park, Jung Han Yoon

    2013-10-15

    Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L) inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB) DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles) treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling.

  3. A novel glucosamine derivative exerts anti-inflammatory actions via inhibition of nuclear factor-kappaB.

    Science.gov (United States)

    Shin, Jin-A; Hwang, Ji-Sun; Kim, Song-Yi; Oh, Sei-Kwan; Nam, Ghilsoo; Han, Inn-Oc

    2013-08-29

    Glucosamine suppresses lipopolysaccharide (LPS)-induced upregulation of pro-inflammatory mediators both in vivo and in culture systems of mouse microglia or macrophage. In the present study, we show that the novel glucosamine derivative, 2-deoxy-2-[(o-methylbenzylidene)]-β-glucopyranoside (NK-4), significantly reduced LPS-induced production of nitric oxide (NO) in BV2 microglia, RAW264.7 macrophage, and primary cultured peritoneal macrophages cells. NK-4 inhibited LPS-induced upregulation of inducible NO synthase (iNOS), cyclooxygenase-2, interleukin-6, tumor necrosis factor-α, and interleukin-1β in RAW264.7 cells in a time- and concentration-dependent manner. Furthermore, administering NK-4 significantly inhibited the induction of inflammatory cytokine mRNAs in the brains of LPS-injected mice. Although NK-4 inhibited LPS-induced nuclear factor-kappaB (NF-κB) activation, IκB-α degradation was not changed. Instead, NK-4 inhibited LPS-induced DNA-binding activity of NF-κB by suppressing p50 and c-Rel binding to NF-κB binding site of the iNOS promoter.

  4. Photomodified fluoranthene exerts more harmful effects as compared to intact fluoranthene by inhibiting growth and photosynthetic processes in wheat.

    Science.gov (United States)

    Tomar, Rupal Singh; Jajoo, Anjana

    2015-12-01

    Polycyclic aromatic hydrocarbons (PAHs) are toxic to plants. Exposure of PAHs to sunlight can result in the formation of photomodified PAHs, which are generally more toxic than the parent compounds. In the present study, biochemical and physiological effects of intact fluoranthene (FLT) and photomodified FLT (P.FLT) in wheat were investigated. Our results demonstrated that the treatment of FLT and P.FLT, inhibited germination, seedling growth and pigment content. However, inhibition observed on primary photochemistry and photosystem II heterogeneity was more prominent in P.FLT treated plants. Both FLT and P.FLT affected the levels of antioxidant enzymes such as POD, SOD, CAT and GR to similar extent. Greater inhibitory effects of P.FLT than FLT may be ascribed to its effects on growth parameters and photochemistry rather than on the activities of various antioxidant enzymes. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. BRAF kinase inhibitor exerts anti-tumor activity against breast cancer cells via inhibition of FGFR2.

    Science.gov (United States)

    Zhang, Zong Xin; Jin, Wen Jun; Yang, Sheng; Ji, Cun Li

    2016-01-01

    Most anti-angiogenic therapies currently being evaluated in clinical trials targetvascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here we identified BRAF kinase inhibitor, vemurafenibas an agent with potential anti-angiogenic and anti-breast cancer activities. Vemurafenib demonstrated inhibition of endothelial cell proliferation, migration, and tube formation in response to basic fibroblast growth factor (bFGF). In ex vivo and in vivo angiogenesis assays, vemurafenib suppressed bFGF-induced microvessel sprouting of rat aortic rings and angiogenesis in vivo. To understand the underlying molecular basis, we examined the effects of vemurafenib on different molecular components in treated endothelial cell, and found that vemurafenib suppressed bFGF-triggered activation of FGFR2 and protein kinase B (AKT). Moreover, vemurafenib directly inhibited proliferation and blocked the oncogenic signaling pathways in breast cancer cell. In vivo, using xenograft models of breast cancer cells MDA-MB-231, vemurafenib showed growth-inhibitory activity associated with inhibition of tumor angiogenesis. Taken together, our results indicate that vemurafenib targets the FGFR2-mediated AKT signaling pathway in endothelial cells, leading to the suppression of tumor growth and angiogenesis.

  6. Telmisartan exerts sustained blood pressure control and reduces blood pressure variability in metabolic syndrome by inhibiting sympathetic activity.

    Science.gov (United States)

    Sueta, Daisuke; Koibuchi, Nobutaka; Hasegawa, Yu; Toyama, Kensuke; Uekawa, Ken; Katayama, Tetsuji; Ma, MingJie; Nakagawa, Takashi; Ogawa, Hisao; Kim-Mitsuyama, Shokei

    2014-12-01

    Accumulating evidence on blood pressure (BP) reduction with various angiotensin II receptor blockers (ARBs) show that the magnitudes and durations of BP control differ across ARBs. However, the mechanism of ARBs is unknown. This work was undertaken to compare telmisartan and valsartan in duration of BP control, BP variability, and effects on the autonomic nervous system. Using radiotelemetry combined with spectral analysis with a fast Fourier transformation algorithm, we compared the effects of various doses of telmisartan and valsartan on BP and its variability during dark (active phase) and light (inactive phase) periods over 5 weeks in SHR/NDmcr-cp(+/+)(SHRcp) rats, a model of metabolic syndrome. We also compared the effects of these ARBs on autonomic nervous system, central oxidative stress, and inflammation in SHRcp rats. Telmisartan exerted a longer-lasting BP-lowering effect and greater attenuation of BP variability in SHRcp than valsartan. Telmisartan decreased low frequency power of systolic BP and increased spontaneous baroreflex gain in SHRcp during both the dark and light periods more than valsartan. Telmisartan reduced 24-hour urinary norepinephrine excretion more than valsartan. Furthermore, telmisartan attenuated oxidative stress and the numbers of gp91(phox)-positive cells and activated microglia and astrocytes in the rostral ventrolateral medulla of SHRcp rats more than valsartan. The superiority of telmisartan over valsartan in sustained BP control and reduction of BP variability was attributed to more suppression of sympathetic activity and more improvement of baroreceptor reflex. The greater suppression of sympathetic activity by telmisartan appeared to be partially mediated by a stronger amelioration of central oxidative stress. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Imatinib Mesylate Exerts Anti-Proliferative Effects on Osteosarcoma Cells and Inhibits the Tumour Growth in Immunocompetent Murine Models

    Science.gov (United States)

    Ory, Benjamin; Charrier, Céline; Brion, Régis; Blanchard, Frederic; Redini, Françoise; Heymann, Dominique

    2014-01-01

    Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma), a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1). Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma) and POS-1 (undifferentiated osteosarcoma). Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R), appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor status of patients

  8. Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways.

    Science.gov (United States)

    Jia, Xiao-Jian; Li, Xi; Wang, Feng; Liu, Han-Qing; Zhang, Da-Jun; Chen, Yun

    2017-01-01

    This study aimed to investigate the anti-inflammatory activity of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis amurensis (Xiao Bo An), and the underlying mechanisms. Macrophages and neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The effects of BER on the expression of pro-inflammatory mediators in macrophages were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the activation and superoxide release of neutrophils were determined with flow cytometry and WST-1 reduction test. The inhibitory effects of BER on the activation of signaling pathways related to inflammatory response in macrophages were evaluated by western blot analysis. In addition, a mouse peritonitis model was made by peritoneal injection of thioglycollate medium and anti-inflammatory effects of BER were investigated in vivo by quantitative analysis of pro-inflammatory factor production and leukocyte exudation. BER significantly inhibited inflammatory factor expression by LPS-stimulated macrophages and suppressed activation and superoxide release of fMLP-stimulated neutrophils. In the mouse peritonitis model, BER significantly inhibited the activation of macrophages and exudation of neutrophils. According to analysis, BER significantly suppressed phosphorylation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways in LPS-stimulated macrophages. Collectively, data from this study suggest that BER has anti-inflammatory potential, which is effected via inhibition of NF-κB and MAPK signaling pathways, and thus holds promise for treatment of inflammatory disease. © 2017 The Author(s). Published by S. Karger AG, Basel.

  9. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  10. Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi.

    Science.gov (United States)

    Díaz, María V; Miranda, Mariana R; Campos-Estrada, Carolina; Reigada, Chantal; Maya, Juan D; Pereira, Claudio A; López-Muñoz, Rodrigo

    2014-06-01

    Pentamidine is an antiprotozoal and fungicide drug used in the treatment of leishmaniasis and African trypanosomiasis. Despite its extensive use as antiparasitic drug, little evidence exists about the effect of pentamidine in Trypanosoma cruzi, the etiological agent of Chagas' disease. Recent studies have shown that pentamidine blocks a polyamine transporter present in Leishmania major; consequently, its might also block these transporters in T. cruzi. Considering that T. cruzi lacks the ability to synthesize putrescine de novo, the inhibition of polyamine transport can bring a new therapeutic target against the parasite. In this work, we show that pentamidine decreases, not only the viability of T. cruzi trypomastigotes, but also the parasite burden of infected cells. In T. cruzi-infected mice pentamidine decreases the inflammation and parasite burden in hearts from infected mice. The treatment also decreases parasitemia, resulting in an increased survival rate. In addition, pentamidine strongly inhibits the putrescine and spermidine transport in T. cruzi epimastigotes and amastigotes. Thus, this study points to reevaluate the utility of pentamidine and introduce evidence of a potential new action mechanism. In the quest of new therapeutic strategies against Chagas disease, the extensive use of pentamidine in human has led to a well-known clinical profile, which could be an advantage over newly synthesized molecules that require more comprehensive trials prior to their clinical use.

  11. n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels.

    Science.gov (United States)

    Fakhrudin, Nanang; Dwi Astuti, Eny; Sulistyawati, Rini; Santosa, Djoko; Susandarini, Ratna; Nurrochmad, Arief; Wahyuono, Subagus

    2017-03-13

    Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n-hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg) demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1).

  12. n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels

    Directory of Open Access Journals (Sweden)

    Nanang Fakhrudin

    2017-03-01

    Full Text Available Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n-hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL. We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8 and Monocyte chemoattractant protein-1 (MCP-1.

  13. Puerarin Exerts an Antiinflammatory Effect by Inhibiting NF-kB and MAPK Activation in Staphylococcus aureus-Induced Mastitis.

    Science.gov (United States)

    Wu, Haichong; Zhao, Gan; Jiang, Kangfeng; Chen, Xiuying; Zhu, Zhe; Qiu, Changwei; Deng, Ganzhen

    2016-10-01

    Mastitis is defined as the inflammation of the mammary gland. There is generally no effective treatment for mastitis in animals. Puerarin, extracted from Radix puerariae, has been proven to possess many biological activities. The present study aims to reveal the potential mechanism that is responsible for the antiinflammatory action of puerarin in Staphylococcus aureus (S. aureus)-induced mastitis in mice. Histopathological changes showed that puerarin ameliorated the inflammatory injury induced by S. aureus. Quantitative real-time polymerase chain reaction and ELISA analysis indicated that puerarin not only suppressed the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 but also promoted the secretion of IL-10. Toll-like receptor 2 (TLR2) is important in the immune defense against S. aureus infection. Research in molecular biology has shown that the expression of TLR2 was inhibited with administration of puerarin. Further studies were performed on NF-kB and mitogen-activated protein kinase signaling pathways using western blot. The results demonstrated that puerarin suppressed phosphorylated IkBα, p65, p38, extracellular signal-regulated kinase 1and 2 (ERK), and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. All of the results suggested that puerarin may be a potential therapy for treating mastitis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. The angiotensin-converting enzyme inhibitor captopril inhibits poly(ADP-ribose)polymerase activation and exerts beneficial effects in an ovine model of burn and smoke injury

    Science.gov (United States)

    Asmussen, Sven; Bartha, Eva; Olah, Gabor; Sbrana, Elena; Rehberg, Sebastian W.; Yamamoto, Yusuke; Enkhbaatar, Perenlei; Hawkins, Hal K.; Ito, Hiroshi; Cox, Robert A.; Traber, Lillian D.; Traber, Daniel L.; Szabo, Csaba

    2011-01-01

    We investigated the effect of the angiotensin converting enzyme (ACE) inhibitor captopril in a clinically relevant ovine model of smoke and burn injury, with special reference to oxidative stress, activation of poly(ADP-ribose) polymerase in the lung and in circulating leukocytes. Female, adult sheep (28–40 kg) were divided into 3 groups. After tracheostomy and under deep anesthesia both vehicle-control (n=5) and captopril (20 mg/kg/d, iv., starting 0.5 hour before the injury) treated (n=5) groups were subjected to 2×20%, third degree burn injury and were insufflated with 48 breaths of cotton smoke. A sham group not receiving burn/smoke was also studied (n=5). Animals were mechanically ventilated and fluid resuscitated for 24 h in the awake state. Burn and smoke injury resulted in an upregulation of ACE in the lung, evidenced by immunohistochemical determination and Western blotting. Burn and smoke injury resulted in pulmonary dysfunction, as well as systemic hemodynamic alterations. Captopril treatment of burn and smoke animals improved PaO2/FiO2 ratio and pulmonary shunt fraction and reduced the degree of lung edema. There was a marked increase in PAR levels in circulating leukocytes after burn/smoke injury, which was significantly decreased by captopril. The pulmonary level of ACE and the elevated pulmonary levels of TGF-β in response to burn and smoke injury were significantly decreased by captopril treatment. Our results suggest that the ACE inhibitor captopril exerts beneficial effects on the pulmonary function in burn/smoke injury. The effects of the ACE inhibitor may be related to the prevention of ROS-induced PARP over-activation. ACE inhibition may also exert additional beneficial effects by inhibiting the expression of the pro-fibrotic mediator TGF-β. PMID:21701415

  15. Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway.

    Science.gov (United States)

    Wu, Xin; Dou, Yannong; Yang, Yan; Bian, Difei; Luo, Jinque; Tong, Bei; Xia, Yufeng; Dai, Yue

    2015-08-15

    Arctigenin, the main effective constituent of Arctium lappa L. fruit, has previously been proven to dramatically attenuate dextran sulfate sodium (DSS)-induced colitis in mice, a frequently used animal model of inflammatory bowel disease (IBD). As Th1 and Th17 cells play a crucial role in the pathogenesis of IBD, the present study addressed whether and how arctigenin exerted anti-colitis efficacy by interfering with the differentiation and activation of Th1/Th17 cells. In vitro, arctigenin was shown to markedly inhibit the differentiation of Th17 cells from naïve T cells, and moderately inhibit the differentiation of Th1 cells, which was accompanied by lowered phosphorylation of STAT3 and STAT4, respectively. In contrast, arctigenin was lack of marked effect on the differentiation of either Th2 or regulatory T cells. Furthermore, arctigenin was shown to suppress the mammalian target of rapamycin complex 1 (mTORC1) pathway in T cells as demonstrated by down-regulated phosphorylation of the downstream target genes p70S6K and RPS6, and it functioned independent of two well-known upstream kinases PI3K/AKT and ERK. Arctigenin was also able to inhibit the activity of mTORC1 by dissociating raptor from mTOR. Interestingly, the inhibitory effect of arctigenin on T cell differentiation disappeared under a status of mTORC1 overactivation via knockdown of tuberous sclerosis complex 2 (TSC2, a negative regulator of mTORC1) or pretreatment of leucine (an agonist of mTOR). In DSS-induced mice, the inhibition of Th1/Th17 responses and anti-colitis effect of arctigenin were abrogated by leucine treatment. In conclusion, arctigenin ameliorates colitis through down-regulating the differentiation of Th1 and Th17 cells via mTORC1 pathway.

  16. Compounds isolated from the aerial part of Crataegus azarolus inhibit growth of B16F10 melanoma cells and exert a potent inhibition of the melanin synthesis.

    Science.gov (United States)

    Mustapha, Nadia; Bzéouich, Imèn Mokdad; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2015-02-01

    Poor therapeutic results have been reported for treatment of malignant melanoma; therefore in this study, we have investigated inhibitory capacity of vitexin-2''-O-rhamnoside as well as the extract from which it was isolated, i.e. the ethyl acetate extract obtained from the leaves of Crataegus azarolus, on mouse melanoma (B16F10) proliferation. Cell viability was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475nm. Ethyl acetate extract and vitexin-2''-O-rhamnoside exhibited significant anti-proliferative activity against B16F10 melanoma cells after incubation for 48hours with IC50s of 50μg/mL and 20μM, respectively. Furthermore, these two compounds have the ability to reduce the melanin content by inhibiting the tyrosinase activity of B16F10 cells. Thus, further investigations are merited to ascertain their potential application in treating hyperpigmentation disorders. Copyright © 2014. Published by Elsevier Masson SAS.

  17. NMDA antagonist, but not nNOS inhibitor, requires AMPA receptors in the ventromedial prefrontal cortex (vmPFC) to induce antidepressant-like effects

    DEFF Research Database (Denmark)

    Pereira, V. S.; Wegener, Gregers; Joca, S. R.

    2013-01-01

    Depressed individuals and stressed animals show enhanced levels of glutamate and neuronal nitric oxide synthase (nNOS) activity in limbic structures, including the vmPFC. Systemic administration of glutamatergic NMDA receptor antagonists or inhibitors of nitric oxide (NO) synthesis induces antide...

  18. MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo

    KAUST Repository

    Yang, Guang

    2014-01-23

    BackgroundRecent studies have revealed that miR-196a is upregulated in glioblastoma multiforme (GBM) and that it correlates with the clinical outcome of patients with GBM. However, its potential regulatory mechanisms in GBM have never been reported.MethodsWe used quantitative real-time PCR to assess miR-196a expression levels in 132 GBM specimens in a single institution. Oncogenic capability of miR-196a was detected by apoptosis and proliferation assays in U87MG and T98G cells. Immunohistochemistry was used to determine the expression of IκBα in GBM tissues, and a luciferase reporter assay was carried out to confirm whether IκBα is a direct target of miR-196a. In vivo, xenograft tumors were examined for an antiglioma effect of miR-196a inhibitors.ResultsWe present for the first time evidence that miR-196a could directly interact with IκBα 3′-UTR to suppress IκBα expression and subsequently promote activation of NF-κB, consequently promoting proliferation of and suppressing apoptosis in GBM cells both in vitro and in vivo. Our study confirmed that miR-196a was upregulated in GBM specimens and that high levels of miR-196a were significantly correlated with poor outcome in a large cohort of GBM patients. Our data from human tumor xenografts in nude mice treated with miR-196 inhibitors demonstrated that inhibition of miR-196a could ameliorate tumor growth in vivo.ConclusionsMiR-196a exerts its oncogenic effect in GBM by inhibiting IκBα both in vitro and in vivo. Our findings provide new insights into the pathogenesis of GBM and indicate that miR-196a may predict clinical outcome of GBM patients and serve as a new therapeutic target for GBM. © 2014 © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

    Science.gov (United States)

    Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

    2016-10-01

    Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

  20. Schisandrin B exerts anti-neuroinflammatory activity by inhibiting the Toll-like receptor 4-dependent MyD88/IKK/NF-κB signaling pathway in lipopolysaccharide-induced microglia.

    Science.gov (United States)

    Zeng, Ke-Wu; Zhang, Tai; Fu, Hong; Liu, Geng-Xin; Wang, Xue-Mei

    2012-10-05

    Microglial-mediated neuroinflammation is now considered to be central to the pathogenesis of various neurodegenerative processes, including Alzheimer's disease and Parkinson's disease. Therefore, rational modulation of microglia function to obtain neuroprotective effects is important for the development of safe and effective anti-inflammatory and neuroprotective agents. Here, we investigated the anti-inflammatory and neuroprotective effects, and potential molecular mechanism of action of Schisandrin B (Sch B); which is isolated from the Schizandra fruit (Schisandra chinesnesis). Sch B exerted significant neuroprotective effects against microglial-mediated inflammatory injury in microglia-neuron co-cultures. In addition, Sch B significantly downregulated pro-inflammatory cytokines, including nitrite oxide (NO), tumor necrosis factor (TNF)-α, prostaglandin E(2) (PGE(2)), interleukin (IL)-1β and IL-6. Additionally, Sch B inhibited the interaction of Toll-like receptor 4 with the Toll adapter proteins MyD88, IRAK-1 and TRAF-6 resulting in an inhibition of the IKK/nuclear transcription factor (NF)-κB inflammatory signaling pathway. Furthermore, Sch B inhibited the production of reactive oxygen species (ROS) and NADPH oxidase activity in microglia. In summary, Sch B may exert neuroprotective activity by attenuating the microglial-mediated neuroinflammatory response by inhibiting the TLR4-dependent MyD88/IKK/NF-κB signaling pathway.

  1. 4-Amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) exerts in vitro growth inhibitory effects that are not only related to S-adenosylmethionine decarboxylase (SAMdc) inhibition

    NARCIS (Netherlands)

    Dorhout, B; Odink, MFG; deHoog, E; Kingma, AW; vanderVeer, E; Muskiet, FAJ

    1997-01-01

    The competitive S-adenosylmethionine decarboxylase (SAMdc; EC 4.1.1.50) inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) inhibits growth more effectively than the irreversible SAMdc inhibitor 5'-{[(Z)-4-amino-2-butenyl]methylamino}-5'-deoxyadenosine (AbeAdo), while having similar

  2. 4-Amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) exerts in vitro growth inhibitory effects that are not only related to S-adenosylmethionine decarboxylase (SAMdc) inhibition

    NARCIS (Netherlands)

    Dorhout, B; Odink, MFG; deHoog, E; Kingma, AW; vanderVeer, E; Muskiet, FAJ

    1997-01-01

    The competitive S-adenosylmethionine decarboxylase (SAMdc; EC 4.1.1.50) inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664A) inhibits growth more effectively than the irreversible SAMdc inhibitor 5'-{[(Z)-4-amino-2-butenyl]methylamino}-5'-deoxyadenosine (AbeAdo), while having similar effe

  3. Combination of temozolomide and Taxol exerts a synergistic inhibitory effect on Taxol‑resistant glioma cells via inhibition of glucose metabolism.

    Science.gov (United States)

    Guan, Ding-Guo; Chen, Han-Min; Liao, Sheng-Fang; Zhao, Tian-Zhi

    2015-11-01

    Malignant gliomas, which comprise the most common type of primary malignant brain tumor, are associated with a poor prognosis and quality of life. Paclitaxel (Taxol) and temozolomide (TMZ) are Food and Drug Administration‑approved anticancer agents, which are known to have therapeutic applications in various malignancies. However, similar to other chemotherapeutic agents, the development of resistance to TMZ and Taxol is common. The aim of the present study was to investigate the regulation of glucose metabolism by TMZ and Taxol in glioma cells. The results demonstrated that glioma cells exhibit decreased glucose uptake and lactate production in response to treatment with TMZ; however, glucose metabolism was increased in response to Taxol treatment. Following analysis of TMZ‑ and Taxol‑resistant cell lines, it was reported that glucose metabolism was decreased in the TMZ‑resistant cells, but was increased in the Taxol‑resistant cells. Notably, a combination of TMZ and Taxol exerted synergistic inhibitory effects on Taxol‑resistant glioma cells. However, the synergistic phenotype was not observed following treatment with a combination of 5‑fluorouracil and Taxol. Furthermore, restoration of glucose metabolism by overexpression of glucose transporter 1 in Taxol‑resistant cells resulted in regained resistance to Taxol. Therefore, the present study proposes a novel mechanism accounting for the synergistic effects of Taxol and TMZ co‑treatment, which may contribute to the development of therapeutic strategies for overcoming chemoresistance in patients with cancer.

  4. Sulindac sulfide inhibits sarcoendoplasmic reticulum Ca2+ ATPase, induces endoplasmic reticulum stress response, and exerts toxicity in glioma cells: relevant similarities to and important differences from celecoxib.

    Science.gov (United States)

    White, M C; Johnson, G G; Zhang, W; Hobrath, J V; Piazza, G A; Grimaldi, M

    2013-03-01

    Malignant gliomas have low survival expectations regardless of current treatments. Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent cell transformation and slow cancer cell growth by mechanisms independent of cyclooxygenase (COX) inhibition. Certain NSAIDs trigger the endoplasmic reticulum stress response (ERSR), as revealed by upregulation of molecular chaperones such as GRP78 and C/EBP homologous protein (CHOP). Although celecoxib (CELE) inhibits the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), an effect known to induce ERSR, sulindac sulfide (SS) has not been reported to affect SERCA. Here, we investigated these two drugs for their effects on Ca(2+) homeostasis, ERSR, and glioma cell survival. Our findings indicate that SS is a reversible inhibitor of SERCA and that both SS and CELE bind SERCA at its cyclopiazonic acid binding site. Furthermore, CELE releases additional Ca(2+) from the mitochondria. In glioma cells, both NSAIDS upregulate GRP78 and activate ER-associated caspase-4 and caspase-3. Although only CELE upregulates the expression of CHOP, it appears that CHOP induction could be associated with mitochondrial poisoning. In addition, CHOP induction appears to be uncorrelated with the gliotoxicity of these NSAIDS in our experiments. Our data suggest that activation of ERSR is primarily responsible for the gliotoxic effect of these NSAIDS. Because SS has good brain bioavailability, has lower COX-2 inhibition, and has no mitochondrial effects, it represents a more appealing molecular candidate than CELE to achieve gliotoxicity via activation of ERSR.

  5. Propofol Inhibits the Activation of p38 through Up-Regulating the Expression of Annexin A1 to Exert Its Anti-Inflammation Effect

    Science.gov (United States)

    Tu, Weifeng; Guo, Yuanbo; Zhao, Zhenlong; Xue, Qiong; Lin, Chunshui; Xiao, Jinfang; Sun, Xuegang; Tao, Tao; Gu, Miaoning; Liu, Youtan

    2011-01-01

    Inflammatory response is a kind of nonspecific immune response, with the central link of vascular response, which is mainly manifested by changes in neutrophils and vascular endothelial cells. In recent years, the in vivo and in vitro role of intravenous anesthetic propofol in inhibiting inflammatory response has been attracting more and more attention, but the anti-inflammatory mechanisms of propofol for mononuclear cells still remain undefined. In this study, proteomics analysis was applied to investigate protein expression profile changes in serum mononuclear cells following intervention of rats with endotoxemia using propofol. After two-dimensional electrophoresis and mass spectrometric identification, it has been found that the protein Annexin A1 was up-regulated in the propofol intervention group. Annexin A1 is a glucocorticoid-dependent anti-inflammatory protein. After detection using ELISA and Western blot assays, it has also been found that propofol can not only promote the expression of Annexin A1, but also inhibit the phosphorylation level of p38 and release of inflammatory factors (IL-1β, IL-6 and TNF-α) in rats with endotoxemia. In order to further determine the role of up-regulated expression of Annexin A1 in anti-inflammation of propofol, this gene was silenced in vitro in human THP-1 cells, to detect the phosphorylation status of p38 and release of inflammatory factors. The results show that Annexin A1 can negatively regulate phosphorylation of p38 and release of IL-1β, IL-6 and TNF-α in THP-1 cells following propofol intervention and lipopolysaccharide (LPS) stimulation. Our results clearly indicate that propofol can up-regulate Annexin A1 to inhibit the phosphorylation level of p38 and release of IL-1β, IL-6 and TNF-α, so as to inhibit inflammatory response. Therefore, it can be speculated that Annexin A1 might be the key signaling protein in the in vivo and in vitro anti-inflammatory mechanisms of propofol. PMID:22164217

  6. Propofol inhibits the activation of p38 through up-regulating the expression of annexin A1 to exert its anti-inflammation effect.

    Directory of Open Access Journals (Sweden)

    Jing Tang

    Full Text Available Inflammatory response is a kind of nonspecific immune response, with the central link of vascular response, which is mainly manifested by changes in neutrophils and vascular endothelial cells. In recent years, the in vivo and in vitro role of intravenous anesthetic propofol in inhibiting inflammatory response has been attracting more and more attention, but the anti-inflammatory mechanisms of propofol for mononuclear cells still remain undefined. In this study, proteomics analysis was applied to investigate protein expression profile changes in serum mononuclear cells following intervention of rats with endotoxemia using propofol. After two-dimensional electrophoresis and mass spectrometric identification, it has been found that the protein Annexin A1 was up-regulated in the propofol intervention group. Annexin A1 is a glucocorticoid-dependent anti-inflammatory protein. After detection using ELISA and Western blot assays, it has also been found that propofol can not only promote the expression of Annexin A1, but also inhibit the phosphorylation level of p38 and release of inflammatory factors (IL-1β, IL-6 and TNF-α in rats with endotoxemia. In order to further determine the role of up-regulated expression of Annexin A1 in anti-inflammation of propofol, this gene was silenced in vitro in human THP-1 cells, to detect the phosphorylation status of p38 and release of inflammatory factors. The results show that Annexin A1 can negatively regulate phosphorylation of p38 and release of IL-1β, IL-6 and TNF-α in THP-1 cells following propofol intervention and lipopolysaccharide (LPS stimulation. Our results clearly indicate that propofol can up-regulate Annexin A1 to inhibit the phosphorylation level of p38 and release of IL-1β, IL-6 and TNF-α, so as to inhibit inflammatory response. Therefore, it can be speculated that Annexin A1 might be the key signaling protein in the in vivo and in vitro anti-inflammatory mechanisms of propofol.

  7. Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Jiang Pu

    2016-08-01

    Full Text Available To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days. Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.

  8. Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses.

    Science.gov (United States)

    Pu, Jiang; Fang, Fan-Fu; Li, Xiu-Qing; Shu, Zhi-Heng; Jiang, Yi-Ping; Han, Ting; Peng, Wei; Zheng, Cheng-Jian

    2016-08-26

    To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.

  9. Clitocypin, a fungal cysteine protease inhibitor, exerts its insecticidal effect on Colorado potato beetle larvae by inhibiting their digestive cysteine proteases.

    Science.gov (United States)

    Šmid, Ida; Rotter, Ana; Gruden, Kristina; Brzin, Jože; Buh Gašparič, Meti; Kos, Janko; Žel, Jana; Sabotič, Jerica

    2015-07-01

    Colorado potato beetle (Leptinotarsa decemlineata Say, CPB) is a major potato pest that adapts readily to insecticides. Several types of protease inhibitors have previously been investigated as potential control agents, but with limited success. Recently, cysteine protease inhibitors from parasol mushroom, the macrocypins, were reported to inhibit growth of CPB larvae. To further investigate the insecticidal potential and mode of action of cysteine protease inhibitors of fungal origin, clitocypin, a cysteine protease inhibitor from clouded agaric (Clitocybe nebularis), was evaluated for its lethal effects on CPB larvae. Clitocypin isolated from fruiting bodies and recombinant clitocypin produced in Escherichia coli slowed growth and reduced survival of CPB larvae in a concentration dependent manner. Clitocypin was also expressed by transgenic potato, but only at low levels. Nevertheless, it reduced larval weight gain and delayed development. We have additionally shown that younger larvae are more susceptible to the action of clitocypin. The inhibition of digestive cysteine proteases, intestains, by clitocypin was shown to be the underlying mode of action. Protease inhibitors from mushrooms are confirmed as promising candidates for biopesticides. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Peptide Fraction pOh2 Exerts Antiadipogenic Activity through Inhibition of C/EBP-α and PPAR-γ Expression in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Thi Tuyet Nhung Nguyen

    2017-01-01

    Full Text Available Many studies have comprehensively examined the venom of Ophiophagus hannah snake. Its venom comprises different compounds exhibiting a wide range of pharmacological activities. In this investigation, four peptide fractions (PFs, ranging from 3 kDa to 10 kDa, isolated from the Vietnamese snake venom of O. hannah were separated by HPLC and investigated for their inhibitory activity on adipogenesis in 3T3-L1 adipocytes. The most effective PF was then further purified, generating two peptides, pOh1 and pOh2. Upon investigation of these two peptides on 3T3-L1 adipocytes, it was revealed that, at 10 μg/mL, pOh2 was able to inhibit the lipid accumulation in 3T3-L1 adipocytes by up to 56%, without affecting cell viability. Furthermore, the pOh2 downregulated the gene expression of important transcription factors C/EBP-α and PPAR-γ. In addition, aP2 and GPDH adipocyte-specific markers were also significantly reduced compared to untreated differentiated cells. Taken together, pOh2 inhibited the expression of key transcription factors C/EBP-α and PPAR-γ and their target genes, aP2 and GPDH, thereby blocking the adipocyte differentiation. In conclusion, this novel class of peptide might have potential for in vivo antiobesity effects.

  11. Heat shock protein 90 inhibition results in altered downstream signaling of mutant KIT and exerts synergistic effects on Kasumi-1 cells when combining with histone deacetylase inhibitor.

    Science.gov (United States)

    Yu, Wenjuan; Wang, Jianxiang; Jin, Jie; Qian, Wenbin; Qian, Jiejing; Cheng, Yizhi; Wang, Lei

    2011-09-01

    KIT mutations may be associated with a poor prognosis in t(8;21) AML. Heat shock protein 90 (Hsp90) is a molecular chaperone frequently used by cancer cells to stabilize mutant oncoproteins. Inhibition of Hsp90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) disrupted downstream signaling pathways of mutant KIT in Kasumi-1 cells. AML1-ETO fusion gene and mutated KIT act as "two-hit" factors in Kasumi-1 cells. Histone deacetylation (HDAC) inhibitors sodium phenylbutyrate (PB) and valproic acid (VPA) block AML1-ETO. Co-treatment with 17-AAG and PB or 17-AAG and VPA resulted in a synergistic effect in Kasumi-1 cells. Our results confirmed that Hsp90 and mutated KIT were valid molecular targets in the therapy of AML. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca2+-induced mitochondrial swelling

    Institute of Scientific and Technical Information of China (English)

    Olusola Olalekan Elekofehinti; Jean Paul Kamdem; Aline Augusti Bolingon; Margareth Linde Athayde; Seeger Rodrigo Lopes; Emily Pansera Waczuk; Ige Joseph Kade; Isaac Gbadura Adanlawo; Joao Batista Teixeira Rocha

    2013-01-01

    Objective: To evaluate the antioxidant and radical scavenging activities of Solanum anguivi fruit (SAG) and its possible effect on mitochondrial permeability transition pore as well as mitochondrial membrane potential (ΔΨm) isolated from rat liver. Methods: Antioxidant activity of SAG was assayed by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, iron chelation and ability to inhibit lipid peroxidation in both liver and brain homogenate of rats. Also, the effect of SAG on mitochondrial membrane potential and mitochondrial swelling were determined. Identification and quantification of bioactive polyphenolics was done by HPLC-DAD. Results: SAG exhibited potent and concentration dependent free radical-scavenging activity (IC50/DPPH=275.03±7.8 µg/mL). Reductive and iron chelation abilities also increase with increase in SAG concentration. SAG also inhibited peroxidation of cerebral and hepatic lipids subjected to iron oxidative assault. SAG protected against Ca2+ (110 µmol/L)-induced mitochondrial swelling and maintained theΔΨm. HPLC analysis revealed the presence of gallic acid [(17.54±0.04) mg/g], chlorogenic acid (21.90±0.02 mg/g), caffeic acid (16.64±0.01 mg/g), rutin [(14.71±0.03) mg/g] and quercetin [(7.39±0.05) mg/g]. Conclusions:These effects could be attributed to the bioactive polyphenolic compounds present in the extract. Our results suggest that SAG extract is a potential source of natural antioxidants that may be used not only in pharmaceutical and food industry but also in the treatment of diseases associated with oxidative stress.

  13. Chronic Exertional Compartment Syndrome

    Science.gov (United States)

    ... through the pain; that can lead to permanent muscle or nerve damage. Sometimes chronic exertional compartment syndrome is mistaken for shin splints, a more common cause of leg pain in young people who do a lot of vigorous weight- ...

  14. C-5-Modified Tetrahydropyrano-Tetrahydofuran-Derived Protease Inhibitors (PIs) Exert Potent Inhibition of the Replication of HIV-1 Variants Highly Resistant to Various PIs, including Darunavir

    Science.gov (United States)

    Aoki, Manabu; Hayashi, Hironori; Yedidi, Ravikiran S.; Martyr, Cuthbert D.; Takamatsu, Yuki; Aoki-Ogata, Hiromi; Nakamura, Teruya; Nakata, Hirotomo; Das, Debananda; Yamagata, Yuriko; Ghosh, Arun K.

    2015-01-01

    ABSTRACT We identified three nonpeptidic HIV-1 protease inhibitors (PIs), GRL-015, -085, and -097, containing tetrahydropyrano-tetrahydrofuran (Tp-THF) with a C-5 hydroxyl. The three compounds were potent against a wild-type laboratory HIV-1 strain (HIV-1WT), with 50% effective concentrations (EC50s) of 3.0 to 49 nM, and exhibited minimal cytotoxicity, with 50% cytotoxic concentrations (CC50) for GRL-015, -085, and -097 of 80, >100, and >100 μM, respectively. All the three compounds potently inhibited the replication of highly PI-resistant HIV-1 variants selected with each of the currently available PIs and recombinant clinical HIV-1 isolates obtained from patients harboring multidrug-resistant HIV-1 variants (HIVMDR). Importantly, darunavir (DRV) was >1,000 times less active against a highly DRV-resistant HIV-1 variant (HIV-1DRVRP51); the three compounds remained active against HIV-1DRVRP51 with only a 6.8- to 68-fold reduction. Moreover, the emergence of HIV-1 variants resistant to the three compounds was considerably delayed compared to the case of DRV. In particular, HIV-1 variants resistant to GRL-085 and -097 did not emerge even when two different highly DRV-resistant HIV-1 variants were used as a starting population. In the structural analyses, Tp-THF of GRL-015, -085, and -097 showed strong hydrogen bond interactions with the backbone atoms of active-site amino acid residues (Asp29 and Asp30) of HIV-1 protease. A strong hydrogen bonding formation between the hydroxyl moiety of Tp-THF and a carbonyl oxygen atom of Gly48 was newly identified. The present findings indicate that the three compounds warrant further study as possible therapeutic agents for treating individuals harboring wild-type HIV and/or HIVMDR. IMPORTANCE Darunavir (DRV) inhibits the replication of most existing multidrug-resistant HIV-1 strains and has a high genetic barrier. However, the emergence of highly DRV-resistant HIV-1 strains (HIVDRVR) has recently been observed in vivo and in

  15. DXXK exerts anti-inflammatory effects by inhibiting the lipopolysaccharide-induced NF-κB/COX-2 signalling pathway and the expression of inflammatory mediators.

    Science.gov (United States)

    Yu, Ya; Li, Xiang; Qu, Liping; Chen, Yang; Dai, Yanping; Wang, Mei; Zou, Wenjun

    2016-02-03

    Diao Xin Xue Kang (DXXK) is the active pharmaceutical ingredient of the traditional Chinese medicinal product DXXK capsules, which have been approved for the treatment of cardiovascular disease and have been widely used clinically in China for many years with distinct curative effects. In March 2012, DXXK capsules were approved in the Netherlands, making them the first traditional herbal medicinal product (THMP) made outside of Europe. To assess the anti-inflammatory effects of DXXK and the underlying mechanisms at the cellular and molecular levels. In this study, lipopolysaccharide (LPS) was used to induce inflammation in RAW 264.7 cells. The sulphorhodamine B (SRB) assay was used to study the effect of DXXK on the proliferation of RAW 264.7 cells. Gene expression levels of cyclooxygenase 1 (COX-1), COX-2, tumour necrosis factor-alpha (TNF-α), IL-1β and IL-6 were assessed by reverse transcription polymerase chain reaction (RT-PCR), while COX-2 protein levels were evaluated using western blotting. The levels of PGE2 in the culture media were detected by enzyme-linked immunosorbent assay (ELISA), while TNF-α, IL-1β and IL-6 levels were detected using a Milliplex Map Mouse Cytokine Panel system. The activation and nuclear translocation of nuclear transcription factor κB (NF-κB) were studied using western blotting. In vivo studies in mice were carried out using the carrageenan-air pouch models of inflammation. In exudates, leucocytes were counted, total protein was determined using the Bradford assay, nitric oxide(NO) levels were assessed using the Griess reagent, and PGE2 and TNF-α levels were quantified by ELISA. The SRB assay showed that at the doses used in this study (10, 20 and 40 μg/mL), DXXK did not affect the proliferation of RAW 264.7 cells. DXXK (10, 20 and 40 μg/mL) inhibited LPS-induced PGE2 production by down-regulating the expression of COX-2, without influencing COX-1 expression. We also demonstrated that DXXK reduced the expression of pro

  16. Gigantol from Dendrobium chrysotoxum Lindl. binds and inhibits aldose reductase gene to exert its anti-cataract activity: An in vitro mechanistic study.

    Science.gov (United States)

    Wu, Jie; Li, Xue; Wan, Wencheng; Yang, Qiaohong; Ma, Weifeng; Chen, Dan; Hu, Jiangmiao; Chen, C-Y Oliver; Wei, Xiaoyong

    2017-02-23

    Dendrobium. chrysotoxum Lindl is a commonly used species of medicinal Dendrobium which belongs to the family of Orchidaceae, locally known as "Shihu" or "Huangcao". D. chrysotoxum Lindl is widely known for medicinal values in traditional Chinese medicine as it possesses anti-inflammatory, anti-hyperglycemic induction, antitumor and antioxidant properties. To characterize the interaction between gigantol extracted from D. chrysotoxum Lindl and the AR gene, and determine gigantol's efficacy against cataractogenesis. Human lens epithelial cells (HLECs) were induced by glucose as the model group. Reverse transcription polymerase chain reaction (RT-PCR) was used to assess AR gene expression. Then, the mode of interaction of gigantol with the AR gene was evaluated by UV-visible spectroscopy, atomic force microscope (AFM) and surface-enhanced Raman spectroscopy (SERS). The binding constant was determined by UV-visible. Gigantol depressed AR gene expression in HLECs. UV-visible spectra preliminarily indicated that interaction between the AR gene and gigantol may follow the groove mode, with a binding constant of 1.85×10(3)L/mol. Atomic force microscope (AFM) data indicated that gigantol possibly bound to insert AR gene base pairs of the double helix. Surface-enhanced Raman spectroscopy (SERS) studies further supported these observations. Gigantol extracted from D. chrysotoxum Lindl not only has inhibitory effects on aldose reductase, but also inhibits AR gene expression. These findings provide a more comprehensive theoretical basis for the use of Dendrobium for the treatment of diabetic cataract. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Soshiho-Tang Aqueous Extract Exerts Antiobesity Effects in High Fat Diet-Fed Mice and Inhibits Adipogenesis in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Sae-Rom Yoo

    2016-01-01

    Full Text Available Soshiho-tang (SST; sho-saiko-to in Japanese; xiaochaihu-tang in Chinese has generally been used to improve liver fibrosis- and cirrhosis-related symptoms in traditional Korean medicine. Although many studies have investigated the pharmacological properties of SST, its antiobesity effect has not been elucidated. Thus, our present study was carried out to evaluate the antiobesity effect of SST using a high fat diet- (HFD induced obese mouse model and 3T3-L1 adipose cells. C57BL/6J mice were randomly divided into four groups (n=6/group, normal diet (ND, HFD-fed group, and HFD- and SST-fed groups (S200: 200 mg/kg of SST; S600: 600 mg/kg of SST and given HFD with or without SST extract for 8 weeks. 3T3-L1 preadipocytes were differentiated into adipocytes for 8 days with or without SST. In the HFD-fed obese mice, body weight and fat accumulation in adipose tissue were significantly reduced by SST administration. Compared with control-differentiated adipocytes, SST significantly inhibited lipid accumulation by decreasing the triglyceride (TG content and leptin concentration in 3T3-L1 adipocytes. SST also decreased the expression of adipogenesis-related genes including lipoprotein lipase (LPL, fatty acid binding protein 4 (FABP4, CCAAT/enhancer-binding protein-alpha (C/EBP-α, and peroxisome proliferator-activated receptor-gamma (PPAR-γ. Our findings suggest that SST has potential as a nontoxic antiobesity medication.

  18. Postnatal PPARdelta activation and myostatin inhibition exert distinct yet complimentary effects on the metabolic profile of obese insulin-resistant mice.

    Directory of Open Access Journals (Sweden)

    Barbara L Bernardo

    Full Text Available BACKGROUND: Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516 and a myostatin antibody and resistance training mimetic (PF-879 on metabolic and performance outcomes in obese insulin resistant mice. METHODOLOGY/PRINCIPAL FINDINGS: Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved. CONCLUSIONS/SIGNIFICANCE: The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM.

  19. Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Ling; Wu, Xiu-Ying; Zhang, Li-Hong; Chen, Wei-Min [Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang (China); Uchiyama, Akinori; Mashimo, Takashi; Fujino, Yuji [Department of Anesthesiology and Intensive Care Medicine, Osaka University Medical School, Osaka (Japan)

    2013-03-15

    We investigated the effect of propofol (Prop) administration (10 mg kg{sup -1} h{sup -1}, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

  20. 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.

  1. Centipede grass exerts anti-adipogenic activity through inhibition of C/EBPβ, C/EBPα, and PPARγ expression and the AKT signaling pathway in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Park Hyoung Joon

    2012-11-01

    Full Text Available Abstract Background Centipede grass (CG originates from China and South America and is reported to contain several C-glycosyl flavones and phenolic constituents, including maysin and luteolin derivatives. This study aimed to investigate, for the first time, the antiobesity activity of CG and its potential molecular mechanism in 3T3-L1 cells. Methods To study the effect of CG on adipogenesis, differentiating 3T3-L1 cells were treated every day with CG at various concentrations (0–100 μg/ml for six days. Oil-red O staining and triglyceride content assay were performed to determine the lipid accumulation in 3T3-L1 cells. The expression of mRNAs or proteins associated with adipogenesis was measured using RT-PCR and Western blotting analysis. We examined the effect of CG on level of phosphorylated Akt in 3T3-L1 cells treated with CG at various concentration s during adipocyte differentiation. Results Differentiation was investigated with an Oil-red O staining assay using CG-treated 3T3-L1 adipocytes. We found that CG suppressed lipid droplet formation and adipocyte differentiation in 3T3-L1 cells in a dose-dependent manner. Treatment of the 3T3-L1 adipocytes with CG resulted in an attenuation of the expression of adipogenesis-related factors and lipid metabolic genes. The expression of C/EBPα and PPARγ, the central transcriptional regulators of adipogenesis, was decreased by the treatment with CG. The expression of genes involved in lipid metabolism, aP2 were significantly inhibited following the CG treatment. Moreover, the CG treatment down-regulated the phosphorylation levels of Akt and GSK3β. Conclusions Taken collectively, these data indicated that CG exerts antiadipogenic activity by inhibiting the expression of C/EBPβ, C/EBPα, and PPARγ and the Akt signaling pathway in 3T3-L1 adipocytes.

  2. Bisphenol A and Related Alkylphenols Exert Nongenomic Estrogenic Actions Through a G Protein-Coupled Estrogen Receptor 1 (Gper)/Epidermal Growth Factor Receptor (Egfr) Pathway to Inhibit Meiotic Maturation of Zebrafish Oocytes.

    Science.gov (United States)

    Fitzgerald, Amanda C; Peyton, Candace; Dong, Jing; Thomas, Peter

    2015-12-01

    Xenobiotic estrogens, such as bisphenol A (BPA), disrupt a wide variety of genomic estrogen actions, but their nongenomic estrogen actions remain poorly understood. We investigated nongenomic estrogenic effects of low concentrations of BPA and three related alkylphenols on the inhibition of zebrafish oocye maturation (OM) mediated through a G protein-coupled estrogen receptor 1 (Gper)-dependent epidermal growth factor receptor (Egfr) pathway. BPA (10-100 nM) treatment for 3 h mimicked the effects of estradiol-17beta (E2) and EGF, decreasing spontaneous maturation of defolliculated zebrafish oocytes, an effect not blocked by coincubation with actinomycin D, but blocked by coincubation with a Gper antibody. BPA displayed relatively high binding affinity (15.8% that of E2) for recombinant zebrafish Gper. The inhibitory effects of BPA were attenuated by inhibition of upstream regulators of Egfr, intracellular tyrosine kinase (Src) with PP2, and matrix metalloproteinase with ilomastat. Treatment with an inhibitor of Egfr transactivation, AG1478, and an inhibitor of the mitogen-activated protein kinase (MAPK) 3/1 pathway, U0126, increased spontaneous OM and blocked the inhibitory effects of BPA, E2, and the selective GPER agonist, G-1. Western blot analysis showed that BPA (10-200 nM) mimicked the stimulatory effects of E2 and EGF on Mapk3/1 phosphorylation. Tetrabromobisphenol A, 4-nonylphenol, and tetrachlorobisphenol A (5-100 nM) also inhibited OM, an effect blocked by cotreatment with AG1478, as well as with the GPER antagonist, G-15, and displayed similar binding affinities as BPA to zebrafish Gper. The results suggest that BPA and related alkylphenols disrupt zebrafish OM by a novel nongenomic estrogenic mechanism involving activation of the Gper/Egfr/Mapk3/1 pathway.

  3. Curcumin exerts antinociceptive effects by inhibiting the activation of astrocytes in spinal dorsal horn and the intracellular extracellular signal-regulated kinase signaling pathway in rat model of chronic constriction injury

    Institute of Scientific and Technical Information of China (English)

    JI Feng-tao; LIANG Jiang-jun; LIU Ling; CAO Ming-hui; LI Feng

    2013-01-01

    Background Activation of glial cells and the extracellular signal-regulated kinase (ERK) signaling pathway play an important role in the development and maintenance of neuropathic pain.Curcumin can alleviate the symptom of inflammatory pain by inhibiting the production and release of interleukin and tumor necrosis factor.However,whether curcumin affects neuropathic pain induced by nerve injury and the possible mechanism involved are still unknown.This study investigated the effects of tolerable doses of curcumin on the activation of astrocytes and ERK signaling in the spinal dorsal horn in rat model of neuropathic pain.Methods Adult male Sprague-Dawley rats were randomly divided into three groups:a control (sham operated) group,and chronic constriction injury groups (to induce neuropathic pain) that were either untreated or treated with curcumin.Thermal and mechanical hyperalgesia thresholds were measured.The distribution and morphological changes of astrocytes were observed by immunofluorescence.Western blotting was used to detect changes in the expression of glial flbrillary acid protein (GFAP) and phosphorylated ERK.Results Injured rats showed obvious mechanical allodynia and thermal hyperalgesia.The number of GFAP-positive astrocytes,and the fluorescence intensity of GFAP were significantly increased in the spinal dorsal horn of injured compared with control rats.The soma of astrocytes also appeared hypertrophied in injured animals.Expression of GFAP and phosphorylated ERK was also significantly increased in the spinal dorsal hom of injured compared with control rats.Curcumin reduced the injury-induced thermal and mechanical hyperalgesia,the increase in the fluorescence intensity of GFAP and the hypertrophy of astrocytic soma,activation of GFAP and phosphorylation of ERK in the spinal dorsal horn.Conclusions Curcumin can markedly alleviate nerve injury-induced neuropathic pain in rats.The analgesic effect of curcumin may be attributed to its inhibition of

  4. Cyanidin-3-O-glucoside inhibits NF-kB signalling in intestinal epithelial cells exposed to TNF-α and exerts protective effects via Nrf2 pathway activation.

    Science.gov (United States)

    Ferrari, Daniela; Speciale, Antonio; Cristani, Mariateresa; Fratantonio, Deborah; Molonia, Maria Sofia; Ranaldi, Giulia; Saija, Antonella; Cimino, Francesco

    2016-12-15

    Chronic intestinal inflammatory disorders, such as Inflammatory Bowel Diseases (IBDs), are characterized by excessive release of proinflammatory mediators, intestinal barrier dysfunction and excessive activation of NF-kB cascade. Previous studies shown that TNF-α plays a central role in intestinal inflammation of IBDs and supported beneficial effects of flavonoids against chronic inflammatory diseases. In this study, we employed an in vitro model of acute intestinal inflammation using intestinal Caco-2 cells exposed to TNF-α. The protective effects of cyanidin-3-glucoside (C3G), an anthocyanin widely distributed in mediterranean diet, were then evaluated. Caco-2 cells exposure to TNF-α activated NF-kB proinflammatory pathway and induced IL6 and COX-2 expression. Cells pretreatment for 24h with C3G (20-40μM) prevented TNF-α-induced changes, and improved intracellular redox status. Our results demonstrated that C3G, also without any kind of stimulus, increased the translocation of the transcription factor Nrf2 into the nucleus so activating antioxidant and detoxifying genes. In conclusion, C3G exhibited protective effects through the inhibition of NF-kB signalling in Caco-2 cells and these beneficial effects appear to be due to its ability to activate cellular protective responses modulated by Nrf2. These data suggest that anthocyanins could contribute, as complementary or preventive approaches, to the management of chronic inflammatory diseases.

  5. The Design of Networked Exertion Games

    Directory of Open Access Journals (Sweden)

    Frank Vetere

    2009-01-01

    Full Text Available Incorporating physical activity and exertion into pervasive gaming applications can provide health and social benefits. Prior research has resulted in several prototypes of pervasive games that encourage exertion as interaction form; however, no detailed critical account of the various approaches exists. We focus on networked exertion games and detail some of our work while identifying the remaining issues towards providing a coherent framework. We outline common lessons learned and use them as the basis for generalizations for the design of networked exertion games. We propose possible directions of further investigation, hoping to provide guidance for future work to facilitate greater awareness and exposure of exertion games and their benefits.

  6. Reflections on the Design of Exertion Games.

    Science.gov (United States)

    Mueller, Florian Floyd; Altimira, David; Khot, Rohit Ashot

    2015-02-01

    The design of exertion games (i.e., digital games that require physical effort from players) is a difficult intertwined challenge of combining digital games and physical effort. To aid designers in facing this challenge, we describe our experiences of designing exertion games. We outline personal reflections on our design processes and articulate analyses of players' experiences. These reflections and analyses serve to highlight the unique opportunities of combining digital games and physical effort. The insights we seek aim to enhance the understanding of exertion game design, contributing to the advancement of the field, and ultimately resulting in better games and associated player experiences.

  7. Design Strategies for Balancing Exertion Games

    DEFF Research Database (Denmark)

    Jensen, Mads Møller; Grønbæk, Kaj

    2016-01-01

    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......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...

  8. Gender and contraction mode on perceived exertion.

    Science.gov (United States)

    Pincivero, D M; Polen, R R; Byrd, B N

    2010-05-01

    The purpose of this study was to examine perceived exertion responses during concentric and eccentric elbow flexor contractions between young adult men and women. Thirty healthy young adults participated in two experimental sessions. During the first session, subjects performed five concentric isokinetic maximal voluntary contractions (MVC) of elbow flexion, followed by nine, randomly-ordered sub-maximal contractions (10-90% MVC). The same procedures were repeated during the second session, with the exception that eccentric contractions were performed. Subjects rated their perceived exertion following the sub-maximal contractions with the Borg category-ratio scale. Perceived exertion was significantly (pMVC. A three-factor interaction between 30-40% MVC indicated that perceived exertion increased more during the eccentric, than concentric, contractions in women, while the opposite pattern was evident for the men. There were no significant contraction mode or gender differences. Power function modeling revealed that perceived exertion increased in a negatively accelerating manner, except for the men performing eccentric exercise. Perceived exertion increases in a similar non-linear manner between men and women during concentric contractions, while men exhibited a statistically linear pattern during eccentric contractions.

  9. Exertion and acute coronary artery injury.

    Science.gov (United States)

    Black, A; Black, M M; Gensini, G

    1975-12-01

    Twelve cases of myocardial infarction as related to strenuous exertion are presented with the pathological findings in several of these cases. Three cases with coronary arteriography are also presented. The pathology of coronary arteriosclerotic plaques and the vulnerability to acute injury is reviewed and discussed. It is concluded that strenuous exertion can cause acute injury to coronary artery plaques due to the unusual stressful whip-like action to which coronary arteries are subject. These injuries may initiate as cracks in the plaques or subintimal hemorrhages and proceed to coronary occlusion and ultimate myocardial infarction. With this concept in mind we use the term of "crack in the plaque" (Black's Crack in the Plaque) to account for the sudden appearance of clinical coronary artery disease appearing during or shortly after exertion, or other stressful situations in patients without previous existing evidence of clinical coronary artery disease. This could also account for exacerbation of symptoms or death occurring after exertion in previously quiescent asymptomatic known coronary artery disease subjects. This concept may explain some of the puzzling features of coronary disease.

  10. Physical exertion may cause high troponin levels.

    Science.gov (United States)

    Agewall, Stefan; Tjora, Solve

    2011-11-15

    It is important to measure troponin levels when acute myocardial infarct is suspected. Many other factors that affect the heart can cause an increase in troponin levels, for example extreme physical exertion. Recent studies have shown that more normal physical activity can also lead to increase in troponin levels in healthy individuals.

  11. Dynamical friction force exerted on spherical bodies

    CERN Document Server

    Esquivel, O

    2007-01-01

    We present a rigorous calculation of the dynamical friction force exerted on a spherical massive perturber moving through an infinite homogenous system of field stars. By calculating the shape and mass of the polarization cloud induced by the perturber in the background system, which decelerates the motion of the perturber, we recover Chandrasekhar's drag force law with a modified Coulomb logarithm. As concrete examples we calculate the drag force exerted on a Plummer sphere or a sphere with the density distribution of a Hernquist profile. It is shown that the shape of the perturber affects only the exact form of the Coulomb logarithm. The latter converges on small scales, because encounters of the test and field stars with impact parameters less than the size of the massive perturber become inefficient. We confirm this way earlier results based on the impulse approximation of small angle scatterings.

  12. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes.

    Science.gov (United States)

    Oláh, Attila; Tóth, Balázs I; Borbíró, István; Sugawara, Koji; Szöllõsi, Attila G; Czifra, Gabriella; Pál, Balázs; Ambrus, Lídia; Kloepper, Jennifer; Camera, Emanuela; Ludovici, Matteo; Picardo, Mauro; Voets, Thomas; Zouboulis, Christos C; Paus, Ralf; Bíró, Tamás

    2014-09-01

    The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.

  13. DCP-LA Exerts an Antiaging Action on the Skin.

    Science.gov (United States)

    Nishizaki, Tomoyuki

    2016-01-01

    The present study assessed the possibility for the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) as an antiaging compound for the skin by assaying senescence-associated β-galactosidase (SA-β-Gal), a biomarker of senescence and cell viability. The nitric oxide (NO) donor sodium nitroprusside (SNP) increased in SA-β-Gal-positive cells in cultured human fibroblasts and mouse keratinocytes, and DCP-LA significantly inhibited the effect of SNP. Moreover, SNP induced cell death in cultured mouse keratinocytes, and DCP-LA significantly prevented NO stress-induced death of keratinocytes. Taken together, these results indicate that DCP-LA exerts an antiaging action on the skin.

  14. 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...... million person-hours, and the attributable proportion was 5.7 percent. The risk was modified by physical fitness, with an increased risk being seen among sedentary subjects as in earlier studies, but the data also suggested a U-shaped association. In addition, the trigger effect was modified...

  15. Understanding the Mismatch Between Coaches' and Players' Perceptions of Exertion

    NARCIS (Netherlands)

    Brink, Michel S.; Kersten, Anna W.; Frencken, Wouter G. P.

    2017-01-01

    A mismatch between the training exertion intended by a coach and the exertion perceived by players is well established in sports. However, it is unknown whether coaches can accurately observe exertion of individual players during training. Furthermore, the discrepancy in coaches' and players' percep

  16. Understanding the Mismatch Between Coaches' and Players' Perceptions of Exertion

    NARCIS (Netherlands)

    Brink, Michel S; Kersten, Anna W; Frencken, Wouter G

    2016-01-01

    A mismatch between the intended training exertion by the coach and the perceived exertion by players is well established in sports. However, it is unknown if coaches are able to accurately observe exertion of individual players during training. Furthermore, the discrepancy in coaches' and players' p

  17. 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.

  18. Mechanisms of exertional fatigue in muscle glycogenoses

    DEFF Research Database (Denmark)

    Vissing, John; Haller, Ronald G

    2012-01-01

    concentrations of extracellular potassium in exercising muscle and (3) exaggerated accumulation of ADP during exercise that may inhibit sodium-potassium and calcium-ATPases. Disorders of muscle glycogenolysis and glycolysis reveal the crucial role of these metabolic processes for supplying both anaerobic...... and aerobic energy for muscle contraction; and the pathological fatigue that occurs when glycogenolysis and/or glycolysis is blocked imply an important role for theses metabolic pathways in normal muscle fatigue....

  19. Validity and reliability of rating perceived exertion in women with fibromyalgia: exertion-pain discrimination.

    Science.gov (United States)

    Soriano-Maldonado, Alberto; Ruiz, Jonatan R; Álvarez-Gallardo, Inmaculada C; Segura-Jiménez, Víctor; Santalla, Alfredo; Munguía-Izquierdo, Diego

    2015-01-01

    The present study aimed (1) to assess the validity and reliability of the Borg category-ratio (CR-10) scale for monitoring exercise intensity in women with fibromyalgia (FM) and (2) to examine whether women with FM can discriminate between perceived exertion and exercise-induced pain. Thirty-three women with FM performed two incremental treadmill tests (1 week separated). Heart rate, oxygen uptake, minute ventilation and respiratory quotient were measured. The ratings of perceived exertion (RPE: CR-10 scale) and exercise-induced pain were obtained at each workload. The Spearman's correlation of RPE with the physiological responses ranged from 0.69 to 0.79. The regression models explained ~50% of the variability of the studied physiological responses. We found "perfect acceptable" agreement in 69% of the observations. Weighted Kappa was 0.66 (95% confidence interval [CI]: 0.59-0.72). There were differences between RPE and pain at workloads 3 (1.50; 95% CI: 0.85-2.16), 4 (2.10; 95% CI: 1.23-2.96), 5 (3.40; 95% CI: 1.29-5.51) and 6 (3.97; 95% CI: 1.61-6.33). The main findings of the present study suggest that the Borg CR-10 scale is valid and moderately reliable for monitoring exercise intensity in women with FM, and these patients were able to discriminate between exertion and exercise-induced pain.

  20. The arylpiperazine derivatives N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide and N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide exert a long-lasting inhibition of human serotonin 5-HT7 receptor binding and cAMP signaling.

    Science.gov (United States)

    Atanes, Patricio; Lacivita, Enza; Rodríguez, Javier; Brea, José; Burgueño, Javier; Vela, José Miguel; Cadavid, María Isabel; Loza, María Isabel; Leopoldo, Marcello; Castro, Marián

    2013-12-01

    We performed a detailed in vitro pharmacological characterization of two arylpiperazine derivatives, compound N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211) previously identified as a high-affinity brain penetrant ligand for 5-hydroxytryptamine (serotonin) type 7 (5-HT7) receptors, and its analog N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide (MEL-9). Both ligands exhibited competitive displacement of [(3)H]-(2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine ([(3)H]-SB-269970) radioligand binding and insurmountable antagonism of 5-carboxamidotryptamine (5-CT)-stimulated cyclic adenosine monophosphate (cAMP) signaling in human embryonic kidney (HEK293) cells stably expressing human 5-HT7 receptors. They also inhibited forskolin-stimulated adenylate cyclase activity in 5-HT7-expressing HEK293 cells but not in the parental cell line. The compounds elicited long-lasting (at least 24 h) concentration-dependent inhibition of radioligand binding at 5-HT7-binding sites in whole-cell radioligand binding assays, after pretreatment of the cells with the compounds and subsequent compound removal. In cAMP assays, pretreatment of cells with the compounds rendered 5-HT7 receptors unresponsive to 5-CT and also rendered 5-HT7-expressing HEK293 cells unresponsive to forskolin. Compound 1-(2-biphenyl)piperazine (RA-7), a known active metabolite of LP-211 present in vivo, was able to partially inhibit 5-HT7 radioligand binding in a long-lasting irreversible manner. Hence, LP-211 and MEL-9 were identified as high-affinity long-acting inhibitors of human 5-HT7 receptor binding and function in cell lines. The detailed in vitro characterization of these two pharmacological tools targeting 5-HT7 receptors may benefit the study of 5-HT7 receptor function and it may lead to the development of novel selective pharmacological tools with defined functional properties at 5-HT7 receptors.

  1. 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…

  2. Cardiovascular Fitness and the Psychophysics of Perceived Exertion.

    Science.gov (United States)

    Mihevic, Patricia M.

    1983-01-01

    The perceptual responses of individuals at different levels of physical fitness to absolute exercise intensities were compared. Perceived exertion, as measured by the Rating of Perceived Exertion scale, did not discriminate between subjects who were physically fit and those who were not, despite differences in physiological strain. (Author/PP)

  3. Using Ratings of Perceived Exertion in Physical Education

    Science.gov (United States)

    Lagally, Kristen M.

    2013-01-01

    Ratings of perceived exertion have been shown to be a valid method of monitoring physical activity intensity for both adults and children. As such, this subjective method may serve as an alternative to objective measurements for assessing students' performance on national standards 2 and 4. The OMNI-Child perceived exertion scales were…

  4. Understanding the Mismatch Between Coaches' and Players' Perceptions of Exertion.

    Science.gov (United States)

    Brink, Michel S; Kersten, Anna W; Frencken, Wouter G P

    2017-04-01

    A mismatch between the training exertion intended by a coach and the exertion perceived by players is well established in sports. However, it is unknown whether coaches can accurately observe exertion of individual players during training. Furthermore, the discrepancy in coaches' and players' perceptions has not been explained. To determine the relation between intended and observed training exertion by the coach and perceived training exertion by the players and establish whether on-field training characteristics, intermittent endurance capacity, and maturity status explain the mismatch. During 2 mesocycles of 4 wk (in November and March), rating of intended exertion (RIE), rating of observed exertion (ROE), and rating of perceived exertion (RPE) were monitored in 31 elite young soccer players. External and internal training loads were objectively quantified with accelerometers (PlayerLoad) and heart-rate monitors (TRIMPmod). Results of an interval shuttle-run test (ISRT) and age at peak height velocity (APHV) were determined for all players. RIE, ROE, and RPE were monitored in 977 training sessions. The correlations between RIE and RPE (r = .58; P players will do and what they actually did on the field. When doing this, they consider the intermittent endurance capacity of individual players.

  5. Acute exertional anterior compartment syndrome in an adolescent female.

    Science.gov (United States)

    Fehlandt, A; Micheli, L

    1995-01-01

    Acute compartment syndromes usually occur as a complication of major trauma. While the chronic exertional anterior tibial compartment syndrome is well described in the sports medicine literature, reports of acute tibial compartment syndromes due to physical exertion, or repetitive microtrauma, are rare. The case of an adolescent female who developed an acute anterior compartment syndrome from running in a soccer game is described in this report. Failure to recognize the onset of an acute exertional compartment syndrome may lead to treatment delay and serious complications. Whereas the chronic exertional anterior compartment syndrome is characterized by pain that diminishes with the cessation of exercise, the onset of the acute exertional anterior compartment syndrome is heralded by pain that continues, or increases, after exercise has stopped. Compartment pressure measurement confirms the clinical diagnosis and helps guide treatment. True compartment syndromes require urgent fasciotomy.

  6. 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.

  7. Type I Interferons Exert Anti-tumor Effect via Reversing Immunosuppression Mediated by Mesenchymal Stromal Cells

    Science.gov (United States)

    Shou, Peishun; Chen, Qing; Jiang, Jingting; Xu, Chunliang; Zhang, Jimin; Zheng, Chunxing; Jiang, Menghui; Velletri, Tania; Cao, Wei; Huang, Yin; Yang, Qian; Han, Xiaoyan; Zhang, Liying; Wei, Lixin; Rabson, Arnold B.; Chin, Y. Eugene; Wang, Ying; Shi, Yufang

    2016-01-01

    Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites to promote tumor growth, but the underlying mechanisms remain largely elusive. Here, we found that IFNα-secreting MSCs showed more dramatic inhibition effect on tumor progression than that of IFNα alone. Interestingly, IFNα-primed MSCs could also effectively suppress tumor growth. Mechanistically, we demonstrated that both IFNα and IFNβ (type I IFNs) reversed the immunosuppressive effect of MSCs on splenocyte proliferation. This effect of type I IFNs was exerted through inhibiting iNOS (inducible nitric oxide synthase) expression in IFNγ and TNFα-stimulated MSCs. Notably, only NO production was inhibited by IFNα; production of other cytokines or chemokines tested was not suppressed. Furthermore, IFNα promoted the switch from Stat1 homodimers to Stat1-Stat2 heterodimers. Studies using the luciferase reporter system and chromatin immunoprecipitation assay revealed that IFNα suppressed iNOS transcription through inhibiting the binding of Stat1 to iNOS promoter. Therefore, the synergistic anti-tumor effects of type I IFNs and MSCs were achieved by inhibiting NO production. This study provides essential information for understanding the mechanisms of MSC-mediated immunosuppression and for the development of better clinical strategies using IFNs and MSCs for cancer immunotherapy. PMID:27109100

  8. H-Ras Exerts Opposing Effects on Type I Interferon Responses Depending on Its Activation Status.

    Science.gov (United States)

    Chen, Guann-An; Lin, Yun-Ru; Chung, Hai-Ting; Hwang, Lih-Hwa

    2017-01-01

    Using shRNA high-throughput screening, we identified H-Ras as a regulator of antiviral activity, whose depletion could enhance Sindbis virus replication. Further analyses indicated that depletion of H-Ras results in a robust increase in vesicular stomatitis virus infection and a decrease in Sendai virus (SeV)-induced retinoic acid-inducible gene-I-like receptor (RLR) signaling. Interestingly, however, ectopic expression of wild-type H-Ras results in a biphasic mode of RLR signaling regulation: while low-level expression of H-Ras enhances SeV-induced RLR signaling, high-level expression of H-Ras significantly inhibits this signaling. The inhibitory effects correlate with the activation status of H-Ras. As a result, oncogenic H-Ras, H-RasV12, strongly inhibits SeV-induced IFN-β promoter activity and type I interferon signaling. Conversely, the positive effects exerted by H-Ras on RLR signaling are independent of its signaling activity, as a constitutively inactive form of H-Ras, H-RasN17, also positively regulates RLR signaling. Mechanistically, we demonstrate that depletion of H-Ras reduces the formation of MAVS-TNF receptor-associated factor 3 signaling complexes. These results reveal that the H-Ras protein plays a role in promoting MAVS signalosome assembly in the mitochondria, whereas oncogenic H-Ras exerts a negative effect on type I IFN responses.

  9. 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-functional calc......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...

  10. Muscle localization of Tc-99m MDP after exertion

    Energy Technology Data Exchange (ETDEWEB)

    Valk, P.

    1984-09-01

    Very high muscle uptake of Tc-99m MDP was seen two days after the start of a program of vigorous weight-lifting exercises. Localization of Tc-99m bone tracer in muscle that has been damaged by exertion may be a more common phenomenon than is recognized at present.

  11. Resveratrol inhibits Trypanosoma cruzi arginine kinase and exerts a trypanocidal activity.

    Science.gov (United States)

    Valera Vera, Edward A; Sayé, Melisa; Reigada, Chantal; Damasceno, Flávia S; Silber, Ariel M; Miranda, Mariana R; Pereira, Claudio A

    2016-06-01

    Arginine kinase catalyzes the reversible transphosphorylation between ADP and phosphoarginine which plays a critical role in the maintenance of cellular energy homeostasis. Arginine kinase from the protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, meets the requirements to be considered as a potential therapeutic target for rational drug design including being absent in its mammalian hosts. In this study a group of polyphenolic compounds was evaluated as potential inhibitors of arginine kinase using molecular docking techniques. Among the analyzed compounds with the lowest free binding energy to the arginine kinase active site (cruzi trypomastigotes bursting from infected CHO K1 cells, with IC50=77μM. Additionally epimastigotes overexpressing arginine kinase were 5 times more resistant to resveratrol compared to controls. Taking into account that: (1) resveratrol is considered as completely nontoxic; (2) is easily accessible due to its low market price; and (3) has as a well-defined target enzyme which is absent in the mammalian host, it is a promising compound as a trypanocidal drug for Chagas disease.

  12. Measurement and Relation between Received and Exerted Violence against Partner

    Directory of Open Access Journals (Sweden)

    José Moral de la Rubia

    2014-07-01

    Full Text Available A female victimization model is often assumed in the study of couple violence, even in general population. In Mexico, a questionnaire of couple violence has been developed. This instrument evaluates suffered and exerted violence. The aims of this paper were to contrast the factor structure of this questionnaire, calculate its internal consistency, describe its distributions, compare means of violence between both sexes and between persons who live or not with their partners, and study the relationship between received and exerted violence. A non-experimental research with a trans-sectional design was performed. The questionnaire was applied to a non probability sample of 223 women and 177 men with heterosexual couples from general population. Confirmatory factor analysis and structural equation modeling were used for data analysis. The factor structure of received violence scale was one-dimensional, and the one of exerted violence scale was two-dimensional. Both sexes reported to exert violence with the same frequency, but men complained to receive violence with more frequency than women. Persons who live with their partners reported to receive more violence and to exert more non-psychological violence than persons who do not live with their partners. The correlations between received and exercised violence were moderate. A recursive model of violent reaction showed a fit to data from good to adequate, and had good properties of invariance between both sexes, and between persons who live or not with their partners. It is concluded that the questionnaire has good properties of factor structure and internal consistency, and data refute a model of female victimization.

  13. Measurement and Relation between Received and Exerted Violence against Partner

    Directory of Open Access Journals (Sweden)

    José Moral de la Rubia

    2014-07-01

    Full Text Available A female victimization model is often assumed in the study of couple violence, even in general population. In Mexico, a questionnaire of couple violence has been developed. This instrument evaluates suffered and exerted violence. The aims of this paper were to contrast the factor structure of this questionnaire, calculate its internal consistency, describe its distributions, compare means of violence between both sexes and between persons who live or not with their partners, and study the relationship between received and exerted violence. A non-experimental research with a trans-sectional design was performed. The questionnaire was applied to a non probability sample of 223 women and 177 men with heterosexual couples from general population. Confirmatory factor analysis and structural equation modeling were used for data analysis. The factor structure of received violence scale was one-dimensional, and the one of exerted violence scale was two-dimensional. Both sexes reported to exert violence with the same frequency, but men complained to receive violence with more frequency than women. Persons who live with their partners reported to receive more violence and to exert more non-psychological violence than persons who do not live with their partners. The correlations between received and exercised violence were moderate. A recursive model of violent reaction showed a fit to data from good to adequate, and had good properties of invariance between both sexes, and between persons who live or not with their partners. It is concluded that the questionnaire has good properties of factor structure and internal consistency, and data refute a model of female victimization.

  14. Riluzole exerts central and peripheral modulating effects in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vucic, Steve; Lin, Cindy Shin-Yi; Cheah, Benjamin C; Murray, Jenna; Menon, Parvathi; Krishnan, Arun V; Kiernan, Matthew C

    2013-05-01

    Riluzole, a benzothiazole derivative, has been shown to be effective in prolonging survival in amyotrophic lateral sclerosis. The mechanisms by which riluzole exerts neuroprotective effects in amyotrophic lateral sclerosis remains to be fully elucidated, although inhibition of glutamatergic transmission and modulation of Na+ channel function have been proposed. In an attempt to determine the mechanisms by which riluzole exerts neuroprotective effects, in particular to dissect the relative contributions of inhibition of glutamatergic transmission and Na+ channel modulation, the present study utilized a combination of cortical and peripheral axonal excitability approaches to monitor changes in excitability and function in patients with amyotrophic lateral sclerosis. Cortical assessment was undertaken by utilising the threshold tracking transcranial magnetic stimulation (TMS) technique and combined with peripheral axonal excitability studies in 25 patients with amyotrophic lateral sclerosis. Studies were performed at baseline and repeated when patients were receiving riluzole 100 mg/day. At the time of second testing all patients were tolerating the medication well. Motor evoked potential and compound muscle action potential responses were recorded over the abductor pollicis brevis muscle. At baseline, features of cortical hyperexcitability were evident in patients with amyotrophic lateral sclerosis, indicated by marked reduction in short interval intracortical inhibition (P amyotrophic lateral sclerosis had significant increases in depolarizing threshold electrotonus [amyotrophic lateral sclerosisbaseline TEd (90-100 ms) 49.1 ± 1.8%; controlsTEd (90-100 ms) 45.2 ± 0.6%, P amyotrophic lateral sclerosisbaseline 30.1 ± 2.3%; control subjects 23.4 ± 1.0%, P amyotrophic lateral sclerosisbaseline 30.1 ± 2.3%; amyotrophic lateral sclerosisON riluzole 27.3 ± 2.3%, P amyotrophic lateral sclerosisbaseline 98.7 ± 10.7%; amyotrophic lateral sclerosisON riluzole 67.8 ± 9

  15. Camphene, a Plant Derived Monoterpene, Exerts Its Hypolipidemic Action by Affecting SREBP-1 and MTP Expression

    Science.gov (United States)

    Vallianou, Ioanna; Hadzopoulou-Cladaras, Margarita

    2016-01-01

    The control of hyperlipidemia plays a central role in cardiovascular disease. Previously, we have shown that camphene, a constituent of mastic gum oil, lowers cholesterol and triglycerides (TG) in the plasma of hyperlipidemic rats without affecting HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. In the present study, we examine the mechanism by which camphene exerts its hypolipidemic action. We evaluated the effect of camphene on the de novo synthesis of cholesterol and TG from [14C]-acetate in HepG2 cells, along with the statin mevinolin. Camphene inhibited the biosynthesis of cholesterol in a concentration-dependent manner, and a maximal inhibition of 39% was observed at 100 μM while mevinolin nearly abolished cholesterol biosynthesis. Moreover, treatment with camphene reduced TG by 34% and increased apolipoprotein AI expression. In contrast, mevinolin increased TG by 26% and had a modest effect on apolipoprotein AI expression. To evaluate the mode of action of camphene, we examined its effects on the expression of SREBP-1, which affects TG biosynthesis and SREBP-2, which mostly affects sterol synthesis. Interestingly, camphene increased the nuclear translocation of the mature form of SREBP-1 while mevinolin was found to increase the amount of the mature form of SREBP-2. The effect of camphene is most likely regulated through SREBP-1 by affecting MTP levels in response to a decrease in the intracellular cholesterol. We propose that camphene upregulates SREBP-1 expression and MTP inhibition is likely to be a probable mechanism whereby camphene exerts its hypolipidemic effect. PMID:26784701

  16. Camphene, a Plant Derived Monoterpene, Exerts Its Hypolipidemic Action by Affecting SREBP-1 and MTP Expression.

    Directory of Open Access Journals (Sweden)

    Ioanna Vallianou

    Full Text Available The control of hyperlipidemia plays a central role in cardiovascular disease. Previously, we have shown that camphene, a constituent of mastic gum oil, lowers cholesterol and triglycerides (TG in the plasma of hyperlipidemic rats without affecting HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. In the present study, we examine the mechanism by which camphene exerts its hypolipidemic action. We evaluated the effect of camphene on the de novo synthesis of cholesterol and TG from [14C]-acetate in HepG2 cells, along with the statin mevinolin. Camphene inhibited the biosynthesis of cholesterol in a concentration-dependent manner, and a maximal inhibition of 39% was observed at 100 μM while mevinolin nearly abolished cholesterol biosynthesis. Moreover, treatment with camphene reduced TG by 34% and increased apolipoprotein AI expression. In contrast, mevinolin increased TG by 26% and had a modest effect on apolipoprotein AI expression. To evaluate the mode of action of camphene, we examined its effects on the expression of SREBP-1, which affects TG biosynthesis and SREBP-2, which mostly affects sterol synthesis. Interestingly, camphene increased the nuclear translocation of the mature form of SREBP-1 while mevinolin was found to increase the amount of the mature form of SREBP-2. The effect of camphene is most likely regulated through SREBP-1 by affecting MTP levels in response to a decrease in the intracellular cholesterol. We propose that camphene upregulates SREBP-1 expression and MTP inhibition is likely to be a probable mechanism whereby camphene exerts its hypolipidemic effect.

  17. A Technique for Establishing True Levels of Muscle Strength Exertion

    Science.gov (United States)

    1980-01-01

    DEV too 40 16.3?4 979.67 2Q.65q 751 40 ze.75 218.44 14.790 502 40 26.85R 207.96 14.421 252 40 19.71? 113.72 10.664 GRANO 160 27.01, !93.46 10.99...4.92Z 10042 GRANO a0 31.189 o6119 16.161 Table 22 - Maintained Level Exertion Component (based upon greatest exertion) ANOVA for Leg Flexion 43 CANDVA...STO DEV tot 40 S6.442 619.91 24.3q 752 40 34e770 195.42 19.685 902 40 30.714 356.41 19.91 252 40 22,028 27907? 16.726 GRANO 160 30.966 436.S4 90.697

  18. Endoscopic Thermal Fasciotomy for Chronic Exertional Compartment Syndrome

    Science.gov (United States)

    Voleti, Pramod B.; Lebrun, Drake G.; Roth, Cameron A.; Kelly, John D.

    2015-01-01

    Chronic exertional compartment syndrome is an activity-induced condition that occurs when intracompartmental pressures within an osteofascial envelope increase during exercise, leading to reversible ischemic symptoms such as pain, cramping, numbness, or weakness. Nonoperative treatment options for this condition have shown limited success and are often undesirable for the patient given the requirement for activity modification. Traditional surgical treatment options involving open or subcutaneous fasciotomies have more favorable results, but these techniques are associated with significant morbidity. Endoscopically assisted fasciotomy techniques afford the advantages of being minimally invasive, providing excellent visualization, and allowing accelerated rehabilitation. The purpose of this article is to describe a technique for performing endoscopically assisted fasciotomies for chronic exertional compartment syndrome of the lower leg using an entirely endoscopic thermal ablating device. The endoscopic thermal fasciotomy technique is associated with minimal morbidity, ensures excellent hemostasis, and affords an early return to sports. PMID:26900549

  19. Cortisol Exerts Bi-Phasic Regulation of Inflammation in Humans

    OpenAIRE

    Yeager, Mark P.; Pioli, Patricia A.; Guyre, Paul M.

    2010-01-01

    Natural and synthetic glucocorticoids (GCs) have been used for decades to suppress inflammation. In this paper, we re-examine the role of the endogenous GC, cortisol, as a primary homeostatic regulator of the human inflammatory response to injury. Our data show that cortisol regulation of innate immunity can be both pro-inflammatory and anti-inflammatory. Using a human model of in vivo cortisol depletion, we first show that baseline (diurnal) cortisol concentrations do not exert an anti-infla...

  20. Phosphodiesterase-5 activity exerts a coronary vasoconstrictor influence in awake swine that is mediated in part via an increase in endothelin production

    NARCIS (Netherlands)

    Z. Zhou (Zhichao); V.J. de Beer (Vincent Jacob); S.B. Bender (Shawn ); A.H.J. Danser (Jan); D. Merkus (Daphne); H. Laughlin (Harold); D.J.G.M. Duncker (Dirk)

    2014-01-01

    textabstractNitric oxide (NO)-induced coronary vasodilation is mediated through production of cyclic guanosine monophosphate (cGMP) and through inhibition of the endothelin-1 (ET) system. We previously demonstrated that phosphodiesterase-5 (PDE5)-mediated cGMP breakdown and ET each exert a vasoconst

  1. The novel combination of chlorpromazine and pentamidine exerts synergistic antiproliferative effects through dual mitotic action.

    Science.gov (United States)

    Lee, Margaret S; Johansen, Lisa; Zhang, Yanzhen; Wilson, Amy; Keegan, Mitchell; Avery, William; Elliott, Peter; Borisy, Alexis A; Keith, Curtis T

    2007-12-01

    Combination therapy has proven successful in treating a wide variety of aggressive human cancers. Historically, combination treatments have been discovered through serendipity or lengthy trials using known anticancer agents with similar indications. We have used combination high-throughput screening to discover the unexpected synergistic combination of an antiparasitic agent, pentamidine, and a phenothiazine antipsychotic, chlorpromazine. This combination, CRx-026, inhibits the growth of tumor cell lines in vivo more effectively than either pentamidine or chlorpromazine alone. Here, we report that CRx-026 exerts its antiproliferative effect through synergistic dual mitotic action. Chlorpromazine is a potent and specific inhibitor of the mitotic kinesin KSP/Eg5 and inhibits tumor cell proliferation through mitotic arrest and accumulation of monopolar spindles. Pentamidine treatment results in chromosomal segregation defects and delayed progression through mitosis, consistent with inhibition of the phosphatase of regenerating liver family of phosphatases. We also show that CRx-026 synergizes in vitro and in vivo with the microtubule-binding agents paclitaxel and vinorelbine. These data support a model where dual action of pentamidine and chlorpromazine in mitosis results in synergistic antitumor effects and show the importance of systematic screening for combinations of targeted agents.

  2. Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain

    Science.gov (United States)

    Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

    2013-01-01

    Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system. PMID:24009718

  3. A virtual rat for simulating environmental and exertional heat stress.

    Science.gov (United States)

    Rakesh, Vineet; Stallings, Jonathan D; Reifman, Jaques

    2014-12-01

    Severe cases of environmental or exertional heat stress can lead to varying degrees of organ dysfunction. To understand heat-injury progression and develop efficient management and mitigation strategies, it is critical to determine the thermal response in susceptible organs under different heat-stress conditions. To this end, we used our previously published virtual rat, which is capable of computing the spatiotemporal temperature distribution in the animal, and extended it to simulate various heat-stress scenarios, including 1) different environmental conditions, 2) exertional heat stress, 3) circadian rhythm effect on the thermal response, and 4) whole body cooling. Our predictions were consistent with published in vivo temperature measurements for all cases, validating our simulations. We observed a differential thermal response in the organs, with the liver experiencing the highest temperatures for all environmental and exertional heat-stress cases. For every 3°C rise in the external temperature from 40 to 46°C, core and organ temperatures increased by ∼0.8°C. Core temperatures increased by 2.6 and 4.1°C for increases in exercise intensity from rest to 75 and 100% of maximal O2 consumption, respectively. We also found differences as large as 0.8°C in organ temperatures for the same heat stress induced at different times during the day. Even after whole body cooling at a relatively low external temperature (1°C for 20 min), average organ temperatures were still elevated by 2.3 to 2.5°C compared with normothermia. These results can be used to optimize experimental protocol designs, reduce the amount of animal experimentation, and design and test improved heat-stress prevention and management strategies.

  4. Pressure garment design tool to monitor exerted pressures.

    Science.gov (United States)

    Macintyre, Lisa; Ferguson, Rhona

    2013-09-01

    Pressure garments are used in the treatment of hypertrophic scarring following serious burns. The use of pressure garments is believed to hasten the maturation process, reduce pruritus associated with immature hypertrophic scars and prevent the formation of contractures over flexor joints. Pressure garments are normally made to measure for individual patients from elastic fabrics and are worn continuously for up to 2 years or until scar maturation. There are 2 methods of constructing pressure garments. The most common method, called the Reduction Factor method, involves reducing the patient's circumferential measurements by a certain percentage. The second method uses the Laplace Law to calculate the dimensions of pressure garments based on the circumferential measurements of the patient and the tension profile of the fabric. The Laplace Law method is complicated to utilise manually and no design tool is currently available to aid this process. This paper presents the development and suggested use of 2 new pressure garment design tools that will aid pressure garment design using the Reduction Factor and Laplace Law methods. Both tools calculate the pressure garment dimensions and the mean pressure that will be exerted around the body at each measurement point. Monitoring the pressures exerted by pressure garments and noting the clinical outcome would enable clinicians to build an understanding of the implications of particular pressures on scar outcome, maturation times and patient compliance rates. Once the optimum pressure for particular treatments is known, the Laplace Law method described in this paper can be used to deliver those average pressures to all patients. This paper also presents the results of a small scale audit of measurements taken for the fabrication of pressure garments in two UK hospitals. This audit highlights the wide range of pressures that are exerted using the Reduction Factor method and that manual pattern 'smoothing' can dramatically

  5. 4-dimethylamino-3',4'-dimethoxychalcone downregulates iNOS expression and exerts anti-inflammatory effects.

    Science.gov (United States)

    Herencia, F; Ferrándiz, M L; Ubeda, A; Guillén, I; Dominguez, J N; Charris, J E; Lobo, G M; Alcaraz, M J

    2001-01-01

    Reactive oxygen and nitrogen species contribute to the pathophysiology of inflammatory conditions. We have studied the effects of a novel superoxide scavenger, 4-dimethylamino-3', 4'-dimethoxychalcone (CH11) in macrophages and in vivo. CH11 has been shown to inhibit the chemiluminescence induced by zymosan in mouse peritoneal macrophages and the cytotoxic effects of superoxide. In the same cells, the modulation by superoxide of nitric oxide (NO) production in response to zymosan was investigated. CH11 was more effective than the membrane-permeable scavenger Tiron for inhibition of inducible nitric oxide synthase (iNOS) protein expression and nitrite production. We have shown that CH11 inhibited chemiluminescence in vivo, as well as cell migration, and eicosanoid and tumor necrosis factor-alpha (TNF-alpha) levels in the mouse air pouch injected with zymosan. This chalcone derivative also exerted anti-inflammatory effects in the carrageenan paw oedema.

  6. Ratings of perceived exertion in adults with chronically physical challenges.

    Science.gov (United States)

    Satonaka, A; Suzuki, N; Kawamura, M

    2012-10-01

    The purposes of this study were to investigate: the relationship between ratings perceived exertion (RPE) and percentage of maximal oxygen uptake (%VO2max) during submaximal exercise; the influence of daily physical activities on RPE; and the influence of aerobic fitness on RPE. The participants were thirty-eight adults with chronically physical challenges. Submaximal exercise testing was conducted to estimate VO2max. The participants themselves declared their perceived exertion just before the end of the exercise testing by indicating the Borg's 6-20 RPE scale. Measurement of continuous heart rates was employed for measurement of the intensity of daily physical activities. The relationship between %VO2max and RPE was analyzed. There was a significant correlation between %VO2max and RPE only in the active men who did daily aerobic physical activities with intensity of 30%HRR and more (N.=9, r=0.74, P=0.02). In the good fitness groups of both women and men, the actual %VO2max in 11 out of 12 participants was lower than the reference value of %VO2max of the RPE while the opposite trend was found in poor aerobic fitness group. Our results recommend that RPE should be used together with objective physiological variables such as HR for assessment of exercise intensity in people with chronically physical challenges, especially who are low in aerobic fitness or who are inactive.

  7. Optimum polygenic profile to resist exertional rhabdomyolysis during a marathon

    Science.gov (United States)

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

    2017-01-01

    Purpose 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). Methods 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 exercise training, might also play a role in the values of CK after damaging exercise. PMID:28257486

  8. Chronic Exertional Compartment Syndrome in a Healthy Young Man.

    Science.gov (United States)

    Joubert, Sonia V; Duarte, Manuel A

    2016-06-01

    The purpose of this case report is to describe a patient who presented with symptoms of exercise-induced compartment syndrome and was later referred for bilateral fasciotomy surgery. A 21-year-old patient presented for chiropractic care with the inability to run due to foot paresthesia and weakness. An exertion test and compartment pressure test diagnosed exercise-induced compartment syndrome. Exertion test and compartment pressure test were used to identify and diagnose exercise-induced compartment syndrome. The patient was diagnosed with exercise-induced compartment syndrome. He was treated conservatively and referred for additional testing. The orthopedic surgeon requested that 12 weeks of conservative care be provided prior to testing; treatment consisted of chiropractic care and rehabilitation exercises. Following the 12 weeks of treatment, the patient did not significantly respond to conservative care. A compartment pressure test confirmed the initial diagnosis of exercise-induced compartment syndrome. The patient underwent a unilateral fasciotomy surgery and recovered fully. Following the surgery, the patient returned to the chiropractic clinic with the same presentation in the contralateral leg. The same protocol of management resulted in the same outcome. Two years after surgical intervention, the patient continues to maintain an active lifestyle, able to run 2 to 3 miles per day without any exacerbations or symptomatology. Clinical awareness, a detailed history, and thorough examination with reproduction of symptomatology are necessary to form a proper diagnosis and treatment plan for these patients. Therefore, multidisciplinary medical communication would prove to be the most beneficial approach for the patient.

  9. NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

    Directory of Open Access Journals (Sweden)

    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.

  10. Acteoside Binds to Caspase-3 and Exerts Neuroprotection in the Rotenone Rat Model of Parkinson's Disease

    Science.gov (United States)

    Wang, Ying; He, Xiao; Zhao, Yuwu

    2016-01-01

    Parkinson’s disease (PD) is characterized by the progressive degeneration of the dopaminergic neurons in the substantia nigra (SN) region. Acteoside has displayed multiple biological functions. Its potential role against PD and the underlying signaling mechanisms are largely unknown. Here, we showed that oral administration of acteoside significantly attenuated parkinsonism symptoms in rotenone-induced PD rats. Further, acteoside inhibited rotenone-induced α-synuclein, caspase-3 upregulation and microtubule-associated protein 2 (MAP2) downregulation in PD rats. The molecular docking and molecular dynamics (MD) simulation results indicated that acteoside may directly bind to and inhibit caspase-3. Acteoside formed hydrogen bonds with at least six residues of caspase-3: ThrA177, SerA178, GlyA238, SerB339, ArgB341 and TrpB348. In addition, a pi-pi interaction was formed between acteoside and caspase-3’s HisA237, which might further stabilize the complex. MD simulation results demonstrated that the binding affinity of the caspase-3-acteoside complex was higher than that of caspase-3 and its native ligand inhibitor. Together, we show that acteoside binds to caspase-3 and exerts neuroprotection in the rotenone rat model of PD. PMID:27632381

  11. Methylprednisolone exerts neuroprotective effects by regulating autophagy and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Wei Gao; Shu-rui Chen; Meng-yao Wu; Kai Gao; Yuan-long Li; Hong-yu Wang; Chen-yuan Li; Hong Li

    2016-01-01

    Methylprednisolone markedly reduces autophagy and apoptosis after secondary spinal cord injury. Here, we investigated whether pretreat-ment of cells with methylprednisolone would protect neuron-like cells from subsequent oxidative damagevia suppression of autophagy and apoptosis. Cultured N2a cells were pretreated with 10 µM methylprednisolone for 30 minutes, then exposed to 100 µM H2O2 for 24 hours. Inverted phase contrast microscope images, MTT assay, lfow cytometry and western blot results showed that, compared to cells ex-posed to 100 µM H2O2 alone, cells pretreated with methylprednisolone had a signiifcantly lower percentage of apoptotic cells, maintained a healthy morphology, and showed downregulation of autophagic protein light chain 3B and Beclin-1 protein expression. These ifndings indicate that methylprednisolone exerted neuroprotective effects against oxidative damage by suppressing autophagy and apoptosis.

  12. Spinal cord stimulation exerts neuroprotective effects against experimental Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Aiko Shinko

    Full Text Available In clinical practice, deep brain stimulation (DBS is effective for treatment of motor symptoms in Parkinson's disease (PD. However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS. We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the

  13. The use of subjective rating of exertion in Ergonomics.

    Science.gov (United States)

    Capodaglio, P

    2002-01-01

    In Ergonomics, the use of psychophysical methods for subjectively evaluating work tasks and determining acceptable loads has become more common. Daily activities at the work site are studied not only with physiological methods but also with perceptual estimation and production methods. The psychophysical methods are of special interest in field studies of short-term work tasks for which valid physiological measurements are difficult to obtain. The perceived exertion, difficulty and fatigue that a person experiences in a certain work situation is an important sign of a real or objective load. Measurement of the physical load with physiological parameters is not sufficient since it does not take into consideration the particular difficulty of the performance or the capacity of the individual. It is often difficult from technical and biomechanical analyses to understand the seriousness of a difficulty that a person experiences. Physiological determinations give important information, but they may be insufficient due to the technical problems in obtaining relevant but simple measurements for short-term activities or activities involving special movement patterns. Perceptual estimations using Borg's scales give important information because the severity of a task's difficulty depends on the individual doing the work. Observation is the most simple and used means to assess job demands. Other evaluations integrating observation are the followings: indirect estimation of energy expenditure based on prediction equations or direct measurement of oxygen consumption; measurements of forces, angles and biomechanical parameters; measurements of physiological and neurophysiological parameters during tasks. It is recommended that determinations of performances of occupational activities assess rating of perceived exertion and integrate these measurements of intensity levels with those of activity's type, duration and frequency. A better estimate of the degree of physical activity

  14. Physiological responses and perceived exertion during cycling with superimposed electromyostimulation.

    Science.gov (United States)

    Wahl, Patrick; Schaerk, Jonas; Achtzehn, Silvia; Kleinöder, Heinz; Bloch, Wilhelm; Mester, Joachim

    2012-09-01

    The goal of the study was to evaluate and to quantify the effects of local electromyostimulation (EMS) during cycling on the cardiorespiratory system, muscle metabolism, and perceived exertion compared with cycling with no EMS. Ten healthy men (age: 24.6 ± 3.2 years, V[Combining Dot Above]O2max: 54.1 ± 6.0 ml·min·kg) performed 3 incremental cycle ergometer step tests, 1 without and 2 with EMS (30 and 85 Hz) until volitional exhaustion. Lactate values and respiratory exchange ratio were significantly higher at intensities ≥75% peak power output (PPO) when EMS was applied. Bicarbonate concentration, base excess (BE), and Pco2 were significantly lower when EMS was applied compared with the control at intensities ≥75% PPO. Saliva cortisol levels increased because of the exercise but were unaffected by EMS. Furthermore, EMS showed greater effects on CK levels 24 hours postexercise than normal cycling did. Rating of perceived exertion was significantly higher at 100% PPO with EMS. No statistical differences were found for heart rate, pH, and Po2 between the tested cycling modes. The main findings of this study are greater metabolic changes (lactate, respiratory exchange ratio, BE, (Equation is included in full-text article.), Pco2) during cycling with EMS compared with normal cycling independent of frequency, mainly visible at higher work rates. Because metabolic alterations are important for the induction of cellular signaling cascades and adaptations, these results lead to the hypothesis that applied EMS stimulations during cycling exercise might be an enhancing stimulus for skeletal muscle metabolism and related adaptations. Thus, superimposed EMS application during cycling could be beneficial to aerobic performance enhancements in athletes and in patients who cannot perform high workloads. However, the higher demand on skeletal muscles involved must be considered.

  15. Self-regulation, ego depletion, and inhibition.

    Science.gov (United States)

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it.

  16. 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

  17. 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.

  18. Licochalcone A exerts antitumor activity in bladder cancer cell lines ...

    African Journals Online (AJOL)

    Abstract. Purpose: To investigate the effect of licochalcone A (LA) on the inhibition of cell proliferation and ... Dye-binding method was used to examine the concentration of ... Flow cytometry was used to measure cellular ... treatment for advanced renal cancers is sunitinib ... from the Laboratory Animal Center, Third Military.

  19. Focus on therapy of the Chapter IV headaches provoked by exertional factors: primary cough headache, primary exertional headache and primary headache associated with sexual activity

    OpenAIRE

    Allena, Marta; Rossi, Paolo; Tassorelli, Cristina; Ferrante, Enrico; Lisotto, Carlo; Nappi, Giuseppe

    2010-01-01

    Primary cough headache, primary exertional headache and primary headache associated with sexual activity are distinct entities, even though they share several features: acute onset, the absence of structural brain disease and exertional factors as precipitating events. In this short review, we illustrate the possible treatment strategies on the basis of information collected from a systematic analysis of the international literature.

  20. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-07-01

    Full Text Available Astaxanthin (ATX is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and peroxisome proliferator-activated receptor gamma (PPARγ. Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  1. Dynamic respiratory mechanics and exertional dyspnoea in pulmonary arterial hypertension.

    Science.gov (United States)

    Laveneziana, Pierantonio; Garcia, Gilles; Joureau, Barbara; Nicolas-Jilwan, Fadia; Brahimi, Toufik; Laviolette, Louis; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc; Similowski, Thomas

    2013-03-01

    Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea.

  2. Chronic exertional compartment syndrome of the forearm in adolescents.

    Science.gov (United States)

    García-Mata, Serafín

    2013-12-01

    Chronic exertional compartment syndrome (CECS) is a well-known process, although rare in the forearm. The diagnosis is based on history, clinical examination, and compartment pressure readings. My objective is to present the largest series of CECS of the forearm in adolescents and describe my experience in its management and evolution. I reviewed 5 patients, 4 male (competing in motorcycling or motocross) and 1 female (CECS in both the legs and forearms), aged between 15 and 18 years. Volar and dorsal compartments were affected in 3 patients and isolated volar in 2 cases. The clinical diagnosis was objectively confirmed by measuring ICP with a low-pressure digital transducer (Stryker). Open fasciotomy was carried out in 4 patients. They resumed their athletic activities 6 weeks after surgery without complications, increasing their athletic performance level in line with their preoperative status. All these patients remained asymptomatic, recovering their previous competitive levels. The results were objectively classified as excellent in all 4 cases. After a mean follow-up of 6 years, the condition has not relapsed in any of the patients. Two of the patients agreed to a new ICP measurement 1 year after the surgery, showing normal values. CECS in the forearm in adolescents is a rare condition that occurs after puberty. A high index of suspicion is necessary to diagnose it. It is based on symptoms and ICP measurements. Most patients are competing motorcyclists. Surgical treatment, involving isolated decompression of the superficial volar compartment, is safe and effective (restoring normal ICP).

  3. Formwork pressure exerted by self-consolidating concrete

    Science.gov (United States)

    Omran, Ahmed Fathy

    Self-consolidating concrete (SCC) is an emerging technology that utilizes flowable concrete that eliminates the need for consolidation. The advantages of SCC lie in a remarkable reduction of the casting time, facilitating the casting of congested and complex structural elements, possibility to reduce labor demand, elimination of mechanical vibrations and noise, improvement of surface appearance, producing a better and premium concrete product. The research focussed on capturing existing knowledge and making recommendations for current practice. An experimental program was undertaken at the Universite de Sherbrooke to evaluate the lateral pressure developed by SCC mixtures. A portable devise (UofS2 pressure column) for measuring and predicting lateral pressure and its rate of decay of SCC was developed and validated. The UofS2 pressure column is cast with 0.5 m high fresh concrete and air pressure is introduced from the top to simulate casting depth up to 13 m. Then, develop and implement test method for field evaluation of relevant plastic and thixotropic properties of SCC that affect formwork pressure were done. Portable vane (PV) test based on the hand-held vane test method used to determine the undrained shear strength property of clay soil was the first setup as well as the inclined plane (IP) test. The IP device involves slumping a small concrete cylinder on a horizontal plate and then lifting up the plate at different durations of rest until the slumped sample starts to move. Identifying role of material constituents, mix design, concrete placement characteristics (casting rate, waiting periods between lifts, and casting depth), temperature, and formwork characteristics that have major influence on formwork pressure exerted by SCC were evaluated in laboratory and validated by actual field measurements. Relating the maximum lateral pressure and its rate of decay to the plastic properties of SCC were established. In the analytical part of the research

  4. HER Specific TKIs Exert Their Antineoplastic Effects on Breast Cancer Cell Lines through the Involvement of STAT5 and JNK.

    Directory of Open Access Journals (Sweden)

    Daphne Gschwantler-Kaulich

    Full Text Available HER-targeted tyrosine kinase inhibitors (TKIs have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood.Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP-1 and immunolabeling for active caspase 3, respectively.All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively.We have shown that HER-TKIs exert a HER2 expression-dependent anti-cancer effect in breast cancer cell lines. This involves blockade of JNK and STAT5A/B signaling, which have been found to be required for in vitro growth of these cell lines.

  5. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

    OpenAIRE

    Oláh, Attila; Tóth, Balázs I.; Borbíró, István; Sugawara, Koji; Szöllõsi, Attila G.; Czifra, Gabriella; Pál, Balázs; Ambrus, Lídia; Kloepper, Jennifer; Camera, Emanuela; Ludovici, Matteo; Picardo, Mauro; Voets, Thomas; Zouboulis, Christos C.; Paus, Ralf

    2014-01-01

    The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including...

  6. Relationship between perceived exertion during exercise and subsequent recovery measurements

    Directory of Open Access Journals (Sweden)

    TN Mann

    2016-12-01

    Full Text Available The return towards resting homeostasis in the post-exercise period has the potential to represent the internal training load of the preceding exercise bout. However, the relative potential of metabolic and autonomic recovery measurements in this role has not previously been established. Therefore the aim of this study was to investigate which of 4 recovery measurements was most closely associated with Borg’s Rating of Perceived Exertion (RPE, a measurement widely acknowledged as an integrated measurement of the homeostatic stress of an exercise bout. A heterogeneous group of trained and untrained participants (n = 36 completed a bout of exercise on the treadmill (3 km at 70% of maximal oxygen uptake followed by 1 hour of controlled recovery. Expired respiratory gases and heart rate (HR were measured throughout the exercise and recovery phases of the trial with recovery measurements used to calculate the magnitude of excess post-exercise oxygen consumption (EPOCMAG, the time constant of the EPOC curve (EPOCτ, 1 min heart rate recovery (HRR60s and the time constant of the HR recovery curve (HRRτ for each participant. RPE taken in the last minute of exercise was significantly associated with HRR60s (r=-0.69, EPOCτ (r=0.52 and HRRτ (r=0.43 but not with EPOCMAG. This finding suggests that, of the 4 recovery measurements under investigation, HRR60s shows modest potential to represent inter-individual variation in the homeostatic stress of a standardized exercise bout, in a group with a range of fitness levels.

  7. Outcomes of exertional rhabdomyolysis following high-intensity resistance training.

    Science.gov (United States)

    Huynh, A; Leong, K; Jones, N; Crump, N; Russell, D; Anderson, M; Steinfort, D; Johnson, D F

    2016-05-01

    High-intensity resistance training (HIRT) programmes are increasingly popular amongst personal trainers and those attending gymnasiums. We report the experience of exertional rhabdomyolysis (ER) at two tertiary hospitals in Melbourne, Australia. To compare the clinical outcomes of ER with other causes of rhabdomyolysis. Retrospective cross-sectional study of patients presenting with a serum creatine kinase (CK) of greater than 25 000 units/L from 1 September 2013 to 31 August 2014 at two tertiary referral hospitals in Melbourne, Australia. Records were examined to identify care measures implemented during hospital stay, clinical outcomes during admission and on subsequent follow up. Thirty four cases of rhabdomyolysis with a CK of greater than 25 000 units/L (normal range: 20-180 units/L) were identified during the 12-month study period. Twelve of the 34 cases (35%) had ER with 10 of 12 related to HIRT. No acute kidney injury, intensive care admission or death were seen among those with ER. All cases were managed conservatively, with 11 admitted and 9 receiving intravenous fluids only. In contrast, patients with rhabdomyolysis from other causes experienced significantly higher rates of intensive care admission (64%, P = 0.0002), acute kidney injury (82%, P = 0.0001) and death (27%, P = 0.069). ER resulting from HIRT appears to have a benign course compared with rhabdomyolysis of other aetiologies in patients with a serum CK greater than 25 000 units/L. Conservative management of ER appears to be adequate, although this requires confirmation in future prospective studies. © 2016 Royal Australasian College of Physicians.

  8. Physiological and Perceived Exertion Responses during International Karate Kumite Competition

    Science.gov (United States)

    Tabben, Montassar; Sioud, Rim; Haddad, Monoem; Franchini, Emerson; Chaouachi, Anis; Coquart, Jeremy; Chaabane, Helmi; Chamari, Karim; Tourny-Chollet, Claire

    2013-01-01

    Purpose Investigate the physiological responses and rating of perceived exertion (RPE) in elite karate athletes and examine the relationship between a subjective method (Session-RPE) and two objective heart-rate (HR)-based methods to quantify training-load (TL) during international karate competition. Methods Eleven karatekas took part in this study, but only data from seven athletes who completed three matches in an international tournament were used (four men and three women). The duration of combat was 3 min for men and 2 min for women, with 33.6±7.6 min for the first interval period (match 1–2) and 14.5±3.1 min for the second interval period (match 2–3). HR was continuously recorded during each combat. Blood lactate [La-] and (RPE) were measured just before the first match and immediately after each match. Results Means total fights time, HR, %HRmax, [La-], and session-RPE were 4.7±1.6 min, 182±9 bpm, 91±3%, 9.02±2.12 mmol.L-1 and 4.2±1.2, respectively. No significant differences in %HRmax, [La-], and RPE were noticed across combats. Significant correlations were observed between RPE and both resting HR (r=0.60; P=0.004) and mean HR (r=0.64; P=0.02), session-RPE and Banister training-impulse (TRIMP) (r=0.84; Pkarate competition elicited near-maximal cardiovascular responses and high [La-]. Training should therefore include exercise bouts that sufficiently stimulate the zone between 90 and 100% HRmax. Karate coaches could use the RPE-method to follow competitor's competition loads and consider it in their technical and tactical training. PMID:24800001

  9. Isolated Chronic Exertional Compartment Syndrome of the Lateral Lower Leg

    Science.gov (United States)

    van Zantvoort, Aniek P.M.; de Bruijn, Johan A.; Winkes, Michiel B.; Dielemans, Jeanne P.; van der Cruijsen-Raaijmakers, Marike; Hoogeveen, Adwin R.; Scheltinga, Marc R.

    2015-01-01

    Background: Exercise-induced lower leg pain may be caused by chronic exertional compartment syndrome (CECS). The anterior (ant-CECS) or deep posterior compartment (dp-CECS) is usually affected. Knowledge regarding CECS of the lateral compartment (lat-CECS) is limited. Purpose: To describe demographic characteristics and symptoms in a consecutive series of patients with isolated CECS of the lateral compartment of the leg. Study Design: Case series; Level of evidence, 4. Methods: Since 2001, patients undergoing dynamic intracompartmental pressure (ICP) measurements for suspected CECS in a single institution were prospectively monitored. Individuals with a history possibly associated with lat-CECS and elevated ICP measurements (Pedowitz criteria) were identified. Exclusion criteria were concomitant ipsilateral ant-CECS/dp-CECS, acute compartment syndrome, recent significant trauma, peroneal nerve entrapment, or vascular claudication. Results: During an 11-year time period, a total of 26 patients with isolated lat-CECS fulfilled study criteria (15 females; median age, 21 years; range, 14-48 years). Frequently identified provocative sports were running (n = 4), walking (n = 4), field hockey (n = 3), soccer (n = 3), and volleyball (n = 2). Exercise-induced lateral lower leg pain (92%) and tightness (42%) were often reported. The syndrome was bilateral in almost two-thirds (62%, n = 16). Delay in diagnosis averaged 24 months (range, 2 months to 10 years). Conclusion: Young patients with exercise-induced pain in the lateral portions of the lower leg may suffer from isolated CECS of the lateral compartment. ICP measurements in the lateral compartment in these patients are recommended. PMID:26740955

  10. Galectin-1 exerts inhibitory effects during DENV-1 infection.

    Directory of Open Access Journals (Sweden)

    Karina Alves Toledo

    Full Text Available Dengue virus (DENV is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1, we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1 inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.

  11. Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

    Science.gov (United States)

    Gavioli, Mariana; Lara, Aline; Almeida, Pedro W. M.; Lima, Augusto Martins; Damasceno, Denis D.; Rocha-Resende, Cibele; Ladeira, Marina; Resende, Rodrigo R.; Martinelli, Patricia M.; Melo, Marcos Barrouin; Brum, Patricia C.; Fontes, Marco Antonio Peliky; Souza Santos, Robson A.; Prado, Marco A. M.; Guatimosim, Silvia

    2014-01-01

    Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the α2A/α2C-adrenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease. PMID:24992197

  12. Cholinergic signaling exerts protective effects in models of sympathetic hyperactivity-induced cardiac dysfunction.

    Directory of Open Access Journals (Sweden)

    Mariana Gavioli

    Full Text Available Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO, and ii the α2A/α2C-adrenergic receptor knockout (KO mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease.

  13. Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development

    Science.gov (United States)

    Peltz, Lindsay; Gomez, Jessica; Marquez, Maribel; Alencastro, Frances; Atashpanjeh, Negar; Quang, Tara; Bach, Thuy; Zhao, Yuanxiang

    2012-01-01

    Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs. PMID:22615926

  14. Nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number.

    Science.gov (United States)

    Targoff, Kimara L; Schell, Thomas; Yelon, Deborah

    2008-10-15

    Heart formation is a complex morphogenetic process, and perturbations in cardiac morphogenesis lead to congenital heart disease. NKX2-5 is a key causative gene associated with cardiac birth defects, presumably because of its essential roles during the early steps of cardiogenesis. Previous studies in model organisms implicate NKX2-5 homologs in numerous processes, including cardiac progenitor specification, progenitor proliferation, and chamber morphogenesis. By inhibiting function of the zebrafish NKX2-5 homologs, nkx2.5 and nkx2.7, we show that nkx genes are essential to establish the original dimensions of the linear heart tube. The nkx-deficient heart tube fails to elongate normally: its ventricular portion is atypically short and wide, and its atrial portion is disorganized and sprawling. This atrial phenotype is associated with a surplus of atrial cardiomyocytes, whereas ventricular cell number is normal at this stage. However, ventricular cell number is decreased in nkx-deficient embryos later in development, when cardiac chambers are emerging. Thus, we conclude that nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number. Our data suggest that morphogenetic errors could originate during early stages of heart tube assembly in patients with NKX2-5 mutations.

  15. Oral administration of Brazilian propolis exerts estrogenic effect in ovariectomized rats.

    Science.gov (United States)

    Okamoto, Yoshinori; Tobe, Takao; Ueda, Koji; Takada, Tatsuyuki; Kojima, Nakao

    2015-04-01

    Propolis, a natural product derived from plants by honeybees, is a mixture of several hundred chemicals, including flavonoids, coumaric acids, and caffeic acids, some of which show estrogen-like activity. In this study, the estrogenic activity of crude ethanolic extract of Brazilian propolis was determined using several in vitro and in vivo assays. Propolis was found to bind to human estrogen receptors (ERs). Furthermore, propolis induced the expression of estrogen-responsive genes in ER-positive MCF-7 and Ishikawa cells. These in vitro assays suggest that propolis exerts estrogenic activity; therefore, in vivo experiments were conducted using ovariectomized rats. Oral administration of propolis (55 or 550 mg/kg/day for 3 days) significantly increased uterine wet weight and luminal epithelium thickness in comparison with the corresponding values in the corn oil-treated control group. Moreover, propolis induced ductal cell proliferation in the mammary glands. These effects were completely inhibited by full ER antagonist ICI 182,780, confirming that the effects of propolis are mediated by the ER. Our data show that oral intake of propolis induces estrogenic activity in ER-expressing organs in vivo and suggest that Brazilian propolis is a useful dietary source of phytoestrogens and a promising treatment for postmenopausal symptoms.

  16. Bilirubin exerts pro-angiogenic property through Akt-eNOS-dependent pathway.

    Science.gov (United States)

    Ikeda, Yasumasa; Hamano, Hirofumi; Satoh, Akiho; Horinouchi, Yuya; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Ishizawa, Keisuke; Aihara, Ken-Ichi; Tsuchiya, Koichiro; Tamaki, Toshiaki

    2015-11-01

    Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner.

  17. Plumbagin exerts an immunosuppressive effect on human T-cell acute lymphoblastic leukemia MOLT-4 cells

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyoung Jun; Lee, Yura [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of); Kim, Soon Ae [Department of Pharmacology, School of Medicine, Daejeon 34824 (Korea, Republic of); Kim, Jiyeon, E-mail: yeon@eulji.ac.kr [Department of Biomedical Laboratory Science, Daejeon 34824 (Korea, Republic of)

    2016-04-22

    Of the hematological disorders typified by poor prognoses and survival rates, T-cell acute lymphoblastic leukemia (T-ALL) is one of the most commonly diagnosed. Despite the development of new therapeutic agents, the treatment options for this cancer remain limited. In this manuscript, we investigated the anti-proliferative effects of plumbagin, mediated by the activation of mitogen-activated protein kinase (MAPK) pathways, and inhibition of NF-κB signaling; the human T-ALL MOLT-4 cell line was used as our experimental system. Plumbagin is a natural, plant derived compound, which exerts an anti-proliferative activity against many types of human cancer. Our experiments confirm that plumbagin induces a caspase-dependent apoptosis of MOLT-4 cells, with no significant cytotoxicity seen for normal peripheral blood mononuclear cells (PBMCs). Plumbagin also inhibited LPS-induced phosphorylation of p65, and the transcription of NF-κB target genes. Our results now show that plumbagin is a potent inhibitor of the NF-κB signaling pathway, and suppressor of T-ALL cell proliferation. - Highlights: • Plumbagin induces caspase-dependent apoptosis in T-ALL MOLT-4 cells. • Plumbagin activates phosphorylation of stress-activated protein kinase (SAPK) JNK and p38. • Plumbagin inhibits LPS-mediated NF-κB signaling cascade. • Plumbagin inhibits LPS-mediated transcriptional activity of pro-inflammatory cytokines.

  18. Se- and s-based thiouracil and methimazole analogues exert different inhibitory mechanisms on type 1 and type 2 deiodinases.

    Science.gov (United States)

    Rijntjes, Eddy; Scholz, Philip Moritz; Mugesh, Govindasamy; Köhrle, Josef

    2013-12-01

    The thioamide anti-thyroid drugs methimazole (MMI) and propylthiouracil (PTU) play a pivotal role in the treatment of hyperthyroidism. MMI exerts its effect via inhibiting one of the key enzymes involved in synthesis of thyroid hormones (TH), thyroid peroxidase (TPO). PTU is both an inhibitor of TPO and type 1 deiodinase (D1), which catalyzes TH deiodination at both aromatic rings. In contrast, no selective inhibitors are known for type 2 deiodinase (D2) or type 3 deiodinase, which deiodinate TH at the phenolic or tyrosyl ring, respectively. We aimed to identify specific inhibitors for D1 or D2. New Se- and S-based PTU and MMI-like compounds have been generated. The D1 and D2 inhibiting capacity of several compounds was tested in vitro. Our data show that compounds based on a PTU and MMI backbone can differentially influence the reaction kinetics of deiodinases. For inhibition of D1, the addition of a phenyl group to the PTU backbone increases potency by at least 10-fold over PTU. For inhibition of D2, the addition of an aromatic ring structure to MMI and its Se isomer increases inhibitory potency by an order of magnitude. Furthermore, S-methylation of the MMI changes its reaction kinetics from non-competitive to uncompetitive with respect to the cofactor dithiothreitol. These results open perspectives for further investigations on identifying specific inhibitors of the deiodinase isoenzymes, potentially based on the addition of aromatic ring structures or alkyl groups to PTU and MMI.

  19. Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus.

    Science.gov (United States)

    Feduchi, E; Alonso, M A; Carrasco, L

    1989-03-01

    The replication of herpes simplex virus type 1 (HSV-1) is not inhibited in either HeLa or HEp-2 cells treated with human alpha interferon (HuIFN-alpha), particularly when high multiplicities of infection are used. However, HuIFN-gamma partially inhibits HSV-1 translation in HEp-2 cells infected at low multiplicities. Under these conditions, the transcription of genes alpha 22, TK, and gamma 0 is greatly diminished. The combined addition of human tumor necrosis factor (TNF) and HuIFN-gamma to HEp-2 cells exerts a synergistic inhibition of HSV-1 translation. Cells treated with both cytokines continue synthesizing cellular proteins, even 20 h after HSV-1 infection. As little as 10 U of IFN-gamma per ml blocked HSV-1 DNA replication, provided that TNF was also present in the medium. Analyses of HSV-1 gene transcription suggest that the action of both TNF and IFN-gamma blocked a step that comes at or prior to early HSV-1 gene expression. This early step in HSV-1 replication inhibited by TNF and IFN-gamma occurs after virus attachment and entry into cells, since the internalization of radioactive HSV-1 virion particles was not blocked by the presence of the two cytokines. Therefore, we conclude that the synergistic action of TNF plus IFN-gamma affects a step in HSV-1 replication that comes after virus entry but before or at the transcription of immediate-early genes.

  20. Penduliflaworosin, a Diterpenoid from Croton crassifolius, Exerts Anti-Angiogenic Effect via VEGF Receptor-2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yeyin Liang

    2017-01-01

    Full Text Available Anti-angiogenesis targeting vascular endothelial growth factor receptor-2 (VEGFR-2 has been considered as an important strategy for cancer therapy. Penduliflaworosin is a diterpenoid isolated from the plant Croton crassifolius. Our previous study showed that this diterpenoid possesses strong anti-angiogenic activity by inhibiting vessel formation in zebrafish. This study was conducted to further investigate the anti-angiogenic activity and mechanism of penduliflaworosin. Results revealed that penduliflaworosin significantly inhibited VEGF-induced angiogenesis processes including proliferation, invasion, migration, and tube formation of human umbilical vein endothelial cells (HUVECs. Moreover, it notably inhibited VEGF-induced sprout formation of aortic rings and blocked VEGF-induced vessel formation in mice. Western blotting studies showed that penduliflaworosin inhibited phosphorylation of the VEGF receptor-2 and its downstream signaling mediators in HUVECs, suggesting that the anti-angiogenic activity was due to an interference with the VEGF/VEGF receptor-2 pathway. In addition, molecular docking simulation indicated that penduliflaworosin could form hydrogen bonds within the ATP-binding region of the VEGF receptor-2 kinase unit. Finally, cytotoxicity assay showed that penduliflaworosin possessed little toxicity toward both cancer and normal cells. Taken together, our findings demonstrate that penduliflaworosin exerts its anti-angiogenic effect via the VEGF receptor-2 signaling pathway. The anti-angiogenic property and low cytotoxicity of penduliflaworosin suggest that it may be useful in cancer treatments.

  1. VALIDATION OF ADULT OMNI PERCEIVED EXERTION SCALES FOR ELLIPTICAL ERGOMETRY12

    Science.gov (United States)

    MAYS, RYAN J.; GOSS, FREDRIC L.; SCHAFER, MARK A.; KIM, KEVIN H.; NAGLE-STILLEY, ELIZABETH F.; ROBERTSON, ROBERT J.

    2012-01-01

    Summary This investigation examined the validity of newly developed Adult OMNI Elliptical Ergometer Ratings of Perceived Exertion Scales. Sixty men and women performed a graded exercise test on an elliptical ergometer. Oxygen consumption (VO2), heart rate (HR) and ratings of perceived exertion were recorded each stage from the Borg 15 Category Scale and two different OMNI scales. One scale employed an elliptical ergometer format of the OMNI Picture System of Perceived Exertion. The second scale modified verbal, numerical, and pictorial descriptors at the low end of the response range. Concurrent and construct validity were established by the positive relation between ratings of perceived exertion from each OMNI scale with VO2, HR and Borg Scale ratings of perceived exertion (men, r = .94–.97; women, r = .93–.98). Validity was established for both OMNI scales, indicating either metric can be used to estimate ratings of perceived exertion during partial weight bearing exercise. PMID:21319623

  2. Surgical Treatment of Chronic Exertional Compartment Syndrome in Pediatric Patients.

    Science.gov (United States)

    Beck, Jennifer J; Tepolt, Frances A; Miller, Patricia E; Micheli, Lyle J; Kocher, Mininder S

    2016-10-01

    Chronic exertional compartment syndrome (CECS) is a cause of leg pain in running athletes and is treated with fasciotomy after failure of nonoperative management. CECS is being seen with increased frequency in younger patients. The demographics and outcomes of fasciotomy for CECS in pediatric patients, including risk factors for treatment failure, have not been described. To describe characteristics of pediatric patients with CECS and determine surgical outcomes of the condition in this population. Case series; Level of evidence, 4. A retrospective review was performed for patients 18 years and younger treated surgically for CECS with compartment release at a single institution from 1995 to 2014. Demographic and condition characteristics, operative procedure, postoperative course, and clinical outcomes were recorded for 286 legs of 155 patients. Compartment pressure testing using the Pedowitz criteria confirmed the diagnosis in all patients. A total of 155 patients were included in the study (average patient age at presentation, 16.4 ± 1.38 years); 136 (88%) were female. All 155 patients presented with leg pain; of these patients, 8 (5%) also had neurologic symptoms, and 131 (85%) presented with bilateral symptoms requiring bilateral compartment release. Symptoms were chronic in nature, with duration over 1 year in 63% of patients. The primary sport was most commonly reported as running (25%), soccer (23%), or field hockey (12%); 50% of patients were multisport athletes. Of 286 legs, 138 (48%) had only anterior and/or lateral compartments released, while 84 (29.4%) had all 4 compartments released. Documented return to sport was seen in 79.5% of patients. Outcomes analysis was performed for 250 of 286 legs. Of these 250 legs, 47 (18.8%) had recurrent CECS requiring reoperation at a median of 1.3 years (interquartile range, 0.8-3.5) after initial compartment release. For each additional month between presentation and release, the odds of recurrence decreased by 12

  3. Do severe systemic sequelae of proteinuria modulate the antiproteinuric response to chronic ACE inhibition?

    NARCIS (Netherlands)

    Bos, H; Henning, RH; de Jong, PE; de Zeeuw, D; Navis, G

    2002-01-01

    Background. ACE inhibition exerts an antiproteinuric and renoprotective effect. However, residual proteinuria is often present. As residual proteinuria is associated with a poor renal outcome, identification of its determinants is important. We found previously that the systemic sequelae of proteinu

  4. Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

    Science.gov (United States)

    Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

    2015-11-01

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies.

  5. Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy

    DEFF Research Database (Denmark)

    Fiocca, R; Mastracci, L; Attwood, S E;

    2012-01-01

    Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals.......Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals....

  6. Dynamics of Perceived Exertion in Constant-Power Cycling: Time- and Workload-Dependent Thresholds

    Science.gov (United States)

    Balagué, Natàlia; Hristovski, Robert; García, Sergi; Aguirre, Cecilia; Vázquez, Pablo; Razon, Selen; Tenenbaum, Gershon

    2015-01-01

    Purpose: The purpose of this study was to test the dynamics of perceived exertion shifts (PES) as a function of time and workload during constant-power cycling. Method: Fifty-two participants assigned to 4 groups performed a cycling task at 4 different constant workloads corresponding to their individual rates of perceived exertion (RPEs = 13, 15,…

  7. Self-Regulating Cycling Using the Children's OMNI Scale of Perceived Exertion.

    Science.gov (United States)

    Robertson, Robert J.; Goss, Fredric L.; Bell, Jill A.; Dixon, Curt B.; Gallagher, Kara I.; Lagally, Kristen M.; Timmer, Jeffrey M.; Abt, Kristie L.; Gallagher, Jere D.; Thompkins, Taylor

    2002-01-01

    Investigated whether normal children could self-regulate intermittent cycle ergometer exercise using a prescribed target rating of perceived exertion (RPE), discriminate between target RPEs, and produce intermittent target RPEs in ascending and descending sequences. RPE was estimated using the Children's OMNI Scale of Perceived Exertion. Overall,…

  8. Fatigue induced by physical and mental exertion increases perception of effort and impairs subsequent endurance performance

    Directory of Open Access Journals (Sweden)

    Benjamin Pageaux

    2016-11-01

    Full Text Available Endurance performance involves the prolonged maintenance of constant or self-regulated power/velocity or torque/force. While the impact of numerous determinants of endurance performance has been previously reviewed, the impact of fatigue on subsequent endurance performance still needs to be documented. This review aims to present the impact of fatigue induced by physical or mental exertion on subsequent endurance performance. For the purpose of this review, endurance performance refers to performance during whole-body or single-joint endurance exercise soliciting mainly the aerobic energy system. First, the impact of physical and mental exertion on force production capacity is presented, with specific emphasize on the fact that solely physical exertion and not mental exertion induces a decrease in force production capacity of the working muscles. Then, the negative impact of fatigue induced by physical exertion and mental exertion on subsequent endurance performance is highlighted based on experimental data. Perception of effort being identified as the variable altered by both prior physical exertion and mental exertion, future studies should investigate the underlying mechanisms increasing perception of effort overtime and in presence of fatigue during endurance exercise. Perception of effort should be considered not only as marker of exercise intensity, but also as a factor limiting endurance performance. Therefore, using a psychophysiological approach to explain the regulation of endurance performance would allow a better understanding of the interaction between physiological and psychological phenomena known to impact endurance performance.

  9. Chronic exertional compartment syndrome of the superficial posterior compartment: Soleus syndrome.

    Science.gov (United States)

    Gross, Christopher E; Parekh, Bela J; Adams, Samuel B; Parekh, Selene G

    2015-01-01

    Chronic exertional compartment syndrome (CECS) represents the second most-common cause of exertional leg pain with incidence of 27-33%. CECS of the superficial posterior compartment, or soleus syndrome, is rare and has only been discussed briefly in the literature. We discuss the management of two patients with bilateral soleus syndrome or CECS of the superficial posterior compartment.

  10. Programmed Physical Exertion in Recovery From Sports-Related Concussion: A Randomized Pilot Study.

    Science.gov (United States)

    Maerlender, Arthur; Rieman, Wanda; Lichtenstein, Jonathan; Condiracci, C

    2015-01-01

    Although no data exist, general practice recommends only rest following concussion. This randomized clinical trial found that programmed physical exertion during recovery produced no significant differences in recovery time between groups of participants. However, high levels of exertion were deleterious. This study provides initial evidence that moderate physical activity is a safe replacement behavior during recovery.

  11. Dynamics of Perceived Exertion in Constant-Power Cycling: Time- and Workload-Dependent Thresholds

    Science.gov (United States)

    Balagué, Natàlia; Hristovski, Robert; García, Sergi; Aguirre, Cecilia; Vázquez, Pablo; Razon, Selen; Tenenbaum, Gershon

    2015-01-01

    Purpose: The purpose of this study was to test the dynamics of perceived exertion shifts (PES) as a function of time and workload during constant-power cycling. Method: Fifty-two participants assigned to 4 groups performed a cycling task at 4 different constant workloads corresponding to their individual rates of perceived exertion (RPEs = 13, 15,…

  12. Mosapride, a selective serotonin 5-HT4 receptor agonist, and alogliptin, a selective dipeptidyl peptidase-4 inhibitor, exert synergic effects on plasma active GLP-1 levels and glucose tolerance in mice.

    Science.gov (United States)

    Nonogaki, Katsunori; Kaji, Takao

    2015-12-01

    Pharmacologic stimulation of serotonin 5-HT4 receptors increased plasma active glucagon-like-peptide-1 (GLP-1) levels independent of feeding, and that pharmacologic stimulation of 5-HT4 receptors and pharmacologic inhibition of dipeptidyl peptidase-4 exerted synergic effects on plasma active GLP-1 levels and glucose tolerance in mice.

  13. Depletion of GTP pool is not the predominant mechanism by which ribavirin exerts its antiviral effect on Lassa virus.

    Science.gov (United States)

    Ölschläger, Stephan; Neyts, Johan; Günther, Stephan

    2011-08-01

    Ribavirin (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is the standard treatment for Lassa fever, though its mode of action is unknown. One possibility is depletion of the intracellular GTP pool via inhibition of the cellular enzyme inosine monophosphate dehydrogenase (IMPDH). This study compared the anti-arenaviral effect of ribavirin with that of two other IMPDH inhibitors, mycophenolic acid (MPA) and 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (EICAR). All three compounds were able to inhibit Lassa virus replication by ≥2 log units in cell culture. Restoring the intracellular GTP pool by exogenous addition of guanosine reversed the inhibitory effects of MPA and EICAR, while ribavirin remained fully active. Analogous experiments performed with Zaire Ebola virus showed that IMPDH inhibitors are also active against this virus, although to a lesser extent than against Lassa virus. In conclusion, the experiments with MPA and EICAR indicate that replication of Lassa and Ebola virus is sensitive to depletion of the GTP pool mediated via inhibition of IMPDH. However, this is not the predominant mechanism by which ribavirin exerts its in-vitro antiviral effect on Lassa virus.

  14. Achyranthes bidentata Polypeptides Reduces Oxidative Stress and Exerts Protective Effects against Myocardial Ischemic/Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

    2013-09-01

    Full Text Available Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP preconditioning on myocardial ischemia/reperfusion (MI/R injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p. or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK/lactate dehydrogenase (LDH activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91phox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP.

  15. Properties of the force exerted by filopodia and lamellipodia and the involvement of cytoskeletal components.

    Directory of Open Access Journals (Sweden)

    Dan Cojoc

    Full Text Available During neuronal differentiation, lamellipodia and filopodia explore the environment in search for the correct path to the axon's final destination. Although the motion of lamellipodia and filopodia has been characterized to an extent, little is known about the force they exert. In this study, we used optical tweezers to measure the force exerted by filopodia and lamellipodia with a millisecond temporal resolution. We found that a single filopodium exerts a force not exceeding 3 pN, whereas lamellipodia can exert a force up to 20 pN. Using metabolic inhibitors, we showed that no force is produced in the absence of actin polymerization and that development of forces larger than 3 pN requires microtubule polymerization. These results show that actin polymerization is necessary for force production and demonstrate that not only do neurons process information, but they also act on their environment exerting forces varying from tenths pN to tens of pN.

  16. Interferon Regulatory Factor-1 Exerts Inhibitory Effect on Neointimal Formation after Vascular Injury

    Institute of Scientific and Technical Information of China (English)

    Zhen Li; Zhong-gao Wang; Ce Bian; Xiao-dong Chen; Jian-wen Li; Xiu Chen; Bing Han; Gao-feng Hou; Jian Chu; Qi Cui

    2009-01-01

    To investigate the effect of interferon regulatory factors (IRFs) on neointimal formation after vascular injury in the mouse, and its possible mechanism.Methods Vascular injury was induced by polyethylene cuff placement around the left femoral artery of IRF-1-deficient mice and C57BL/6J mice. The mRNA expressions of IRF-1, IRF-2, angiotensin Ⅱ type 2 (AT) receptor, interleukin-1β converting enzyme (ICE), inducible nitric oxide synthase (iNOS) were detected by RT-PCR and immunohistochemical staining.Results Neointimal formation after vascular injury was significantly greater in IRF-1-deficient mice than that in C57BL/6J mice (P<0.05). In contrast, TUNEL-positive nuclei to total nuclei in the neointima and media in vascular smooth muscle cell (VSMC) in the injured artery significantly attenuated in IRF-1-deficient mice compared to C57BL/6J mice (P<0.05). The expressions of AT2 receptor as well as pro-apoptotic genes such as ICE and iNOS in C57BL/6J mice were up-regulated in response to vascular injury, but this upregulation was attenuated in IRF-1-deficient mice.Conclusions Our results suggest that IRF-1 induces VSMC apoptosis and inhibits neointimal formation after vascular injury at least partly due to the upregulation of AT2 receptor, ICE and iNOS expressions. These results indicate that IRF-1 exerts an inhibitory effect on neointimal formation through the induction of apoptosis inVSMCs.

  17. Supramolecular nanoparticles that target phosphoinositide-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy.

    Science.gov (United States)

    Kulkarni, Ashish A; Roy, Bhaskar; Rao, Poornima S; Wyant, Gregory A; Mahmoud, Ayaat; Ramachandran, Madhumitha; Sengupta, Poulomi; Goldman, Aaron; Kotamraju, Venkata Ramana; Basu, Sudipta; Mashelkar, Raghunath A; Ruoslahti, Erkki; Dinulescu, Daniela M; Sengupta, Shiladitya

    2013-12-01

    The centrality of phosphoinositide-3-kinase (PI3K) in cancer etiology is well established, but clinical translation of PI3K inhibitors has been limited by feedback signaling, suboptimal intratumoral concentration, and an insulin resistance "class effect." This study was designed to explore the use of supramolecular nanochemistry for targeting PI3K to enhance antitumor efficacy and potentially overcome these limitations. PI3K inhibitor structures were rationally modified using a cholesterol-based derivative, facilitating supramolecular nanoassembly with L-α-phosphatidylcholine and DSPE-PEG [1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polythylene glycol)]. The supramolecular nanoparticles (SNP) that were assembled were physicochemically characterized and functionally evaluated in vitro. Antitumor efficacy was quantified in vivo using 4T1 breast cancer and K-Ras(LSL/+)/Pten(fl/fl) ovarian cancer models, with effects on glucose homeostasis evaluated using an insulin sensitivity test. The use of PI103 and PI828 as surrogate molecules to engineer the SNPs highlighted the need to keep design principles in perspective; specifically, potency of the active molecule and the linker chemistry were critical principles for efficacy, similar to antibody-drug conjugates. We found that the SNPs exerted a temporally sustained inhibition of phosphorylation of Akt, mTOR, S6K, and 4EBP in vivo. These effects were associated with increased antitumor efficacy and survival as compared with PI103 and PI828. Efficacy was further increased by decorating the nanoparticle surface with tumor-homing peptides. Notably, the use of SNPs abrogated the insulin resistance that has been associated widely with other PI3K inhibitors. This study provides a preclinical foundation for the use of supramolecular nanochemistry to overcome current challenges associated with PI3K inhibitors, offering a paradigm for extension to other molecularly targeted therapeutics being explored for cancer

  18. Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts anabolic effect on osteoporotic bone.

    Science.gov (United States)

    Khedgikar, V; Kushwaha, P; Gautam, J; Verma, A; Changkija, B; Kumar, A; Sharma, S; Nagar, G K; Singh, D; Trivedi, P K; Sangwan, N S; Mishra, P R; Trivedi, R

    2013-01-01

    Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic β subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation. WFA increased expression of osteoblast-specific transcription factor and mineralizing genes, promoted osteoblast survival and suppressed inflammatory cytokines. In osteoclast, WFA treatment decreased osteoclast number directly by decreasing expression of tartarate-resistant acid phosphatase and receptor activator of nuclear factor kappa-B (RANK) and indirectly by decreasing osteoprotegrin/RANK ligand ratio. Our data show that in vitro treatment of WFA to calvarial osteoblast cells decreased expression of E3 ubiquitin ligase, Smad ubiquitin regulatory factor 2 (Smurf2), preventing degradation of Runt-related transcription factor 2 (RunX2) and relevant Smad proteins, which are phosphorylated by bone morphogenetic protein 2. Increased Smurf2 expression due to exogenous treatment of tumor necrosis factor α (TNFα) to primary osteoblast cells was decreased by WFA treatment. This was corroborated by using small interfering RNA against Smurf2. Further, WFA also blocked nuclear factor kappa-B (NF-kB) signaling as assessed by tumor necrosis factor stimulated nuclear translocation of p65-subunit of NF-kB. Overall data show that in vitro proteasome inhibition by WFA simultaneously promoted osteoblastogenesis by stabilizing RunX2 and suppressed osteoclast differentiation, by inhibiting osteoclastogenesis. Oral administration of WFA to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased expression of osteogenic genes. WFA

  19. Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

    Directory of Open Access Journals (Sweden)

    Zhang Yawei

    2009-08-01

    Full Text Available Abstract Background Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As2O3 with cisplatin (DDP on A549 and H460 non-small cell lung cancer (NSCLC cells were explored. Methods A549 and H460 human lung cancer cells were treated with As2O3 and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5-dimethylthiahiazo (-z-y1-3,5-di-phenytetrazoliumromide (MTT method, clonogenic assay, and flow cytometry (FCM. Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot. Results MTT and clonogenic assay showed As2O3 within 10-2 μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As2O3 exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As2O3 with DDP. FCM showed As2O3 did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As2O3 and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As2O3 and/or DDP. FCM and TUNEL staining illustrated that the combination of As2O3 and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As2O3 and/or DDP treatments compared with controls. The

  20. The formyl peptide receptor 1 exerts a tumor suppressor function in human gastric cancer by inhibiting angiogenesis.

    Science.gov (United States)

    Prevete, N; Liotti, F; Visciano, C; Marone, G; Melillo, R M; de Paulis, A

    2015-07-01

    N-formyl peptide receptors (FPR1, FPR2 and FPR3) are involved in innate immunity, inflammation and cancer. FPR expression, initially described in immune cells, was later observed in non-hematopoietic cell populations and tissues. Several studies suggested a role for FPRs in the progression of various tumor histotypes, including gastric cancer (GC), for which a positive association with a specific FPR1 polymorphism has recently been described. We previously showed that FPRs are expressed on gastric epithelium and are required for wound repair and restitution of barrier integrity. Here we assess the role of FPRs in GC. We characterized the functions of FPRs in GC epithelial cells (MKN28, AGS and MKN45) cultured in vitro by assessing migration, proliferation, resistance to apoptosis and activation of the epithelial-to-mesenchymal transition. Activation of each FPR induced the epithelial-to-mesenchymal transition, proliferation, resistance to apoptosis and migration of GC cells in culture. Blocking compounds or RNA interference of each FPR reverted these effects. We also defined the in vivo tumorigenic potential of GC epithelial cells silenced for FPRs by xenograft experiments in immunocompromised mice. Interestingly, FPR1 silencing in GC cells (shFPR1) significantly enhanced xenograft growth with respect to shCTR, shFPR2 and shFPR3 xenografts, because of augmented vessel density and cell proliferation. Accordingly, HIF-1α and VEGF mRNA levels were higher in shFPR1 xenografts than in controls. Moreover, the in vitro production of proangiogenic factors in response to FPR2/3 agonists (WKYMVm, LL-37, uPA, uPAR84-95, AnxA1) or to other proinflammatory mediators (IL-1α) was higher in shFPR1 GC cells than in shCTR, shFPR2 and shFPR3 cells, suggesting that FPR1 functions as an inhibitor of CG angiogenesis. Thus, we propose that FPR1 stimulation may represent a novel therapeutic approach to counteract tumor angiogenesis.

  1. Ajoene exerts potent effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing apoptosis.

    Science.gov (United States)

    Ambati, Suresh; Yang, Jeong-Yeh; Rayalam, Srujana; Park, Hea Jin; Della-Fera, Mary Anne; Baile, Clifton A

    2009-04-01

    This paper describes effects of several sulfur-containing compounds from garlic on the cell viability, apoptosis and adipogenesis in 3T3-L1 adipocytes. In both preadipocytes and mature adipocytes, 100 and 200 microM ajoene significantly decreased cell viability and increased apoptosis. The effect on apoptosis was further confirmed with Hoechst staining. In contrast, diallyl sulfide, diallyl disulfide, diallyl trisulfide, deoxyalliin, and allyl methyl sulfide had no significant effect on cell viability or apoptosis in either preadipocytes or mature adipocytes. In maturing preadipocytes ajoene significantly decreased lipid accumulation in a dose-dependent manner and these results were further confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining. There was no significant change in lipid accumulation in maturing preadipocytes treated with other garlic derivatives. Thus, despite the same source of origin, garlic, ajoene was the only one with potent effects on cell viability, apoptosis and adipogenesis in 3T3-L1 adipocytes.

  2. Radiation exposure exerts its adverse effects on sperm maturation through estrogen-induced hypothalamohypophyseal axis inhibition in rats

    CSIR Research Space (South Africa)

    Makinta, MJ

    2005-10-01

    Full Text Available motility. Sprague Dawley rats with body mass of 300-400 g were selected at random. Two experimental groups received acute 6 degrees Co gamma-radiation doses of 3.5 and 6.0 Gy, respectively. Data were collected 2, 7, 14, 21, 28 and 35 days post...

  3. 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....

  4. 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...... 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......: 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...

  5. 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....

  6. At 1 antagonism and renin inhibition in mice: Pivotal role of targeting angiotensin II in chronic kidney disease

    NARCIS (Netherlands)

    C. Fraune (Christoph); S. Lange (Simon); C. Krebs (Christian); A. Hölzel (Alexandra); J. Baucke (Jana); N. Divac (Nevena); E. Schwedhelm (Edzard); T. Streichert (Thomas); J. Velden (Joachim); I.M. Garrelds (Ingrid); A.H.J. Danser (Jan); A.-R. Frenay (Anne-Roos); H. van Goor (Harry); J.A. Jankowski (Janusz Antoni); R. Stahl (Rolf); G. Nguyen (Genevieve); U. Wenzel (Ulrich)

    2012-01-01

    textabstractThe role of the renin-angiotensin system in chronic kidney disease involves multiple peptides and receptors. Exerting antipodal pathophysiological mechanisms, renin inhibition and AT 1 antagonism ameliorate renal damage. However, it is unclear which mechanism exerts better nephroprotecti

  7. Berberine exerts anti-adipogenic activity through up-regulation of C/EBP inhibitors, CHOP and DEC2.

    Science.gov (United States)

    Pham, Truc P T; Kwon, Jeongho; Shin, Jaekyoon

    2011-09-23

    Berberine exerts an anti-adipogenic activity that is associated with the down-regulation of C/EBPα and PPARγ. Stimulation of AMP-activated kinase (AMPK) caused by inhibition of mitochondrial respiration has been suggested to underlie such molecular regulation. In the present study, we show that berberine up-regulated the expression of two different sets of C/EBP inhibitors, CHOP and DEC2, while down-modulating C/EBPα, PPARγ and other adipogenic markers and effectors in differentiating 3T3-L1 preadipocytes and mature adipocytes. Data also suggested that the berberine-induced up-regulation of CHOP and DEC2 was attributable to selective activation of an unfolded protein response (UPR) and modified extracellular environment, respectively. As a result, the anti-adipogenic activity of berberine was diminished remarkably by adjusting the differentiation culture media and limitedly but consistently by knockdown of CHOP expression. Together, up-regulation of C/EBP inhibitors appears to underlie the berberine-induced repression of C/EBPα and PPARγ and, so, the inhibition of adipogenesis.

  8. Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells.

    Science.gov (United States)

    Jing, Zhao; Fei, Weiqiang; Zhou, Jichun; Zhang, Lumin; Chen, Liuxi; Zhang, Xiaomin; Liang, Xiao; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming

    2016-09-20

    Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway.

  9. Berteroin Present in Cruciferous Vegetables Exerts Potent Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin

    Directory of Open Access Journals (Sweden)

    Yoo Jin Jung

    2014-11-01

    Full Text Available Berteroin (5-methylthiopentyl isothiocyanate is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of κBα (IκBα and nuclear factor-κB p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor β activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent.

  10. Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK-mediated glucose uptake and adipogenesis pathways.

    Directory of Open Access Journals (Sweden)

    Nami Kim

    Full Text Available Dibenzoylmethane (DBM has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor. DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK, which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4 was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC, the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS, was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

  11. Luteolin Exerts Cardioprotective Effects through Improving Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats during Ischemia/Reperfusion In Vivo

    Directory of Open Access Journals (Sweden)

    Changsheng Nai

    2015-01-01

    Full Text Available The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R injury in vitro, which was related with sarcoplasmic reticulum Ca2+-ATPase (SERCA2a activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R-induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications.

  12. 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.

  13. Assessment of decision-making performance and in-game physical exertion of Australian football umpires.

    Science.gov (United States)

    Larkin, Paul; O'Brien, Brendan; Mesagno, Christopher; Berry, Jason; Harvey, Jack; Spittle, Michael

    2014-01-01

    The aim of this study is to investigate the effects of in-game physical exertion on decision-making performance of Australian football umpires. Fifteen Australian football umpires (Mage = 36, s = 13.5 years; Mgames umpired = 235.2, s = 151.3) volunteered to participate in the study. During five competitive Australian football pre-season games, measures of in-game physical exertion (blood lactate levels, global positioning system [GPS]) and decision-making performance (video-based test) were obtained. There were no significant correlations between physical exertion in a particular quarter and decision-making performance in either the same quarter or any other quarter. Video-based decision-making performance was effected by time in game χ(2)(3) = 24.24, P = 0.001, with Quarter 4 performance significantly better than both Quarter 2 and Quarter 3. In-game physical exertion (blood lactate) significantly decreased over the course of the game χ(2)(3) = 11.58, P = 0.009. Results indicate no definable link between in-game physical exertion and decision-making performance. It is, however, presumed that decision-making performance may be affected by the time or context of the game. Future research is warranted to explore the relationship between physical exertion and decision-making performance to potentially inform Australian football umpire training programmes that replicate in-game physical and decision-making demands.

  14. Cough, exertional, and sexual headaches: an analysis of 72 benign and symptomatic cases.

    Science.gov (United States)

    Pascual, J; Iglesias, F; Oterino, A; Vázquez-Barquero, A; Berciano, J

    1996-06-01

    We analyzed our experience with cough, exertional, and vascular sexual headaches, evaluated the interrelationships among them, and examined the possible symptomatic cases. Seventy-two patients consulted us because of headaches precipitated by coughing (n = 30), physical exercise (n = 28), or sexual excitement (n = 14). Thirty (42%) were symptomatic. The 17 cases of symptomatic cough headache were secondary to Chiari type I malformation, while the majority of cases of symptomatic exertional headaches and the only case of symptomatic sexual headache were secondary to subarachnoid hemorrhage. Although the precipitant was the same, benign and symptomatic headaches differed in several clinical aspects, such as age at onset, associated clinical manifestations, or response to pharmacologic treatment. Although sharing some properties, such as male predominance, benign cough headache and benign exertional headache are clinically separate conditions. Benign cough headache began significantly later, 43 years on average, than benign exertional headache. By contrast, our findings suggest that there is a close relationship between benign exertional headache and benign vascular sexual headache. We conclude that benign and symptomatic cough headaches are different from both benign and symptomatic exertional and sexual headaches.

  15. Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Li-Li; Wu, Xue-Feng; Liu, Hai-Liang; Guo, Wen-Jie; Luo, Qiong; Tao, Fei-Fei; Ge, Hui-Ming; Shen, Yan; Tan, Ren-Xiang; Xu, Qiang, E-mail: molpharm@163.com; Sun, Yang, E-mail: yangsun@nju.edu.cn

    2013-03-01

    In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. - Graphical abstract: Vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, exerts more intensive immunosuppressive activity than its precursor resveratrol does in vitro and in vivo. Its mechanism may involve multiple effects against activated T cells: regulation of signalings involved in cell proliferation, G0/G1 arrest of T cells, as well as an apoptosis induction in activated effector T cells. Highlights: ► Vaticaffinol, a resveratrol tetramer, exerts more potent activity than its precursor. ► It inhibited T cells proliferation and prevented them from entering

  16. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hals, Ingrid K., E-mail: ingrid.hals@ntnu.no [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ogata, Hirotaka; Pettersen, Elin [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ma, Zuheng; Bjoerklund, Anneli [Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden); Skorpen, Frank [Department of Laboratory Medicine, NTNU, Trondheim (Norway); Egeberg, Kjartan Wollo [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Grill, Valdemar [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer The impact of UCP-2 over expression on mitochondrial function is controversial. Black-Right-Pointing-Pointer We tested mitochondrial functions at defined levels of overexpression. Black-Right-Pointing-Pointer We find minor increases of fatty acid oxidation and uncoupling. Black-Right-Pointing-Pointer Effects were seen only at high level (fourfold) of over expression. Black-Right-Pointing-Pointer Hence it is doubtful whether these effects are of importance in diabetes. -- Abstract: Evidence is conflicting as to the impact of elevated levels of uncoupling protein-2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a fourfold induction of UCP-2 protein primarily on mitochondrial parameters and tested for replication of positive findings at a lower level of induction. We transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure to 1 {mu}g/ml of doxycycline (dox) induced UCP-2 fourfold (424 {+-} 113%, mean {+-} SEM) and 0.1 {mu}g/ml twofold (178 {+-} 29%, n = 3). Fourfold induced cells displayed normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose-induced insulin secretion (+27 {+-} 11%) as well as D-[U-{sup 14}C]-glucose oxidation (+5 {+-} 9% at 11 mM glucose). Oxidation of [1-{sup 14}C]-oleate was increased from 4088 to 5797 fmol/{mu}g prot/2 h at 3.3 mM glucose, p < 0.03. Oxidation of L-[{sup 14}C(U)]-glutamine was unaffected. Induction of UCP-2 did not significantly affect measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited oxygen consumption (a measure of mitochondrial uncoupling) was marginally increased, the effect being significant in comparison with dox-only treated cells, p < 0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were decreased by 30%, p < 0.025. Testing for the lower level of UCP-2 induction did not reproduce any of the

  17. Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer

    Institute of Scientific and Technical Information of China (English)

    Bing-Feng Chu; Yi-Yu Qin; Sheng-Lai Zhang; Zhi-Wei Quan; Ming-Di Zhang; Jian-Wei Bi

    2016-01-01

    Background:The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells.The role of NRARP in carcinogenesis deserves extensive investigations.This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation,apoptosis,cell cycle,and invasion in thyroid cancer.Methods:Thirty-four cases with thyroid cancer were collected from the Department of General Surgery,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine between 2011 and 2012.Immunohistochemistry was used to detect the level of NRARP in cancer tissues.Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression.Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay.Apoptosis and cell cycle distribution were determined by flow cytometry.Cell invasion was tested using Transwell invasion assay.In addition,expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection.Student's t-test,one-way analysis of variance (ANOVA),or Kaplan-Meier were used to analyze the differences between two group or three groups.Results:NRARP was highly expressed in thyroid cancer tissues.Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05).Lenti-NRARP-shRNA-induced G1 arrest (BHT 101:72.57% ± 5.32%;8305C:75.45% ± 5.26%) by promoting p21 expression,induced apoptosis by promoting bax expression and suppressing bcl-2 expression,and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression.Conclusion:Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer,that suggests a potential role of NRARP in thyroid cancer targeted

  18. Supraphysiological Doses of Performance Enhancing Anabolic-Androgenic Steroids Exert Direct Toxic Effects on Neuron-like Cells

    Directory of Open Access Journals (Sweden)

    John Robert Basile

    2013-05-01

    Full Text Available Anabolic-androgenic steroids (AAS are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  19. Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yun-feng Lou

    Full Text Available Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor synergized with gefitinib (an EGFR inhibitor to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1 which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon

  20. The effect of passive heating and face cooling on perceived exertion during exercise in the heat.

    Science.gov (United States)

    Armada-da-Silva, P A S; Woods, J; Jones, D A

    2004-05-01

    Increased body temperature is thought to be an important component of the higher perception of exertion that is a feature of fatigue during exercise in the heat but a causal relationship has yet to be demonstrated. We have investigated the effect of passive heating on the perception of exertion during a standard bout of exercise and also assessed the effect of cooling the head on compensating for the increased body temperature on the feelings of exertion. Ten male subjects performed a 14-min cycling exercise [average power approximately 63% of maximum power output ( W(max))] at an ambient temperature of 35 degrees C at resting rectal temperature [mean (SD): 37.49 (0.27) degrees C; control (CON) trial] on one occasion, and after sitting in a sauna to raise rectal temperature [mean (SD): 38.95(0.13) degrees C; sauna (SAU) trial]. During the exercise, subjects reported their ratings of overall perceived exertion (RPE), perceived exertion of the legs (RPE(legs)) and thermal comfort (TC). A blood sample was collected by the end of the exercise for determination of plasma glucose, lactate and prolactin and haematocrit. RPE values were significantly elevated after passive heating [mean (SE): 14.5 (0.7) units in CON and 17.2 (0.5) units in SAU, at the end of exercise; PFAN) and SAU(FAN)) that was achieved by combining face fanning and spraying the face with a mist of cooled water. Face cooling decreased RPE values after sauna to a point that no differences between the two conditions existed. RPE(legs) scores and heart rate, however, remained higher in SAU(FAN) compared with CON(FAN) ( P<0.05). We conclude that hyperthermia is a causative element of the increased perception of exertion during submaximal exercise in the heat and that the effect of increased core temperature on the feelings of exertion is modulated by face cooling.

  1. Physical exercise at the workplace reduces perceived physical exertion during healthcare work: cluster randomized controlled trial.

    Science.gov (United States)

    Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel; Jay, Kenneth; Aagaard, Per; Andersen, Lars L

    2015-11-01

    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 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. 200 female healthcare workers (age: 42.0, body mass index: 24.1, average pain intensity: 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 week and up to five group-based coaching sessions on motivation for regular physical exercise, or (2) home-based physical exercise (HOME) performed during leisure time for 5×10 minutes per week. Physical exertion was assessed at baseline and at 10-week follow-up. 2.2 (SD: 1.1) and 1.0 (SD: 1.2) training sessions were performed per week in WORK and HOME, respectively. Physical exertion was reduced more in WORK than HOME (pworkplace appears more effective than home-based exercise in reducing physical exertion during daily work tasks in healthcare workers. © 2015 the Nordic Societies of Public Health.

  2. The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines.

    Science.gov (United States)

    Sandra, Niro; Ester, Pereira; Marie-Agnès, Pélissier; Robert, Morfin; Olivier, Hennebert

    2012-04-01

    7β-Hydroxy-epiandrosterone (7β-OH-EpiA), an endogenous androgenic derivative of dehydroepiandrosterone, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-Δ(12,14)-PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-OH-EpiA (1-100nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogen-dependent mammary cancers. Estrogen induced PGE2 production and cell proliferation via its binding to estrogen receptors (ERs) in these tumors. Our objective was to test the effects of 7β-OH-EpiA on the proliferation (by counting with trypan blue exclusion), cell cycle and cell apoptosis (by flow cytometry) of breast cancer cell lines MCF-7 (ERα+, ERβ+, G-protein coupled receptor 30: GPR30+) and MDA-MB-231 (ERα-, ERβ+, GPR30+) and to identify a potential target of this steroid in these cell lineages (by transactivations) and in the nuclear ER-negative SKBr3 cells (GPR30+) (by proliferation assays). 7β-OH-EpiA exerted anti-estrogenic effects in MCF-7 and MDA-MB-231 cells associated with cell proliferation inhibition and cell cycle arrest. Moreover, transactivation and proliferation with ER agonists assays indicated that 7β-OH-EpiA interacted with ERβ. Data from proliferation assays on the MCF-7, MDA-MB-231 and SKBr3 cell lines suggested that 7β-OH-EpiA may also act through the membrane GPR30 receptor. These results support that this androgenic steroid acts as an anti-estrogenic compound. Moreover, this is the first evidence that low doses of androgenic steroid exert antiproliferative effects in these mammary cancer cells. Further investigations are needed to improve understanding of the observed actions of endogenous 7β-OH-EpiA.

  3. α-MSH exerts direct postsynaptic excitatory effects on NTS neurons and enhances GABAergic signaling in the NTS.

    Science.gov (United States)

    Mimee, A; Kuksis, M; Ferguson, A V

    2014-03-14

    The central melanocortin system plays an essential role in the regulation of energy balance. While anorexigenic effects of α-melanocyte-stimulating hormone (α-MSH) acting in the nucleus of the solitary tract (NTS), a critical medullary autonomic control center, have been established, the cellular events underlying these effects are less well characterized. In this study, we used whole-cell patch-clamp electrophysiology to examine firstly whether α-MSH exerts direct postsynaptic effects on the membrane potential of rat NTS neurons in slice preparation, and secondly whether α-MSH influences GABAergic signaling in the NTS. In normal artificial cerebrospinal fluid, perfusion of α-MSH (500 nM) resulted in a depolarization in 39% of cells (n=16, mean 6.14±0.54 mV), and a hyperpolarization in 22% of cells (n=9, -6.79±1.02 mV). Studies using tetrodotoxin to block neuronal communication revealed α-MSH exerts direct depolarizing effects on some NTS neurons, and indirect inhibitory effects on others. A third subset of neurons is simultaneously directly depolarized and indirectly hyperpolarized by α-MSH, resulting in a net lack of effect on membrane potential. The inhibitory inputs influenced by α-MSH were identified as GABAergic, as α-MSH increased the frequency, but not amplitude, of inhibitory postsynaptic currents (IPSCs) in 50% of NTS neurons. α-MSH had no effect on the frequency or amplitude of miniature IPSCs. Furthermore, pharmacological blockade of GABAA and GABAB receptors, and physical removal of all synaptic inputs via cellular dissociation, abolished hyperpolarizations induced by α-MSH. We conclude α-MSH exerts direct, postsynaptic excitatory effects on a subset of NTS neurons. By exciting GABAergic NTS neurons and presynaptically enhancing GABAergic signaling, α-MSH also indirectly inhibits other NTS cells. These findings provide critical insight into the cellular events underlying medullary melanocortin anorexigenic effects, and expand the

  4. Physical exertion as a trigger of myocardial infarction and sudden cardiac death.

    Science.gov (United States)

    Mittleman, M A; Siscovick, D S

    1996-05-01

    The data reviewed in this article indicate that physical exertion can trigger the onset of nonfatal myocardial infarction and sudden cardiac death. In addition, it is clear that although the relative risk associated with heavy exertion may be high, the absolute risk is actually quite small. It also is clear that regular exercise reduces the risk of triggering of myocardial infarction and sudden cardiac death by isolated bouts of exertion. Thus, these data provide further support for encouragement of regular exercise, as recommended by the American Heart Association. Such a program is likely to lower the overall risk of myocardial infarction and sudden cardiac death because it may lower the baseline risk and also decrease the relative risk that an episode of exertion will trigger a myocardial infarction or sudden cardiac death. Specific recommendations for patients with a history of myocardial infarction or angina are complex. Patients with coronary artery disease have the same relative risk of myocardial infarction and sudden cardiac death as those with no such history. Because of their elevated and variable baseline risk, however, specific recommendations regarding the risks and benefits of heavy physical exertion must be provided by their individual physicians, acting on recommended guidelines for exercise in such patients.

  5. 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.

  6. Exertional responses to sprint interval training: a comparison of 30-sec. and 60-sec. conditions.

    Science.gov (United States)

    Kilpatrick, Marcus W; Greeley, Samuel J

    2014-06-01

    The purpose of this study was to assess the effect of sprint interval training on rating of perceived exertion. 20 healthy participants (11 men, 9 women; M age = 23 yr.) completed a maximal cycle ergometer test and two high-intensity interval training cycling sessions. Each session utilized the same work-to-rest ratio (1:1), work intensity (90% max), recovery intensity (10% work intensity), and session duration (16 min.). Trials differed on duration of the interval segment, with a 30-sec. trial and a 60-sec. trial. Sessions required the same amount of total work over the duration of the trial. Rating of perceived exertion assessed before, during, and after exercise were higher for the 60-sec. trial than the 30-sec. trial despite no difference in total work. High intensity interval training trials utilizing the same total external work but differing in interval length produced different ratings of perceived exertion. Perceived exertion is significantly higher for sessions of exercise that utilize longer work intervals. These findings suggest that shorter intervals may produce more favorable exertional responses that could positively affect future behavior.

  7. Ways of increasing muscular activity by means of isometric muscular exertion

    Science.gov (United States)

    Kovalik, A. V.

    1980-01-01

    The effect of isometric muscular exertion on the human body was investigated by having subjects perform basic movements in a sitting position in the conventional manner with additional muscle tension at 50% maximum force and at maximum force. The pulse, arterial pressure, skin temperature, respiratory rate, minute respiratory volume and electrical activity of the muscles involved were all measured. Performance of the exercises with maximum muscular exertion for 20 sec and without movement resulted in the greatest shifts in these indices; in the conventional manner substantial changes did not occur; and with isometric muscular exertion with 50% maximum force with and without movement, optimal functional shifts resulted. The latter is recommended for use in industrial exercises for the prevention of hypodynamia. Ten exercises are suggested.

  8. Acute liver failure due to non-exertional heatstroke after sauna.

    Science.gov (United States)

    Erarslan, Elife; Yüksel, Ilhami; Haznedaroglu, Serap

    2012-01-01

    Acute liver failure is defined as rapid loss of liver function that patients without previously recognized liver disease sustain a liver damage. Acute liver failure due to non-exertional heatstroke has rarely been reported. We reported here an unusual case of heat stroke induced acute liver failure (ALF) after sauna. A 63 year old man without previously recognized liver and other systemic disease was admitted for loss of consciousness and impaired liver function after sauna. Despite intensive supportive care, ALF developed. Liver transplantation was planned but the patient died on the sixth day of hospitalization. Non-exertional heatstroke induced ALF is a rare and serious condition. ALF caused by non-exertional heatstroke which requires liver transplantation for definitive solution should be kept in mind in early period.

  9. Resonance-Radiation Force Exerted by a Circularly Polarized Light on an Atomic Wave Packet

    Institute of Scientific and Technical Information of China (English)

    YE Yong-Hua; ZENG Gao-Jian; LI Jin-Hui

    2006-01-01

    We study the behaviour of an atomic wave packet in a circularly polarized light, and especially give the calculation of the radiative force exerted by the circularly polarized light on the atomic wave packet under the resonance condition. A general method of the calculation is presented and the result is interesting. For example, under the condition that the wave packet is very narrow or/and the interaction is very strong, no matter whether the atom is initially in its ground state or excited state, as time approaches to infinity, the resonance-radiation force exerted by the light on the atom approaches to zero. If the atom is initially in its ground state and excited state with the probability 1/2 respectively, and if the momentum density is a even function, then the resonance-radiation force exerted by the light on the atom is equal to zero.

  10. Ultrasound-Guided Fasciotomy for Anterior Chronic Exertional Compartment Syndrome of the Leg.

    Science.gov (United States)

    Balius, Ramon; Bong, David A; Ardèvol, Jordi; Pedret, Carles; Codina, David; Dalmau, Antonio

    2016-04-01

    Chronic exertional compartment syndrome is characterized by exertional pain and elevated intracompartmental pressures affecting the leg in physically active young people. In patients who have failed conservative measures, fasciotomy is the treatment of choice. This study presents a new method for performing fasciotomy using high-resolution ultrasound (US) guidance and reports on the clinical outcomes in a group of these patients. Over a 3-year period, 7 consecutive patients with a total of 9 involved legs presented clinically with anterior compartment chronic exertional compartment syndrome, which was confirmed by intracompartmental pressure measurements before and after exercise. After a US examination, fasciotomy under US guidance was performed. Preoperative and postoperative pain and activity levels were assessed as well as number of days needed to "return to play." All patients had a decrease in pain, and all except 1 returned to presymptomatic exercise levels with a median return to play of 35 days. © 2016 by the American Institute of Ultrasound in Medicine.

  11. 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.

  12. Cardiac risk of coronary patients after reintegration into occupations with heavy physical exertion.

    Science.gov (United States)

    Wolf, R; Habel, F; Heiermann, M; Jäkel, R; Sinn, R

    2005-04-01

    The job related reintegration of patients with coronary artery disease (CAD) is a central part of cardiac rehabilitation. However, specific occupational demands like jobs with heavy physical exertion (> 6 METs) could increase the cardiovascular risk because the relative risk for acute myocardial infarction (MI) and cardiac death is temporarily elevated after vigorous exertion ("hazard period"). Thus, in 2001 any male patient with proven CAD who performed a job with heavy exertion until the occurrence of an index event (MI/ACS, any interventional or surgical revascularization measure) received a questionnaire after an average of 20 months. Complete data were available in 108 from 119 included patients (90.8%), aged 51.8+/-7.8 years. Ejection fraction was 61.5+/-13.1% and the functional capacity at the time of hospital discharge averaged 130.1+/-31.2 W. 75% of the patients had a previous MI and 59.3% underwent bypass surgery. During follow-up the previous job with heavy exertion was performed over a cumulated time of 74 years. The aim of the study was to compare the observed and the expected incidence of MI and cardiac death with and without job performance. The expected ("basal") risk for MI and cardiac death without heavy physical exertion was determined from pooled study results and assumed to be 5.2% per year. The combined risk due to performing an occupation with strenuous exertion can be calculated from time periods with and without working hours and amounts to 11.9%. There could be expected 0.119 . 74=8.8 cardiac events related to the job. In contrast, 5 MIs (4 NSTEMI, 1 STEMI) were observed (6.8%). The relative risk for an expected event compared to the basal risk without heavy exertion was 2.3 (95% CI: 0.7-7.4). The relative risk for the observed cardiac events amounts to 1.3 (95% CI: 0.4-4.8). The lower observed risk is probably due to the high grade of physical fitness in this patient group. In spite of several limitations, our study showed no convincing

  13. The role of (dis)inhibition in creativity: decreased inhibition improves idea generation.

    Science.gov (United States)

    Radel, Rémi; Davranche, Karen; Fournier, Marion; Dietrich, Arne

    2015-01-01

    There is now a large body of evidence showing that many different conditions related to impaired fronto-executive functioning are associated with the enhancement of some types of creativity. In this paper, we pursue the possibility that the central mechanism associated with this effect might be a reduced capacity to exert inhibition. We tested this hypothesis by exhausting the inhibition efficiency through prolonged and intensive practice of either the Simon or the Eriksen Flanker task. Performance on another inhibition task indicated that only the cognitive resources for inhibition of participants facing high inhibition demands were impaired. Subsequent creativity tests revealed that exposure to high inhibition demands led to enhanced fluency in a divergent thinking task (Alternate Uses Task), but no such changes occurred in a convergent task (Remote Associate Task; studies 1a and 1b). The same manipulation also led to a hyper-priming effect for weakly related primes in a Lexical Decision Task (Study 2). Together, these findings suggest that inhibition selectively affects some types of creative processes and that, when resources for inhibition are lacking, the frequency and the originality of ideas was facilitated.

  14. Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF-κB.

    Science.gov (United States)

    Aye, Irving L M H; Waddell, Brendan J; Mark, Peter J; Keelan, Jeffrey A

    2012-07-01

    Oxidized cholesterol metabolites (oxysterols) promote inflammation in a variety of cell types and are thought to be involved in a number of disease pathologies. Oxysterol concentrations are increased in pregnancy, together with systemic oxidative stress and inflammation. We tested the hypothesis that oxysterols 25-hydroxycholesterol (25-OHC) and 7-ketocholesterol (7-ketoC) promote placental trophoblast inflammation, and determined the mechanisms involved. Treatment of primary trophoblasts in culture with 25-OHC and 7-ketoC increased the production of proinflammatory cytokines (interleukin-6, macrophage inflammatory protein-1β and tumour necrosis factor-α) in a concentration-dependent fashion. Inhibition of TLR4 activation using selective inhibitors of TLR4 complex formation (OxPAPC) or signalling transmission (CLI095) prevented lipopolysaccharide (LPS)- and oxysterol-induced inflammatory cytokine production. Pretreatment of trophoblasts with selective inhibitors of I-kB kinase activity (parthenolide and TPCA-1) reduced oxysterol- and LPS-stimulated inflammatory responses, consistent with the involvement of the nuclear factor kappa B (NF-κB) pathway downstream of TLR4 signalling. Both oxysterols also increased the phosphorylation and nuclear localization of NF-κB subunit p65/RelA. Oxysterols are also known to activate liver X receptors (LXRs) which can inhibit inflammatory signalling, either directly or indirectly via membrane cholesterol reduction. Treatment with the LXR agonist, T0901317, exerted significant anti-inflammatory effects, reducing LPS- and oxysterol-driven cytokine production. Treatment with methyl-β-cyclodextrin to deplete membrane microdomain cholesterol and thereby disrupt TLR4 signalling, similarly abrogated their effects. Together, these findings indicate that although oxysterols likely activate both pro- and anti-inflammatory pathways in the placenta, the predominant effect is the promotion of placental inflammation via TLR4-dependent

  15. Saving the Seneca Outdoor Recreation Program: A Case Study in Exerting Political Influence.

    Science.gov (United States)

    Magee, Clare

    1998-01-01

    This case study demonstrates the process of exerting political influence in faculty's systematic efforts to save the outdoor recreation program at Seneca College (Ontario). A chart and explanatory list present a seven-stage plan for influencing political decision-making. (SAS)

  16. Effect of Carbohydrate Ingestion on Ratings of Perceived Exertion during a Marathon.

    Science.gov (United States)

    Utter, Alan C.; Kang, Jie; Robertson, Robert J.; Nieman, David C.; Chaloupka, Edward C.; Suminski, Richard R.; Piccinni, Cristiana R.

    2002-01-01

    Investigated the effects of carbohydrate substrate availability on ratings of perceived exertion (RPE) and hormonal regulation during a competitive marathon. Data on marathon runners randomly assigned to receive carbohydrate or placebo indicated that those who ingested carbohydrate rather than placebo beverages were able to run at a higher…

  17. 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

  18. 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 thereb

  19. Citrus-derived flavonoid naringenin exerts uterotrophic effects in female mice at human relevant doses

    DEFF Research Database (Denmark)

    Breinholt, Vibeke Miller; Svendsen, Gitte Winkel; Dragsted, Lars Ove

    2004-01-01

    ingestion of 400-760 ml of orange juice (Erlund et al. 2001). This could be taken to suggests that ingestion of orange juice and other citrus fruits and juices may give rise to sufficiently high tissue levels of naringenin in man to exert a biological effect....

  20. Coordination of strength exertion during the chair-rise movement in very old people

    NARCIS (Netherlands)

    Lindemann, Ulrich; Muche, Rainer; Stuber, Michael; Zijlstra, Wiebren; Hauer, Klaus; Becker, Clemens

    Background. Changes in performance of standing up from a chair have been related to measures of strength or power. However, the sit-to-stand (STS) transfer requires that the individual exerts forces with appropriate magnitude and timing. These coordinative aspects have received less attention. This

  1. 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® (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

  2. 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.; van Brunschot, C.; Schipper, P.; Korte-Bouws, G.; van Luijtelaar, G.; 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 there

  3. Influence of ambient music on perceived exertion during a pulmonary rehabilitation session: a randomized crossover study.

    Science.gov (United States)

    Reychler, Gregory; Mottart, Florian; Boland, Maelle; Wasterlain, Emmanuelle; Pieters, Thierry; Caty, Gilles; Liistro, Giuseppe

    2015-05-01

    Pulmonary rehabilitation is a key element in the treatment of COPD. Music has been shown to have a positive effect on parameters related to a decrease in exercise tolerance. The aim of this study was to evaluate the effect of listening to ambient music on perceived exertion during a pulmonary rehabilitation session for COPD subjects. COPD subjects randomly performed a session of pulmonary rehabilitation with or without ambient music. Perceived exertion (Borg scales), anxiety (Hospital Anxiety and Depression Scale-Anxiety Subscale), dyspnea (visual analog scale), and cardiorespiratory parameters were compared at the end of both sessions. Forty-one subjects were analyzed. The characteristics of the COPD subjects were as follows: age, 70.5 ± 8.4 y; body mass index, 22.7 ± 3.9 kg/m(2); and FEV1, 38.6 ± 12.5 % predicted. Perceived exertion was not modified by ambient music, but anxiety was improved (P = .02). Dyspnea, fatigue and cardiorespiratory parameters were not influenced by music during a typical session of the pulmonary rehabilitation program. This study demonstrates that perceived exertion during one pulmonary rehabilitation session was not influenced by ambient music. However, a positive effect on anxiety was observed. (ClinicalTrials.gov registration NCT01833260.). Copyright © 2015 by Daedalus Enterprises.

  4. Oxytocin microinjected into the central amygdaloid nuclei exerts anti-aggressive effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Stubbendorff, Christine; Meyer, Neele; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jacob

    2015-01-01

    We recently demonstrated that acute and chronic intracerebroventricular enhancement of brain OXT levels induces potent anti-aggressive and pro-social explorative effects during social challenges. However, the exact anatomical location in the brain where OXT exerts its action is still elusive. In the

  5. Understanding the effect of speed of exertion on isokinetic strength using a multiaxial dynamometer.

    Science.gov (United States)

    Nimbarte, Ashish D; Aghazadeh, Fereydoun; Bogolu, Sai Chaitanya R; Rajulu, Sudhakar L

    2009-01-01

    In this study a multiaxial isokinetic dynamometer was used to measure strength during various upper-body isokinetic exertions. Ten male participants performed 7 different upper-body isokinetic exertions. In addition, to evaluate the effect of speed on strength, each participant performed sitting pull exertions at the speed of 0.026, 0.130, and 0.260 m/s. Average isokinetic strength increased from 236.6 +/- 39.1 to 291.8 +/- 65.8 N with the initial increase in speed from 0.026 to 0.130 m/s. The average isokinetic strength decreased to 276.7 +/- 87.2 N with a further increase in speed to 0.260 m/s. The curve between isokinetic strength and speed followed a bell-shaped curve (fitted with the Gaussian function, R(2) = .9). The results of this study could be useful in deciding on the work pace of various manual material handling tasks requiring maximal and/or near maximal exertions.

  6. Cardio-Respiratory and Perceived Exertion Responses to Different Cranking Rates during Maximal Arm Ergometry.

    Science.gov (United States)

    Israel, Richard G.; And Others

    This study compared cardio-respiratory and perceived exertion responses for four cranking rates (50, 60, 70 and 80 rpm) during a continuous maximal arm ergometry protocol in order to determine the most efficient cranking rate for maximal testing. Fifteen male volunteers from 18-30 years of age performed a continuous arm ergometry stress test in…

  7. 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 subs

  8. Exertional dyspnoea in chronic heart failure: the role of the lung and respiratory mechanical factors

    Directory of Open Access Journals (Sweden)

    Bruno-Pierre Dubé

    2016-09-01

    Full Text Available Exertional dyspnoea is among the dominant symptoms in patients with chronic heart failure and progresses relentlessly as the disease advances, leading to reduced ability to function and engage in activities of daily living. Effective management of this disabling symptom awaits a better understanding of its underlying physiology. Cardiovascular factors are believed to play a major role in dyspnoea in heart failure patients. However, despite pharmacological interventions, such as vasodilators or inotropes that improve central haemodynamics, patients with heart failure still complain of exertional dyspnoea. Clearly, dyspnoea is not determined by cardiac factors alone, but likely depends on complex, integrated cardio-pulmonary interactions. A growing body of evidence suggests that excessively increased ventilatory demand and abnormal “restrictive” constraints on tidal volume expansion with development of critical mechanical limitation of ventilation, contribute to exertional dyspnoea in heart failure. This article will offer new insights into the pathophysiological mechanisms of exertional dyspnoea in patients with chronic heart failure by exploring the potential role of the various constituents of the physiological response to exercise and particularly the role of abnormal ventilatory and respiratory mechanics responses to exercise in the perception of dyspnoea in patients with heart failure.

  9. Matrix stiffness exerts biphasic control over monocyte-endothelial adhesion via Rho-mediated ICAM-1 clustering.

    Science.gov (United States)

    Scott, Harry A; Quach, Boi; Yang, Xiao; Ardekani, Soroush; Cabrera, Andrea P; Wilson, Randall; Messaoudi-Powers, Ilhem; Ghosh, Kaustabh

    2016-08-01

    Leukocyte-endothelial adhesion is a critical early step in chronic vascular inflammation associated with diabetes, emphysema, and aging. Importantly, these conditions are also marked by abnormal subendothelial matrix crosslinking (stiffness). Yet, whether and how abnormal matrix stiffness contributes to leukocyte-endothelial adhesion remains poorly understood. Using a co-culture of human monocytic cells and human microvascular endothelial cells (ECs) grown on matrices of tunable stiffness, we demonstrate that matrix stiffness exerts biphasic control over monocyte-EC adhesion, with both matrix softening and stiffening eliciting a two-fold increase in this adhesive interaction. This preferential endothelial adhesivity on softer and stiffer matrices was consistent with a significant increase in α-actinin-4-associated endothelial ICAM-1 clustering, a key determinant of monocyte-EC adhesion. Further, the enhanced ICAM-1 clustering on soft and stiff matrices correlated strongly with an increase in Rho activity and ROCK2 expression. Importantly, inhibition of Rho/ROCK activity blocked the effects of abnormal matrix stiffness on ICAM-1 clustering and monocyte-EC adhesion. Thus, these findings implicate matrix stiffness-dependent ICAM-1 clustering as an important regulator of vascular inflammation and provide the rationale for closely examining mechanotransduction pathways as new molecular targets for anti-inflammatory therapy.

  10. Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment.

    Science.gov (United States)

    Zuo, Fu-Xing; Bao, Xin-Jie; Sun, Xi-Cai; Wu, Jun; Bai, Qing-Ran; Chen, Guo; Li, Xue-Yuan; Zhou, Qiang-Yi; Yang, Yuan-Fan; Shen, Qin; Wang, Ren-Zhi

    2015-11-05

    Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.

  11. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy.

    Science.gov (United States)

    Bae, Min-Jung; See, Hye-Jeong; Choi, Gyeyoung; Kang, Chang-Yuil; Shon, Dong-Hwa; Shin, Hee Soon

    2016-01-01

    The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  12. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy

    Directory of Open Access Journals (Sweden)

    Min-Jung Bae

    2016-01-01

    Full Text Available The prevalence of allergic disorders including atopic dermatitis (AD and food allergy (FA has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3+CD4+ regulatory T cells (Tregs. The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3+CD4+ Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3+CD4+ Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  13. Salidroside exerts protective effects against chronic hypoxia-induced pulmonary arterial hypertension via AMPKα1-dependent pathways.

    Science.gov (United States)

    Chen, Mayun; Cai, Hui; Yu, Chang; Wu, Peiliang; Fu, Yangyang; Xu, Xiaomei; Fan, Rong; Xu, Cunlai; Chen, Yanfan; Wang, Liangxing; Huang, Xiaoying

    2016-01-01

    Salidroside, an active ingredient isolated from Rhodiola rosea, has shown to exert protective effects against chronic hypoxia-induced pulmonary arterial hypertension (PAH). However, the underlying mechanisms were not well known. Based on our recent reports, we predicted the involvement of adenosine monophosphate-activated protein kinase (AMPK) mediated effects in salidroside regulation of PAH. Firstly, to prove the hypothesis, rats were exposed to chronic hypoxia and treated with increasing concentrations of salidroside or a selective AMPK activator-5'-aminoimidazole-4-carboxamide ribonucleoside (AICAR) for 4 weeks. After salidroside or AICAR treatment, the chronic hypoxia-induced right ventricular hypertrophy and pulmonary artery remodeling were attenuated. Then the effects of salidroside or AICAR on hypoxia-induced excess cellular proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs), which contributed to pulmonary arterial remodeling, were investigated. Our results suggested salidroside, as well as AICAR, reversed hypoxia-induced PASMCs proliferation and apoptosis resistance while AMPK inhibitor Compound C enhanced the effects of hypoxia. To reveal the potential cellular mechanisms, activation of AMPKα1 and expression of the genes related to proliferation and apoptosis were analyzed in PASMCs after salidroside treatment under hypoxia conditions. The results demonstrated salidroside as well as AICAR might inhibit chronic hypoxia-induced PASMCs proliferation via AMPKα1-P53-P27/P21 pathway and reverse apoptosis resistance via AMPKα1-P53-Bax/Bcl-2-caspase 9-caspase 3 pathway.

  14. The synthetic melanocortin (CKPV2 exerts anti-fungal and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization.

    Directory of Open Access Journals (Sweden)

    Hai-xia Ji

    Full Text Available In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH22 or (CKPV2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6 release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP production was also induced by (CKPV2 administration in macrophages. These above effects on macrophages by (CKPV2 were almost reversed by melanocortin receptor-1(MC1R siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation.

  15. The Synthetic Melanocortin (CKPV)2 Exerts Anti-Fungal and Anti-Inflammatory Effects against Candida albicans Vaginitis via Inducing Macrophage M2 Polarization

    Science.gov (United States)

    Jia, Zhi-rong; Li, Xian-jing; Wang, Zhuo; Li, Li; Li, Yong-wen; Liu, Gen-yan; Tong, Ming-Qing; Li, Xiao-yi; Zhang, Guo-hui; Dai, Xiang-rong; He, Ling; Li, Zhi-yu; Cao, Cong; Yang, Yong

    2013-01-01

    In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH2)2 or (CKPV)2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV)2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV)2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV)2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV)2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP) production was also induced by (CKPV)2 administration in macrophages. These above effects on macrophages by (CKPV)2 were almost reversed by melanocortin receptor-1(MC1R) siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV)2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation. PMID:23457491

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Ladan Amin

    Full Text Available 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.

  18. Inhibition of cullin RING ligases by cycle inhibiting factor: evidence for interference with Nedd8-induced conformational control.

    Science.gov (United States)

    Boh, Boon Kim; Ng, Mei Ying; Leck, Yee Chin; Shaw, Barry; Long, Jed; Sun, Guang Wen; Gan, Yunn Hwen; Searle, Mark S; Layfield, Robert; Hagen, Thilo

    2011-10-21

    Cycle inhibiting factor (Cif) is produced by pathogenic intracellular bacteria and injected into the host cells via a type III secretion system. Cif is known to interfere with the eukaryotic cell cycle by inhibiting the function of cullin RING E3 ubiquitin ligases (CRLs). Cullin proteins form the scaffold protein of CRLs and are modified with the ubiquitin-like protein Nedd8, which exerts important conformational control required for CRL activity. Cif has recently been shown to catalyze the deamidation of Gln40 in Nedd8 to Glu. Here, we addressed how Nedd8 deamidation inhibits CRL activity. Our results indicate that Burkholderia pseudomallei Cif (also known as CHBP) inhibits the deconjugation of Nedd8 in vivo by inhibiting binding of the deneddylating COP9 signalosome (CSN) complex. We provide evidence that the reduced binding of CSN and the inhibition of CRL activity by Cif are due to interference with Nedd8-induced conformational control, which is dependent on the interaction between the Nedd8 hydrophobic patch and the cullin winged-helix B subdomain. Of note, mutation of Gln40 to Glu in ubiquitin, an additional target of Cif, inhibits the interaction between the hydrophobic surface of ubiquitin and the ubiquitin-binding protein p62/SQSTM1, showing conceptually that Cif activity can impair ubiquitin/ubiquitin-like protein non-covalent interactions. Our results also suggest that Cif may exert additional cellular effects by interfering with the association between ubiquitin and ubiquitin-binding proteins.

  19. Phenethyl isothiocyanate, a cancer chemopreventive constituent of cruciferous vegetables, inhibits cap-dependent translation by regulating the level and phosphorylation of 4E-BP1

    National Research Council Canada - National Science Library

    Hu, Jing; Straub, Jonathan; Xiao, Dong; Singh, Shivendra V; Yang, Hsin-Sheng; Sonenberg, Nahum; Vatsyayan, Jaya

    2007-01-01

    Phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables, exerts significant protection against chemically induced cancer in animal models and inhibits growth of cancer cells in culture and in vivo...

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

    Directory of Open Access Journals (Sweden)

    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

  1. Diagnosis and Treatment of Chronic Exertional Compartment Syndrome - a Proposition for an Algorithm

    DEFF Research Database (Denmark)

    Larsen, Peter Birk; Jensen, Steffen Skov

    Title: Diagnosis and treatment of chronic exertional compartment syndrome - a proposition for an algorithm based on case series of patients treated at Sports Medicine Division, Department of Orthopaedic Surgery, Viborg Regional Hospital, Denmark Background: Chronic exertional compartment syndrome...... that specific activity induced strain (SAIS) can be used to diagnose the specific affected compartments, and in this way be able to safely and effectively treat this disorder using endoscopic assisted selective fasciotomy (EASF). Materials and Methods: Retrospective follow-up study of 13 consecutive selected...... in conjunction with a thorough medical history formed the basis for the diagnosis. Results: 11 patients were offered surgical treatment consisting of EASF of the affected compartment (10 bilateral and 1 unilateral, 8 affected in specific compartments and 3 affected in all compartments. Only 1 patient required...

  2. A field test comparison of hiking stick use on heartrate and rating of perceived exertion.

    Science.gov (United States)

    Jacobson, B H; Wright, T

    1998-10-01

    The purpose of this study was to compare heartrate carrying a load and rating of perceived exertion with and without hiking sticks while ascending and descending a slope. 11 novice, moderately fit volunteers, ages 18 to 21 years (M = 19.3 yr.) completed two alternate 50-meter, uphill and downhill hikes on a 40 degrees slope during randomly ordered trials with and without fitted hiking sticks and backpacks (15 kg). Paired t test comparisons for 4 trials indicated that mean heartrate was significantly lower only following the first ascent by those using hiking sticks than those without sticks. Rating of perceived exertion also was significantly lower (p heartrate may be lower at the onset of climbing using hiking sticks, but as the duration the hike is extended, heartrates become comparable, presumably due to the transfer of energy utilization from the legs to the upper body.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-02-01

    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.

  4. Experimental Study of Forces Exerted on Ships Due to the Vertical Walls of Navigation Channels

    Directory of Open Access Journals (Sweden)

    Mohammadreza Fathi Kazerooni

    2015-06-01

    Full Text Available Ship maneuvering in restricted waters of harbor basins and navigation channels had been the main concern in recent years due to sudden increase of ship’s size. When the ship enters a navigation channel the lateral boundary of the channel exerts a transverse force and turning moment on the ship hull. These forces are so important in the analysis of safety of ship navigation in the channels. Ship model test in the towing tank is a reliable method to evaluate these forces. Therefore systematic model tests are held for modeling of the forces exerted on the tanker ship and dhow model traveling alongside a vertical wall. A database of the interaction forces is developed and the specific hydrodynamic effects related to the phenomena are discussed. The results can be used for simulation of ship maneuvering and assessment of safety limits for navigation of ships alongside the quay walls and breakwaters.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Virtual Exertions: a user interface combining visual information, kinesthetics and biofeedback for virtual object manipulation.

    Science.gov (United States)

    Ponto, Kevin; Kimmel, Ryan; Kohlmann, Joe; Bartholomew, Aaron; Radwin, Robert G

    2012-01-01

    Virtual Reality environments have the ability to present users with rich visual representations of simulated environments. However, means to interact with these types of illusions are generally unnatural in the sense that they do not match the methods humans use to grasp and move objects in the physical world. We demonstrate a system that enables users to interact with virtual objects with natural body movements by combining visual information, kinesthetics and biofeedback from electromyograms (EMG). Our method allows virtual objects to be grasped, moved and dropped through muscle exertion classification based on physical world masses. We show that users can consistently reproduce these calibrated exertions, allowing them to interface with objects in a novel way.

  7. Occlusion of sight, sound and smell during Green Exercise influences mood, perceived exertion and heart rate.

    Science.gov (United States)

    Wooller, John-James; Barton, Jo; Gladwell, Valerie F; Micklewright, Dominic

    2016-01-01

    This study's aim was to identify the relative contribution of sight, sound and smell to the Green Exercise effect. It was hypothesised that visual occlusion while exercising in a natural environment would have the greatest diminishing effect on perceived exertion and mood compared to auditory and olfactory occlusion. Twenty-nine healthy participants were randomly assigned to one of the three groups: visual (n = 10), auditory (n = 9) and olfactory occlusion (n = 10). Each performed six, 5-min bouts of exercise alternating between full sensory and occlusion. Rate of perceived exertion (RPE), heart rate (HR) and mood were recorded at the end of each bout. Sensory-occlusion increased mood, RPE and HR; effects were strongest when sounds were blocked but virtually absent when vision was blocked. During sensory occlusion, mood changes were characterised by increased Fatigue and Confusion, and reduced Vigour. Reductions in Tension and Vigour and increases in Fatigue were found during full sensory exercise, consistent with previous research findings.

  8. ADJUSTMENT ERRORS IN ASCENDING AND DESCENDING PHASES OF TARGET LEVEL IN CONTROLLED FORCE EXERTION.

    Science.gov (United States)

    Kubota, Hiroshi; Demura, Shinichi

    2015-10-01

    Hand grip force adjustment errors to ascending and descending phases of a sinusoidal target force in a controlled force exertion (CFE) test were measured and the laterality of responses evaluated. 75 men (M age = 19.6 yr., SD = 1.6) performed the CFE test after one practice trial by matching handgrip force to target level (5-25% of maximal grip force). The CFE errors in ascending and descending phases of the target force were calculated as the absolute differences between actual force and target force in each phase. There were significantly smaller CFE errors in the ascending phase for both dominant and non-dominant hands, but CFE error for the dominant hand was significantly smaller in both phases. Therefore, error in force exertion in the ascending and descending phases of the target force differed, and laterality influenced error in both phases.

  9. Inhibition of the gravitropic bending response of flowering shoots by salicylic acid.

    Science.gov (United States)

    Friedman, Haya; Meir, Shimon; Halevy, Abraham H; Philosoph-Hadas, Sonia

    2003-10-01

    The upward gravitropic bending of cut snapdragon, lupinus and anemone flowering shoots was inhibited by salicylic acid (SA) applied at 0.5 mM and above. This effect was probably not due to acidification of the cytoplasm, since other weak acids did not inhibit bending of snapdragon shoots. In order to study its mode of inhibitory action, we have examined in cut snapdragon shoots the effect of SA on three processes of the gravity-signaling pathway, including: amyloplast sedimentation, formation of ethylene gradient across the stem, and differential growth response. The results show that 1 mM SA inhibited differential ethylene production rates across the horizontal stem and the gravity-induced growth, without significantly inhibiting vertical growth or amyloplast sedimentation following horizontal placement. However, 5 mM SA inhibited all three gravity-induced processes, as well as the growth of vertical shoots, while increasing flower wilting. It may, therefore, be concluded that SA inhibits bending of various cut flowering shoots in a concentration-dependent manner. Thus, at a low concentration SA exerts its effect in snapdragon shoots by inhibiting processes operating downstream to stimulus sensing exerted by amyloplast sedimentation. At a higher concentration SA inhibits bending probably by exerting general negative effects on various cellular processes.

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

    Science.gov (United States)

    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).

  11. Effectiveness of cold water immersion for treating exertional heat stress when immediate response is not possible.

    Science.gov (United States)

    Flouris, A D; Friesen, B J; Carlson, M J; Casa, D J; Kenny, G P

    2015-06-01

    Immediate treatment with cold water immersion (CWI) is the gold standard for exertional heatstroke. In the field, however, treatment is often delayed due to delayed paramedic response and/or inaccurate diagnosis. We examined the effect of treatment (reduction of rectal temperature to 37.5 °C) delays of 5, 20, and 40 min on core cooling rates in eight exertionally heat-stressed (40.0 °C rectal temperature) individuals. We found that rectal temperature was elevated above baseline (P  0.05). Rectal core cooling rates were similar among conditions (5 min: 0.20 ± 0.01; 20 min: 0.17 ± 0.02; 40 min: 0.17 ± 0.01 °C/min; P > 0.05). The rectal temperature afterdrop following CWI was similar across conditions (5 min: 35.95; 20 min: 35.61; 40 min: 35.87 °C; P > 0.05). We conclude that the effectiveness of 2 °C CWI as a treatment for exertional heat stress remains high even when applied with a delay of 40 min. Therefore, our results support that CWI is the most appropriate treatment for exertional heatstroke as it is capable of quickly reversing hyperthermia even when treatment is commenced with a significant delay.

  12. Ascending evacuation in long stairways: Physical exertion, walking speed and behaviour

    OpenAIRE

    Ronchi, Enrico; Norén, Johan; Delin, Mattias; Kuklane, Kalev; Halder, Amitava; Arias, Silvia; Fridolf, Karl

    2015-01-01

    This is the final report of the project “Ascending evacuation in long stairways: Physical exertion, walking speed and behaviour”. This project investigated the effects of fatigue on walking speeds, physiological performance and behaviours in case of long ascending evacuation. The report includes a literature review on, at the time when the project began, existing material on ascending evacuation on long stairs and escalators. Experimental research was conducted and the results are presented i...

  13. 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…

  14. Exertional dyspnoea in chronic heart failure: the role of the lung and respiratory mechanical factors

    OpenAIRE

    Bruno-Pierre Dubé; Piergiuseppe Agostoni; Pierantonio Laveneziana

    2016-01-01

    Exertional dyspnoea is among the dominant symptoms in patients with chronic heart failure and progresses relentlessly as the disease advances, leading to reduced ability to function and engage in activities of daily living. Effective management of this disabling symptom awaits a better understanding of its underlying physiology. Cardiovascular factors are believed to play a major role in dyspnoea in heart failure patients. However, despite pharmacological interventions, such as vasodilators o...

  15. 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 (Phorses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, Phorses (3/14) and significantly (Phorses had disrupted myofibrillar alignment and large desmin and αβ-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of β-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. In a subset of Arabian horses with intermittent episodes of exertional rhabdomyolysis, 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

  16. Effect of induced leg muscle fatigue on exertional dyspnea in healthy subjects.

    Science.gov (United States)

    Sharma, Pramod; Morris, Norman R; Adams, Lewis

    2015-01-01

    The genesis of dyspnea is complex. It appears to be related to central respiratory drive although prevailing leg fatigue could independently potentiate dyspnea. We hypothesized that experimentally induced leg fatigue generates more intense exertional dyspnea for a given level of ventilatory drive. Following familiarization, 19 healthy subjects (32.2 ± 7.6 yr; 11 men) performed a 5-min treadmill test (speed: ∼4 km/h; grade: ∼25%) on two separate days randomized between control (C) and experimentally induced leg fatigue (E) achieved by repeated knee extension against 40% body weight until task failure. Oxygen uptake (V̇o2, l/min), carbon dioxide output (V̇co2, l/min), ventilation (V̇e, l/min), and respiratory rate (fR) were measured breath by breath. Heart rate (HR) and perceived dyspnea intensity (0-10 numerical scale) were recorded continuously. Data were averaged over 30-s intervals. Exertional dyspnea during E was statistically significantly higher (E vs. C: 4.2 ± 0.2 vs. 3.4 ± 0.2, P leg fatigue. These findings support the hypothesis that the intensity of exertional dyspnea is exacerbated by peripheral afferent information from fatigued leg muscles.

  17. Chronic exertional compartment syndrome of the forearm in motocross racers: findings on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Gielen, Jan Louis [Antwerp University Hospital, Department of Radiology, Antwerp (Belgium); Antwerp University Hospital, Multidisciplinary Department of Sports Medicine, Antwerp (Belgium); Peersman, Benjamin; Dyck, Pieter van; Vanhoenacker, Filip [Antwerp University Hospital, Department of Radiology, Antwerp (Belgium); Peersman, Geert [ZNA, Department of Orthopaedic Surgery, Antwerp (Belgium); Roelant, Ella [Antwerp University Hospital, Department of Scientific Coordination, Antwerp (Belgium); Roeykens, Johan [Antwerp University Hospital, Multidisciplinary Department of Sports Medicine, Antwerp (Belgium)

    2009-12-15

    The purpose of this prospective study was to demonstrate the findings of MRI in motocross racers with chronic exertional compartment syndrome (CECS) of the forearm. Racers with proven CECS and without CECS and male individuals not involved in strenuous activities with the forearm were included. Signal intensity (SI) and signal-to-noise ratio (SNR) obtained before and after exercise were compared (D-SNR). Magnetic resonance imaging after exercise showed an increase in SI and SNR in the muscles on T2-WI. The SI increase was obvious in the flexor digitorum superficialis (FDS) and profundus (FDP) in all CECS patients. In addition, a minor SI and SNR increase in the extensor carpi radialis longus (ECRL) was noted. In the non-symptomatic group of motocross racers, there was only a minor increase in SI and the SNR, which was similar in the FDP and ECRL muscles. In the untrained individuals a remarkable increase in the SI and SNR of the FDS/FDP-ECRL was noted. This increased SI and SNR was not present in the majority of non-symptomatic racers. Post-exertional MRI produces significant findings in CECS of the forearm. The motocross racers without post-exertional oedema in the FDP/FDS had no CECS. (orig.)

  18. 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.

  19. Exertional rhabdomyolysis after spinning: case series and review of the literature.

    Science.gov (United States)

    Ramme, Austin J; Vira, Shaleen; Alaia, Michael J; VAN DE Leuv, Jonathan; Rothberg, Robert C

    2016-06-01

    Spinning is a popular indoor stationary cycling program that uses group classes as a motivational tool. Exertional rhabdomyolysis (ER) is frequently reported in athletes and military recruits; however, infrequently it has been reported after spinning class. ER is diagnosed by clinical history, physical exam, and laboratory values. Hydration, electrolyte management, and pain control are key components to treatment of this condition. Severe cases can be complicated by acute renal failure, compartment syndrome, arrhythmia, and disseminated intravascular coagulation. We describe three cases of admission due to rhabdomyolysis after spinning. The diagnosis, admission criteria, and medical treatment of ER are presented in the context of a literature review. A retrospective review of three cases with review of the current literature. The medical and laboratory records of three patient cases were reviewed. A search of the PubMed database was used to perform a comprehensive review of exertional rhabdomyolysis. Our institution's IRB reviewed this study. We report three cases of exertional rhabdomyolysis after spinning and describe the diagnostic workup and medical management of these patients. The diagnosis of ER is made by clinical history, physical exam, and laboratory values. The disease spectrum ranges from mild to severe with the potential of serious complications in some patients. We demonstrate three cases of ER in deconditioned individuals who presented to the emergency department for evaluation. Careful medical management and patient monitoring resulted in improved patient symptomatology and eventual return to physical activity.

  20. Consistency and variation in phenotypic selection exerted by a community of seed predators.

    Science.gov (United States)

    Benkman, Craig W; Smith, Julie W; Maier, Monika; Hansen, Leif; Talluto, Matt V

    2013-01-01

    Phenotypic selection that is sustained over time underlies both anagenesis and cladogenesis, but the conditions that lead to such selection and what causes variation in selection are not well known. We measured the selection exerted by three species of predispersal seed predators of lodgepole pine (Pinus contorta latifolia) in the South Hills, Idaho, and found that net selection on different cone and seed traits exerted by red crossbills (Loxia curvirostra) and cone borer moths (Eucosma recissoriana) over 10 years of seed crops was similar to that measured in another mountain range. We also found that the strength of selection increased as seed predation increased, which provides a mechanism for the correlation between the escalation of seed defenses and the density of seed predators. Red crossbills consume the most seeds and selection they exert accounts for much of the selection experienced by lodgepole pine, providing additional support for a coevolutionary arms race between crossbills and lodgepole pine in the South Hills. The third seed predator, hairy woodpeckers (Picoides villosus), consumed less than one-sixth as many seeds as crossbills. Across the northern Rocky Mountains, woodpecker abundance and therefore selective impact appears limited by the elevated seed defenses of lodgepole pine.

  1. Motivation as a factor of perceived exertion in purposeful versus nonpurposeful activity.

    Science.gov (United States)

    Kircher, M A

    1984-03-01

    Perceived exertion during the performance of purposeful and nonpurposeful activity was studied in 26 women. The subjects acted as their own controls in the performance of both kinds of exercise. The two exercises were jumping rope, defined as a purposeful activity, and jumping in place without a rope, defined as a nonpurposeful activity. In each activity the subjects exercised to reach the subjective point of "very hard work" on the Borg Scale of Perceived Exertion. Duration and cessation of exercise were entirely controlled by the performers. Heart rate responses during and immediately after cessation of exercise, measured by electrocardiographic telemetry, and duration of exercise in seconds were compared for the two types of exercise. Results showed that heart rate increase at a given rate of perceived exertion was significantly higher (.001) for jumping rope. This raises the possibility that workload was inadvertently perceived by the performers to be greater in nonpurposeful activity and provides support for the hypothesis that purposeful activity serves as an intrinsic motivator to the performer.

  2. A Study of Exertional Headache’s Prevalence and Characteristics Among Conscripts

    Directory of Open Access Journals (Sweden)

    Tofangchiha

    2016-05-01

    Full Text Available Background Headache is one of the most common complaints in today's society. Patterns and prevalence of headache, especially headaches associated with physical activity (Exertional Headache in the population of conscripts in our country is unknown. Objectives In this cross sectional study we tried to answer these questions to some extent. Patients and Methods Using a Persian questionnaire based on international headache society criteria of headache types (ICHD-II and a sample size of 300, filled by two trained medical doctors, we gathered our data and analyzed it with an acceptable P value of < 0.05 and a confidence interval of 95%. Results Headache prevalence among our conscript participants was 78.7%. The prevalence of exertional headache was 12.7%. EH sufferers’ mean age was 22.16 (SD: 2.60 years. EH was found more often bilaterally and almost equally pulsating or compressive. The main location of pain was frontotemporal region. The most common aggravating and alleviating factors of EH were hot environment and discontinuation of exercise respectively. Conclusions Our team provided a reasonable database of exertional headache and its characteristics in conscripts’ population which could be used in further investigations to improve their general health and function.

  3. Quercetin does not affect rating of perceived exertion in athletes during the Western States endurance run.

    Science.gov (United States)

    Utter, Alan C; Nieman, David C; Kang, Jie; Dumke, Charles L; Quindry, John C; McAnulty, Steven R; McAnulty, Lisa S

    2009-01-01

    The purpose of this study was to measure the influence of quercetin supplementation on ratings of perceived exertion in ultramarathon runners competing in the 160-km Western States Endurance Run (WSER). Sixty-three runners were randomized to quercetin (Q) and placebo (P) groups, and under double blinded methods ingested four supplements per day with or without 250 mg quercetin for 3 weeks before the WSER. Thirty-nine of the 63 subjects (quercetin N = 18, placebo N = 21) finished the race. At the completion of exercise ratings of perceived exertion (RPE) were assessed at aid stations located at 40, 90, 125, 150, and 160 km (finish line). The pattern of change in RPE over time was not significantly different between the Q and P groups. Ratings of perceived exertion (RPE) did not significantly increase throughout the race (15.2 +/- 2.9 at 40 km -14.2 +/- 4.0 at 160 km) for both groups combined. Race times were not different between the groups (Q = 26.4 +/- 0.7 h and P = 27.5 +/- 0.6 h). Significant time main effects (p fashion but instead fluctuated nonmonotonically throughout the self-paced endurance running event.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Chronic exertional compartment syndrome of the forearm in motocross racers: findings on MRI.

    Science.gov (United States)

    Gielen, Jan Louis; Peersman, Benjamin; Peersman, Geert; Roelant, Ella; Van Dyck, Pieter; Vanhoenacker, Filip; Roeykens, Johan

    2009-12-01

    The purpose of this prospective study was to demonstrate the findings of MRI in motocross racers with chronic exertional compartment syndrome (CECS) of the forearm. Racers with proven CECS and without CECS and male individuals not involved in strenuous activities with the forearm were included. Signal intensity (SI) and signal-to-noise ratio (SNR) obtained before and after exercise were compared (D-SNR). Magnetic resonance imaging after exercise showed an increase in SI and SNR in the muscles on T2-WI. The SI increase was obvious in the flexor digitorum superficialis (FDS) and profundus (FDP) in all CECS patients. In addition, a minor SI and SNR increase in the extensor carpi radialis longus (ECRL) was noted. In the non-symptomatic group of motocross racers, there was only a minor increase in SI and the SNR, which was similar in the FDP and ECRL muscles. In the untrained individuals a remarkable increase in the SI and SNR of the FDS/FDP-ECRL was noted. This increased SI and SNR was not present in the majority of non-symptomatic racers. Post-exertional MRI produces significant findings in CECS of the forearm. The motocross racers without post-exertional oedema in the FDP/FDS had no CECS.

  7. Selective Fasciotomy for Chronic Exertional Compartment Syndrome Detected With Exercise Magnetic Resonance Imaging.

    Science.gov (United States)

    Park, Sehan; Lee, Ho Seong; Seo, Sang Gyo

    2017-06-15

    Chronic exertional compartment syndrome that is refractory to conservative management should be treated with surgical fasciotomy. However, owing to the limitations of intracompartmental needle manometry in reaching a definite diagnosis, the appropriate timing for fasciotomy and on which compartment remain unclear. The authors report the case of a 22-year-old male military cadet who reported pain in his left calf when running or walking for long distances. The pain was located at the lateral aspect of the calf, from the mid-calf level to the ankle. At another hospital, nonenhanced magnetic resonance imaging had been performed, which showed no considerable abnormality. The authors used exercise magnetic resonance imaging to diagnose chronic exertional compartment syndrome. They performed selective fasciotomy on the compartment that showed a high signal intensity. As a military cadet, the patient was required to jog for more than an hour per day and perform strenuous muscle exercises. He reported that he did not have calf pain or discomfort during such activities 13 months postoperatively. The authors obtained a follow-up exercise magnetic resonance image. Compared with the preoperative magnetic resonance image, the follow-up exercise magnetic resonance image did not show high signal intensity at the lateral compartment. Exercise magnetic resonance imaging is useful in confirming the diagnosis of chronic exertional compartment syndrome and enables the performance of selective fasciotomy on the affected compartment. [Orthopedics. 201x; xx(x):xx-xx.]. Copyright 2017, SLACK Incorporated.

  8. Single minimal incision fasciotomy for chronic exertional compartment syndrome of the lower leg.

    Science.gov (United States)

    Maffulli, Nicola; Loppini, Mattia; Spiezia, Filippo; D'Addona, Alessio; Maffulli, Gayle D

    2016-05-24

    Chronic exertional compartment syndrome (CECS) involves a painful increase in compartment pressure caused by exercise and relieved by rest, common in athletes. The most common site for CECS in the lower limbs is the anterior leg compartment. The aim of this study is to evaluate the outcomes of a single minimal incision fasciotomy in athletes and their capability to return to high level sport activity. The study reports mid-term results in a series of 18 consecutive athletes with chronic exertional compartment syndrome of the leg who had undergone minimally invasive fasciotomy. Between 2000 and 2007, we prospectively enrolled 18 consecutive athletes (12 males and six females, median age 27 years) with unilateral or bilateral chronic exertional compartment syndrome undergoing unilateral or bilateral minimally invasive fasciotomy. Clinical outcomes were assessed with Short-Form Health Survey-36 (SF-36) and European Quality of Life-5 Dimension (EQ-5D) scale. The ability to participate in sport before and after surgery and the time to return to training (RTT) and to sport (RTS) were recorded. The median follow-up after surgery was 36 months. Both questionnaires showed a statistically significant improvement (P compartment syndrome of the anterior and lateral compartments of the leg with good results in the mid-term.

  9. Caffeine and theanine exert opposite effects on attention under emotional arousal.

    Science.gov (United States)

    Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Taylor, Holly A; Kanarek, Robin B

    2017-01-01

    Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p Caffeine reduced flanker conflict difference scores on the Attention Network Test (p caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.

  10. Defining the focus of attention: effects of attention on perceived exertion and fatigue.

    Science.gov (United States)

    Lohse, Keith R; Sherwood, David E

    2011-01-01

    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, 2007a) compared to associative/dissociative (e.g., Stevinson and 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Coleusin factor exerts cytotoxic activity by inducing G0/G1 cell cycle arrest and apoptosis in human gastric cancer BGC-823 cells.

    Science.gov (United States)

    Sun, Bo; Geng, Shuo; Huang, Xiaojia; Zhu, Jin; Liu, Shu; Zhang, Yajing; Ye, Jian; Li, Yongjin; Wang, Jingze

    2011-02-01

    Coleusin factor (CF), a kind of diterpenoids, is isolated and purified from the root of a Chinese tropical plant Coleus forskohlii by our laboratory. Our previous studies have demonstrated that CF significantly inhibits growth in some kinds of cancer cell lines. Here, we found that CF remarkably inhibited growth in human gastric cancer BGC-823 cells by decreasing cell proliferation, inducing G(0)/G(1) cell cycle arrest and apoptosis. CF also decreased the mitochondrial membrane potential in BGC-823 cells. Immunoblotting analysis revealed that CF significantly decreased the expressions of cyclinD1, Bcl-2, and Bcl-x(L), increased the expressions of cytosol cytochrome c, p53, p21, and Rb. In addition, CF significantly increased the expressions and activities of caspase-3 and -9. More importantly, CF potently inhibited the growth of BGC-823 cells xenografted in athymic nude mice with negligible body weight loss and damage towards the spleen. These results indicate that CF exerts a cytotoxic effect on BGC-823 cells by inducing cell cycle arrest and apoptosis.

  13. Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

    OpenAIRE

    Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, Maria A.; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Jordan K. Zjawiony; Izzo, Angelo A; Capasso, Raffaele; Roviezzo, Fiorentina

    2017-01-01

    Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice we...

  14. 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.

  15. Butanol isomers exert distinct effects on voltage-gated calcium channel currents and thus catecholamine secretion in adrenal chromaffin cells.

    Directory of Open Access Journals (Sweden)

    Sarah McDavid

    Full Text Available Butanol (C4H10OH has been used both to dissect the molecular targets of alcohols/general anesthetics and to implicate phospholipase D (PLD signaling in a variety of cellular functions including neurotransmitter and hormone exocytosis. Like other primary alcohols, 1-butanol is a substrate for PLD and thereby disrupts formation of the intracellular signaling lipid phosphatidic acid. Because secondary and tertiary butanols do not undergo this transphosphatidylation, they have been used as controls for 1-butanol to implicate PLD signaling. Recently, selective pharmacological inhibitors of PLD have been developed and, in some cases, fail to block cellular functions previously ascribed to PLD using primary alcohols. For example, exocytosis of insulin and degranulation of mast cells are blocked by primary alcohols, but not by the PLD inhibitor FIPI. In this study we show that 1-butanol reduces catecholamine secretion from adrenal chromaffin cells to a much greater extent than tert-butanol, and that the PLD inhibitor VU0155056 has no effect. Using fluorescent imaging we show the effect of these drugs on depolarization-evoked calcium entry parallel those on secretion. Patch-clamp electrophysiology confirmed the peak amplitude of voltage-gated calcium channel currents (I(Ca is inhibited by 1-butanol, with little or no block by secondary or tert-butanol. Detailed comparison shows for the first time that the different butanol isomers exert distinct, and sometimes opposing, effects on the voltage-dependence and gating kinetics of I(Ca. We discuss these data with regard to PLD signaling in cellular physiology and the molecular targets of general anesthetics.

  16. Butanol isomers exert distinct effects on voltage-gated calcium channel currents and thus catecholamine secretion in adrenal chromaffin cells.

    Science.gov (United States)

    McDavid, Sarah; Bauer, Mary Beth; Brindley, Rebecca L; Jewell, Mark L; Currie, Kevin P M

    2014-01-01

    Butanol (C4H10OH) has been used both to dissect the molecular targets of alcohols/general anesthetics and to implicate phospholipase D (PLD) signaling in a variety of cellular functions including neurotransmitter and hormone exocytosis. Like other primary alcohols, 1-butanol is a substrate for PLD and thereby disrupts formation of the intracellular signaling lipid phosphatidic acid. Because secondary and tertiary butanols do not undergo this transphosphatidylation, they have been used as controls for 1-butanol to implicate PLD signaling. Recently, selective pharmacological inhibitors of PLD have been developed and, in some cases, fail to block cellular functions previously ascribed to PLD using primary alcohols. For example, exocytosis of insulin and degranulation of mast cells are blocked by primary alcohols, but not by the PLD inhibitor FIPI. In this study we show that 1-butanol reduces catecholamine secretion from adrenal chromaffin cells to a much greater extent than tert-butanol, and that the PLD inhibitor VU0155056 has no effect. Using fluorescent imaging we show the effect of these drugs on depolarization-evoked calcium entry parallel those on secretion. Patch-clamp electrophysiology confirmed the peak amplitude of voltage-gated calcium channel currents (I(Ca)) is inhibited by 1-butanol, with little or no block by secondary or tert-butanol. Detailed comparison shows for the first time that the different butanol isomers exert distinct, and sometimes opposing, effects on the voltage-dependence and gating kinetics of I(Ca). We discuss these data with regard to PLD signaling in cellular physiology and the molecular targets of general anesthetics.

  17. Right hemisphere dominance directly predicts both baseline V1 cortical excitability and the degree of top-down modulation exerted over low-level brain structures.

    Science.gov (United States)

    Arshad, Q; Siddiqui, S; Ramachandran, S; Goga, U; Bonsu, A; Patel, M; Roberts, R E; Nigmatullina, Y; Malhotra, P; Bronstein, A M

    2015-12-17

    Right hemisphere dominance for visuo-spatial attention is characteristically observed in most right-handed individuals. This dominance has been attributed to both an anatomically larger right fronto-parietal network and the existence of asymmetric parietal interhemispheric connections. Previously it has been demonstrated that interhemispheric conflict, which induces left hemisphere inhibition, results in the modulation of both (i) the excitability of the early visual cortex (V1) and (ii) the brainstem-mediated vestibular-ocular reflex (VOR) via top-down control mechanisms. However to date, it remains unknown whether the degree of an individual's right hemisphere dominance for visuospatial function can influence, (i) the baseline excitability of the visual cortex and (ii) the extent to which the right hemisphere can exert top-down modulation. We directly tested this by correlating line bisection error (or pseudoneglect), taken as a measure of right hemisphere dominance, with both (i) visual cortical excitability measured using phosphene perception elicited via single-pulse occipital trans-cranial magnetic stimulation (TMS) and (ii) the degree of trans-cranial direct current stimulation (tDCS)-mediated VOR suppression, following left hemisphere inhibition. We found that those individuals with greater right hemisphere dominance had a less excitable early visual cortex at baseline and demonstrated a greater degree of vestibular nystagmus suppression following left hemisphere cathodal tDCS. To conclude, our results provide the first demonstration that individual differences in right hemisphere dominance can directly predict both the baseline excitability of low-level brain structures and the degree of top-down modulation exerted over them.

  18. A candidate anti-HIV reservoir compound, auranofin, exerts a selective 'anti-memory' effect by exploiting the baseline oxidative status of lymphocytes.

    Science.gov (United States)

    Chirullo, B; Sgarbanti, R; Limongi, D; Shytaj, I L; Alvarez, D; Das, B; Boe, A; DaFonseca, S; Chomont, N; Liotta, L; Petricoin, E Iii; Norelli, S; Pelosi, E; Garaci, E; Savarino, A; Palamara, A T

    2013-12-05

    Central memory (T(CM)) and transitional memory (T(TM)) CD4(+) T cells are known to be the major cellular reservoirs for HIV, as these cells can harbor a transcriptionally silent form of viral DNA that is not targeted by either the immune system or current antiretroviral drug regimens. In the present study, we explored the molecular bases of the anti-HIV reservoir effects of auranofin (AF), a pro-oxidant gold-based drug and a candidate compound for a cure of AIDS. We here show that T(CM) and T(TM) lymphocytes have lower baseline antioxidant defenses as compared with their naive counterpart. These differences are mirrored by the effects exerted by AF on T-lymphocytes: AF was able to exert a pro-differentiating and pro-apoptotic effect, which was more pronounced in the memory subsets. AF induced an early activation of the p38 mitogen-activated protein kinase (p38 MAPK) followed by mitochondrial depolarization and a final burst in intracellular peroxides. The pro-differentiating effect was characterized by a downregulation of the CD27 marker expression. Interestingly, AF-induced apoptosis was inhibited by pyruvate, a well-known peroxide scavenger, but pyruvate did not inhibit the pro-differentiating effect of AF, indicating that the pro-apoptotic and pro-differentiating effects involve different pathways. In conclusion, our results demonstrate that AF selectively targets the T(CM)/T(TM) lymphocyte subsets, which encompass the HIV reservoir, by affecting redox-sensitive cell death pathways.

  19. Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2–NFκB pathways

    Energy Technology Data Exchange (ETDEWEB)

    Das, Joydeep; Ghosh, Jyotirmoy; Roy, Anandita; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

    2012-04-01

    Mangiferin, a xanthone glucoside, is well known to exhibit antioxidant, antiviral, antitumor, anti-inflammatory and gene-regulatory effects. In the present study, we isolated mangiferin from the bark of Mangifera indica and assessed its beneficial role in galactosamine (GAL) induced hepatic pathophysiology. GAL (400 mg/kg body weight) exposed hepatotoxic rats showed elevation in the activities of serum ALP, ALT, levels of triglycerides, total cholesterol, lipid-peroxidation and reduction in the levels of serum total proteins, albumin and cellular GSH. Besides, GAL exposure (5 mM) in hepatocytes induced apoptosis and necrosis, increased ROS and NO production. Signal transduction studies showed that GAL exposure significantly increased the nuclear translocation of NFκB and elevated iNOS protein expression. The same exposure also elevated TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18 and decreased IL-10 mRNA expressions. Furthermore, GAL also decreased the protein expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1 and GSTα. However, mangiferin administration in GAL intoxicated rats or coincubation of hepatocytes with mangiferin significantly altered all these GAL-induced adverse effects. In conclusion, the hepatoprotective role of mangiferin was due to induction of antioxidant defense via the Nrf2 pathway and reduction of inflammation via NFκB inhibition. Highlights: ►Galactosamine induces hepatocytes death via oxidative and nitrosative stress. ►Mangiferin exerts hepatoprotective effect/antioxidant defense via Nrf2 pathway. ►Mangiferin exerts anti-inflammatory responses by inhibiting NF-κB. ►Mangiferin suppresses galactosamine-induced repression of IL-10 mRNA.

  20. Core Muscle Activity, Exercise Preference, and Perceived Exertion during Core Exercise with Elastic Resistance versus Machine

    Directory of Open Access Journals (Sweden)

    Jonas Vinstrup

    2015-01-01

    Full Text Available Objectives. To investigate core muscle activity, exercise preferences, and perceived exertion during two selected core exercises performed with elastic resistance versus a conventional training machine. Methods. 17 untrained men aged 26–67 years participated in surface electromyography (EMG measurements of five core muscles during torso-twists performed from left to right with elastic resistance and in the machine, respectively. The order of the exercises was randomized and each exercise consisted of 3 repetitions performed at a 10 RM load. EMG amplitude was normalized (nEMG to maximum voluntary isometric contraction (MVC. Results. A higher right erector spinae activity in the elastic exercise compared with the machine exercise (50% [95% CI 36–64] versus 32% [95% CI 18–46] nEMG was found. By contrast, the machine exercise, compared with the elastic exercise, showed higher left external oblique activity (77% [95% CI 64–90] versus 54% [95% CI 40–67] nEMG. For the rectus abdominis, right external oblique, and left erector spinae muscles there were no significant differences. Furthermore, 76% preferred the torso-twist with elastic resistance over the machine exercise. Perceived exertion (Borg CR10 was not significantly different between machine (5.8 [95% CI 4.88–6.72] and elastic exercise (5.7 [95% CI 4.81–6.59]. Conclusion. Torso-twists using elastic resistance showed higher activity of the erector spinae, whereas torso-twist in the machine resulted in higher activity of the external oblique. For the remaining core muscles the two training modalities induced similar muscular activation. In spite of similar perceived exertion the majority of the participants preferred the exercise using elastic resistance.

  1. Fructose addition to a glucose supplement modifies perceived exertion during strength and endurance exercise.

    Science.gov (United States)

    Da Silva-Grigoletto, Marzo E; Fernández, Juan M; de Sá, Clodoaldo A; Gómez-Puerto, José R; Vaamonde, Diana; Pérez-Jiménez, Francisco

    2010-12-01

    The addition of fructose (F) to a glucose (G) supplement may modify the metabolic response during exercise; however, its effect on perceived exertion (PE) and its influence on postprandial metabolism have not been jointly studied in different types of exercise. This study sought to assess the acute effects of F addition to a G supplement on PE and on the postprandial metabolic response during a single bout of either strength exercise (SE) or endurance exercise (EE). Twenty physically trained men ingested an oral dose of G or GF 15 minutes before starting a 30-minute session of SE (10 sets of 10 repetitions of half squat) or EE (cycling). The combination resulted in 4 randomized interventions in a crossover design in which all subjects performed all experimental conditions: G + SE, GF + SE, G + EE, and GF + SE. Perceived exertion, heart rate (HR), G, insulin, lactate, and urinary catecholamine levels were measured before exercise, during the exercise, and during acute recovery. Perceived exertion during exercise was lower for GF than for G during SE and EE (mean ± SD; 8.95 ± 0.62 vs. 9.26 ± 0.65, p vs. 7.74 ± 0.93, p < 0.05, respectively). The glycemic peak in GF + SE was lower than in G + SE (p < 0.05), and there was a second peak during recovery (p < 0.05), whereas in EE, no difference in blood G levels was noted between G and GF supplements. Moreover, HR, urinary adrenalin, and noradrenalin were lower in GF than in G (p < 0.05), though only for EE. The results showed that PE is positively affected by GF supplementation for both SE and EE and thus may be a useful dietary strategy for helping to achieve higher training loads.

  2. Exertion and pain do not alter coordination variability in runners with iliotibial band syndrome.

    Science.gov (United States)

    Hafer, Jocelyn F; Brown, Allison M; Boyer, Katherine A

    2017-08-01

    Iliotibial band syndrome is a common overuse running injury which results in altered mechanics. While injuries alter discrete mechanics, they may also cause a change in coordination variability, the stride-to-stride organization of runners' movement patterns. Uninjured and injured runners may experience a change in coordination variability during a run to exertion due to fatigue, pain, or a combination of these factors. The aim of the current study was to determine if runners with iliotibial band syndrome and uninjured runners display different segment coordination variability across the course of a run to exertion. 3D kinematics were collected as 13 uninjured runners and 12 runners with iliotibial band syndrome ran on a treadmill. A modified vector coding technique was used to calculate coordination variability during stance for segment couples of interest. Coordination variability was compared between uninjured and injured runners at the beginning and end of the run. The influence of pain on coordination variability was also examined. There were no differences in coordination variability at the beginning or end of the run between uninjured runners and those with iliotibial band syndrome. The change in coordination variability due to the run was not different between uninjured runners, injured runners who experienced no change in pain, and injured runners who did experience a change in pain. Runners do not constrain the patterns of segment motion they use in response to exertion nor does it appear that occurrence of pain during running results in a differential change in coordination variability. Copyright © 2017. Published by Elsevier Ltd.

  3. Cerebellar cortical inhibition and classical eyeblink conditioning.

    Science.gov (United States)

    Bao, Shaowen; Chen, Lu; Kim, Jeansok J; Thompson, Richard F

    2002-02-01

    The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning/memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a gamma-aminobutyric acid type A receptor (GABA(A)R) agonist and a noncompetitive GABA(A)R antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABA(A)Rs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.

  4. Optical measurement of torque exerted on an elongated object by a non-circular laser beam

    CERN Document Server

    Parkin, S J; Heckenberg, N R; Rubinsztein-Dunlop, H; Parkin, Simon J.; Nieminen, Timo A.; Heckenberg, Norman R.; Rubinsztein-Dunlop, Halina

    2004-01-01

    We have developed a scheme to measure the optical torque, exerted by a laser beam on a phase object, by measuring the orbital angular momentum of the transmitted beam. The experiment is a macroscopic simulation of a situation in optical tweezers, as orbital angular momentum has been widely used to apply torque to microscopic objects. A hologram designed to generate LG02 modes and a CCD camera are used to detect the orbital component of the beam. Experimental results agree with theoretical numerical calculations, and the strength of the orbital component suggest its usefulness in optical tweezers for micromanipulation.

  5. High-Output Heart Failure from a Hepatic Hemangioma With Exertion-Induced Hypoxia.

    Science.gov (United States)

    Smith, Aaron A H; Nelson, Matthew

    2016-01-01

    Patients with hepatic hemangiomas have been known to have high-output heart failure as a result of left-to-right arteriovenous shunting. We report a patient with a hepatic hemangioma that presented with high-output heart failure with hypoxia on exertion. After embolization of the hemangioma, the patient's hypoxia resolved and ejection fraction improved. In the absence of cardiopulmonary pathophysiology, we presume that our patient's hemangioma was causing a right-to-left shunt as opposed to an expected left-to-right shunt.

  6. 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

    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...

  7. Global Partnership China and India seek to exert a positive influence on-the world

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    China and India seek to exert a positive influence on-the world Chinese Premier Wen Jiabao dis- played his signature smile as he and his visiting Indian counter- part Manmohan Singh signed a document to upgrade China-India relations in the Great Hall of the People in Beijing on January 14.Wen had good rea- son to be confident.Having just concluded a fruitful meeting in which the two leaders reached a consensus on a wide range of top- ics,they were now reaffirming in a written document the two countries’commitment to intensifying bilateral cooperation from a global perspective.

  8. Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro

    Science.gov (United States)

    Shen, Xin; Zhou, Nan; Mi, Le; Hu, Zishuo; Wang, Libin; Liu, Xueying; Zhang, Shengyong

    2017-01-01

    The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph). In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6) myotubes. Daily oral treatment with Ph for 4 weeks significantly (PGLUT4 were upregulated in skeletal muscle of type 2 diabetes (T2D) rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes. PMID:28223777

  9. 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.

  10. Fruit extract of the medicinal plant Crataegus oxyacantha exerts genotoxic and mutagenic effects in cultured cells.

    Science.gov (United States)

    de Quadros, Ana Paula Oliveira; Mazzeo, Dania Elisa Christofoletti; Marin-Morales, Maria Aparecida; Perazzo, Fábio Ferreira; Rosa, Paulo Cesar Pires; Maistro, Edson Luis

    2017-01-01

    Crataegus oxyacantha, a plant of the Rosaceae family also known "English hawthorn, haw, maybush, or whitethorn," has long been used for medicinal purposes such as digestive disorders, hyperlipidemia, dyspnea, inducing diuresis, and preventing kidney stones. However, the predominant use of this plant has been to treat cardiovascular disorders. Due to a lack of studies on the genotoxicity of C. oxyacantha, this investigation was undertaken to determine whether its fruit extract exerts cytotoxic, genotoxic, or clastogenic/aneugenic effects in leukocytes and HepG2 (liver hepatocellular carcinoma) cultured human cells, or mutagenic effects in TA100 and TA98 strains of Salmonella typhimurium bacterium. Genotoxicity analysis showed that the extract produced no marked genotoxic effects at concentrations of 2.5 or 5 µg/ml in either cell type; however, at concentrations of 10 µg/ml or higher significant DNA damage was detected. The micronucleus test also demonstrated that concentrations of 10 µg/ml or higher produced clastogenic/aneugenic responses. In the Ames test, the extract induced mutagenic effects in TA98 strain of S. typhimurium with metabolic activation at all tested concentrations (2.5 to 500 µg/ml). Data indicate that, under certain experimental conditions, the fruit extract of C. oxyacantha exerts genotoxic and clastogenic/aneugenic effects in cultured human cells, and with metabolism mutagenicity occurs in bacteria cells.

  11. 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

    2015-03-12

    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.

  12. Analysis of the effect of different intensities and rest interval on the perceived exertion of athletes

    Directory of Open Access Journals (Sweden)

    V.O. Damasceno

    2011-01-01

    Full Text Available The research examined the effects of different intensities and different rest intervals of strength training on the rating of perceived exertion (RPE in young athletes. Participated in the study 23 young men, aged 17.06 ± .73 years, 68.01 ± 8.09 kg of body mass, and 173.65 �� 5.61 cm of height. They were submitted to the appropriateness of charges (5 RM, 10 RM or 15 RM and rest intervals (30, 60 or 120 s and then asked to point perceived exertion according to the OMNI-RES scale. A two-way ANOVA was used and significant differences were analyzed by post-hoc Bonferroni. For RPE there were no significant differences between the intensities in the recovery intervals evaluated. For intervals with the same intensity, there were differences between 15 RM and range of 120 and 60 s with 15 RM and 30 s intervals. Intensities of 10 and 5 RM, in the range of 120 s showed significant differences. It follows that the smaller the rest interval the greater the levels of fatigue regardless of the number of repetitions performed in all intensities and it may be inferred that the RPE was sensitive to reduction in the rest interval.

  13. Witnesses in action: the effect of physical exertion on recall and recognition.

    Science.gov (United States)

    Hope, Lorraine; Lewinski, William; Dixon, Justin; Blocksidge, David; Gabbert, Fiona

    2012-04-01

    Understanding memory performance under different operational conditions is critical in many occupational settings. To examine the effect of physical exertion on memory for a witnessed event, we placed two groups of law-enforcement officers in a live, occupationally relevant scenario. One group had previously completed a high-intensity physical-assault exercise, and the other had not. Participants who completed the assault exercise showed impaired recall and recognition performance compared with the control group. Specifically, they provided significantly less accurate information concerning critical and incidental target individuals encountered during the scenario, recalled less briefing information, and provided fewer briefing updates than control participants did. Exertion was also associated with reduced accuracy in identifying the critical target from a lineup. These results support arousal-based competition accounts proposing differential allocation of resources under physiological arousal. These novel findings relating to eyewitness memory performance have important implications for victims, ordinary citizens who become witnesses, and witnesses in policing, military, and related operational contexts.

  14. 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 attention. Via psychological mechanisms alone, visual nature facilitates attention restoration during moderate-intensity exercise.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Adenovirus with p16 gene exerts antitumor effect on laryngeal carcinoma Hep2 cells.

    Science.gov (United States)

    Yang, Zhengang; Hu, Jingxia; Li, Dajun; Pan, Xinliang

    2016-08-01

    Laryngeal cancer is an uncommon form of cancer. The tumor suppressor P16, known to be mutated or deleted in various types of human tumor, including laryngeal carcinoma, is involved in the formation and development of laryngeal carcinoma. It has been previously reported that the inactivation or loss of P16 is associated with the acquisition of malignant characteristics. The current study hypothesized that restoring wild‑type P16 activity into P16‑null malignant Hep2 cells may exert an antitumor effect. A recombinant adenovirus carrying the P16 gene (Ad‑P16) was used to infect and express high levels of P16 protein in P16‑null Hep2 cells. Cell proliferation and invasion assays and polymerase chain reaction were performed to evaluate the effects of the P16 gene on cell proliferation and the antitumor effect on Hep2 cells. The results demonstrated that the Hep2 cells infected with Ad‑P16 exhibited significantly reduced cell proliferation, invasion and tumor volume compared with untreated or control adenovirus cells. Furthermore, the expression of laryngeal carcinoma‑associated genes, EGFR, survivin and cyclin D1, were measured in Ad‑P16‑infected cells and were significantly reduced compared with control groups. The results of the current study demonstrate that restoring wild‑type P16 activity into P16-null Hep2 cells exerts an antitumor effect.

  17. 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.

  18. Raw and thermally treated cement asbestos exerts different cytotoxicity effects on A549 cells in vitro.

    Science.gov (United States)

    Pugnaloni, Armanda; Lucarini, Guendalina; Rubini, Corrado; Smorlesi, Arianna; Tomasetti, Marco; Strafella, Elisabetta; Armeni, Tatiana; Gualtieri, Alessandro F

    2015-01-01

    Raw cement asbestos (RCA) undergoes a complete solid state transformation when heated at high temperatures. The secondary raw material produced, high temperatures-cement asbestos (HT-CA) is composed of newly-formed crystals in place of the asbestos fibers present in RCA. Our previous study showed that HT-CA exerts lower cytotoxic cell damage compared to RCA. Nevertheless further investigations are needed to deepen our understanding of pathogenic pathways involving oxidative and nitrative damage. Our aim is to deepen the understanding of the biological effects on A549 cells of these materials regarding DNA damage related proteins (p53, its isoform p73 and TRAIL) and nitric oxide (NO) production during inducible nitric oxide synthase (iNOS)-mediated inflammation. Increments of p53/p73 expression, iNOS positive cells and NO concentrations were found with RCA, compared to HT-CA and controls mainly at 48 h. Interestingly, ferrous iron causing reactive oxygen species (ROS)-mediated DNA damage was found in RCA as a contaminant. HT-CA thermal treatment induces a global recrystallization with iron in a crystal form poorly released in media. HT-CA slightly interferes with genome expression and exerts lower inflammatory potential compared to RCA on biological systems. It could represent a safe approach for storing or recycling asbestos and an environmentally friendly alternative to asbestos waste.

  19. EXERTIONAL COMPARTMENT SYNDROME: REVIEW OF THE LITERATURE AND PROPOSED REHABILITATION GUIDELINES FOLLOWING SURGICAL RELEASE

    Science.gov (United States)

    2011-01-01

    Background: There is little published information regarding postoperative management of patients with Chronic Exertional Compartment Syndrome (CECS). Reports of recurrence of symptoms following surgical decompression exist, and are not uncommon depending on the specific technique used. Recurrence suggests that more time and effort may need to be spent on implementing strategic post-operative rehabilitation management in order to avoid repeat surgical intervention or prolonged symptoms. Objective: To summarize relevant literature regarding CECS and propose scientifically-based guidelines for rehab following compartment release with the rationale based on tissue healing, muscle loading, and scar tissue formation and consideration of all tissues contained in the involved compartment. Literature review: A literature search was performed in PubMed, SPORTDiscus, CINAHL, PEDRO, and Google Scholar using the phrase: “chronic exertional compartment syndrome.” Results: No specific rehabilitation guidelines following surgical compartment release for lower extremity CECS were found in the literature search performed for this clinical commentary. Discussion: The development of the proposed post-operative guidelines may allow for improved long-term outcomes following anterior compartment release. Summary: Adequate description of long-term follow-up of outcomes following compartment release for CECS is lacking in current literature. The proposed guidelines for rehab following compartment release include consideration of tissue healing, muscle loading, scar tissue formation, and consideration of soft tissues contained in the involved compartment. Utilization of the proposed guidelines may allow for future research to be performed in order to assess outcomes following surgical intervention for CECS. PMID:21713230

  20. OMNI Scale of Perceived Exertion: mixed gender and race validation for Singapore children during cycle exercise.

    Science.gov (United States)

    Balasekaran, Govindasamy; Loh, Mun Keong; Govindaswamy, Visvasuresh Victor; Robertson, Robert J

    2012-10-01

    The children's OMNI Scale of Perceived Exertion (RPE) has not been validated for children of Asian origin. The purpose was to validate the RPE for Singapore children, 12-15 years. 81 children of male and female of Chinese, Malay, and Indian ethnicities participated in the study. A cross-sectional, perceptual estimation paradigm using a multistage cycle ergometer protocol was used. Oxygen consumption ([Formula: see text]; ml min(-1)), heart rate (HR; beats min(-1)), and RPE for the Overall body (RPE-O), Legs (RPE-L), and Chest (RPE-C) were determined at the end of each continuously administered 3-min power output stage (PO) starting at 25 W with 25 W increments until exhaustion. For validation, linear regression analysis for all PO revealed that RPE-O, RPE-L, and RPE-C for each of the six gender-race and combined cohort distributed as positive linear functions of both [Formula: see text] (ml min(-1), ml kg(-1) min(-1)) and HR (beats min(-1)). All regression functions were statistically significant (P validity was established for male and female Asian children of Chinese, Malay, and Indian origin. Male and female children did not perceive the intensity of exertional perceptions to differ between the legs and the chest. As there were no differences between the undifferentiated and differentiated perceptual responses, a dominant signal was not observed.

  1. Absence of exertional hyperthermia in a 17-year-old boy with severe burns.

    Science.gov (United States)

    McEntire, Serina J; Lee, Jong O; Herndon, David N; Suman, Oscar E

    2009-01-01

    An important safety concern when exercising burned patients is the potential for an excessive increase in core body temperature (hyperthermia=body core temperature>39 degrees C) during exercise. We examined the thermoregulatory response to exercise in the heat (31 degrees C, relative humidity 40%) in a 17-year-old boy with a 99% TBSA burn. A 30-minute exercise test was performed at an intensity of 75% of his peak aerobic capacity. Intestinal temperature was assessed via telemetry with an ingestible capsule. Intestinal temperature was measured before, during, and postexercise. The patient completed 12 minutes of the 30-minute exercise test. Starting core temperature was 36.98 degrees C and increased 0.69 degrees C during exercise. After exercise, intestinal temperature continued to increase, but no hyperthermia was noted. It has been reported that burned children can safely exercise at room temperature; however, the response in the heat is unknown. This patient did not develop exertional hyperthermia, which we propose is due to his low-fitness level and heat intolerance. However, the potential for hyperthermia would be increased if he was forced to maintain a high relative workload in the heat. We propose that severely burned individuals should be able to safely participate in physical activities. However, the decision to stop exercising should be accepted to avoid development of exertional hyperthermia.

  2. Exertional dyspnea as initial manifestation of Takayasu's arteritis – A case report and literature review

    Directory of Open Access Journals (Sweden)

    Bachmann Lucas M

    2001-12-01

    Full Text Available Abstract Background Takayasu's arteritis is a chronic systemic inflammatory disease that usually affects the aorta, its primary branches and occasionally the pulmonary and coronary arteries. Female gender in reproductive age and Asian origin are known factors associated with higher disease prevalence. The clinical manifestations vary considerably and are typically caused by limb or organ ischemia illness and fever. The estimated incidence rate in the western world is 2.6 cases per million persons per year. Occasionally, exertional dyspnea can be the sole primary clinical manifestation of Takayasu's arteritis. Case presentation We report the case of a 57-year-old woman who was referred to our institution with increasing exertional dyspnea caused by pulmonary artery involvement in Takayasu's arteritis. In a review of the literature we discuss demographic data, clinical and radiographic findings and available therapeutic options. Conclusions Dyspnea due to pulmonary artery involvement can be the initial symptom of Takayasu's arteritis. Simple clinical tests, including a complete pulse-status and blood pressure measuring at both arms can lead to the right diagnosis and should always be done beyond the auscultation of the heart and lungs in patients with dyspnea.

  3. 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.

  4. New perspectives on self-control development: Highlighting the role of intentional inhibition

    NARCIS (Netherlands)

    Schel, M.; Scheres, A.P.J.; Crone, E.A.M.

    2014-01-01

    The ability to exert self-control over one׳s thoughts and actions is crucial for successful functioning in daily life. To date, self-control development has been primarily studied from the perspective of externally driven inhibition. In this review, we introduce a new perspective on the development

  5. Self-Reported Low Vitality, Poor Mental Health, and Low Dietary Restraint Are Associated with Overperception of Physical Exertion

    Directory of Open Access Journals (Sweden)

    Paula C. Chandler-Laney

    2010-01-01

    Conclusion. Women with low vitality or poor mental health, and poor dietary control may overperceive exertion. Such overperception may be a barrier to engage in physical activity and thus increase susceptibility to weight gain.

  6. Precision, Accuracy, and Performance Outcomes of Perceived Exertion vs. Heart Rate Guided Run-training.

    Science.gov (United States)

    Johnson, Evan C; Pryor, Riana R; Casa, Douglas J; Ellis, Lindsay A; Maresh, Carl M; Pescatello, Linda S; Ganio, Matthew S; Lee, Elaine C; Armstrong, Lawrence E

    2017-03-01

    Johnson, EC, Pryor, RR, Casa, DJ, Ellis, LA, Maresh, CM, Pescatello, LS, Ganio, MS, Lee, EC, and Armstrong, LE. Precision, accuracy, and performance outcomes of perceived exertion vs. heart rate guided run-training. J Strength Cond Res 31(3): 630-637, 2017-The purpose of this investigation was to compare run-prescription by heart rate (HR) vs. rating of perceived exertion (RPE) during 6 weeks to determine which is superior for consistent achievement of target intensities and improved performance. Forty untrained men participated in this laboratory-controlled and field-controlled trial. Participants were divided into heart rate (HRTG) and rating of perceived exertion training groups (RPETG). All underwent maximal-graded exercise testing and a 12-minute run test before and after training. Intensity was prescribed as either a target HR or RPE that corresponded to 4 relative intensity levels: 45, 60, 75, and 90% V[Combining Dot Above]O2 reserve (V[Combining Dot Above]O2R). Mean exercise intensity over the 6 weeks did not differ between HRTG (65.6 ± 7.2%HRR) and RPETG (61.9 ± 9.0%HRR). V[Combining Dot Above]O2max (+4.1 ± 2.5 ml·kg·min) and 12 minutes run distance (+240.1 ± 150.1 m) improved similarly in HRTG and RPETG (p > 0.05). HRTG displayed lower coefficients of variation (CV) (5.9 ± 4.1%, 3.3 ± 3.8%, and 3.0 ± 2.2%) and %error (4.1 ± 4.7%, 2.3 ± 4.1% and 2.6 ± 3.2%) at 45, 60, and 75% V[Combining Dot Above]O2R compared with RPETG (CV 11.1 ± 5.0%, 7.7 ± 4.1% and 5.6 ± 3.2%; all p < 0.005) %error (15.7 ± 9.2%, 10.6 ± 9.2% and 6.7 ± 3.2%; all p < 0.001), respectively. Overall, HR-prescribed and RPE-prescribed run-training resulted in similar exercise intensity and performance outcomes over 6 weeks. Differences in the CV and %error suggest use of HR monitoring for individuals that are new to running as it improves precision and accuracy but does not increase performance improvements across 6 weeks.

  7. 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

  8. An endocannabinoid uptake inhibitor from black pepper exerts pronounced anti-inflammatory effects in mice.

    Science.gov (United States)

    Reynoso Moreno, Inés; Najar-Guerrero, Israel; Escareno, Noe; Flores, Mario Eduardo; Gertsch, Jürg; Viveros-Paredes, Juan Manuel

    2017-09-24

    Guineensine is a dietary N-isobutylamide widely present in black and long pepper (Piper nigrum and P. longum) previously shown to inhibit cellular endocannabinoid uptake. Given the role of endocannabinoids in inflammation and pain reduction, here we evaluated guineensine in mouse models of acute and inflammatory pain and endotoxemia. Significant dose-dependent anti-inflammatory effects (95.6 ± 3.1 % inhibition of inflammatory pain at 2.5 mg/kg i.p. and 50.0 ± 15.9 % inhibition of edema formation at 5 mg/kg i.p.) and acute analgesia (66.1 ± 28.1 % inhibition at 5.0 mg/kg i.p.) were observed. Moreover, guineensine inhibited pro-inflammatory cytokine production in endotoxemia. Intriguingly, guineensine and LPS independently induced catalepsy but in combination this effect was abolished. Both hypothermia and analgesia were blocked by the CB1 receptor inverse agonist rimonabant but the pronounced hypolocomotion was CB1 receptor-independent. A subsequent screen of 45 CNS-related receptors, ion channels and transporters revealed apparent interactions of guineensine with the dopamine transporter DAT, 5HT2A and sigma receptors, uncovering its prospective polypharmacology. The described potent pharmacological effects of guineensine might relate to the reported anti-inflammatory effects of pepper.

  9. Oxymatrine inhibits microglia activation via HSP60-TLR4 signaling.

    Science.gov (United States)

    Ding, Feijia; Li, Yunhong; Hou, Xiaolin; Zhang, Rui; Hu, Shuting; Wang, Yin

    2016-11-01

    Oxymatrine (OMT) is an alkaloid extracted from Sophora flavescens, which has broad anti-inflammatory, antitumor and immunosuppressant actions. However, the underlying molecular mechanisms have remained elusive. Heat shock protein 60 (HSP60) has recently been shown to have an important role in autoimmune reactions. The present study aimed to investigate whether OMT exerts its anti-inflammatory effects by inhibiting microglial activation and examined the role of HSP60 in this process. Western blot analysis and ELISA showed that OMT decreased the expression and release of HSP60 by LPS-activated BV2 cells. The expression of heat shock factor 1, the transcription factor of HSP60, was also suppressed by OMT. Extracellular HSP60 has been previously indicated to induce microglial apoptosis through the Toll-like receptor (TLR)-4 pathway. Flow cytometric analysis demonstrated that LPS treatment induced apoptosis of BV2 cells, which was inhibited by OMT in parallel with inhibition of LPS-induced expression of TLR-4. Furthermore, OMT was shown to suppress the levels of myeloid differentiation factor (MYD)88, nuclear factor (NF)-κB, caspase-3, inducible nitric oxide synthase, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. In light of these results, it was concluded that OMT may exert its neuroprotective effects via HSP60/TLR-4/MYD88/NF-κB signaling pathways to inhibit microglial activation. OMT may therefore offer substantial therapeutic potential for treating neurodegenerative diseases associated with microglial activation.

  10. Startle stimuli exert opposite effects on human cortical and spinal motor system excitability in leg muscles

    DEFF Research Database (Denmark)

    Ilic, T V; Pötter-Nerger, M; Holler, I

    2011-01-01

    Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains...... (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of approximately 0.5 mV in the slightly preinervated soleus muscle (SOL). In the second experiment, the startling AS was used to condition the size of the H-reflex in SOL muscle. Mean MEP amplitude...... was calculated for each ISI. The conditioning AS suppressed MEP amplitude at ISIs of 30-80 ms. By contrast, H-reflex amplitude was augmented at ISIs of 100-200 ms. In conclusions, acoustic stimulation exerts opposite and ISI-specific effects on the amplitude of MEPs and H-reflex in the SOL muscle, indicating...

  11. 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 horses with overt clinical signs and plasma CK >100 000 IU/L). It was found that plasma creatol (CTL) was positively correlated (p stress in renal injury associated with severe rhabdomyolysis in horses. It is suggested that exaggeration of oxidative stress associated with increased muscle membrane leakage plays a key role in acute kidney injury in Baladi horses with severe rhabdomyolysis.

  12. Perceived exertion is related to muscle activity during leg extension exercise.

    Science.gov (United States)

    Duncan, Michael J; Al-Nakeeb, Yahya; Scurr, Joanna

    2006-01-01

    This study examined the relationship between ratings of perceived exertion and muscle activity during dynamic leg extension exercise using a resistance exercise specific OMNI-RPE scale. Twenty volunteers (10 males, 10 females, age 22.2 +/- 3.1 yr) performed one set of leg extension exercise at 30%, 60%, and 90% of their one-repetition maximum (1-RM). OMNI-RPE responses were assessed for both the active muscle (OMNI-AM) and the overall body (OMNI-O) following each intensity. Electromyography (EMG) data were collected from the rectus femoris, vastus lateralis, and vastus medialis muscles. A two-factor repeated measures ANOVA showed a significant OMNI-RPE (region) X intensity interaction (p muscle groups (all p Muscle activity was significantly and positively related to OMNI-RPE in both the active muscle and overall body (all p < 0.01). The OMNI-Res RPE scale may be a promising technique for regulating resistance training intensity.

  13. Association between the Rating Perceived Exertion, Heart Rate and Blood Lactate in Successive Judo Fights (Randori)

    Science.gov (United States)

    Branco, Braulio H.M.; Massuça, Luis M.; Andreato, Leonardo V.; Marinho, Bruno F.; Miarka, Bianca; Monteiro, Luis; Franchini, Emerson

    2013-01-01

    Purpose This study aims to investigate the association between the rating of perceived exertion (RPE), heart rate (HR) and the blood lactate concentration ([La]) in successive judo fight simulations (randori). Methods Ten athletes participated in the study (age: 25.6±2.1 years; stature: 1.75±0.07 m; body mass: 75.6±14.9kg; %BF: 11.5±7.8%; practice: 14.5±6.2 years) and completed 4 judo fight simulations (T1 to T4) with duration of 5 min separated by 5 min passive recovery periods. Before each randori, [La] and HR were collected, and after each randori, the same measures and the RPE (CR-10 scale) were collected. Results Significant correlations were observed between: (1) CR-10 and HR (T2: r =0.70; T3: r =0.64; both, Pjudo fight simulations (Pjudo, should be done with caution. PMID:23802054

  14. Numerical estimation of 3D mechanical forces exerted by cells on non-linear materials.

    Science.gov (United States)

    Palacio, J; Jorge-Peñas, A; Muñoz-Barrutia, A; Ortiz-de-Solorzano, C; de Juan-Pardo, E; García-Aznar, J M

    2013-01-04

    The exchange of physical forces in both cell-cell and cell-matrix interactions play a significant role in a variety of physiological and pathological processes, such as cell migration, cancer metastasis, inflammation and wound healing. Therefore, great interest exists in accurately quantifying the forces that cells exert on their substrate during migration. Traction Force Microscopy (TFM) is the most widely used method for measuring cell traction forces. Several mathematical techniques have been developed to estimate forces from TFM experiments. However, certain simplifications are commonly assumed, such as linear elasticity of the materials and/or free geometries, which in some cases may lead to inaccurate results. Here, cellular forces are numerically estimated by solving a minimization problem that combines multiple non-linear FEM solutions. Our simulations, free from constraints on the geometrical and the mechanical conditions, show that forces are predicted with higher accuracy than when using the standard approaches.

  15. Postural discomfort and perceived exertion in standardized box-holding postures.

    Science.gov (United States)

    Olendorf, M R; Drury, C G

    2001-12-15

    To help in the design or redesign of workplaces it would be helpful to know in advance the postural stress consequences of a wide range of body postures. This experiment evaluated 168 postures chosen to represent those in the Ovako Working-posture Analysing System (OWAS) using Rated Perceived Exertion (RPE) and Body Part Discomfort (BPD) measures. The postures comprised all combinations of three arm postures, four back postures, seven leg postures and two forces (weights of held boxes). Twelve male subjects held each posture for a fixed duration (20 s) before providing RPE and BPD ratings. Analysis of the ratings gave highly significant main effects, with the major driver being the object weight. As each factor was varied, the largest effect was on the body region corresponding to that factor. A simple main-effects-only additive model explained 91% of the variance of RPE means for the postures.

  16. Effects of Perceived Fitness Level of Exercise Partner on Intensity of Exertion

    Directory of Open Access Journals (Sweden)

    Thomas G.   Plante

    2010-01-01

    Full Text Available Problem statement: Social comparison theory was used to examine if exercising with a research confederate posing as either high fit or low fit would increase the exertion in exercising. Approach: 91 college students were randomly assigned to one of three conditions: Biking alone, biking with a high fit confederate, or biking with a low fit confederate. All participants were instructed to complete 20 min of exercise at 60-70% of their maximum target heart rate. Results: Results indicated that participants in the high fit condition exercised harder than those in the low fit condition. However, no mood differences emerged between conditions. Conclusion: Social comparison theory predicts exercise outcome such that participants gravitate towards the behavior (high fit or low fit of those around them.

  17. Construct and concurrent validation of OMNI-Kayak rating of Perceived Exertion Scale.

    Science.gov (United States)

    Nakamura, Fábio Y; Perandini, Luiz A; Okuno, Nilo M; Borges, Thiago O; Bertuzzi, Rômulo C M; Robertson, Robert J

    2009-06-01

    This study tested the concurrent and construct validity of a newly developed OMNI-Kayak Scale, testing 8 male kayakers who performed a flatwater load-incremented "shuttle" test over a 500-m course and 3 estimation-production trials over a 1,000-m course. Velocity, blood lactate concentration, heart rate, and rating of perceived exertion (RPE), using the OMNI-Kayak RPE Scale and the Borg 6-20 Scale were recorded. OMNI-Kayak Scale RPE was highly correlated with velocity, the Borg 6-20 Scale RPE, blood lactate, and heart rate for both load-incremented test (rs = .87-.96), and estimation trials (rs = .75-.90). There were no significant differences among velocities, heart rate and blood lactate concentration between estimation and production trials. The OMNI-Kayak RPE Scale showed concurrent and construct validity in assessing perception of effort in flatwater kayaking and is a valid tool for self-regulation of exercise intensity.

  18. The rating of perceived exertion during competitive running scales with time.

    Science.gov (United States)

    Faulkner, James; Parfitt, Gaynor; Eston, Roger

    2008-11-01

    This study assessed the relationship of the rating of perceived exertion (RPE) with heart rate and pacing strategy during competitive running races of differing distance and course elevation. Nine men and women competed in a 7-mile road race (7-MR) and the Great West Run half marathon (GWR; 13.1 miles). Heart rate, split mile time, and RPE were recorded throughout the races. The RPE was regressed against time and %time to complete the 7-MR and GWR. Although the rate of increase in RPE was greater in the 7-MR, there were no differences when expressed against %time (inferring that the brain uses a scalar timing mechanism). As the course elevation, distance, pacing strategy, and heart rate response varied between conditions, this study has provided evidence that the perceptual response may have distinct temporal characteristics during distance running. The results provide further evidence that RPE scales with the proportion of exercise time that remains.

  19. Recording forces exerted on the bowel wall during colonoscopy: in vitro evaluation.

    Science.gov (United States)

    Dogramadzi, S; Virk, G S; Bell, G D; Rowland, R S; Hancock, J

    2005-12-01

    A novel system for distributed force measurement between the bowel wall and the shaft of a colonoscope is presented. The system, based on the piezoresistive method, involves the integration of soft miniature transducers to a colonoscope to enable a wide range of forces to be sensed. The attached sensing sheath does not restrict the propulsion of the colonoscope nor notably alter its flexibility. The addition of the sensor sheath increases the colonoscope diameter by 15-20% depending on the type of the colonoscope (adult or paediatric). The transducer's accuracy is +/-20 grammes if it is not subjected to extensive static forces. Under large static force conditions the errors may increase to +/-50 grammes. The tactile force measuring sensors have provided preliminary results from experiments on a model of the large bowel. The force measurements confirm the predictions on the location and magnitude of the forces and that most of the forces are exerted whilst the instrument is looping.

  20. Statins can exert dual, concentration dependent effects on HCV entry in vitro.

    Science.gov (United States)

    Blanchet, Matthieu; Le, Quoc-Tuan; Seidah, Nabil G; Labonté, Patrick

    2016-04-01

    Statins are used daily by a large and increasing number of individuals worldwide. They were initially designed as 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) inhibitors to treat patients with hypercholesterolemia. Recent studies on HCV chronically infected individuals have suggested that their use in vivo in combination with PEG-IFN and ribavirin favor the sustained viral response (SVR). Herein, we describe the effects of a set of statins on HCV entry and on HCV key entry factors in vitro. Our results suggest that all tested statins exert a proviral effect through the upregulation of LDLR. Interestingly, at higher concentration, we also provide evidence of a yet unknown competing antiviral effect of statins (except for pravastatin) through the downregulation of CLDN-1. Importantly, this work enlightens the blunt proviral effect of pravastatin at the entry step of HCV in vitro.

  1. Analysis for the axial force exerted on a micro-particle in the optical vortex

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The axial force exerting to a micro-particle in the TEM01* doughnut mode is calculated by using the ray-optic model. The calculated results show that the optical vortex possesses two advantages in trapping the high-index micro-particles compared with that of the conventional optical tweezers,of which one is the axial force induced by the optical vortex and is three times as great as that of the optical tweezers under the same power level, and the other is of two equilibrium positions in the optical vortex, which indicates that optical vortex is more suitable in trapping particles. Furthermore, the optical vortex can trap the low-index micro-particles, which can not by the conventional optical tweezers.

  2. 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.

  3. Reliability and Validity of the OMNI-Vibration Exercise Scale of Perceived Exertion

    Science.gov (United States)

    Marín, Pedro J.; Santos-Lozano, Alejandro; Santin-Medeiros, Fernanda; Robertson, Robert J.; Garatachea, Nuria

    2012-01-01

    This study examined reliability and concurrent validity of the newly developed OMNI-vibration exercise scale (OMNI-VIBRO) to measure Ratings of Perceived Exertion (RPE) during vibration exercise in twenty recreationally active students (12 males and 8 females). The criterion variables were muscle activity of the Vastus Medialis (VM), Vastus Lateralis (VL), Biceps Femoris (BF), and Medial Gastrocnemius (MG) muscles, as well as accelerations (12.5, 20.2, 30.9, 36.3, 60.1, and 88.4 m·s-2). RPE was registered during the final of each 30 s condition. Each participant attended two laboratory testing sessions. Positive linear regression coefficients (p < 0.001) were found between RPE (OMNI-VIBRO) and acceleration (r = 0.976) and muscle activity of lower-body muscles (r = 0.942). Between session (test-retest), reliability of RPE (OMNI-VIBRO) was good (ICC: 0.790. 95% CI: 0.699-0.854). Conclusions: findings provided concurrent validation of the OMNI-VIBRO to measure RPE for the active muscle and overall body in recreationally active students performing lower-body vibration exercise. Key pointsThe pictorial-verbal category scale of perception of exertion (OMNI-VIBRO) during lower body vibration exercise on a vibration platform showed good concurrent validity.The OMNI-VIBRO method in conjunction with WBV exercise would allow coaches, fitness professionals, or health-care personnel to assess the intensity that corresponds to the level of the vibratory stimulus.The OMNI-VIBRO could be a useful tool of measuring the different intensities of a vibratory-training session and altering the vibratory stimulus in a periodized fashion. PMID:24149351

  4. 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

    2017-03-17

    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.

  5. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters.

    Science.gov (United States)

    Hofmaier, Tina; Luf, Anton; Seddik, Amir; Stockner, Thomas; Holy, Marion; Freissmuth, Michael; Ecker, Gerhard F; Schmid, Rainer; Sitte, Harald H; Kudlacek, Oliver

    2014-07-01

    Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect "fades out" the levamisole/aminorex effect "kicks in".

  6. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters☆

    Science.gov (United States)

    Hofmaier, Tina; Luf, Anton; Seddik, Amir; Stockner, Thomas; Holy, Marion; Freissmuth, Michael; Ecker, Gerhard F.; Schmid, Rainer; Sitte, Harald H.; Kudlacek, Oliver

    2014-01-01

    Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30 μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect “fades out” the levamisole/aminorex effect “kicks in”. PMID:24296074

  7. ASSESSMENT OF SUBJECTIVE PERCEIVED EXERTION AT THE ANAEROBIC THRESHOLD WITH THE BORG CR-10 SCALE

    Directory of Open Access Journals (Sweden)

    Antonio R. Zamunér

    Full Text Available The purpose of this study was to evaluate the anaerobic threshold (AT with a graphic visual method for estimating the intensity of ventilatory and metabolic exertion and to determine the ratings of perceived exertion (RPE on the Borg CR-10 scale during a continuous ramp type exercise test (CT-R. Forty healthy, physically active and sedentary young women (age 23.1 ± 3.52 years were divided into two groups according to their fitness level: active group (AG and sedentary group (SG and were submitted to a CT-R on a cycloergometer with 20 to 25 W/min increments. Shortly before the end of each one-minute period, the subjects were asked to rate dyspnea (RPE-D and leg fatigue (RPE-L on the Borg CR-10 scale. After the AT was determined with the graphic visual method, the score that the volunteers gave on the Borg CR10 scale was verified. Data were analyzed using the Mann-Whitney and Spearman correlation tests with the significance level set at 5%. The mean ratings of RPE-L and RPE-D at the AT level were not significantly different between groups (p > 0.05. Significant correlations were found between VO2, heart rate (HR, power output and RPE for both groups. The muscular and respiratory RPE, according to the Borg CR-10 scale, were correlated with the AT, suggesting that scores close to 5, which correspond to a "strong" perception, may be used as parameters for quantifying aerobic exercise intensity for active and sedentary individuals. The similar perception of exercise intensity, which corresponded to the AT of different individuals, makes it possible to prescribe exercise at an intensity equivalent to the AT by means of the RPE.

  8. Social variables exert selective pressures in the evolution and form of primate mimetic musculature.

    Science.gov (United States)

    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

  9. The effects of physical exertion on decision-making performance of Australian football umpires.

    Science.gov (United States)

    Paradis, Kasey; Larkin, Paul; O'Connor, Donna

    2016-08-01

    Decision-making is a key component of an umpire's in-game performance, with each decision potentially having a direct impact on the result of the game. Additionally, umpires have to be physically fit to ensure they keep up with the gameplay. While research has identified the decision-making demands and running demands of umpires separately, few have explored the relationship between them. The aim of this investigation was to examine the relationship between physical exertion and decision-making performance of Australian football umpires at the sub-elite and junior levels. A total of 18 Australian football umpires (sub-elite, n = 10; junior n = 8) performed 10 × 300 m runs, with each repetition immediately followed by a video-based decision-making test, then 1 min of recovery. A Mann-Whitney U assessment indicated a significant difference between the sub-elite and junior level umpires for decision-making accuracy (U = 13.00, z = -2.43, P = 0.016, r = -0.5). However, there was no significant difference in response time (U = 28.00, z = -1.07, P = 0.315, r = -0.25). The sub-elite umpires completed the running efforts in significantly less time than the junior umpires (P decision-making performance and running times for either skill level (P > 0.05). This suggests decision-making performance may not be affected by physical exertion. Therefore, it may be suggested coaches of football umpires allocate more time to the decision-making development of their umpires instead of focusing largely on the physical fitness side, as is currently the trend.

  10. Delayed onset muscle soreness and perceived exertion following blood flow restriction exercise.

    Science.gov (United States)

    Brandner, Christopher R; Warmington, Stuart A

    2017-01-11

    The purpose of this study was to determine the perceptual responses to resistance exercise with either heavy-loads (80% 1 repetition maximum [1-RM]), light-loads (20% 1-RM), or light-loads in combination with blood flow restriction (BFR). Despite the use of light-loads, it has been suggested that the adoption of BFR resistance exercise may be limited due to increases in delayed onset muscle soreness (DOMS) and perceived exertion. Seventeen healthy untrained males participated in this balanced, randomized cross-over study. Following four sets of elbow-flexion exercise, participants reported ratings of perceived exertion (RPE), with DOMS also recorded for seven days following each trial. DOMS was significantly greater for low-pressure continuous BFR (until 48 h post-exercise) and high-pressure intermittent BFR (until 72 h post-exercise) compared with traditional heavy-load and light-load resistance exercise. In addition, RPE was higher for heavy-load resistance exercise and high-pressure intermittent BFR compared with low-pressure continuous BFR, with all trials greater than light-load resistance exercise. For practitioners working with untrained participants, this study provides evidence to suggest that in order to minimize the perception of effort and post-exercise muscle soreness associated with BFR resistance exercise, continuous low-pressure application may be more preferential compared with intermittent high-pressure application. Importantly, these perceptual responses are relatively short-lived (∼2 days) and have previously been shown to subside after a few exercise sessions. Combined with smaller initial training volumes (set x repetitions) this may limit RPE and DOMS to strengthen uptake and adherence, and assist in program progression for muscle hypertrophy and gains in strength.

  11. 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.

  12. Familial basis of exertional rhabdomyolysis in quarter horse-related breeds.

    Science.gov (United States)

    Valberg, S J; Geyer, C; Sorum, S A; Cardinet, G H

    1996-03-01

    To trace pedigrees from affected horses, identify likely contributing founder horses, and determine the conditional probability of founder genotypes. Muscle biopsy records from the Neuromuscular Disease Laboratory at the University of California-Davis and the University of Minnesota were searched to identify horses with a polysaccharide storage myopathy and exercise intolerance/rhabdomyolysis. Pedigrees containing 5 to 6 generations were obtained where possible. 13 Quarter Horses, 4 American Paint Horses, 3 Appaloosas, and 3 Quarter Horse crossbreds (16 mares, 4 geldings, and 3 stallions) were identified with polysaccharide storage myopathy. Pedigrees were available for 18 horses. Inbreeding coefficients, founder contributions, and conditional probability of founder genotypes were calculated. Three stallions (A, B, and C) were featured prominently in the pedigrees. Stallions A and B descended from a common sire. On average, A contributed 8.8% (range, 0 to 23%) of the genes in affected horses, B contributed 4.2% (range, 0 to 14%), and C contributed 3.0% (range, 0 to 14%). The sire and dam of 4 horses were descendants of stallion A, the sire and dam of 1 horse were descendants of stallion B, and the sire and dam of 11 horses were descendants of a combination of stallions A and B. The pattern of inheritance resembled an autosomal recessive disorder. Assuming this pattern of inheritance, the conditional probability that these founders were carriers or recessive for the trait was > 99.29% for stallions A and B and 92% for stallion C. Results support a familial basis for polysaccharide storage myopathy and associated exertional rhabdomyolysis in Quarter Horse-related breeds. The strong contribution of particular founder stallions to the gene pool in some lines of Quarter Horses may explain the high incidence of exertional rhabdomyolysis in these horses.

  13. 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.

    2017-03-01

    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.

  14. Different selective effects on rhizosphere bacteria exerted by genetically modified versus conventional potato lines.

    Directory of Open Access Journals (Sweden)

    Armando Cavalcante Franco Dias

    Full Text Available BACKGROUND: In this study, we assessed the actively metabolizing bacteria in the rhizosphere of potato using two potato cultivars, i.e. the genetically-modified (GM cultivar Modena (having tubers with altered starch content and the near-isogenic non-GM cultivar Karnico. To achieve our aims, we pulse-labelled plants at EC90 stage with (13C-CO2 and analysed their rhizosphere microbial communities 24 h, 5 and 12 days following the pulse. In the analyses, phospholipid fatty acid/stable isotope probing (PLFA-SIP as well as RNA-SIP followed by reverse transcription and PCR-DGGE and clone library analysis, were used to determine the bacterial groups that actively respond to the root-released (13C labelled carbonaceous compounds. METHODOLOGY/PRINCIPAL FINDINGS: The PLFA-SIP data revealed major roles of bacteria in the uptake of root-released (13C carbon, which grossly increased with time. Gram-negative bacteria, including members of the genera Pseudomonas and Burkholderia, were strong accumulators of the (13C-labeled compounds at the two cultivars, whereas Gram-positive bacteria were lesser responders. PCR-DGGE analysis of cDNA produced from the two cultivar types showed that these had selected different bacterial, alpha- and betaproteobacterial communities at all time points. Moreover, an effect of time was observed, indicating dynamism in the structure of the active bacterial communities. PCR-DGGE as well as clone library analyses revealed that the main bacterial responders at cultivar Karnico were taxonomically affiliated with the genus Pseudomonas, next to Gluconacetobacter and Paracoccus. Cultivar Modena mainly attracted Burkholderia, next to Moraxella-like (Moraxellaceae family and Sphingomonas types. CONCLUSIONS/SIGNIFICANCE: Based on the use of Pseudomonas and Burkholderia as proxies for differentially-selected bacterial genera, we conclude that the selective forces exerted by potato cultivar Modena on the active bacterial populations differed

  15. Salvianolic Acid B inhibits platelet adhesion under conditions of flow by a mechanism involving the collagen receptor alpha 2 beta 1

    NARCIS (Netherlands)

    Wu, Ya Ping; Zhao, Xiao Min; Pan, Shao Dong; Guo, De An; Wei, Ran; Han, Ji Ju; Kainoh, Mie; Xia, Zuo Li; de Groot, Philip G.; Lisman, Ton

    2008-01-01

    Salvianolic acid B (SAB) is a component of Danshen, a herb widely used in Chinese medicine, and was previously shown to exert a number of biological activities including inhibition of platelet function, but the exact mechanisms involved are unclear. SAB dose-dependently inhibited platelet deposition

  16. Simvastatin inhibits CD44 fragmentation in chondrocytes.

    Science.gov (United States)

    Terabe, Kenya; Takahashi, Nobunori; Takemoto, Toki; Knudson, Warren; Ishiguro, Naoki; Kojima, Toshihisa

    2016-08-15

    In human osteoarthritic chondrocytes, the hyaluronan receptor CD44 undergoes proteolytic cleavage at the cell surface. CD44 cleavage is thought to require transit of CD44 into cholesterol-rich lipid rafts. The purpose of this study was to investigate whether statins exert a protective effect on articular chondrocytes due to diminution of cholesterol. Three model systems of chondrocytes were examined including human HCS-2/8 chondrosarcoma cells, human osteoarthritic chondrocytes and normal bovine articular chondrocytes. Treatment with IL-1β + Oncostatin M resulted in a substantial increase in CD44 fragmentation in each of the three chondrocyte models. Pre-incubation with simvastatin prior to treatment with IL-1β + Oncostatin M decreased the level of CD44 fragmentation, decreased the proportion of CD44 that transits into the lipid raft fractions, decreased ADAM10 activity and diminished the interaction between CD44 and ADAM10. In HCS-2/8 cells and bovine articular chondrocytes, fragmentation of CD44 was blocked by the knockdown of ADAM10. Inhibition of CD44 fragmentation by simvastatin also resulted in improved retention of pericellular matrix. Addition of cholesterol and farnesyl-pyrophosphate reversed the protective effects of simvastatin. Thus, the addition of simvastatin exerts positive effects on chondrocytes including reduced CD44 fragmentation and enhanced the retention of pericellular matrix. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Inhibition of acetylcholinesterase by Tea Tree oil.

    Science.gov (United States)

    Mills, Clive; Cleary, Brian J; Gilmer, John F; Walsh, John J

    2004-03-01

    Pediculosis is a widespread condition reported in schoolchildren. Treatment most commonly involves the physical removal of nits using fine-toothcombs and the chemical treatment of adult lice and eggs with topical preparations. The active constituents of these preparations frequently exert their effects through inhibition of acetylcholinesterase (AChE, EC 3.1.1.7). Increasing resistance to many preparations has led to the search for more effective treatments. Tea Tree oil, otherwise known as Melaleuca oil, has been added to several preparations as an alternative treatment of head lice infestations. In this study two major constituents of Tea Tree oil, 1,8-cineole and terpinen-4-ol, were shown to inhibit acetylcholinesterase at IC50 values (inhibitor concentrations required to give 50% inhibition) of 0.04 and 10.30 mM, respectively. Four samples of Tea Tree oil tested (Tisserand, Body Treats, Main Camp and Irish Health Culture Association Pure Undiluted) showed anticholinesterase activity at IC50 values of 0.05, 0.10, 0.08 and 0.11 microL mL(-1), respectively. The results supported the hypothesis that the insecticidal activity of Tea Tree oil was attributable, in part, to the anticholinesterase activity of Tea Tree oil.

  18. A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan); Kameshima, Satoshi; Usui, Tatsuya; Okada, Muneyoshi; Hara, Yukio [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Chemerin is a novel adipocytokine with almost unknown function in vasculature. Black-Right-Pointing-Pointer Chemerin activates Akt/eNOS/NO pathways in endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-{alpha}-induced monocyte adhesion to endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-induced VCAM-1 via suppressing NF-{kappa}B and p38 signal. Black-Right-Pointing-Pointer Chemerin is anti-inflammatory through producing NO in vascular endothelium. -- Abstract: Chemerin is a recently identified adipocytokine which plays a role on inflammation and adipocytes metabolism. However, its function in vasculature is largely unknown. We examined the effects of chemerin on vascular endothelial inflammatory states. Treatment of human umbilical vein endothelial cells with chemerin (300 ng/ml, 20 min) induced phosphorylation of Akt (Ser473) and endothelial nitric oxide (NO) synthase (eNOS) (Ser1177). Consistently, chemerin increased intracellular cyclic GMP content. Pretreatment with chemerin (1-300 ng/ml, 24 h) significantly inhibited phosphorylation of nuclear factor (NF)-{kappa}B p65 (Ser536) and p38 as well as vascular cell adhesion molecule (VCAM)-1 expression induced by tumor necrosis factor (TNF)-{alpha} (5 ng/ml, 20 min-6 h). Inhibitor of NF-{kappa}B or p38 significantly inhibited the TNF-{alpha}-induced VCAM-1 expression. Chemerin also inhibited TNF-{alpha}-induced VCAM-1 expression in rat isolated aorta. Moreover, chemerin significantly inhibited monocytes adhesion to TNF-{alpha}-stimulated endothelial cells. The inhibitory effect of chemerin on TNF-{alpha}-induced VCAM-1 was reversed by a NOS inhibitor. Conversely, an NO donor, sodium nitroprusside significantly inhibited TNF-{alpha}-induced VCAM-1. The present results for the first time demonstrate that chemerin plays anti-inflammatory roles by preventing TNF-{alpha}-induced VCAM-1 expression and monocytes adhesion in vascular

  19. Sulforaphane exerts anti-inflammatory effects against lipopolysaccharide-induced acute lung injury in mice through the Nrf2/ARE pathway.

    Science.gov (United States)

    Qi, Tianjie; Xu, Fei; Yan, Xixin; Li, Shuai; Li, Haitao

    2016-01-01

    Sulforaphane (1-isothiocyanate-4-methyl sulfonyl butane) is a plant extract (obtained from cruciferous vegetables, such as broccoli and cabbage) and is known to exert anticancer, antioxidant and anti-inflammatory effects. It stimulates the generation of human or animal cells, which is beneficial to the body. The aim of the current study was to determine whether sulforaphane protects against lipopolysaccharide (LPS)‑induced acute lung injury (ALI) through its anti-inflammatory effects, and to investigate the signaling pathways involved. For this purpose, male BALB/c mice were treated with sulforaphane (50 mg/kg) and 3 days later, ALI was induced by the administration of LPS (5 mg/kg) and we thus established the model of ALI. Our results revealed that sulforaphane significantly decreased lactate dehydrogenase (LDH) activity (as shown by LDH assay), the wet-to-dry ratio of the lungs and the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) (measured by ELISA), as well as nuclear factor-κB protein expression in mice with LPS-induced ALI. Moreover, treatment with sulforaphane significantly inhibited prostaglandin E2 (PGE2) production, and cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9) protein expression (as shown by western blot analysis), as well as inducible nitric oxide synthase (iNOS) activity in mice with LPS-induced ALI. Lastly, we noted that pre-treatment with sulforaphane activated the nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in the mice with LPS-induced ALI. These findings demonstrate that sulforaphane exerts protective effects against LPS-induced ALI through the Nrf2/ARE pathway. Thus, sulforaphane may be a potential a candidate for use in the treatment of ALI.

  20. Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells

    Directory of Open Access Journals (Sweden)

    Juan Li

    2014-03-01

    Full Text Available Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis.

  1. Positively charged biomaterials exert antimicrobial effects on gram-negative bacilli in rats

    NARCIS (Netherlands)

    Gottenbos, B; van der Mei, HC; Klatter, F; Grijpma, DW; Feijen, J; Nieuwenhuis, P; Busscher, HJ

    Biomaterial-centered infection is a much-dreaded complication associated with the use of biomedical implants. Although positively charged biomaterial surfaces stimulate bacterial adhesion, it has been suggested that surface growth of adhering Gram-negative bacilli is inhibited on positively charged

  2. Positively charged biomaterials exert antimicrobial effects on gram-negative bacilli in rats

    NARCIS (Netherlands)

    Gottenbos, B; van der Mei, HC; Klatter, F; Grijpma, DW; Feijen, J; Nieuwenhuis, P; Busscher, HJ

    2003-01-01

    Biomaterial-centered infection is a much-dreaded complication associated with the use of biomedical implants. Although positively charged biomaterial surfaces stimulate bacterial adhesion, it has been suggested that surface growth of adhering Gram-negative bacilli is inhibited on positively charged

  3. Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma.

    Science.gov (United States)

    Zhu, Yongxia; Ye, Tinghong; Yu, Xi; Lei, Qian; Yang, Fangfang; Xia, Yong; Song, Xuejiao; Liu, Li; Deng, Hongxia; Gao, Tiantao; Peng, Cuiting; Zuo, Weiqiong; Xiong, Ying; Zhang, Lidan; Wang, Ningyu; Zhao, Lifeng; Xie, Yongmei; Yu, Luoting; Wei, Yuquan

    2016-02-02

    Melanoma is a highly malignant neoplasm of melanocytes with considerable metastatic potential and drug resistance, explaining the need for new candidates that inhibit tumor growth and metastasis. The signal transducer and activator of the transcription 3 (Stat3) signaling pathway plays an important role in melanoma and has been validated as promising anticancer target for melanoma therapy. In this study, nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3, was evaluated for its anti-melanoma activity in vitro and in vivo. It had potent anti-proliferative activity against various melanoma cell lines and could induce G2/M phase arrest and cell apoptosis. Moreover, nifuroxazide markedly impaired melanoma cell migration and invasion by down-regulating phosphorylated-Src, phosphorylated-FAK, and expression of matrix metalloproteinase (MMP) -2, MMP-9 and vimentin. It also significantly inhibited tumor growth without obvious side effects in the A375-bearing mice model by inducing apoptosis and reducing cell proliferation and metastasis. Notably, nifuroxazide significantly inhibited pulmonary metastases, which might be associated with the decrease of myeloid-derived suppressor cells (MDSCs). These findings suggested that nifuroxazide might be a potential agent for inhibiting the growth and metastasis of melanoma.

  4. A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II

    Science.gov (United States)

    Cui, Guozhen; Chan, Judy Yuet-Wa; Wang, Li; Li, Chuwen; Shan, Luchen; Xu, Changjiang; Zhang, Qingwen; Wang, Yuqiang; Di, Lijun; Lee, Simon Ming-Yuen

    2016-01-01

    The mitochondrial respiratory chain, including mitochondrial complex II, has emerged as a potential target for cancer therapy. In the present study, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), DT-010, was synthesized. Our results showed that DT-010 is more potent than its parental compounds separately or in combination, in inhibiting the proliferation of MCF-7 and MDA-MB-231 cells by inducing cytotoxicity and promoting cell cycle arrest. It also inhibited the growth of 4T1 breast cancer cells in vivo. DT-010 suppressed the fundamental parameters of mitochondrial function in MCF-7 cells, including basal respiration, ATP turnover, maximal respiration. Treatment with DT-010 in MCF-7 and MDA-MB-231 cells resulted in the loss of mitochondrial membrane potential and decreased ATP production. DT-010 also promoted ROS generation, while treatment with ROS scavenger, NAC (N-acetyl-L-cysteine), reversed DT-010-induced cytotoxicity. Further study showed that DT-010 suppressed succinate-induced mitochondrial respiration and impaired mitochondrial complex II enzyme activity indicating that DT-010 may inhibit mitochondrial complex II. Overall, our results suggested that the antitumor activity of DT-010 is associated with inhibition of mitochondrial complex II, which triggers ROS generation and mitochondrial dysfunction in breast cancer cells. PMID:27081033

  5. Inhibition of Quorum Sensing in Staphylococcus spp.

    Science.gov (United States)

    Brackman, Gilles; Coenye, Tom

    2015-01-01

    The Gram-positive, facultative anaerobic coccus-shaped bacteria of the genus Staphylococcus are among the most important causative agents of acute and chronic bacterial infections in humans as well as in animals. Treatment of Staphylococcus infections has become increasingly challenging due to the growing problem of antibiotic resistance. For this reason innovative antimicrobials with novel targets and modes of action are needed. Since the discovery that QS is used by Staphylococcus spp. to coordinate the expression of several genes involved in virulence, biofilm formation and pathogenicity, QS inhibition has gained increasing attention as an alternative anti-pathogenic strategy. A major advantage compared with antibiotic therapy is that QSIs are used in concentrations that do not affect bacterial growth. For this reason, it is expected that these compounds would exert less pressure towards the development of resistance. However, some important points still need to be addressed. Although several inhibitors have proven to be active antipathogenic agents in vitro and in several in vivo models, it is still unknown whether these compounds will also be useful in humans. Furthermore, several fundamental mechanisms by which the different QS systems in Staphylococcus spp. exert their regulatory functions and how they are inhibited by QSIs are still poorly understood. In order to achieve real-life applications with QSIs, these challenges should be addressed and more research will be needed. In this article, we will discuss the different QS systems present in Staphylococcus spp., how they are used to control virulence and biofilm formation and how they can be blocked.

  6. The effect of a seasonal stratification variation on the load exerted by internal solitary waves on a cylindrical pile

    Institute of Scientific and Technical Information of China (English)

    CAI Shuqun; XU Jiexin; CHEN Zhiwu; XIE Jieshuo; DENG Xiaodong; LV Haibin

    2014-01-01

    On the basis of Morison’s empirical formula and modal separation method in estimating the force and torque exerted by internal solitary waves (ISWs) on a cylindrical pile, it is found that the loads exerted by the ISWs change largely in different seasons at the same site of the continental shelf in the South China Sea (SCS) even under the condition that the amplitudes of ISWs are the same. Thus, the effect of a seasonal water stratification variation on the force and torque exerted by the ISWs is investigated, and a three-parameter stratification model is employed. It is shown that the loads exerted by the ISWs depend largely on the wa-ter stratification. The stronger the water stratification, the larger the force and the torque;when the depth where the maximum thermocline appears is deepened, the force decreases but the torque increases;when the width of the thermocline is narrowed, the force increases but the torque decreases. The seasonal varia-tion of the force and the torque exerted by the ISWs in four seasons in the SCS is thus explained.

  7. Three-minute constant rate step test for detecting exertional dyspnea relief after bronchodilation in COPD

    Directory of Open Access Journals (Sweden)

    Borel B

    2016-11-01

    Full Text Available Benoit Borel,1,2 Courtney A Wilkinson-Maitland,3 Alan Hamilton,4 Jean Bourbeau,5 Hélène Perrault,6 Dennis Jensen,3,5,7 François Maltais2 1Laboratoire HAVAE, Université de Limoges, Limoges, France; 2Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, 3Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, McGill University, Montréal, QC, 4Boehringer Ingelheim (Canada Limited, Burlington, ON, 5Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Center, Montreal, QC, 6Faculty of Health Sciences, University of Ottawa, Ottawa, ON, 7Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada Background: The aim of this study was to evaluate the responsiveness of the 3-minute constant rate step test (3-MST to detect the relief of exertional dyspnea (respiratory discomfort after acute bronchodilation in COPD patients. Patients and methods: A total of 40 patients with moderate-to-severe COPD (mean forced expiratory volume in 1 second: 45.7 (±14.7, % predicted performed four 3-MSTs at randomly assigned stepping rates of 14, 16, 20 and 24 steps/min after inhalation of nebulized ipratropium bromide (500 µg/salbutamol (2.5 mg and saline placebo, which were randomized to order. Patients rated their intensity of perceived dyspnea at the end of each 3-MST using Borg 0–10 category ratio scale. Results: A total of 37 (92.5%, 36 (90%, 34 (85% and 27 (67.5% patients completed all 3 minutes of exercise at 14, 16, 20 and 24 steps/min under both treatment conditions, respectively. Compared with placebo, ipratropium bromide/salbutamol significantly decreased dyspnea at the end of the third minute of exercise at 14 steps/min (by 0.6±1.0 Borg 0–10 scale units, P<0.01 and 16 steps/min (by 0.7±1.3 Borg 0–10 scale

  8. 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.

  9. Role of Repeat Muscle Compartment Pressure Measurements in Chronic Exertional Compartment Syndrome of the Lower Leg

    Science.gov (United States)

    van Zantvoort, Aniek P. M.; de Bruijn, Johan A.; Winkes, Michiel B.; Hoogeveen, Adwin R.; Teijink, Joep A. W.; Scheltinga, Marc R.

    2017-01-01

    Background: The diagnostic gold standard for diagnosing chronic exertional compartment syndrome (CECS) is a dynamic intracompartmental pressure (ICP) measurement of the muscle. The potential role of a repeat ICP (re-ICP) measurement in patients with persistent lower leg symptoms after surgical decompression or with ongoing symptoms after an earlier normal ICP is unknown. Purpose: To study whether re-ICP measurements in patients with persistent CECS-like symptoms of the lower leg may contribute to the diagnosis of CECS after both surgical decompression and a previously normal ICP measurement. Study Design: Case series; Level of evidence, 4. Methods: Charts of patients who underwent re-ICP measurement of lower leg compartments (anterior [ant], deep posterior [dp], and/or lateral [lat] compartments) between 2001 and 2013 were retrospectively studied. CECS was diagnosed on the basis of generally accepted cutoff pressures for newly onset CECS (Pedowitz criteria: ICP at rest ≥15 mmHg, ≥30 mmHg after 1 minute, or ≥20 mmHg 5 minutes after a provocative test). Factors predicting recurrent CECS after surgery or after a previously normal ICP measurement were analyzed. Results: A total of 1714 ICP measurements were taken in 1513 patients with suspected CECS over a 13-year observation period. In all, 201 (12%) tests were re-ICP measurements for persistent lower leg symptoms. Based on the proposed ICP cutoff values, CECS recurrence was diagnosed in 16 of 62 previously operated compartments (recurrence rate, 26%; 53 patients [64% female]; median age, 24 years; age range, 15-78 years). Recurrence rates were not different among the 3 lower leg CECS compartments (ant-CECS, 17%; dp-CECS, 33%; lat-CECS, 30%; χ2 = 1.928, P = .381). Sex (χ2 = 0.058, P = .810), age (U = 378, z = 1.840, P = .066), bilaterality (χ2 = 0.019, P = .889), and prefasciotomy ICP did not predict recurrence. Re-ICP measurements evaluating 20 compartments with previously normal ICP measurements (15

  10. Role of Repeat Muscle Compartment Pressure Measurements in Chronic Exertional Compartment Syndrome of the Lower Leg.

    Science.gov (United States)

    van Zantvoort, Aniek P M; de Bruijn, Johan A; Winkes, Michiel B; Hoogeveen, Adwin R; Teijink, Joep A W; Scheltinga, Marc R

    2017-06-01

    The diagnostic gold standard for diagnosing chronic exertional compartment syndrome (CECS) is a dynamic intracompartmental pressure (ICP) measurement of the muscle. The potential role of a repeat ICP (re-ICP) measurement in patients with persistent lower leg symptoms after surgical decompression or with ongoing symptoms after an earlier normal ICP is unknown. To study whether re-ICP measurements in patients with persistent CECS-like symptoms of the lower leg may contribute to the diagnosis of CECS after both surgical decompression and a previously normal ICP measurement. Case series; Level of evidence, 4. Charts of patients who underwent re-ICP measurement of lower leg compartments (anterior [ant], deep posterior [dp], and/or lateral [lat] compartments) between 2001 and 2013 were retrospectively studied. CECS was diagnosed on the basis of generally accepted cutoff pressures for newly onset CECS (Pedowitz criteria: ICP at rest ≥15 mmHg, ≥30 mmHg after 1 minute, or ≥20 mmHg 5 minutes after a provocative test). Factors predicting recurrent CECS after surgery or after a previously normal ICP measurement were analyzed. A total of 1714 ICP measurements were taken in 1513 patients with suspected CECS over a 13-year observation period. In all, 201 (12%) tests were re-ICP measurements for persistent lower leg symptoms. Based on the proposed ICP cutoff values, CECS recurrence was diagnosed in 16 of 62 previously operated compartments (recurrence rate, 26%; 53 patients [64% female]; median age, 24 years; age range, 15-78 years). Recurrence rates were not different among the 3 lower leg CECS compartments (ant-CECS, 17%; dp-CECS, 33%; lat-CECS, 30%; χ(2) = 1.928, P = .381). Sex (χ(2) = 0.058, P = .810), age (U = 378, z = 1.840, P = .066), bilaterality (χ(2) = 0.019, P = .889), and prefasciotomy ICP did not predict recurrence. Re-ICP measurements evaluating 20 compartments with previously normal ICP measurements (15 patients [53% female]; mean age, 31 ± 10 years

  11. Inhibition of Mycobacterium tuberculosis topoisomerase I by m-AMSA, a eukaryotic type II topoisomerase poison.

    Science.gov (United States)

    Godbole, Adwait Anand; Ahmed, Wareed; Bhat, Rajeshwari Subray; Bradley, Erin K; Ekins, Sean; Nagaraja, Valakunja

    2014-04-18

    m-AMSA, an established inhibitor of eukaryotic type II topoisomerases, exerts its cidal effect by binding to the enzyme-DNA complex thus inhibiting the DNA religation step. The molecule and its analogues have been successfully used as chemotherapeutic agents against different forms of cancer. After virtual screening using a homology model of the Mycobacterium tuberculosis topoisomerase I, we identified m-AMSA as a high scoring hit. We demonstrate that m-AMSA can inhibit the DNA relaxation activity of topoisomerase I from M. tuberculosis and Mycobacterium smegmatis. In a whole cell assay, m-AMSA inhibited the growth of both the mycobacteria.

  12. Repulsive guidance molecule a blockade exerts the immunoregulatory function in DCs stimulated with ABP and LPS.

    Science.gov (United States)

    Xu, Xuxu; Gao, Yan; Zhai, Zhiyong; Zhang, Shuo; Shan, Fengping; Feng, Juan

    2016-08-02

    Repulsive guidance molecule a (RGMa) is an axonal guidance molecule that has recently found to exert function in immune system. This study evaluated the function of RGMa in modulation of dendritic cells (DCs) function stimulated with Achyranthes bidentata polysaccharide (ABP) and lipopolysaccharide (LPS) using a RGMa-neutralizing antibody. Compared with the Control-IgG/ABP and Control-IgG/LPS groups, DCs in the Anti-RGMa/ABP and Anti-RGMa/LPS groups 1) showed small, round cells with a few cell processes and organelles, and many pinocytotic vesicles; 2) had decreased MHC II, CD86, CD80, and CD40 expression; 3) displayed the decreased IL-12p70, IL-1β and TNF-α levels and increased IL-10 secretion; 4) had a high percentage of FITC-dextran uptake; and 5) displayed a reduced ability to drive T cell proliferation and reinforced T cell polarization toward a Th2 cytokine pattern. We conclude that DCs treated with RGMa-neutralizing antibodies present with tolerogenic and immunoregulatory characteristics, which provides new insights into further understanding of the function of RGMa.

  13. Effective range of reproductive interference exerted by an alien dandelion, Taraxacum officinale, on a native congener.

    Science.gov (United States)

    Takakura, Koh-Ichi; Matsumoto, Takashi; Nishida, Takayoshi; Nishida, Sachiko

    2011-03-01

    Reproductive interference (RI), defined as the fitness cost of interspecific sexual interactions, such as interspecific pollen transfer (IPT) in plants, is ecologically important. Theoretically, RI could result in competitive exclusion, as it operates in a frequency-dependent manner. Additionally, IPT may have a greater range than resource competition, although information about the range of IPT is lacking. In the present study, we measured the range of IPT exerted by Taraxacum officinale (an alien species) on a native dandelion, T. japonicum. We used two approaches. In one, we analyzed the RI effect on a native seed set at three spatial scales. In the second, we tracked IPT from alien to native flower heads using fluorescent pigments as markers. We estimated that pollination distances were in the order of several meters. These distances exceeded the mean distance from each native plant to the nearest alien. As hypothesized, the effect of RI reached farther than neighboring individuals. These data indicate the spatial range from which alien dandelions should be removed to allow the conservation of natives.

  14. Physical Activity and Exertional Desaturation Are Associated with Mortality in Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Vainshelboim, Baruch; Kramer, Mordechai Reuven; Izhakian, Shimon; Lima, Ricardo M.; Oliveira, Jose

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that manifests in hypoxemia, inactivity, and poor prognosis. This study aimed to assess the prognostic role of physical activity (PA) and exertional desaturation (ED) with mortality in IPF. At baseline, 34 IPF patients (68 (50–81) years) were interviewed using the International Physical Activity Questionnaire (IPAQ), and SpO2 was assessed pre to post 6-min walking test (∆SpO2). Patients were prospectively followed up for 40 months. Receiver operating characteristics curve analysis determined cut-off points associated with mortality, and Cox proportional hazard ratio (HR) were conducted. Thresholds for increased mortality risk in IPF patients were determined as IPAQ ≤ 417 metabolic equivalent task (METS)-min/week, p = 0.004 (HR; 9.7, CI 95% (1.3–71.9), p = 0.027), and ∆SpO2 ≥ 10%, p = 0.002, (HR; 23.3, CI 95% (1.5–365), p = 0.025). This study demonstrated a significant association of PA and ED with mortality in IPF patients. The findings emphasize the clinical importance of PA and ED assessments to aid in IPF risk stratification, prognosis prediction, and in providing early appropriate treatments, such as pulmonary rehabilitation, PA consultation, oxygen supplementation, and lung transplantation referral. These results underscore that even low levels of PA corresponding to 100–105 min/week were associated with a reduced mortality risk and better survival in IPF. PMID:27548238

  15. Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system.

    Science.gov (United States)

    Lenzi, Juliana; Rodrigues, Andre Felipe; Rós, Adriana de Sousa; de Castro, Amanda Blanski; de Castro, Bianca Blanski; de Lima, Daniela Delwing; Magro, Débora Delwing Dal; Zeni, Ana Lúcia Bertarello

    2015-12-01

    Oxidative stress has been claimed a place in pathophysiology of depression; however, the details of the neurobiology of this condition remains incompletely understood. Recently, treatments employing antioxidants have been thoroughly researched. Ferulic acid (FA) is a phenolic compound with antioxidant and antidepressant-like effects. Herein, we investigated the involvement of the antioxidant activity of chronic oral FA treatment in its antidepressant-like effect using the tail suspension test (TST) and the forced swimming test (FST) in mice. The modulation of antioxidant system in blood, hippocampus and cerebral cortex was assessed after stress induction through TST and FST. Our results show that FA at the dose of 1 mg/kg has antidepressant-like effect without affecting locomotor activity. The stress induced by despair tests was able to decrease significantly the activities of superoxide dismutase (SOD) in the blood, catalase (CAT) in the blood and cerebral cortex and glutathione peroxidase (GSH-Px) in the cerebral cortex. Thiobarbituric acid-reactive substances (TBA-RS) levels were increased significantly in the cerebral cortex. Furthermore, the results show that FA was capable to increase SOD, CAT and GSH-Px activities and decrease TBA-RS levels in the blood, hippocampus and cerebral cortex. These findings demonstrated that FA treatment in low doses is capable to exert antidepressant-like effect with the involvement of the antioxidant defense system modulation.

  16. Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

    Science.gov (United States)

    Ishizawa, Keisuke; Izawa-Ishizawa, Yuki; Yamano, Noriko; Urushihara, Maki; Sakurada, Takumi; Imanishi, Masaki; Fujii, Shoko; Nuno, Asami; Miyamoto, Licht; Kihira, Yoshitaka; Ikeda, Yasumasa; Kagami, Shoji; Kobori, Hiroyuki; Tsuchiya, Koichiro; Tamaki, Toshiaki

    2014-01-01

    Diabetic nephropathy (DN) is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF) is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice), NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM)-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS) knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT) excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

  17. Pulmonary antioxidants exert differential protective effects against urban and industrial particulate matter

    Indian Academy of Sciences (India)

    L L Greenwell; T Moreno; R J Richards

    2003-02-01

    This investigation focuses on the application of an in vitro assay in elucidating the role of lung lining fluid antioxidants in the protection against inhaled particles, and to compare the toxicities of different airborne particulate matter (PM), PM10, collections from South Wales, UK. PM collections from both urban and industrial sites caused 50% oxidative degradation of DNA in vitro at concentrations as low as 12.9 ± 2.1 g ml–1 and 4.9 ± 0.9 mg ml–1 respectively. The primary source of this bioreactivity was found to be the soluble fraction of both particle collections. The coarser PM10–2.5 fraction also showed greater oxidative bioreactivity than the PM2.5–0.1 in both cases. When repeated in the presence of a low molecular weight fraction of fresh pulmonary lavage fluid, as well as in artificial lung lining fluid (200 M urate, glutathione and ascorbate), the DNA damage was significantly reduced in all cases ( < 0.05). The antioxidants exerted a greater effect on the industrial samples than on the urban samples, and on the PM10–2.5 fractions than on the PM2.5–0.1 fractions, supporting the previous findings that respirable PM and urban samples contain fewer free radical sources than inhalable PM and industrial samples.

  18. Nanoprecipitated catestatin released from pharmacologically active microcarriers (PAMs) exerts pro-survival effects on MSC.

    Science.gov (United States)

    Angotti, C; Venier-Julienne, M C; Penna, C; Femminò, S; Sindji, L; Paniagua, C; Montero-Menei, C N; Pagliaro, P

    2016-11-22

    Catestatin (CST), a fragment of Chromogranin-A, exerts angiogenic, arteriogenic, vasculogenic and cardioprotective effects. CST is a very promising agent for revascularization purposes, in "NOOPTION" patients. However, peptides have a very short half-life after administration and must be conveniently protected. Fibronectin-coated pharmacologically active microcarriers (FN-PAM), are biodegradable and biocompatible polymeric microspheres that can convey mesenchymal stem cell (MSCs) and therapeutic proteins delivered in a prolonged manner. In this study, we first evaluated whether a small peptide such as CST could be nanoprecipitated and incorporated within FN-PAMs. Subsequently, whether CST may be released in a prolonged manner by functionalized FN-PAMs (FN-PAM-CST). Finally, we assessed the effect of CST released by FN-PAM-CST on the survival of MSCs under stress conditions of hypoxia-reoxygenation. An experimental design, modifying three key parameters (ionic strength, mixing and centrifugation time) of protein nanoprecipitation, was used to define the optimum condition for CST. An optimal nanoprecipitation yield of 76% was obtained allowing encapsulation of solid CST within FN-PAM-CST, which released CST in a prolonged manner. In vitro, MSCs adhered to FN-PAMs, and the controlled release of CST from FN-PAM-CST greatly limited hypoxic MSC-death and enhanced MSC-survival in post-hypoxic environment. These results suggest that FN-PAM-CST are promising tools for cell-therapy.

  19. Apico-basal forces exerted by apoptotic cells drive epithelium folding.

    Science.gov (United States)

    Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

    2015-02-12

    Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

  20. RELIABILITY AND VALIDITY OF THE OMNI-VIBRATION EXERCISE SCALE OF PERCEIVED EXERTION

    Directory of Open Access Journals (Sweden)

    Pedro J. Marín

    2012-09-01

    Full Text Available This study examined reliability and concurrent validity of the newly developed OMNI-vibration exercise scale (OMNI-VIBRO to measure Ratings of Perceived Exertion (RPE during vibration exercise in twenty recreationally active students (12 males and 8 females. The criterion variables were muscle activity of the Vastus Medialis (VM, Vastus Lateralis (VL, Biceps Femoris (BF, and Medial Gastrocnemius (MG muscles, as well as accelerations (12.5, 20.2, 30.9, 36.3, 60.1, and 88.4 m·s-2. RPE was registered during the final of each 30 s condition. Each participant attended two laboratory testing sessions. Positive linear regression coefficients (p < 0.001 were found between RPE (OMNI-VIBRO and acceleration (r = 0.976 and muscle activity of lower-body muscles (r = 0.942. Between session (test-retest, reliability of RPE (OMNI-VIBRO was good (ICC: 0.790. 95% CI: 0.699-0.854. Conclusions: findings provided concurrent validation of the OMNI-VIBRO to measure RPE for the active muscle and overall body in recreationally active students performing lower-body vibration exercise

  1. Effect of coffee ingestion on physiological responses and ratings of perceived exertion during submaximal endurance exercise.

    Science.gov (United States)

    Demura, Shinichi; Yamada, Takayoshi; Terasawa, Naoko

    2007-12-01

    This study examined the effect of coffee ingestion on physiological responses and ratings of perceived exertion (RPE) during submaximal endurance exercises by 10 healthy young adults. Participants performed a submaximal endurance cycling exercise corresponding to 60% of maximum oxygen uptake capacity for 60 min. They drank either caffeinated coffee with a caffeine content of 6 mg/kg body-mass of each participant (Caf) or a decaffeinated coffee (Dec) 60 min. before starting exercise. Participants participated in the blind design experiment under both conditions at a one-week interval. Oxygen uptake, respiratory exchange ratio, heart rate, RPE, and plasma lactate concentration were measured during the endurance exercise. The RPE under the Caffeinated coffee condition during the last 60 min. of endurance exercise was significantly lower than that in the Decaffeinated coffee condition. However, no significant differences in any physiological response were observed between conditions. Thus, caffeine ingestion 60 min. before starting exercise had an insignificant effect on the physiological responses, except for RPE during submaximal endurance exercises for 60 min. Caffeine ingestion before endurance exercise of relatively low intensity may have a beneficial effect on psychological responses.

  2. Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

    Science.gov (United States)

    Matsui, Nobuaki; Akae, Haruka; Hirashima, Nana; Kido, Yuki; Tanabe, Satoshi; Koseki, Mayumi; Fukuyama, Yoshiyasu; Akagi, Masaaki

    2016-11-01

    Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Flagellar biosynthesis exerts temporal regulation of secretion of specific Campylobacter jejuni colonization and virulence determinants.

    Science.gov (United States)

    Barrero-Tobon, Angelica M; Hendrixson, David R

    2014-09-01

    The Campylobacter jejuni flagellum exports both proteins that form the flagellar organelle for swimming motility and colonization and virulence factors that promote commensal colonization of the avian intestinal tract or invasion of human intestinal cells respectively. We explored how the C. jejuni flagellum is a versatile secretory organelle by examining molecular determinants that allow colonization and virulence factors to exploit the flagellum for their own secretion. Flagellar biogenesis was observed to exert temporal control of secretion of these proteins, indicating that a bolus of secretion of colonization and virulence factors occurs during hook biogenesis with filament polymerization itself reducing secretion of these factors. Furthermore, we found that intramolecular and intermolecular requirements for flagellar-dependent secretion of these proteins were most reminiscent to those for flagellin secretion. Importantly, we discovered that secretion of one colonization and virulence factor, CiaI, was not required for invasion of human colonic cells, which counters previous hypotheses for how this protein functions during invasion. Instead, secretion of CiaI was essential for C. jejuni to facilitate commensal colonization of the natural avian host. Our work provides insight into the versatility of the bacterial flagellum as a secretory machine that can export proteins promoting diverse biological processes.

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

    Directory of Open Access Journals (Sweden)

    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 

  5. Sam68 exerts separable effects on cell cycle progression and apoptosis

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    Resnick Ross J

    2004-01-01

    Full Text Available Abstract Background The RNA-binding protein Sam68 has been implicated in a number of cellular processes, including transcription, RNA splicing and export, translation, signal transduction, cell cycle progression and replication of the human immunodeficiency virus and poliovirus. However, the precise impact it has on essential cellular functions remains largely obscure. Results In this report we show that conditional overexpression of Sam68 in fibroblasts results in both cell cycle arrest and apoptosis. Arrest in G1 phase of the cell cycle is associated with decreased levels of cyclins D1 and E RNA and protein, resulting in dramatically reduced Rb phosphorylation. Interestingly, cell cycle arrest does not require the specific RNA binding ability of Sam68. In marked contrast, induction of apoptosis by Sam68 absolutely requires a fully-functional RNA binding domain. Moreover, the anti-cancer agent trichostatin A potentiates Sam68-driven apoptosis. Conclusions For the first time we have shown that Sam68, an RNA binding protein with multiple apparent functions, exerts functionally separable effects on cell proliferation and survival, dependent on its ability to bind specifically to RNA. These findings shed new light on the ability of signal transducing RNA binding proteins to influence essential cell function. Moreover, the ability of a class of anti-cancer therapeutics to modulate its ability to promote apoptosis suggests that Sam68 status may impact some cancer treatments.

  6. Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing

    Directory of Open Access Journals (Sweden)

    Matteo Bonini

    2017-02-01

    Full Text Available Interstitial lung diseases (ILDs represent a heterogeneous group of pathologies characterised by alveolar and interstitial damage, pulmonary inflammation (usually associated with fibrosis, decreased lung function and impaired gas exchange, which can be attributed to either a known or an unknown aetiology. Dyspnoea is one of the most common and disabling symptoms in patients with ILD, significantly impacting quality of life. The mechanisms causing dyspnoea are complex and not yet fully understood. However, it is recognised that dyspnoea occurs when there is an imbalance between the central respiratory efferent drive and the response of the respiratory musculature. The respiratory derangement observed in ILD patients at rest is even more evident during exercise. Pathophysiological mechanisms responsible for exertional dyspnoea and reduced exercise tolerance include altered respiratory mechanics, impaired gas exchange, cardiovascular abnormalities and peripheral muscle dysfunction. This review describes the respiratory physiology of ILD, both at rest and during exercise, and aims to provide comprehensive and updated evidence on the clinical utility of the cardiopulmonary exercise test in the assessment and management of these pathological entities. In addition, the role of exercise training and pulmonary rehabilitation programmes in the ILD population is addressed.

  7. Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

    Directory of Open Access Journals (Sweden)

    Keisuke Ishizawa

    Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

  8. Investigation of a cuboidal permanent magnet’s force exerted on a robotic capsule

    Directory of Open Access Journals (Sweden)

    Yang W

    2014-08-01

    Full Text Available Wan’an Yang,1 Chengbing Tang,2 Fengqing Qin1 1School of Computer and Information Engineering, Yibin University, Yibin, 2CNPC Chuanqing Geophysical Prospecting Company Research Center Computer Department, Chengdu, Sichuan, People’s Republic of China Abstract: To control and drive a robotic capsule accurately from outside a patient’s body, we present a schema in which the capsule enclosing the imaging device, circuits, batteries, etc is looped by a permanent magnet ring that acts as an actuator. A cuboidal permanent magnet situated outside the patient's body attracts or pushes the magnet ring from different directions to make the capsule move or rotate. A mathematic model of attractive or repulsive force that the cuboidal magnet exerts on the magnet ring is presented for accurate calculation of force. The experiments showed that the measuring force was in agreement with the theoretical one, and the relations between the dimensions of the cuboidal magnet and force are useful to produce a cuboidal magnet with optimal shape to get appropriate force. Keywords: control and drive, robotic capsule, permanent magnet ring, optimal dimension, force model

  9. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

    Directory of Open Access Journals (Sweden)

    Heidi Wichmann

    2016-05-01

    Full Text Available The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP, produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA, a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2. Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells.

  10. Apelin-13 exerts antidepressant-like and recognition memory improving activities in stressed rats.

    Science.gov (United States)

    Li, E; Deng, Haifeng; Wang, Bo; Fu, Wan; You, Yong; Tian, Shaowen

    2016-03-01

    Apelin is the endogenous ligand for the G-protein-coupled receptor (APJ). The localization of APJ in limbic structures suggests a potential role for apelin in emotional processes. However, the role of apelin in the regulation of stress-induced responses such as depression and memory impairment is largely unknown. In the present study, we evaluated the role of apelin-13 in the regulation of stress-induced depression and memory impairment in rats. We report that repeated intracerebroventricular injections of apelin-13 reversed behavioral despair (immobility) in the forced swim (FS) test, a model widely used for the selection of new antidepressant agents. Apelin-13 also reversed behavioral deficits (escape failure) in the learned helplessness test. The magnitude of the antiimmobility and anti-escape failure effects of apelin-13 was comparable to that of imipramine, a classic antidepressant used as a positive control. Rats exposed to FS stress showed memory performance impairment in the novel object recognition test, and this impairment was improved by apelin-13 treatment. Apelin-13 did not affect recognition memory performance in non-stressed rats. Furthermore, the pretreatment of LY294002 (PI3K inhibitors) or PD98059 (ERK1/2 inhibitor) blocked apelin-13-mediated activities in FS-stressed rats. These findings suggest that apelin-13 exerts antidepressant-like and recognition memory improving activities through activating PI3K and ERK1/2 signaling pathways in stressed rats.

  11. Aerobic exercise training without weight loss reduces dyspnea on exertion in obese women

    Science.gov (United States)

    Bernhardt, Vipa; Stickford, Jonathon L.; Bhammar, Dharini M.; Babb, Tony G.

    2015-01-01

    Dyspnea on exertion (DOE) is a common symptom in obesity. We investigated whether aerobic exercise training without weight loss could reduce DOE. Twenty-two otherwise healthy obese women participated in a 12-week supervised aerobic exercise training program, exercising 30 min/day at 70–80% heart rate reserve, 4 days/week. Subjects were grouped based on their Ratings of Perceived Breathlessness (RPB) during constant load 60W cycling: +DOE (n = 12, RPB ≥ 4, 37 ± 7 years, 34 ± 4kg/m2) and −DOE (n = 10, RPB ≤ 2, 32 ± 6 years, 33 ± 3kg/m2). No significant differences between the groups in body composition, pulmonary function, or cardiorespiratory fitness were observed pre-training. Post-training, peak was improved significantly in both groups (+DOE: 12 ± 7, −DOE: 14 ± 8%). RPB was significantly decreased in the + DOE (4.7 ± 1.0–2.5 ± 1.0) and remained low in the −DOE group (1.2 ± 0.6–1.3 ± 1.0) (interaction p exercise training improved cardiorespiratory fitness and DOE and thus appears to be an effective treatment for DOE in obese women. PMID:26593640

  12. Seed predation and selection exerted by a seed predator influence subalpine tree densities.

    Science.gov (United States)

    Siepielski, Adam M; Benkman, Craig W

    2008-10-01

    Strongly interacting species often have pronounced direct and indirect effects on other species. Here we focus of the effects of pine squirrels (Tamiasciurus spp.), which are a dominant pre-dispersal seed predator of many conifers including limber pines (Pinus flexilis) and whitebark pines (P. albicaulis). Pine squirrels depress seed abundance by harvesting most limber and whitebark pine cones on their territories. Pine squirrels further reduce seed availability for Clark's Nutcrackers (Nucifraga columbiana), the primary seed disperser of these pines, because selection exerted by pine squirrels has reduced the number of seeds per cone and causes seeds to be less accessible. We predicted that, if fewer seeds were available for dispersal by nutcrackers, pine recruitment should be suppressed in areas with pine squirrels. In support of this prediction, stand densities were about two times greater in areas where pine squirrels are absent than in areas where they are present. Alternative explanations that we considered do not account for these differences; however, precipitation may limit stand densities in the absence of seed limitation by pine squirrels. In sum, pine squirrels apparently depress limber and whitebark pine stand densities, with the potential for ecosystem impacts because these pines are foundation species within Western subalpine ecosystems.

  13. Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

    Directory of Open Access Journals (Sweden)

    Sangeetha Ravi Kumar

    2013-12-01

    Full Text Available Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing influence via different molecules and pathways including the Bcl-2 proteins, MAPK, NFκB, Caspases, GADD45, and several other molecules that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in addition to decreasing the frequency of occurrence and growth of tumours, fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this effect is selective, i.e., fucoxanthin has the capability to target cancer cells only, leaving normal physiological cells unaffected/less affected. Hence, fucoxanthin and its metabolites show great promise as chemotherapeutic agents in cancer.

  14. Acute effects of exercise and active video games on adults' reaction time and perceived exertion.

    Science.gov (United States)

    Guzmán, José F; López-García, Jesús

    2016-11-01

    The purpose of the present study was to examine the acute effects of resting, aerobic exercise practised alone, and aerobic exercise with active video games (AVG), on complex reaction time (CRT) and the post-exercise acute rate of perceived exertion (RPE) in young healthy adults. The experimental group was composed of 92 healthy young adults, 78 males and 13 females (age M = 21.9 ± 2.7 years) who completed two sessions, A and B. In session A, participants rode 30 min on an ergometer, while in session B they exercised for 30 min on an ergometer while playing an AVG on a Wii. The control group was composed of 30 young adults, 26 males and 4 females (age M = 21.4 ± 2.9 years) who rested for 30 min. In each session, a CRT task was performed before and after exercising or resting, and post-exercise global RPE was noted. Repeated measures general linear model (GLM) and Wilcoxon tests were performed. (1) Both aerobic exercise alone and aerobic exercise combined with AVG improved CRT, while resting did not; (2) aerobic exercise combined with AVG did not improve CRT more than aerobic exercise only; and (3) RPE was lower after aerobic exercise combined with AVG compared with aerobic exercise only. In young adults, exercise produces acute benefits on CRT, and practising exercise with AVG helps to decrease RPE.

  15. Interleukin-1β and anaphylatoxins exert a synergistic effect on NGF expression by astrocytes

    Directory of Open Access Journals (Sweden)

    Patte Christine

    2006-04-01

    Full Text Available Abstract C3a and C5a anaphylatoxins are proinflammatory polypeptides released during complement activation. They exert their biological activities through interaction with two G protein-coupled receptors named C3aR and C5aR, respectively. In the brain, these receptors are expressed on glial cells, and some recent data have suggested that anaphylatoxins could mediate neuroprotection. In this study, we used RT-PCR and ribonuclease protection assays (RPA to investigate the role of anaphylatoxins on neurotrophin expression by the human glioblastoma cell line T98G and by rat astrocytes. Our data show that for both cell types, anaphylatoxins upregulate expression of NGF mRNA. This response depended on a G protein-coupled pathway since pre-treatment of cells with pertussis toxin (PTX completely blocked NGF mRNA increases. This effect was anaphylatoxin-specific since pre-incubation with anti-C3a or anti-C5aR antibodies abolished the effects of C3a and C5a, respectively. The regulation of NGF mRNA by anaphylatoxins was not accompanied by translation into protein expression, but there was a significant synergic effect of anaphylatoxins/IL-1b costimulation. Our demonstration of involvement of anaphylatoxins in the NGF release process by astrocytes suggests that C3a and C5a could modulate neuronal survival in the CNS.

  16. The Effect of Ramadan Fasting on Physical Performances, Mood State and Perceived Exertion in Young Footballers

    Science.gov (United States)

    Chtourou, Hamdi; Hammouda, Omar; Souissi, Hichem; Chamari, Karim; Chaouachi, Anis; Souissi, Nizar

    2011-01-01

    Purpose This study was designed to assess the effects of Ramadan fasting on the profile of mood state and perceived exertion in young soccer players and aerobic and anaerobic performances during the Yo-Yo, repeated sprint ability (RSA) and the Wingate tests. Methods Twenty junior male soccer players completed the Yo-Yo, the RSA, and the Wingate tests on three different occasions: one-week before Ramadan (BR), the second week (SWR) and the fourth week (ER) of Ramadan. The total distance (TD) covered and the estimated maximal aerobic velocity (MAV) during the Yo-Yo test were recorded. During the RSA test, peak power (PP) during each sprint, the percentage of decrement of PP (PD) and total work (Wtotal) were calculated. During the Wingate test, peak (Ppeak) and mean (Pmean) powers and fatigue index (FI) were recorded. Results TD and MAV (P=0.01) during the Yo-Yo test and PP (P=0.01, P=0.004, P=0.001, P=0.01, P=0.03 for sprints 1, 2, 3, 4, and 5, respectively) and Wtotal (P=0.02) during the RSA test were significantly higher during BR than ER. Furthermore, muscle fatigue during the RSA test increased significantly from BR to ER (P=0.01). Ppeak and Pmean during the Wingate test decreased significantly from BR to SWR and ER (PRSA and the Wingate tests were affected by Ramadan fasting in young soccer players. PMID:22375237

  17. Acoustic radiation force and torque exerted on a small viscoelastic particle in an ideal fluid

    CERN Document Server

    Leao-Neto, J P

    2015-01-01

    We provide a detailed analysis on the acoustic radiation force and torque exerted on a homogeneous viscoelastic particle in the long-wave limit (the particle radius is much smaller than the incident wavelength) by an arbitrary wave. We assume that the particle behaves as a linear viscoelastic solid, which obeys the fractional Kelvin-Voigt model. Simple analytical expressions for the radiation force and torque are obtained considering the low- and high-frequency approximation in the viscoelastic model. The developed theory is used to describe the interaction of acoustic waves (traveling and standing plane waves, and zero- and first-order Bessel beams) with a low- and high-density polyethylene particle chosen as examples. Negative axial radiation force and torque are predicted when the ratio of the longitudinal to shear relaxation times is smaller than a constant that depends on the speed of sound in the particle. In addition, a full 3D tractor Bessel vortex beam acting on the high-density polyethylene is depic...

  18. PABPC1 exerts carcinogenesis in gastric carcinoma by targeting miR-34c.

    Science.gov (United States)

    Zhu, Jie; Ding, Hao; Wang, Xiaohong; Lu, Qi

    2015-01-01

    As one of the common malignant tumors that threaten human health severely, gastric carcinoma is the second highest cause of cancer death and the fourth most common cancer globally. However, the mechanism underlying gastric cancer is still not fully understood. PABPC1 plays an important role in translation, control the rate of mRNA deadenylation and participates in mRNA decay, which is involved in carcinogenesis. Here in present study, we reported that PABPC1 is an oncogenic protein in gastric carcinoma. The results showed that PABPC1 is upregulated in gastric carcinoma tissues, and high PABPC1 expression predicts poor survival. PABPC1 regulates proliferation and transformation of gastric cancer cells in vitro and in vivo. PABPC1 knockdown induces apoptosis by upregulating pro-apoptotic proteins and downregulating anti-apoptotic proteins. In addition, miR-34c is a target of PABPC1, and miR-34c is critically essential for the function of PABPC1. In summary, PABPC1 exerts carcinogenesis and promotes growth and survival of gastric cancer cells by regulating miR-34c.

  19. Cattle tick-associated bacteria exert anti-biofilm and anti-Tritrichomonas foetus activities.

    Science.gov (United States)

    Zimmer, K R; Seixas, A; Conceição, J M; Zvoboda, D A; Barros, M P; Tasca, T; Macedo, A J; Termignoni, C

    2013-05-31

    Research on microbiota in cattle tick and the evaluation of its activity against other microorganisms can contribute to identify new molecules potentially useful to control infections caused by bacteria and protozoa. Biofilms pose increasing problems worldwide, mainly due to their resistance to antimicrobial therapies and host immune response. In this study we investigate the ability Rhipicephalus (Boophilus) microplus-associated bacteria may exhibit to produce anti-biofilm and trichomonicidal compounds. Gut, ovary, salivary glands, and Gené organ were collected from engorged R. microplus female. Homogenates of each tissue were inoculated onto 15 distinct culture media. Anti-biofilm and trichomonicidal activities were analyzed by culturing each bacterium isolated in a liquid medium. Results showed that R. microplus cattle tick microflora varies for different tissues. Bacteria belonging to different genera (Aeromonas, Bacillus, Brevibacillus, Castelaniella, Comamonas, Kocuria, and Microbacterium) were identified. Interestingly, all bacterial species found displayed pronounced activity against Staphylococcus epidermidis and Pseudomonas aeruginosa biofilms, and also against the cattle pathogen Tritrichomonas foetus, confirming the hypothesis that cattle tick could be a source of bacteria active against pathogens. This is the first study showing that bacteria isolated from a tick exert anti-biofilm and trichomonicidal activities.

  20. Rating of perceived exertion after 12 weeks of high-intensity, intermittent sprinting.

    Science.gov (United States)

    Heydari, Mehrdad; Boutcher, Stephen H

    2013-02-01

    The effect of a 12-week high-intensity intermittent exercise (HIIE) intervention on the rating of perceived exertion (RPE) response of young males was examined. Participants (N = 38; M BMI = 28.7 kg x m(-2), SD = 3.1; M age = 24.9 yr., SD = 4.3) were randomly assigned to either an exercise or control group. The exercise group received HIIE three times per week, 20 min. per session, for 12 weeks. RPE was assessed before and after HIIE training and during pre- and post-maximal oxygen uptake (VO2 max) testing. After HIIE training, RPE was significantly higher in Weeks 11-12 compared to Weeks 1-2. In contrast, heart rate was similar throughout training. Comparing post- to pre-VO2 max test, RPE was significantly lower in the exercise group, whereas for controls, RPE was similar. Aerobic power improved 15% for the exercise group, with no significant change for controls. HIIE resulted in significant increases in RPE, whereas RPE during the VO2 max test was significantly decreased.

  1. Amyloidogenic amyloid-β-peptide variants induce microbial agglutination and exert antimicrobial activity

    Science.gov (United States)

    Spitzer, Philipp; Condic, Mateja; Herrmann, Martin; Oberstein, Timo Jan; Scharin-Mehlmann, Marina; Gilbert, Daniel F.; Friedrich, Oliver; Grömer, Teja; Kornhuber, Johannes; Lang, Roland; Maler, Juan Manuel

    2016-01-01

    Amyloid-β (Aβ) peptides are the main components of the plaques found in the brains of patients with Alzheimer’s disease. However, Aβ peptides are also detectable in secretory compartments and peripheral blood contains a complex mixture of more than 40 different modified and/or N- and C-terminally truncated Aβ peptides. Recently, anti-infective properties of Aβ peptides have been reported. Here, we investigated the interaction of Aβ peptides of different lengths with various bacterial strains and the yeast Candida albicans. The amyloidogenic peptides Aβ1-42, Aβ2-42, and Aβ3p-42 but not the non-amyloidogenic peptides Aβ1-40 and Aβ2-40 bound to microbial surfaces. As observed by immunocytochemistry, scanning electron microscopy and Gram staining, treatment of several bacterial strains and Candida albicans with Aβ peptide variants ending at position 42 (Aβx-42) caused the formation of large agglutinates. These aggregates were not detected after incubation with Aβx-40. Furthermore, Aβx-42 exerted an antimicrobial activity on all tested pathogens, killing up to 80% of microorganisms within 6 h. Aβ1-40 only had a moderate antimicrobial activity against C. albicans. Agglutination of Aβ1-42 was accelerated in the presence of microorganisms. These data demonstrate that the amyloidogenic Aβx-42 variants have antimicrobial activity and may therefore act as antimicrobial peptides in the immune system. PMID:27624303

  2. Endoscopic Fascia Release for Forearm Chronic Exertional Compartment Syndrome: Case Report and Surgical Technique.

    Science.gov (United States)

    Miller, Elizabeth A; Cobb, Anna L; Cobb, Tyson K

    2017-09-01

    Chronic exertional compartment syndrome (CECS) of the forearm is traditionally treated with open compartment release requiring large incisions that can result in less than optimal esthetic results. The purpose of this study is to describe a case report of 2 professional motocross patients with forearm CECS treated endoscopically using a minimally invasive technique. Two professional motocross racers presented with a history of chronic proximal volar forearm pain when motocross riding. Other symptoms included paresthesia and weakness, which, at times, led to an inability to continue riding. Both failed conservative management. Compartment pressure measurements were performed before and after provocative exercises to confirm diagnosis of CECS. Release of both the volar and dorsal compartments was performed endoscopically through a single incision. Symptoms resolved after surgery. The first patient resumed riding at 1 week, competing at 3 weeks, and continues to ride competitively without symptoms at 3 years postoperative. The second patient began riding at 1 week and won second place in the National Supercross finals 5 weeks after simultaneous bilateral release. This technique is simple and effective. The cannula used protects the superficial nerves while allowing release through a small, cosmetically pleasing incision.

  3. BDNF-secreting capsule exerts neuroprotective effects on epilepsy model of rats.

    Science.gov (United States)

    Kuramoto, Satoshi; Yasuhara, Takao; Agari, Takashi; Kondo, Akihiko; Jing, Meng; Kikuchi, Yoichiro; Shinko, Aiko; Wakamori, Takaaki; Kameda, Masahiro; Wang, Feifei; Kin, Kyohei; Edahiro, Satoru; Miyoshi, Yasuyuki; Date, Isao

    2011-01-12

    Brain-derived neurotrophic factor (BDNF) is a well neurotrophic factor with neuroprotective potentials for various diseases in the central nervous system. However several previous studies demonstrated that BDNF might deteriorate symptoms for epilepsy model of animals by progression of abnormal neurogenesis. We hypothesized that continuous administration of BDNF at low dose might be more effective for epilepsy model of animals because high dose of BDNF was used in many studies. BDNF-secreting cells were genetically made and encapsulated for transplantation. Rats receiving BDNF capsule showed significant amelioration of seizure stage and reduction of the number of abnormal spikes at 7 days after kainic acid administration, compared to those of control group. The number of BrdU and BrdU/doublecortin positive cells in the hippocampus of BDNF group significantly increased, compared to that of control group. NeuN positive cells in the CA1 and CA3 of BDNF group were significantly preserved, compared to control group. In conclusion, low dose administration using encapsulated BDNF-secreting cells exerted neuroprotective effects with enhanced neurogenesis on epilepsy model of rats. These results might suggest the importance of the dose and administrative way of this neurotrophic factor to the epilepsy model of animals.

  4. Netrin-1 exerts oncogenic activities through enhancing Yes-associated protein stability.

    Science.gov (United States)

    Qi, Qi; Li, Dean Y; Luo, Hongbo R; Guan, Kun-Liang; Ye, Keqiang

    2015-06-09

    Yes-associated protein (YAP), a transcription coactivator, is the major downstream effector of the Hippo pathway, which plays a critical role in organ size control and cancer development. However, how YAP is regulated by extracellular stimuli in tumorigenesis remains incompletely understood. Netrin-1, a laminin-related secreted protein, displays proto-oncogenic activity in cancers. Nonetheless, the downstream signaling mediating its oncogenic effects is not well defined. Here we show that netrin-1 via its transmembrane receptors, deleted in colorectal cancer and uncoordinated-5 homolog, up-regulates YAP expression, escalating YAP levels in the nucleus and promoting cancer cell proliferation and migration. Inactivating netrin-1, deleted in colorectal cancer, or uncoordinated-5 homolog B (UNC5B) decreases YAP protein levels, abrogating cancer cell progression by netrin-1, whereas knockdown of mammalian STE20-like protein kinase 1/2 (MST1/2) or large tumor suppressor kinase 1/2 (Lats1/2), two sets of upstream core kinases of the Hippo pathway, has no effect in blocking netrin-1-induced up-regulation of YAP. Netrin-1 stimulates phosphatase 1A to dephosphorylate YAP, which leads to decreased ubiquitination and degradation, enhancing YAP accumulation and signaling. Hence, our findings support that netrin-1 exerts oncogenic activity through YAP signaling, providing a mechanism coupling extracellular signals to the nuclear YAP oncogene.

  5. Victorianizing Guangxu: Arresting Flows, Minting Coins, and Exerting Authority in Early Twentieth-Century Kham

    Directory of Open Access Journals (Sweden)

    Scott Relyea

    2016-06-01

    Full Text Available In the late Qing and early Republican eras, eastern Tibet (Kham was a borderland on the cusp of political and economic change. Straddling Sichuan Province and central Tibet, it was coveted by both Chengdu and Lhasa. Informed by an absolutist conception of territorial sovereignty, Sichuan officials sought to exert exclusive authority in Kham by severing its inhabitants from regional and local influence. The resulting efforts to arrest the flow of rupees from British India and the flow of cultural identity entwined with Buddhism from Lhasa were grounded in two misperceptions: that Khampa opposition to Chinese rule was external, fostered solely by local monasteries as conduits of Lhasa’s spiritual authority, and that Sichuan could arrest such influence, the absence of which would legitimize both exclusive authority in Kham and regional assertions of sovereignty. The intersection of these misperceptions with the significance of Buddhism in Khampa identity determined the success of Sichuan’s policies and the focus of this article, the minting and circulation of the first and only Qing coin emblazoned with an image of the emperor. It was a flawed axiom of state and nation builders throughout the world that severing local cultural or spiritual influence was possible—or even necessary—to effect a borderland’s incorporation.

  6. Isolated Chronic Exertional Compartment Syndrome of the Lateral Lower Leg: A Case Series.

    Science.gov (United States)

    van Zantvoort, Aniek P M; de Bruijn, Johan A; Winkes, Michiel B; Dielemans, Jeanne P; van der Cruijsen-Raaijmakers, Marike; Hoogeveen, Adwin R; Scheltinga, Marc R

    2015-11-01

    Exercise-induced lower leg pain may be caused by chronic exertional compartment syndrome (CECS). The anterior (ant-CECS) or deep posterior compartment (dp-CECS) is usually affected. Knowledge regarding CECS of the lateral compartment (lat-CECS) is limited. To describe demographic characteristics and symptoms in a consecutive series of patients with isolated CECS of the lateral compartment of the leg. Case series; Level of evidence, 4. Since 2001, patients undergoing dynamic intracompartmental pressure (ICP) measurements for suspected CECS in a single institution were prospectively monitored. Individuals with a history possibly associated with lat-CECS and elevated ICP measurements (Pedowitz criteria) were identified. Exclusion criteria were concomitant ipsilateral ant-CECS/dp-CECS, acute compartment syndrome, recent significant trauma, peroneal nerve entrapment, or vascular claudication. During an 11-year time period, a total of 26 patients with isolated lat-CECS fulfilled study criteria (15 females; median age, 21 years; range, 14-48 years). Frequently identified provocative sports were running (n = 4), walking (n = 4), field hockey (n = 3), soccer (n = 3), and volleyball (n = 2). Exercise-induced lateral lower leg pain (92%) and tightness (42%) were often reported. The syndrome was bilateral in almost two-thirds (62%, n = 16). Delay in diagnosis averaged 24 months (range, 2 months to 10 years). Young patients with exercise-induced pain in the lateral portions of the lower leg may suffer from isolated CECS of the lateral compartment. ICP measurements in the lateral compartment in these patients are recommended.

  7. Chronic Exertional Compartment Syndrome of the Hand: Case Report and Literature Review.

    Science.gov (United States)

    Dwyer, C Liam; Soong, Maximillian C; Kasparyan, N George

    2017-05-01

    Chronic exertional compartment syndrome (CECS) is characterized by activity-induced pain, swelling, and decreased muscle function due to increased pressure and decreased circulation within a confined muscle compartment. Although well-known to occur in the leg, involvement of the hand has rarely been reported in the literature. We present a 44 year old male with CECS involving bilateral thenar and hypothenar compartments. Symptoms were reproduced on exam by driving screws into wood with a screwdriver. Elevated compartment pressures were confirmed with a hand-held digital device which employs a rigid needle that is readily directed to specific compartments. Selective releases of the thenar and hypothenar compartments were performed under local anesthesia and forearm tourniquet in the ambulatory surgery center. At 3-month follow-up, the patient reported full use of his right hand, including woodworking, with excellent relief of symptoms. At 5 months postoperatively, he underwent identical surgical releases on the contralateral left side, with similar relief. CECS of the hand is a rare condition. Our case is unique among prior reports with regard to pattern of compartment involvement, as well as provocative maneuvers and compartment testing methods employed. This report should help foster clinical suspicion, facilitate diagnosis, and demonstrate success of targeted surgical treatment.

  8. Intramuscular compartment pressure measurement in chronic exertional compartment syndrome: new and improved diagnostic criteria.

    Science.gov (United States)

    Roscoe, David; Roberts, Andrew J; Hulse, David

    2015-02-01

    Patients with chronic exertional compartment syndrome (CECS) have pain during exercise that subsides with rest. Diagnosis is usually confirmed by intramuscular compartment pressure (IMCP) measurement. Controversy exists regarding the accuracy of existing diagnostic criteria. (1) To compare dynamic IMCP measurement and anthropometric factors between patients with CECS and asymptomatic controls and (2) to establish the diagnostic utility of dynamic IMCP measurement. Cohort study (diagnosis); Level of evidence, 2. A total of 40 men aged 21 to 40 years were included in the study: 20 with symptoms of CECS of the anterior compartment and 20 asymptomatic controls. Diagnoses other than CECS were excluded with rigorous inclusion criteria and magnetic resonance imaging. The IMCP was measured continuously before, during, and after participants exercised on a treadmill, wearing identical footwear and carrying a 15-kg load. Pain experienced by study subjects increased incrementally as the study progressed (P compartment IMCP is elevated immediately upon standing at rest in subjects with CECS. In patients with symptoms consistent with CECS, diagnostic utility of IMCP measurement is improved when measured continuously during exercise. A cutoff of 105 mm Hg in phase 2 provides better diagnostic accuracy than do the Pedowitz criteria of 30 mm Hg and 20 mm Hg at 1 and 5 minutes after exercise, respectively. © 2014 The Author(s).

  9. Rating of Perceived Exertion and Physiological Responses in Water-Based Exercise

    Directory of Open Access Journals (Sweden)

    Santana Pinto Stephanie

    2015-12-01

    Full Text Available The aim of the present study was to relate the overall rating of perceived exertion (RPE-overall with cardiorespiratory and neuromuscular variables during stationary running with the elbow flexion/extension performed with water-floating equipment. The sample consisted of eleven women that performed the water-based exercise at submaximal cadences. The heart rate, oxygen uptake, ventilation, and electromyographic signal (EMG from biceps brachii (%EMG BB, triceps brachii (%EMG TB, biceps femoris (%EMG BF and rectus femoris (%EMG RF muscles were measured during the exercise, and the overall RPE was measured immediately following its completion. The Pearson product-moment linear correlation was used to investigate associations between the variables analyzed in the present study. Significant relationships were observed between the RPE-overall and all the cardiorespiratory variables, with the r values ranging from 0.60 to 0.70 (p<0.05. In addition, the RPE-overall showed a significant (p<0.05 relationship with %EMG BB (r=0.55 and %EMG BF (r=0.50. These results suggest an association between the RPE-overall with all cardiorespiratory and two neuromuscular variables during the execution of a water-based aerobic exercise using water-floating equipment.

  10. YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers.

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    Claudia Stein

    2015-08-01

    Full Text Available YAP1 is a major effector of the Hippo pathway and a well-established oncogene. Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1 amplification is observed in several types of human cancers. Here we investigated its genomic binding landscape in YAP1-activated cancer cells, as well as in non-transformed cells. We demonstrate that TEAD transcription factors mediate YAP1 chromatin-binding genome-wide, further explaining their dominant role as primary mediators of YAP1-transcriptional activity. Moreover, we show that YAP1 largely exerts its transcriptional control via distal enhancers that are marked by H3K27 acetylation and that YAP1 is necessary for this chromatin mark at bound enhancers and the activity of the associated genes. This work establishes YAP1-mediated transcriptional regulation at distal enhancers and provides an expanded set of target genes resulting in a fundamental source to study YAP1 function in a normal and cancer setting.

  11. YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers.

    Science.gov (United States)

    Stein, Claudia; Bardet, Anaïs Flore; Roma, Guglielmo; Bergling, Sebastian; Clay, Ieuan; Ruchti, Alexandra; Agarinis, Claudia; Schmelzle, Tobias; Bouwmeester, Tewis; Schübeler, Dirk; Bauer, Andreas

    2015-08-01

    YAP1 is a major effector of the Hippo pathway and a well-established oncogene. Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1 amplification is observed in several types of human cancers. Here we investigated its genomic binding landscape in YAP1-activated cancer cells, as well as in non-transformed cells. We demonstrate that TEAD transcription factors mediate YAP1 chromatin-binding genome-wide, further explaining their dominant role as primary mediators of YAP1-transcriptional activity. Moreover, we show that YAP1 largely exerts its transcriptional control via distal enhancers that are marked by H3K27 acetylation and that YAP1 is necessary for this chromatin mark at bound enhancers and the activity of the associated genes. This work establishes YAP1-mediated transcriptional regulation at distal enhancers and provides an expanded set of target genes resulting in a fundamental source to study YAP1 function in a normal and cancer setting.

  12. Photokinetic analysis of the forces and torques exerted by optical tweezers carrying angular momentum

    Science.gov (United States)

    Yevick, Aaron; Evans, Daniel J.; Grier, David G.

    2017-02-01

    The theory of photokinetic effects expresses the forces and torques exerted by a beam of light in terms of experimentally accessible amplitude and phase profiles. We use this formalism to develop an intuitive explanation for the performance of optical tweezers operating in the Rayleigh regime, including effects arising from the influence of light's angular momentum. First-order dipole contributions reveal how a focused beam can trap small objects, and what features limit the trap's stability. The first-order force separates naturally into a conservative intensity-gradient term that forms a trap and a non-conservative solenoidal term that drives the system out of thermodynamic equilibrium. Neither term depends on the light's polarization; light's spin angular momentum plays no role at dipole order. Polarization-dependent effects, such as trap-strength anisotropy and spin-curl forces, are captured by the second-order dipole-interference contribution to the photokinetic force. The photokinetic expansion thus illuminates how light's angular momentum can be harnessed for optical micromanipulation, even in the most basic optical traps. This article is part of the themed issue 'Optical orbital angular momentum'.

  13. Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro

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    Shen X

    2017-02-01

    Full Text Available Xin Shen,1,* Nan Zhou,1,* Le Mi,1 Zishuo Hu,2 Libin Wang,1 Xueying Liu,1 Shengyong Zhang1 1Department of Medicinal Chemistry, School of Pharmacy, 2Student Brigade, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Abstract: The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph. In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6 myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05 reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD–POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of T2D rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes. Keywords: phloretin, diabetes, insulin sensitivity, blood glucose consumption, skeletal muscle

  14. Rating of perceived exertion during cycling is associated with subsequent running economy in triathletes.

    Science.gov (United States)

    Bonacci, Jason; Vleck, Veronica; Saunders, Philo U; Blanch, Peter; Vicenzino, Bill

    2013-01-01

    To determine which commonly measured variables of cycling intensity are related to subsequent running economy in triathletes. Cross-sectional laboratory study. Running economy was compared between a control run (no preceding cycle) and a run performed after a 45 min high-intensity cycle in eighteen triathletes. Power output, heart rate, rating of perceived exertion (RPE) and blood lactate concentration were monitored throughout the cycle. The relationship between measures of cycle intensity and the change in running economy was evaluated using Pearson's product moment correlation. Changes in running economy were also interpreted using the smallest worthwhile change (>2.4%) and grouped accordingly (i.e. impaired, no change, or improved running economy). Triathletes' RPE at the end of the cycling bout was significantly associated with the change in running economy after cycling (r=0.57, p=0.01). Average RPE of the cycle bout and RPE at the end of the cycling bout were significantly different between groups, with higher RPE scores being related to impairments in running economy (p=0.04 and p=0.02 respectively). RPE during cycling is associated with subsequent running economy in triathletes. RPE is a simple, cost-effective measure that triathletes and their coaches can use in competition and training to control cycling intensity without the need for specialist equipment such as crank systems or blood analysers. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  15. A Herbal Formula, CGXII, Exerts Antihepatofibrotic Effect in Dimethylnitrosamine-Induced SD Rat Model

    Science.gov (United States)

    Kim, Hyo-Seon; Kim, Hyeong-Geug; Lee, Hye-Won; Lee, Sung-Bae; Lee, Jin-Seok; Im, Hwi-Jin; Kim, Won-Yong; Lee, Dong-Soo; Son, Chang-Gue

    2016-01-01

    We aimed to evaluate the antihepatofibrotic effects of CGXII, an aqueous extract which is composed of A. iwayomogi, A. xanthioides, and S. miltiorrhiza, against dimethylnitrosamine- (DMN-) induced hepatofibrosis. Male Sprague Dawley rats were intraperitoneally injected with 10 mg/kg of DMN for 4 weeks (three consecutive days weekly). Rats were orally given distilled water, CGXII (50 or 100 mg/kg), or dimethyl dimethoxy biphenyl dicarboxylate (50 mg/kg) daily. DMN injection caused substantial alteration of total body weight and liver and spleen mass, whereas they were notably normalized by CGXII. CGXII treatment also markedly attenuated the elevation of serum aspartate aminotransferase and alanine aminotransferase levels, hepatic lipid peroxidation, and protein carbonyl contents. Collagen accumulation in hepatic tissue evidenced by histopathological analysis and quantitative assessment of hepatic hydroxyproline was ameliorated by CGXII. Immunohistochemistry analysis revealed decreased α-smooth muscle actin supporting the antihepatofibrotic effect of CGXII. The profibrogenic cytokines transforming growth factor-β, platelet-derived growth factor-β, and connective tissue growth factor were increased by DMN injection. Administration of CGXII normalized the protein and gene expression levels of these cytokines. Our findings suggest that CGXII lowers the levels of profibrogenic cytokines and thereby exerts antifibrotic effects. PMID:27340416

  16. A Herbal Formula, CGXII, Exerts Antihepatofibrotic Effect in Dimethylnitrosamine-Induced SD Rat Model

    Directory of Open Access Journals (Sweden)

    Hyo-Seon Kim

    2016-01-01

    Full Text Available We aimed to evaluate the antihepatofibrotic effects of CGXII, an aqueous extract which is composed of A. iwayomogi, A. xanthioides, and S. miltiorrhiza, against dimethylnitrosamine- (DMN- induced hepatofibrosis. Male Sprague Dawley rats were intraperitoneally injected with 10 mg/kg of DMN for 4 weeks (three consecutive days weekly. Rats were orally given distilled water, CGXII (50 or 100 mg/kg, or dimethyl dimethoxy biphenyl dicarboxylate (50 mg/kg daily. DMN injection caused substantial alteration of total body weight and liver and spleen mass, whereas they were notably normalized by CGXII. CGXII treatment also markedly attenuated the elevation of serum aspartate aminotransferase and alanine aminotransferase levels, hepatic lipid peroxidation, and protein carbonyl contents. Collagen accumulation in hepatic tissue evidenced by histopathological analysis and quantitative assessment of hepatic hydroxyproline was ameliorated by CGXII. Immunohistochemistry analysis revealed decreased α-smooth muscle actin supporting the antihepatofibrotic effect of CGXII. The profibrogenic cytokines transforming growth factor-β, platelet-derived growth factor-β, and connective tissue growth factor were increased by DMN injection. Administration of CGXII normalized the protein and gene expression levels of these cytokines. Our findings suggest that CGXII lowers the levels of profibrogenic cytokines and thereby exerts antifibrotic effects.

  17. Load variation effects on the pressure fluctuations exerted on a Kaplan turbine runner

    Science.gov (United States)

    Amiri, K.; Mulu, B.; Raisee, M.; Cervantes, M. J.

    2014-03-01

    Introduction of intermittent electricity production systems like wind power and solar systems to electricity market together with the consumption-based electricity production resulted in numerous start/stops, load variations and off-design operation of water turbines. The hydropower systems suffer from the varying loads exerted on the stationary and rotating parts of the turbines during load variations which they are not designed for. On the other hand, investigations on part load operation of single regulated turbines, i.e., Francis and propeller, proved the formation of rotating vortex rope (RVR) in the draft tube. The RVR induces oscillating flow both in plunging and rotating modes which results in oscillating force with two different frequencies on the runner blades, bearings and other rotating parts of the turbine. The purpose of this study is to investigate the effect of transient operations on the pressure fluctuations on the runner and mechanism of the RVR formation/mitigation. Draft tube and runner blades of the Porjus U9 model, a Kaplan turbine, were equipped with pressure sensors. The model was run in off-cam mode during different load variation conditions to check the runner performance under unsteady condition. The results showed that the transients between the best efficiency point and the high load happens in a smooth way while transitions to/from the part load, where rotating vortex rope (RVR) forms in the draft tube induces high level of fluctuations with two frequencies on the runner; plunging and rotating mode of the RVR.

  18. Acute responses of blood pressure, heart rate and rating of perceived exertion in hypertensive patients

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    César Giovanni García Cardona

    2007-06-01

    Full Text Available Objective: To assess and compare acute responsesin arterial blood pressure (BP, heartrate (HR and rating of perceived exertion scale(PES during a variable-resistance weight-liftingcircuit (WC versus submaximal aerobicexercise in cycloergometer (AE in individualswith hypertension scaled I and II.Methods: 21 subjects with controlled hypertensionscaled I and II (8 males and 13 females,15 actives and 6 sedentary, age 56±5.9 yearswere evaluated. All the participants receivedtraining about warm-up, use of PES, and respiratoryand weight lifting machines techniquesin exercise. All underwent a single session ofWC in six stations at 50% 1RM and a singlesession of AE at 70%-80% FCmax, in intervalsof one week. BP, HR and PES was measured inboth exercises.Results: To compare responses in both typesof exercise, at Test was used. It found a lowerresponse of HR (p<0.001, systolic BP (p<0.005and PES (p<0.005 during WC. Greater diastolicBP response was found in WC, although it wasnot significative (p=0.139. Sedentary subjectsshowed greater increases. Responses of variableswere similar between stations in WC.Conclusion: This study evidenced a similarbehavior of acute cardiovascular responses and PESduring WC versus AE in hypertensive subjects. Itshowed a lower pressure response during WC insubjects with previous aerobic training.

  19. A Novel Approach to Measure the Forces Exerted by Cells on Elastic Substrates

    Science.gov (United States)

    Guan, E.; Muralidhar, Sravanesh; Ghosh, Kaustabh; Clark, Richard; Rafailovich, Miriam; Sokolov, Jonathan

    2004-03-01

    We have observed that the cytoskeleton of a cell is very sensitive to the mechanical rigidty of the substrate. Furthermore we have found that this rearrangement is correlated to the attempt by the cell to match its modulus, as closely as possible, to that of the substrate. We postulate that the driving force for this phenomenon is the minimization of the large forces exerted at the contact line by the substrate on the cell. It is therefore important to be able to measure both the modulus of the cell as well as the surface forces on the same sample. In this study, we introduced a novel approach to measure the traction force. Instead of just measuring the 2-dimensional displacement of patterned features on a surface [1], the three-dimensional displacement field inside the sample was measured with the help of z-scan function of confocal microscope. Three-dimensional strain at the substrate surface was then calculated with numerical differentiation. Knowing the shear modulus of substrate, the traction force was computed simply by the application of Hooke's law, which is a simple linear relation. In this method the Fredholm integral can be avoided and the force locations can be determined without specific staining of the adherins once the force field is obtained. [1] Karen Beningo and Yu-Li Wang, TRENDS in Cell Biology, Vol.12 No.2 Feb 2002, pp79-84.

  20. Biomechanical differences between cases with chronic exertional compartment syndrome and asymptomatic controls during walking and marching gait.

    Science.gov (United States)

    Roberts, Andrew; Roscoe, David; Hulse, David; Bennett, Alexander N; Dixon, Sharon

    2017-07-18

    Chronic exertional compartment syndrome is a significant problem in military populations that may be caused by specific military activities. This study aimed to investigate the kinematic and kinetic differences in military cases with chronic exertional compartment syndrome and asymptomatic controls. 20 males with symptoms of chronic exertional compartment syndrome of the anterior compartment and 20 asymptomatic controls were studied. Three-dimensional lower limb kinematics and kinetics were compared during walking and marching. Cases were significantly shorter in stature and took a relatively longer stride in relation to leg length than controls. All kinematic differences identified were at the ankle. Cases demonstrated increased ankle plantarflexion from mid-stance to toe-off. Cases also demonstrated less ankle inversion at the end of stance and early swing phases. Lower ankle inversion moments were observed during mid-stance. The anthropometric and biomechanical differences demonstrated provide a plausible mechanism for the development of chronic exertional compartment syndrome in this population. The shorter stature in combination with the relatively longer stride length observed in cases may result in an increased demand on the anterior compartment musculature during ambulation. The results of this study, together with clinical insights and the literature suggest that the suppression of the walk-to-run stimulus during group marches may play a significant role in the development of chronic exertional compartment syndrome within a military population. The differences in joint angles and moments also suggest an impairment of the muscular control of ankle joint function, such as a reduced effectiveness of tibialis anterior. It is unclear whether this is a cause or consequence of chronic exertional compartment syndrome. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  1. α-Iso-cubebene exerts neuroprotective effects in amyloid beta stimulated microglia activation.

    Science.gov (United States)

    Park, Sun Young; Park, Se Jin; Park, Nan Jeong; Joo, Woo Hong; Lee, Sang-Joon; Choi, Young-Whan

    2013-10-25

    Schisandra chinensis is commonly used for food and as a traditional remedy for the treatment of neuronal disorders. However, it is unclear which component of S. chinensis is responsible for its neuropharmacological effects. To answer this question, we isolated α-iso-cubebene, a dibenzocyclooctadiene lignin, from S. chinensis and determined if it has any anti-neuroinflammatory and neuroprotective properties against amyloid β-induced neuroinflammation in microglia. Microglia that are stimulated by amyloid β increased their production of pro-inflammatory cytokines and chemokines, prostaglandin E2 (PGE2), nitric oxide (NO) and reactive oxygen species (ROS) and the enzymatic activity of matrix metalloproteinase 9 (MMP-9). We found this was all inhibited by α-iso-cubebene. Consistent with these results, α-iso-cubebene inhibited the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and MMP-9 in amyloid β-stimulated microglia. Subsequent mechanistic studies revealed that α-iso-cubebene inhibited the phosphorylation and degradation of IκB-α, the phosphorylation and transactivity of NF-κB, and the phosphorylation of MAPK in amyloid β-stimulated microglia. These results suggest that α-iso-cubebene impairs the amyloid β-induced neuroinflammatory response of microglia by inhibiting the NF-κB and MAPK signaling pathways. Importantly, α-iso-cubebene can provide critical neuroprotection for primary cortical neurons against amyloid β-stimulated microglia-mediated neurotoxicity. To the best of our knowledge, this is the first report showing that α-iso-cubebene can provide neuroprotection against, and influence neuroinflammation triggered by, amyloid β activation of microglia.

  2. Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma

    OpenAIRE

    2016-01-01

    Melanoma is a highly malignant neoplasm of melanocytes with considerable metastatic potential and drug resistance, explaining the need for new candidates that inhibit tumor growth and metastasis. The signal transducer and activator of the transcription 3 (Stat3) signaling pathway plays an important role in melanoma and has been validated as promising anticancer target for melanoma therapy. In this study, nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3, was evaluated f...

  3. Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells

    Science.gov (United States)

    Montgomery, Amanda; Adeyeni, Temitope; San, KayKay; Heuertz, Rita M.; Ezekiel, Uthayashanker R.

    2016-01-01

    We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer. PMID:27390600

  4. Alpha oscillatory correlates of motor inhibition in the aged brain

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    Marlene eBoenstrup

    2015-10-01

    Full Text Available Exerting inhibitory control is a cognitive ability mediated by functions known to decline with age. The goal of this study is to add to the mechanistic understanding of cortical inhibition during motor control in aged brains. Based on behavioral findings of impaired inhibitory control with age we hypothesized that elderly will show a reduced or a lack of EEG alpha-power increase during tasks that require motor inhibition. Since inhibitory control over movements has been shown to rely on prior motor memory formation, we investigated cortical inhibitory processes at two points in time - early after learning and after an overnight consolidation phase and hypothesized an overnight increase of inhibitory capacities. Young and elderly participants acquired a complex finger movement sequence and in each experimental session brain activity during execution and inhibition of the sequence was recorded with multi-channel EEG. We assessed cortical processes of sustained inhibition by means of task-induced changes of alpha oscillatory power. During inhibition of the learned movement, young participants showed a significant alpha power increase at the sensorimotor cortices whereas elderly did not. Interestingly, for both groups, the overnight consolidation phase improved up-regulation of alpha power during sustained inhibition. This points to deficits in the generation and enhancement of local inhibitory mechanisms at the sensorimotor cortices in aged brains. However, the alpha power increase in both groups implies neuroplastic changes that strengthen the network of alpha power generation over time in young as well as elderly brains.

  5. Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals

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    Tzu-Yu Lin

    2015-03-01

    Full Text Available The effect of palmitoylethanolamide (PEA, an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes was investigated. PEA inhibited the Ca2+-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca2+ concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca2+ release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca2+ influx mediated by Cav2.1 (P/Q-type channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway.

  6. African eggplant (Solanum anguivi Lam. fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca2+-induced mitochondrial swelling

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    Olusola Olalekan Elekofehinti

    2013-10-01

    Conclusions: These effects could be attributed to the bioactive polyphenolic compounds present in the extract. Our results suggest that SAG extract is a potential source of natural antioxidants that may be used not only in pharmaceutical and food industry but also in the treatment of diseases associated with oxidative stress.

  7. Zerumbone inhibits growth of hormone refractory prostate cancer cells by inhibiting JAK2/STAT3 pathway and increases paclitaxel sensitivity.

    Science.gov (United States)

    Jorvig, Jessica E; Chakraborty, Arup

    2015-02-01

    Zerumbone, a phytochemical isolated from Zingiber zerumbet has been shown previously to exhibit antineoplastic activity. But, the effect of zerumbone in prostate cancer has not been evaluated. Prostate cancer is frequently associated with elevated levels of interleukin-6 (IL-6), which exerts its oncogenic effects through activation of Janus kinase 2 (JAK2) followed by activation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Here, we investigated whether the anticancer effects of zerumbone are mediated through inhibition of the JAK2/STAT3 signaling pathway and whether zerumbone can increase the paclitaxel (PTX) sensitivity of prostate cancer cells. Zerumbone exerted significant cytotoxicity of DU145 versus PC3 prostate cancer cells through cell cycle arrest at G0/G1 phase followed by apoptosis. Zerumbone selectively inhibited JAK2 in both DU145 and PC3 cells. However, the biological axis of IL-6/JAK2/STAT3 was inhibited only in DU145 cells as no STAT3 phosphorylation was detected in PC3 cells even after IL-6 stimulation. Other signaling pathways in DU145 cells remained unaffected. The expression of prostate cancer-associated genes, including cyclin D1, IL-6, COX2, and ETV1, was blocked. Zerumbone also synergistically increased the sensitivity to PTX. Further preclinical study might reveal the potential use of zerumbone as a chemotherapeutic agent for hormone refractory prostate cancer where IL-6/JAK2/STAT3 signaling is aberrantly active and may be combined with PTX.

  8. Enzyme-treated asparagus extract promotes expression of heat shock protein and exerts antistress effects.

    Science.gov (United States)

    Ito, Tomohiro; Maeda, Takahiro; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Sato, Atsuya

    2014-03-01

    A novel enzyme-treated asparagus extract (ETAS) has been developed as a functional material produced from asparagus stem. Studies were conducted to determine the effect of ETAS on heat shock protein 70 (HSP70) expression and alleviation of stress. HeLa cells were treated with ETAS, and HSP70 mRNA and protein levels were measured using a reverse transcription-polymerase chain reaction (RT-PCR) assay and an enzyme-linked immunosorbent assay (ELISA), respectively. ETAS showed significant increases in HSP70 mRNA at more than 0.125 mg/mL and the protein at more than 1.0 mg/mL. The antistress effect was evaluated in a murine sleep-deprivation model. A sleep-deprivation stress load resulted in elevation of blood corticosterone and lipid peroxide concentrations, while supplementation with ETAS at 200 and 1000 mg/kg body weight was associated with significantly reduced levels of both stress markers, which were in the normal range. The HSP70 protein expression level in mice subjected to sleep-deprivation stress and supplemented with ETAS was significantly enhanced in stomach, liver, and kidney, compared to ETAS-untreated mice. A preliminary and small-sized human study was conducted among healthy volunteers consuming up to 150 mg/d of ETAS daily for 7 d. The mRNA expression of HSP70 in peripheral leukocytes was significantly elevated at intakes of 100 or 150 mg/d, compared to their baseline levels. Since HSP70 is known to be a stress-related protein and its induction leads to cytoprotection, the present results suggest that ETAS might exert antistress effects under stressful conditions, resulting from enhancement of HSP70 expression.

  9. Syringin may exert sleep-potentiating effects through the NOS/NO pathway.

    Science.gov (United States)

    Cui, Yue; Zhang, Ying; Liu, Gang

    2015-04-01

    Sleep is essential for basic survival as well as for optimal physical and cognitive performance in both human beings and animals. To investigate the effect of syringin on sleep of anesthetized mice and the potential mechanisms, 35 male Kunming mice were randomly divided into six experimental groups (n = 5) and one control group (n = 5). Sleep latency and sleep duration, as well as nitric oxide (NO) content and nitric oxide synthase (NOS) activity, were determined after syringin administration. The NO precursor l-Arginine (l-Arg) or NOS inhibitor NG-Nitro-l-arginine methyl ester (l-NAME) was administered alone or in combination with syringin, and time for sleep latency and duration was recorded. After intragastric administration of syringin, sleep latency decreased in a dose- and time-dependent manner, concomitant with increased sleep duration. The optimal sleep performance was obtained when syringin was given at a dose of 80 mg/kg for eight consecutive days. Syringin significantly reduced NO concentration and NOS activity. Administration of l-Arg prolonged sleep latency and shortened sleep duration, and the effects were fully reversed by syringin coadministration. Administration of L-NAME induced a significant reduction in sleep latency and a corresponding increase in sleep duration, and coadministration of syringin further enhanced the effects. The finding of our study demonstrated that syringin could exert sleep-potentiating effects on anesthetized mice in a time- and dose-dependent manner, and these effects may be intimately correlated with the NO/NOS pathway. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  10. Rhodiola rosea exerts anti-viral activity in athletes following a competitive marathon race

    Directory of Open Access Journals (Sweden)

    Maryam eAhmed

    2015-07-01

    Full Text Available Rhodiola rosea, a medicinal plant with demonstrated adaptogenic properties, has recently been reported to contain active compounds with antimicrobial activity. The goal of this study was to measure the antiviral and antibacterial properties of the bioactive metabolites of Rhodiola rosea in the serum of experienced marathon runners following supplementation. Marathon runners, randomly divided into two group, ingested 600mg/day of Rhodiola rosea (n=24, 6 female, 18 male or placebo (n=24, 7 female, 17 male for 30 days prior to, the day of, and seven days post-marathon. Blood serum samples were collected the day before, 15 minutes post- and 1.5 hours post-marathon. Serum from Rhodiola rosea supplemented runners collected after marathon running did not attenuate the marathon-induced susceptibility of HeLa cells to killing by vesicular stomatitis virus (VSV. However, the use of Rhodiola rosea induced antiviral activity at early times post-infection by delaying an exercise-dependent increase in virus replication (P=0.013 compared to placebo. Serum from both groups collected 15 minutes post-marathon significantly promoted the growth of Escherichia coli in culture as compared to serum collected the day before the marathon (P=0.003, all subjects. Furthermore, the serum from subjects ingesting Rhodiola rosea did not display antibacterial properties at any time point as indicated by a lack of group differences immediately (P=0.785 or 1.5 hours (P=0.633 post-marathon. These results indicate that bioactive compounds in the serum of subjects ingesting Rhodiola rosea may exert protective effects against virus replication following intense and prolonged exercise by inducing antiviral activity.

  11. EXERTION DURING UPHILL, LEVEL AND DOWNHILL WALKING WITH AND WITHOUT HIKING POLES

    Directory of Open Access Journals (Sweden)

    Stephane Perrey

    2008-03-01

    Full Text Available This study examined the effects of poles when walking on the rate of perceived exertion (RPE, physiological and kinematics parameters, and upon the mean ratio between locomotor and respiratory rhythms. Twelve healthy male and female volunteers, aged 22 to 49 years old, completed on a motorized treadmill in a counterbalanced randomized order 12 walking trials for 10 min at an individually preferred walking speed, with three grades (horizontal level, uphill or downhill with a slope of 15%, with and without hiking poles and a load carriage of 15% of body mass. During all testing sessions, heart rate (HR, oxygen consumption (VO2, ventilation (VE, tidal volume (VT, breathing frequency (Bf, and stride frequency were recorded continuously during the last 5-min of each trial. At the end of each trial, subjects were asked to give RPE. Energy cost (EC and VE increased significantly with the grade (-15% < 0% < +15% and with the carrying load. VT was significantly less important with hiking poles, while Bf was significantly more elevated. VO2 and EC increased (p < 0.05 with the use of the hiking poles only during the downhill trials. No significant effect of poles was observed on HR, RPE, and preferred walking speed. The average ratio between the locomotor and respiratory frequencies was significantly influenced by the three experimental factors tested. There was a significant relationship between average ratio of leg movement per breath and EC of walking among all conditions (r = 0.83, n = 12. These results suggest that the use of the hiking poles had a significant influence on the respiratory and energetic responses only during downhill walking

  12. Exertion during uphill, level and downhill walking with and without hiking poles.

    Science.gov (United States)

    Perrey, Stephane; Fabre, Nicolas

    2008-01-01

    This study examined the effects of poles when walking on the rate of perceived exertion (RPE), physiological and kinematics parameters, and upon the mean ratio between locomotor and respiratory rhythms. Twelve healthy male and female volunteers, aged 22 to 49 years old, completed on a motorized treadmill in a counterbalanced randomized order 12 walking trials for 10 min at an individually preferred walking speed, with three grades (horizontal level, uphill or downhill with a slope of 15%), with and without hiking poles and a load carriage of 15% of body mass. During all testing sessions, heart rate (HR), oxygen consumption (VO2), ventilation (VE), tidal volume (VT), breathing frequency (Bf), and stride frequency were recorded continuously during the last 5-min of each trial. At the end of each trial, subjects were asked to give RPE. Energy cost (EC) and VE increased significantly with the grade (-15% walking speed. The average ratio between the locomotor and respiratory frequencies was significantly influenced by the three experimental factors tested. There was a significant relationship between average ratio of leg movement per breath and EC of walking among all conditions (r = 0.83, n = 12). These results suggest that the use of the hiking poles had a significant influence on the respiratory and energetic responses only during downhill walking. Key pointsEnergetic cost, respiratory responses, stride rate, respiratory to cycle rate ratio were significantly influenced by the use of hiking poles according to the grade at self-selected walking speed.Hiking poles induced an increase in respiratory frequency, VE and energetic cost during downhill, while little changes were observed during level and uphill terrain.The original results obtained in downhill necessitate supplementary studies in the field in order to confirm these first tendencies on treadmill.

  13. Arachidonic and oleic acid exert distinct effects on the DNA methylome

    Science.gov (United States)

    Silva-Martínez, Guillermo A.; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda; Vaquero, Alejandro; Esteller, Manel; Carmona, F. Javier; Moran, Sebastian; Nielsen, Finn C.; Wickström-Lindholm, Marie; Wrobel, Katarzyna; Wrobel, Kazimierz; Barbosa-Sabanero, Gloria; Zaina, Silvio; Lund, Gertrud

    2016-01-01

    ABSTRACT Abnormal fatty acid metabolism and availability are landmarks of metabolic diseases, which in turn are associated with aberrant DNA methylation profiles. To understand the role of fatty acids in disease epigenetics, we sought DNA methylation profiles specifically induced by arachidonic (AA) or oleic acid (OA) in cultured cells and compared those with published profiles of normal and diseased tissues. THP-1 monocytes were stimulated with AA or OA and analyzed using Infinium HumanMethylation450 BeadChip (Illumina) and Human Exon 1.0 ST array (Affymetrix). Data were corroborated in mouse embryonic fibroblasts. Comparisons with publicly available data were conducted by standard bioinformatics. AA and OA elicited a complex response marked by a general DNA hypermethylation and hypomethylation in the 1–200 μM range, respectively, with a maximal differential response at the 100 μM dose. The divergent response to AA and OA was prominent within the gene body of target genes, where it correlated positively with transcription. AA-induced DNA methylation profiles were similar to the corresponding profiles described for palmitic acid, atherosclerosis, diabetes, obesity, and autism, but relatively dissimilar from OA-induced profiles. Furthermore, human atherosclerosis grade-associated DNA methylation profiles were significantly enriched in AA-induced profiles. Biochemical evidence pointed to β-oxidation, PPAR-α, and sirtuin 1 as important mediators of AA-induced DNA methylation changes. In conclusion, AA and OA exert distinct effects on the DNA methylome. The observation that AA may contribute to shape the epigenome of important metabolic diseases, supports and expands current diet-based therapeutic and preventive efforts. PMID:27088456

  14. Dialysability of magnesium and calcium from hospital duplicate meals: influence exerted by other elements.

    Science.gov (United States)

    Velasco-Reynold, Carlos; Navarro-Alarcon, Miguel; Lopez-Ga de la Serrana, Herminia; Perez-Valero, Vidal; Agil, Ahmad; Lopez-Martinez, Maria C

    2010-03-01

    Total and dialysable magnesium and calcium levels and corresponding dialysabilities were measured in duplicate meals (n = 108) during 36 consecutive days. The interaction exerted by other nutrients and energy on them was also performed. Total mean magnesium and calcium fractions of 113.9 +/- 98.3 and 337.2 +/- 278.9 mg/meal respectively, were found. The Mg and Ca levels supplied by meals are positively (p < 0.05) correlated with macronutrient contents (carbohydrates and proteins). The mean dialysable Mg and Ca fractions were 56.9 +/- 36.3 and 127.4 +/- 112.3 mg/meal (50.4 +/- 13.2 and 37.8 +/- 10.7% as dialysabilities, respectively). Total Mg and Ca levels are significantly correlated with corresponding element dialysabilities (p < 0.05). For both minerals, significant correlations between their total and dialysable fractions and between their dialysable level and dialysabilities were noted (p < 0.01). The mean Mg and Ca daily dietary intakes (DDI) were 341.7 +/- 68.0 and 1,011.6 +/- 424.4 mg/day, respectively. For Ca and Mg the existence of similarities in their behaviour in meals and absorptive processes has been found. Duplicate meals with raw vegetables are good sources of bioaccessible Mg. High Ca dialysability has been found in the analysed meals. The fish and products constitute a good source of bioaccessible Ca. Mg, Ca, zinc, and chromium levels enhanced significantly the Mg dialysability. The Ca dialysability rose significantly with dialysable Ca and chromium fractions (p < 0.05).

  15. Copper nanoparticles exert size and concentration dependent toxicity on somatosensory neurons of rat

    Science.gov (United States)

    PRABHU, BADANAVALU M.; ALI, SYED F.; MURDOCK, RICHARD C.; HUSSAIN, SABER M.; SRIVATSAN, MALATHI

    2010-01-01

    Metal nanoparticles, due to their unique properties and important applications in optical, magnetic, thermal, electrical, sensor devices and cosmetics, are beginning to be widely manufactured and used. This new and rapidly growing field of technology warrants a thorough examination of the material’s bio-compatibility and safety. Ultra-small particles may adversely affect living cells and organisms since they can easily penetrate the body through skin contact, inhalation and ingestion. Retrograde transport of copper nanoparticles from nerve endings on the skin can reach the somatosensory neurons in dorsal root ganglion (DRG). Since copper nanoparticles have industrial and healthcare applications, we determined the concentration and size-dependant effects of their exposure on survival of DRG neurons of rat in cell culture. The neurons were exposed to copper nanoparticles of increasing concentrations (10–100 μM) and sizes (40, 60 and 80 nm) for 24 h. Light microscopy, histochemical staining for copper, lactate dehydrogenase (LDH) assay for cell death, and MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay for cell viability were performed to measure the resultant toxicity and cell survival. DRG neurons exposed to copper nanoparticles displayed vacuoles and detachment of some neurons from the substratum. Neurons also exhibited disrupted neurite network. LDH and MTS assays revealed that exposure to copper nanoparticles had significant toxic effect with all the sizes tested when compared to unexposed control cultures. Further analysis of the results showed that copper nanoparticles of smaller size and higher concentration exerted the maximum toxic effects. Rubeanic acid staining showed intracellular deposition of copper. These results demonstrate that copper nanoparticles are toxic in a size- and concentration-dependent manner to DRG neurons. PMID:20543894

  16. PSP-I/PSP-II spermadhesin exert a decapacitation effect on highly extended boar spermatozoa.

    Science.gov (United States)

    Caballero, Ignacio; Vazquez, Juan M; Mayor, Gloria M; Almiñana, Carmen; Calvete, Juan J; Sanz, Libia; Roca, Jordi; Martinez, Emilio A

    2009-10-01

    PSP-I/PSP-II heterodimer is a major protein of boar seminal plasma that is able to preserve, in vitro, the viability, motility and mitochondrial activity of highly-extended boar spermatozoa. However, a relationship between the protective effects of the heterodimer and sperm capacitation is still unclear. The present study investigated the effect of the PSP-I/PSP-II (1.5 mg/mL) on membrane stability, intracellular calcium concentration ([Ca(2+)](I)) and plasma membrane and acrosome integrity of highly extended boar spermatozoa. Boar spermatozoa were diluted to 1 x 10(6) spermatozoa/mL and incubated at 38 degrees C in Phosphate-buffered saline (PBS) for 10, 30, 60, 120 and 300 min or in modified Tris-buffered medium (mTBM) for 10, 20, 30, 60 and 120 min. After each incubation time, the membrane stability (using Merocyanine-540/Yo-Pro-1), elevation of [Ca(2+)](I) (using Fluo-3-AM/PI) and the sperm plasma membrane and acrosome integrity (using SYBR-14/PI/PE-PNA) were evaluated by flow cytometry. As expected, exposure of the spermatozoa to the PSP-I/PSP-II preserved the plasma membrane and acrosome integrity compared to non-exposed spermatozoa in both media PBS and mTBM (p PSP-I/PSP-II compared to controls irrespective of the dilution media. The evaluation of the [Ca(2+)](I) levels showed that while spermatozoa incubated in mTBM and exposed to PSP-I/PSP-II had lower [Ca(2+)](I) than controls (39.08% vs. 47.97%, respectively; p PSP-I/PSP-II. In conclusion, PSP-I/PSP-II exert a non-permanent decapacitation effect on highly extended boar spermatozoa that is related with a delay in the increase of [Ca(2+)](I) levels.

  17. Regulating explosive resistance training intensity using the rating of perceived exertion.

    Science.gov (United States)

    Row, Brandi S; Knutzen, Kathleen M; Skogsberg, Nikolaus J

    2012-03-01

    Explosive resistance training (ERT) improves older adults' strength and power, and methods to make this form of training more accessible and useful to older adults are needed. The purpose of this study was to evaluate whether the rating of perceived exertion (RPE) scale would predict a broad range of ERT intensities on the leg press with older adults. If successful, then a load-RPE relationship could be used to regulate the intensity of training loads for ERT with older adults, allowing the elimination of maximal strength testing. Twenty-one older adults (≥65 years) with resistance training experience took part in 2 testing sessions. Session 1: Subjects performed high-velocity repetitions on the leg press for up to 9 loads (from 60 to 140% body weight) presented in quasi-randomized order, and then reported their RPE for each load. Session 2: A 1 repetition maximum (1RM) strength test was conducted. Regression analysis revealed that the average RPE across subjects for each load strongly predicted the average %1RM across subjects (R2 = 99.5%; p < 0.001). This allows the establishment of a load-RPE relationship for use in selecting ERT loads for older adults on the leg press. For example, high-intensity loads (70-90% 1RM) that would elicit both strength and power gains when used with ERT aligned with an RPE of 14-16. Lighter loads that may be useful for training for power, but not strength (<70% 1RM), were identified with RPE scores of 13 and lower. The load-RPE relationship may simplify the regulation of intensity of ERT with older adults on the leg press, where the exercising older adult could be guided to select loads according to their RPE.

  18. Vegetation exerts a greater control on litter decomposition than climate warming in peatlands.

    Science.gov (United States)

    Ward, Susan E; Orwin, Kate H; Ostle, Nicholas J; Briones, J I; Thomson, Bruce C; Griffiths, Robert I; Oakley, Simon; Quirk, Helen; Bardget, Richard D

    2015-01-01

    Historically, slow decomposition rates have resulted in the accumulation of large amounts of carbon in northern peatlands. Both climate warming and vegetation change can alter rates of decomposition, and hence affect rates of atmospheric CO2 exchange, with consequences for climate change feedbacks. Although warming and vegetation change are happening concurrently, little is known about their relative and interactive effects on decomposition processes. To test the effects of warming and vegetation change on decomposition rates, we placed litter of three dominant species (Calluna vulgaris, Eriophorum vaginatum, Hypnum jutlandicum) into a peatland field experiment that combined warming.with plant functional group removals, and measured mass loss over two years. To identify potential mechanisms behind effects, we also measured nutrient cycling and soil biota. We found that plant functional group removals exerted a stronger control over short-term litter decomposition than did approximately 1 degrees C warming, and that the plant removal effect depended on litter species identity. Specifically, rates of litter decomposition were faster when shrubs were removed from the plant community, and these effects were strongest for graminoid and bryophyte litter. Plant functional group removals also had strong effects on soil biota and nutrient cycling associated with decomposition, whereby shrub removal had cascading effects on soil fungal community composition, increased enchytraeid abundance, and increased rates of N mineralization. Our findings demonstrate that, in addition to litter quality, changes in vegetation composition play a significant role in regulating short-term litter decomposition and belowground communities in peatland, and that these impacts can be greater than moderate warming effects. Our findings, albeit from a relatively short-term study, highlight the need to consider both vegetation change and its impacts below ground alongside climatic effects when

  19. Interactive effects of body position and perceived exertion during spinning exercises.

    Science.gov (United States)

    Rendos, Nicole K; Musto, Anthony A; Signorile, Joseph F

    2015-03-01

    Spinning is a popular group exercise taught in health and fitness facilities worldwide. Throughout a Spinning workout session, intensity is variable and is controlled by body position on the Spinning stationary cycle and perceived resistance. This study examined the effects of 3 body positions and 4 levels of perceived exertion (RPE) on cardiorespiratory response and vastus lateralis normalized electromyographical activity (NrmsEMGVL). Eleven participants (24.4 ± 6.3 years) with 3.2 ± 2.2 years of Spinning experience completed twelve 3-minute randomly assigned Spinning conditions across 4 separate testing days after an 8-hour fast. Conditions were determined by body position (seated, running, and standing climb [SC]) and RPE (low, low-medium, medium-high, and high). Cardiorespiratory data and NrmsEMGVL were recorded continuously during each Spinning condition. Respiratory rate and oxygen consumption were significantly higher for running and SC than seated, and minute ventilation was significantly higher for running than seated. All cardiorespiratory values were higher at medium-high and high RPE, than low or medium-low RPE, and high RPE generated higher respiratory rate and respiratory exchange ratio than medium-high RPE. Significant body position × RPE interactions were observed for heart rate (HR) and NrmsEMGVL with running and SC producing higher HRs than seated at low and high RPE, and running producing higher NrmsEMGVL than seated at low RPE. Results indicate that running and SC provide the greatest cardiorespiratory responses, and maximal efforts are not needed for these responses. Additionally, HR seems to be a poor marker of oxygen consumption, especially at high RPEs.

  20. Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Li-sha ZHANG; Rong HAN; Bo GAO; Xiao-qian LIU; Zheng-hong QIN

    2011-01-01

    Alm: To examine the effects of a mixed formulation composed of prostaglandin E1 and lithium (PGE1+Li mixture) on brain damage after cerebral ischemia. The effects of the mixture on protein expression of heat shock proteins (HSPs), p53, and Bcl-2 were also determined.Methods: Brain ischemia was induced with a permanent middle cerebral artery occlusion (pMCAO) in rats. Rats were treated with a single intravenous administration of PGE1, lithium or a PGE1+Li mixture immediately after the ischemic insult. The infarct volume and motor behavior deficits were analyzed 24 h after the ischemic insult. The protein levels of HSP70, glucose-regulated protein 78 (GRP78), HSP60, Bcl-2, and p53 in the striatum of the ipsilateral hemisphere were examined using immunoblotting.Results: The mixture (PGE1 22.6 nmol/kg+Li 0.5 mmol/kg) reduced infarct volume and neurological deficits induced by focal cerebral ischemia. Moreover, the mixture had a greater neuroprotective effect against cerebral ischemia compared with PGE1 or lithium alone.The mixture was effective even if it was administered 3 h after ischemia. PGE1+Li also significantly upregulated cytoprotective HSP70,GRP78, HSP60, and Bcl-2 protein levels, while decreasing p53 expression.Conclusion: These results demonstrated a PGE1+Li mixture with a therapeutic window of up to 3 h for clinical treatment of cerebral ischemia. The PGE1+Li mixture potentially exerts a protective effect after stroke through the induction of HSPs and Bcl-2 proteins.

  1. Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation

    Science.gov (United States)

    Cho, Kyu Suk; Jeon, Se Jin; Kwon, Oh Wook; Jang, Dae Sik; Kim, Sun Yeou; Ryu, Jong Hoon; Choi, Ji Woong

    2017-01-01

    Microglial activation and its-driven neuroinflammation are characteristic pathogenetic features of neurodiseases, including focal cerebral ischemia. The Artemisia asiatica (Asteraceae) extract and its active component, eupatilin, are well-known to reduce inflammatory responses. But the therapeutic potential of eupatilin against focal cerebral ischemia is not known, along with its anti-inflammatory activities on activated microglia. In this study, we investigated the neuroprotective effect of eupatilin on focal cerebral ischemia through its anti-inflammation, particularly on activated microglia, employing a transient middle cerebral artery occlusion/reperfusion (tMCAO), combined with lipopolysaccharide-stimulated BV2 microglia. Eupatilin exerted anti-inflammatory responses in activated BV2 microglia, in which it reduced secretion of well-known inflammatory markers, including nitrite, IL-6, TNF-α, and PGE2, in a concentration-dependent manner. These observed in vitro effects of eupatilin led to in vivo neuroprotection against focal cerebral ischemia. Oral administration of eupatilin (10 mg/kg) in a therapeutic paradigm significantly reduced brain infarction and improved neurological functions in tMCAO-challenged mice. The same benefit was also observed when eupatilin was given even within 5 hours after MCAO induction. In addition, the neuroprotective effects of a single administration of eupatilin (10 mg/kg) immediately after tMCAO challenge persisted up to 3 days after tMCAO. Eupatilin administration reduced the number of Iba1-immunopositive cells across ischemic brain and induced their morphological changes from amoeboid into ramified in the ischemic core, which was accompanied with reduced microglial proliferation in ischemic brain. Eupatilin suppressed NF-κB signaling activities in ischemic brain by reducing IKKα/β phosphorylation, IκBα phosphorylation, and IκBα degradation. Overall, these data indicate that eupatilin is a neuroprotective agent against

  2. The influence of physical exertion on basic hematological parameters values and heart rate in trotters

    Directory of Open Access Journals (Sweden)

    Slijepčević Dajana

    2014-01-01

    Full Text Available One of very important prerequisites for achieving good results in races, in addition to genetic predisposition, quality training and good health, are optimal values for number of erythrocytes, concentration of haemoglobin and hematocrit, of which depends efficient oxygen supply of muscles during great efforts. The stated values, along with data on heart rate, are useful indicators of the degree of horse fitness and readiness for horse race. The influence of physical exertion on the values of basic hematological parameters as well as on heart rate, was investigated on 6 trotters, in training at the Belgrade racetrack (one head of Italian trotter, male, 3 years old; 3 heads of American trotter, male, 3,4 and 6 years old and two heads of Serbian trotter, female, 4 and 5 years old. The blood samples for hematological tests were taken by punction of jugular vein in resting phase - immediately before the commencement of work, after light trot warming for 3000 m and fast trot for 1000 m, with 30 minutes rest between the two runnings. The heart rate was monitored continuously by radio telemetry cardiometer, from the moment they were taken from their boxes and harnessing to the completion of work. The obtained results confirm the relationship between the rise of heart rate and hematocrit values: maximal hematocrit values were determined after the first running (0.49±0.05, in regard to 0.42±0.03 in resting phase, but 30 minutes after the second running there was a slight drop of hematocrit values (0.46±0.04. The blood samples in both cases were taken after fast trot during which there were recorded maximal pulse values, so in the moment of sampling the pulse lowered close to the values in resting - after the first running from 192.23±19.66, and after the second from 180.33±17.22 to 40.67±5.76.

  3. Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis.

    Science.gov (United States)

    McKenzie, E C; Eyrich, L V; Payton, M E; Valberg, S J

    2016-10-01

    A previous report suggests a substantial incidence of exertional rhabdomyolysis (ER) in Arabian horses performing endurance racing. This study compared formalin histopathology and clinical and metabolic responses to a standardised field exercise test (SET) between Arabians with and without ER. Arabian horses with (n = 10; age 15.4 ± 5.6 years) and without (n = 9; 12.9 ± 6.1 years) prior ER were stall-rested for 24-48 h, after which paired ER and control horses were fitted with a telemetric ECG and performed a 47 min submaximal SET. Plasma glucose, lactate, electrolyte and total protein concentrations and packed cell volume were measured before and immediately after exercise. Blood and percutaneous gluteal muscle samples were also obtained before and 3 h after exercise for measurement of plasma creatine kinase (CK) activity and muscle glycogen concentration, respectively. Histopathologic analysis of formalin-fixed pre-exercise muscle sections was performed. Data were analyzed by ANOVA and non-parametric tests (P exercise, and plasma CK increased similarly in ER and control Arabians. Muscle glycogen, heart rate, and remaining plasma variables did not differ between horses with ER and control horses. Horses with ER had more internalised nuclei in mature myofibers, more aggregates of cytoplasmic glycogen and desmin, and higher myopathic scores than control horses. Although many horses with ER had histopathologic evidence of chronic myopathy, muscle glycogen concentrations and metabolic exercise responses were normal. Results did not support a consistent metabolic myopathy or a glycogen storage disorder in Arabians with ER.

  4. Ecological Validity of the Session Rating of Perceived Exertion for Quantifying Internal Training Load in Fencing.

    Science.gov (United States)

    Turner, Anthony N; Buttigieg, Conor; Marshall, Geoff; Noto, Angelo; Phillips, James; Kilduff, Liam

    2017-01-01

    Session rating of perceived exertion (sRPE) is known to significantly relate to heart-rate (HR) -based methods of quantifying internal training load (TL) in a variety of sports. However, to date this has not been investigated in fencing and was therefore the aim of this study. TL was calculated by multiplying the sRPE with exercise duration and through HR-based methods calculated using Banister and Edwards TRIMP. Seven male elite foil fencers (mean ± SD age 22.3 ± 1.6 y, height 181.3 ± 6.5 cm, body mass 77.7 ± 7.6 kg) were monitored over the period of 1 competitive season. The sRPE and HR of 67 training sessions and 3 competitions (87 poule bouts and 12 knockout rounds) were recorded and analyzed. Correlation analysis was used to determine any relationships between sRPE- and HR-based methods, accounting for individual variation, mode of training (footwork drills vs sparring sessions), and stage of competition (poules vs knockouts). Across 2 footwork sessions, sRPE and Banister and Edwards TRIMP were found to be reliable, with coefficient of variation values of 6.0%, 5.2%, and 4.5%, respectively. Significant correlations with sRPE for individual fencers (r = .84-.98) and across mode of exercise (r = .73-.85) and competition stages (r = .82-.92) were found with HR-based measures. sRPE is a simple and valuable tool coaches can use to quantify TL in fencing.

  5. Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing

    Science.gov (United States)

    Lewis, Gregory D.; Opotowsky, Alexander R.; Waxman, Aaron B.; Systrom, David M.

    2016-01-01

    Abstract To determine whether low ventricular filling pressures are a clinically relevant etiology of unexplained dyspnea on exertion, a database of 619 consecutive, clinically indicated invasive cardiopulmonary exercise tests (iCPETs) was reviewed to identify patients with low maximum aerobic capacity (V̇o2max) due to inadequate peak cardiac output (Qtmax) with normal biventricular ejection fractions and without pulmonary hypertension (impaired: n = 49, V̇o2max = 53% predicted [interquartile range (IQR): 47%–64%], Qtmax = 72% predicted [62%–76%]). These were compared to patients with a normal exercise response (normal: n = 28, V̇o2max = 86% predicted [84%–97%], Qtmax = 108% predicted [97%–115%]). Before exercise, all patients received up to 2 L of intravenous normal saline to target an upright pulmonary capillary wedge pressure (PCWP) of ≥5 mmHg. Despite this treatment, biventricular filling pressures at peak exercise were lower in the impaired group than in the normal group (right atrial pressure [RAP]: 6 [IQR: 5–8] vs. 9 [7–10] mmHg, P = 0.004; PCWP: 12 [10–16] vs. 17 [14–19] mmHg, P < 0.001), associated with decreased stroke volume (SV) augmentation with exercise (+13 ± 10 [standard deviation (SD)] vs. +18 ± 10 mL/m2, P = 0.014). A review of hemodynamic data from 23 patients with low RAP on an initial iCPET who underwent a second iCPET after saline infusion (2.0 ± 0.5 L) demonstrated that 16 of 23 patients responded with increases in Qtmax ([+24% predicted [IQR: 14%–34%]), V̇o2max (+10% predicted [7%–12%]), and maximum SV (+26% ± 17% [SD]). These data suggest that inadequate ventricular filling related to low venous pressure is a clinically relevant cause of exercise intolerance. PMID:27162614

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

    Science.gov (United States)

    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.

  7. Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats

    Directory of Open Access Journals (Sweden)

    Hui-Qin Li

    2016-01-01

    Full Text Available Spontaneous intracerebral hemorrhage (ICH is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20 exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa’s scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH (P<0.05. In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

  8. Copper and quaternary ammonium cations exert synergistic bactericidal and antibiofilm activity against Pseudomonas aeruginosa.

    Science.gov (United States)

    Harrison, Joe J; Turner, Raymond J; Joo, Daniel A; Stan, Michelle A; Chan, Catherine S; Allan, Nick D; Vrionis, Helen A; Olson, Merle E; Ceri, Howard

    2008-08-01

    Biofilms are slimy aggregates of microbes that are likely responsible for many chronic infections as well as for contamination of clinical and industrial environments. Pseudomonas aeruginosa is a prevalent hospital pathogen that is well known for its ability to form biofilms that are recalcitrant to many different antimicrobial treatments. We have devised a high-throughput method for testing combinations of antimicrobials for synergistic activity against biofilms, including those formed by P. aeruginosa. This approach was used to look for changes in biofilm susceptibility to various biocides when these agents were combined with metal ions. This process identified that Cu(2+) works synergistically with quaternary ammonium compounds (QACs; specifically benzalkonium chloride, cetalkonium chloride, cetylpyridinium chloride, myristalkonium chloride, and Polycide) to kill P. aeruginosa biofilms. In some cases, adding Cu(2+) to QACs resulted in a 128-fold decrease in the biofilm minimum bactericidal concentration compared to that for single-agent treatments. In combination, these agents retained broad-spectrum antimicrobial activity that also eradicated biofilms of Escherichia coli, Staphylococcus aureus, Salmonella enterica serovar Cholerasuis, and Pseudomonas fluorescens. To investigate the mechanism of action, isothermal titration calorimetry was used to show that Cu(2+) and QACs do not interact in aqueous solutions, suggesting that each agent exerts microbiological toxicity through independent biochemical routes. Additionally, Cu(2+) and QACs, both alone and in combination, reduced the activity of nitrate reductases, which are enzymes that are important for normal biofilm growth. Collectively, the results of this study indicate that Cu(2+) and QACs are effective combinations of antimicrobials that may be used to kill bacterial biofilms.

  9. Copper and Quaternary Ammonium Cations Exert Synergistic Bactericidal and Antibiofilm Activity against Pseudomonas aeruginosa▿

    Science.gov (United States)

    Harrison, Joe J.; Turner, Raymond J.; Joo, Daniel A.; Stan, Michelle A.; Chan, Catherine S.; Allan, Nick D.; Vrionis, Helen A.; Olson, Merle E.; Ceri, Howard

    2008-01-01

    Biofilms are slimy aggregates of microbes that are likely responsible for many chronic infections as well as for contamination of clinical and industrial environments. Pseudomonas aeruginosa is a prevalent hospital pathogen that is well known for its ability to form biofilms that are recalcitrant to many different antimicrobial treatments. We have devised a high-throughput method for testing combinations of antimicrobials for synergistic activity against biofilms, including those formed by P. aeruginosa. This approach was used to look for changes in biofilm susceptibility to various biocides when these agents were combined with metal ions. This process identified that Cu2+ works synergistically with quaternary ammonium compounds (QACs; specifically benzalkonium chloride, cetalkonium chloride, cetylpyridinium chloride, myristalkonium chloride, and Polycide) to kill P. aeruginosa biofilms. In some cases, adding Cu2+ to QACs resulted in a 128-fold decrease in the biofilm minimum bactericidal concentration compared to that for single-agent treatments. In combination, these agents retained broad-spectrum antimicrobial activity that also eradicated biofilms of Escherichia coli, Staphylococcus aureus, Salmonella enterica serovar Cholerasuis, and Pseudomonas fluorescens. To investigate the mechanism of action, isothermal titration calorimetry was used to show that Cu2+ and QACs do not interact in aqueous solutions, suggesting that each agent exerts microbiological toxicity through independent biochemical routes. Additionally, Cu2+ and QACs, both alone and in combination, reduced the activity of nitrate reductases, which are enzymes that are important for normal biofilm growth. Collectively, the results of this study indicate that Cu2+ and QACs are effective combinations of antimicrobials that may be used to kill bacterial biofilms. PMID:18519726

  10. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya, E-mail: jyli@mail.shcnc.ac.cn; Nan, Fa-Jun, E-mail: fjnan@mail.shcnc.ac.cn; Li, Jia, E-mail: jli@mail.shcnc.ac.cn

    2013-12-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.

  11. Epidemiological and genetic study of exertional rhabdomyolysis in a Warmblood horse family in Switzerland.

    Science.gov (United States)

    Johlig, L; Valberg, S J; Mickelson, J R; Klukowska, J; Reusser, H R; Straub, R; Gerber, V

    2011-03-01

    Exertional rhabdomyolysis (ER) and its familial basis in Warmblood horses is incompletely understood. To describe the case details, clinical signs and management of ER-affected Warmblood horses from a family with a high prevalence of ER, to determine if histopathological signs of polysaccharide storage myopathy (PSSM) and the glycogen synthase (GYS1) mutation are associated with ER in this family, and to investigate potential risk factors for development of ER. A family consisting of a sire with ER and 71 of his descendants was investigated. History of episodes of ER, husbandry, feeding and use was assessed by interviewing horse owners using a standardised questionnaire. All horses were genotyped for GYS1. In 10 ER-affected horses, muscle histopathology was evaluated. Signs of ER were reported in 39% of horses and 51% of the entire family possessed the GYS1 mutation. Horses possessing the GYS1 mutation had a 7.1-times increased risk for developing ER compared to those with the normal genotype (95% confidence interval [CI] 2.37-21.23, P = 0.0005). All muscle samples from horses in the family with ER showed polysaccharide accumulation typical for PSSM, amylase-resistant in 9/10 cases. There was evidence (odds ratio 5.6, CI 1.00-31.32, P = 0.05) that fat or oil feeding improved clinical signs of ER. No other effects of environmental factors associated with clinical signs of ER were identified. PSSM associated with the GYS1 mutation is one identifiable cause of ER in Warmblood horses. Signs of ER are not always manifest in GYS1 positive horses and there are also other causes for ER in Warmblood horses. Breeding animals with the GYS1 mutation results in a high prevalence of ER due to its dominant mode of inheritance. © 2010 EVJ Ltd.

  12. Single minimal incision fasciotomy for the treatment of chronic exertional compartment syndrome: outcomes and complications.

    Science.gov (United States)

    Drexler, Michael; Rutenberg, T Frenkel; Rozen, N; Warschawski, Y; Rath, E; Chechik, O; Rachevsky, G; Morag, G

    2017-01-01

    Chronic exertional compartment syndrome (CECS) is a common injury in young athletes, causing pain in the involved leg compartment during strenuous exercise. The gold standard treatment is fasciotomy, but most of the reports on its effectiveness include relatively small cohorts and relatively short follow-up periods. This study reports the long-term results of a large cohort of young athletes who underwent single-incision fasciotomy for CECS. This a retrospective case-series study. All patients treated by fasciotomies performed for CECS between 2007 and 2011, in a tertiary medical institution. CECS was diagnosed following history taking and clinical evaluation, and confirmed by compartment pressure measurements. Ninety-five legs that underwent single-incision subcutaneous fasciotomy were included. Data on the numerical analog scale (NAS), Tegner activity score, and quality-of-life (QOL) as measured via the short form-12 (SF-12) were retrieved from all patients preoperatively and at the end of follow-up. The average time to diagnosis was 22 months and the mean follow-up was 50.1 months. Sixty-three legs underwent anterior compartment fasciotomy (an additional 30 legs also underwent lateral compartment release), and two legs underwent lateral and peroneal compartment releases. The average change in Tegner score was an improvement of 14.6 points. Similarly, the patients reported a significant improvement in the SF-12 and NAS scores. Satisfaction rates were high (average 75.5 %). The main complications were wound infection (2 patients) and nerve injuries (4 patients). Eight patients had recurrence. Single-incision fasciotomy leads to long-term improvement in the activity level and QOL of patients with CECS.

  13. PERCEIVED EXERTION AS AN EXERCISE INTENSITY INDICATOR IN CHRONIC HEART FAILURE PATIENTS ON BETA-BLOCKERS

    Directory of Open Access Journals (Sweden)

    Allan Davie

    2004-11-01

    Full Text Available The Rating of Perceived Exertion (RPE has been used as a supplementary tool for prescription of exercise training intensity for healthy and special populations. Despite the wide use of the RPE scale, there is an inconsistency regarding the accuracy of that scale for chronic heart failure (CHF patients treated with beta-blockers. The study examined the correlation between RPE and heart rate (HR, percentage of maximal HR (%MHR, ventilation (VE and oxygen consumption (VO2 during graded treadmill testing and examined the RPE scale as a guideline for training intensity for CHF patients treated with beta-blockers. Fourteen men age 57.7 ± 10.2 yrs diagnosed with CHF and treated with beta-blockers participated in the study. During a Balke treadmill test the subjects RPE, HR, VE and VO2 ml·kg-1·min-1 were monitored. Low to moderate significant correlations were found between RPE and HR, %MHR, VE and VO2 ml·kg-1·min-1 (r = 0.44, 0.43, 0.55 and 0.69 respectively, all p < 0.001. Some subjects exhibited clinical symptoms (e.g. fall of systolic blood pressure, ST depression/elevation despite relatively low RPE. The RPE may be used to indicate the level of exercise intensity; however it may not represent the HR responses in CHF patients on beta-blocker medication. Therefore, it is recommended to monitor the HR in combination with RPE when prescribing exercise intensity for CHF patients on beta blocker medication.

  14. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  15. Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver: Role for omega-3 epoxides

    OpenAIRE

    López-Vicario, Cristina; Alcaraz-Quiles, José; García-Alonso, Verónica; Rius, Bibiana; Hwang, Sung H.; Titos, Esther; Lopategi, Aritz; Hammock, Bruce D.; Arroyo, Vicente; Clària, Joan

    2014-01-01

    Our study demonstrates that stabilization of cytochrome P-450 epoxides derived from omega-3 polyunsaturated fatty acids through inhibition of the inactivating enzyme soluble epoxide hydrolase (sEH) exerts beneficial actions in counteracting metabolic disorders associated with obesity. In addition, our study sheds more light on the role of sEH in cellular homeostasis by providing evidence that omega-3 epoxides and sEH inhibition regulate autophagy and endoplasmic reticulum stress in insulin-se...

  16. Doxycycline exerts multiple anti-allergy effects to attenuate murine allergic conjunctivitis and systemic anaphylaxis.

    Science.gov (United States)

    Su, Wenru; Wan, Qian; Han, Longhui; Huang, Jingwen; Chen, Xiaoqing; Chen, Guihua; Zheng, Song Guo; Liang, Dan

    2014-10-01

    Allergic diseases, which affect up to 20-30% of the world population, are still therapeutic challenge for allergists. Tetracyclines, which belong to an antibiotic drug family that possesses a striking variety of non-antibiotic properties, have been successfully applied to a wide range of diseases. However, their roles in allergic conjunctivitis and anaphylaxis and their underlying anti-allergy mechanisms remain elusive. Here, we reported that treatment with doxycycline significantly reduced IgE release from mouse B cells and the degranulation and inflammatory cytokines production of mouse mast cells (MCs) activated by IgE-dependent way. Furthermore, doxycycline treatment significantly inhibited histamine-induced vascular hyperpermeability in vitro. Mechanistically, the doxycycline-mediated inhibition of B cells, MCs and histamine may occur via modulation of the PI3K/Akt pathway. In vivo, our results demonstrated that treatment with doxycycline significantly attenuated clinical symptoms of mouse models of experimental allergic conjunctivitis (EAC) with a significant decrease in inflammatory cell frequency, IgE production, histamine release, and a decrease in TNF-α and IL-4 production. Using mouse models of MCs-dependent passive systemic anaphylaxis (PSA), we further confirmed anti-allergy effects of doxycycline and doxycycline-mediated inhibitory effects on MCs. Furthermore, our results showed that doxycycline significantly attenuate histamine-induced systemic anaphylaxis-like reaction (HISA) with a significantly downregulation of PI3K/Akt/eNOS/VE-cadherin pathway. The doxycycline-mediated anti-allergy effects during EAC, PSA and HISA were abrogated when an Akt activator, SC79, was administered. These findings suggest that doxycycline inhibits B cell, MC and histamine function and attenuates experimental allergic conjunctivitis and systemic anaphylaxis by possible modulating the PI3K/Akt pathway.

  17. Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

    Directory of Open Access Journals (Sweden)

    Asuka Baba

    2016-01-01

    Full Text Available Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm, the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Relatively lower concentrations of tranilast (100, 250 µM and ketotifen (1, 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM and ketotifen (50, 100 µM almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

  18. DUFS and DEFS : development, reliability and validity of the Dutch Fatigue Scale and the Dutch Exertion Fatigue Scale

    NARCIS (Netherlands)

    Tiesinga, LJ; Dassen, TWN; Halfens, RJG

    1998-01-01

    The purpose of this study among patients with chronic heart failure (n = 138) was to develop and test both the Dutch Fatigue Scale (DUFS) and the Dutch Exertion Fatigue Scale (DEFS). Psychometric testing of these scales included measurement of internal consistency, construct validity and criterion-r

  19. PREDICTION OF VO2PEAK USING OMNI RATINGS OF PERCEIVED EXERTION FROM A SUBMAXIMAL CYCLE EXERCISE TEST

    Science.gov (United States)

    Mays, Ryan J.; Goss, Fredric L.; Nagle-Stilley, Elizabeth F.; Gallagher, Michael; Schafer, Mark A.; Kim, Kevin H.; Robertson, Robert J.

    2015-01-01

    Summary The primary aim of this study was to develop statistical models to predict peak oxygen consumption (VO2peak) using OMNI Ratings of Perceived Exertion measured during submaximal cycle ergometry. Men (mean ± standard error: 20.90 ± 0.42 yrs) and women (21.59 ± 0.49 yrs) participants (n = 81) completed a load-incremented maximal cycle ergometer exercise test. Simultaneous multiple linear regression was used to develop separate VO2peak statistical models using submaximal ratings of perceived exertion for the overall body, legs, and chest/breathing as predictor variables. VO2peak (L·min−1) predicted for men and women from ratings of perceived exertion for the overall body (3.02 ± 0.06; 2.03 ± 0.04), legs (3.02 ± 0.06; 2.04 ± 0.04) and chest/breathing (3.02 ± 0.05; 2.03 ± 0.03) were similar with measured VO2peak (3.02 ± 0.10; 2.03 ± 0.06, ps > .05). Statistical models based on submaximal OMNI Ratings of Perceived Exertion provide an easily administered and accurate method to predict VO2peak. PMID:25068750

  20. Ratings of Perceived Exertion, Heart Rate, and Power Output in Predicting Maximal Oxygen Uptake During Submaximal Cycle Ergometry.

    Science.gov (United States)

    Wilmore, Jack H.; And Others

    1986-01-01

    Sixty-two subjects completed a four-stage submaximal cycle ergometer test to determine if estimates of maximal oxygen uptake could be improved by using ratings of perceived exertion singly or in combination with easily obtainable physiological measures. These procedures could be used to estimate the aerobic power of patients and athletes. (MT)

  1. Does experience influence the forces exerted on maxillary incisors during laryngoscopy? A manikin study using the Macintosh laryngoscope

    NARCIS (Netherlands)

    M.J.L. Bucx (Martin); R.T.M. van Geel (R. T M); J.T. Wegener (J.); C. Robers (C.); Th. Stijnen (Theo)

    1995-01-01

    textabstractThe influence of the level of experience of the laryngoscopist on the duration of laryngoscopy, the forces exerted on the tongue and on the maxillary incisors during laryngoscopy, were investigated. Five groups (anaesthetists, residents in anaesthesia, nurse anaesthetists, surgeons and m

  2. Reciprocal inhibition in man.

    Science.gov (United States)

    Crone, C

    1993-11-01

    Reciprocal inhibition is the automatic antagonist alpha motor neurone inhibition which is evoked by contraction of the agonist muscle. This so-called natural reciprocal inhibition is a ubiquitous and pronounced phenomenon in man and must be suspected of playing a major role in the control of voluntary movements. The spinal pathways underlying this inhibitory phenomenon were studied. The disynaptic reciprocal Ia inhibitory pathway between the tibial anterior muscle and the soleus alpha motor neurones was identified and described in man. It was shown that the inhibition can be evoked in most healthy subjects at rest, but the degree of inhibition varies considerably from one subject to another. It was concluded that it corresponds to the disynaptic reciprocal Ia inhibitory pathway which has been extensively described in animal experiments. The disynaptic reciprocal inhibition was shown to increase during the dynamic phase of a dorsiflexion movement of the foot, but not during the tonic phase. However, when the peripheral afferent feedback from the contracting muscle was blocked by ischaemia, an increase of the inhibition was revealed also during the tonic phase of the dorsiflexion. The concealment of this increase during unrestrained peripheral feedback from the muscle was thought to be due to the post-activation depression mechanism; a mechanism which was described further and which probably involves reduced transmitter release at Ia afferent terminals as a result of previous activation of these afferent fibers. Hence the hypothesis was supported that alpha motor neurones and the corresponding inhibitory interneurones, which project reciprocal inhibition to the antagonist motor neurones, are activated in parallel during voluntary contraction of agonist muscles. An additional reciprocal inhibitory mechanism, the long latency reciprocal inhibition, was described between the tibial anterior muscle and the soleus alpha motor neurones. It was shown to be evoked by group I

  3. Salvinorin A exerts opposite presynaptic controls on neurotransmitter exocytosis from mouse brain nerve terminals.

    Science.gov (United States)

    Grilli, Massimo; Neri, Elisa; Zappettini, Stefania; Massa, Francesca; Bisio, Angela; Romussi, Giovanni; Marchi, Mario; Pittaluga, Anna

    2009-01-01

    We investigated the effects of salvinorin A on the basal and the 12 mM K(+)-evoked release of preloaded [(3)H]noradenaline ([(3)H]NA) and [(3)H]serotonin ([(3)H]5-HT) from mouse hippocampal nerve terminals (synaptosomes), as well as on the basal and 12mM K(+)-evoked release of preloaded [(3)H]dopamine ([(3)H]DA) from mouse striatal and prefrontal cortex (PFc) synaptosomes. Salvinorin A (0.1-1000 nM) failed to affect the basal release of amines, but inhibited the 12 mM K(+)-evoked, Ca(2+)-dependent, exocytotic-like release of [(3)H]5-HT and [(3)H]DA. At the same concentration, salvinorin A facilitated the 12 mM K(+)-evoked, Ca(2+)-dependent, exocytotic-like release of [(3)H]NA. These effects could not be observed in pertussis toxin (PTx) entrapped synaptosomes. The broad spectrum kappa-opioid receptor (KOR) antagonist norbinaltorphimine (norBNI, 1-100 nM) antagonized the inhibition of [(3)H]5-HT and [(3)H]DA exocytosis as well as the facilitation of [(3)H]NA overflow induced by 100 nM salvinorin A. The KOR agonist U69593 (1-100 nM) mimicked salvinorin A in inhibiting [(3)H]5-HT and of [(3)H]DA exocytosis, its effect being prevented by norBNI, but leaving unchanged the K(+)-evoked release of [(3)H]NA. The effects of Salvinorin A on neurotransmitter exocytosis were not prevented by the selective mu opioid (MOR) receptor antagonist CTAP (10-100 nM), whereas facilitation of [(3)H]NA exocytosis, but not inhibition of [(3)H]5-HT and [(3)H]DA K(+)-evoked release, was counteracted by the delta opioid receptor (DOR) antagonist naltrindole (1-100 nM). We conclude that salvinorin A presynaptically modulates central NA, 5-HT, and DA exocytosis evoked by a mild depolarizing stimulus by acting at presynaptic opioid receptors having different pharmacological profiles.

  4. CAP1 (Cyclase-Associated Protein 1) Exerts Distinct Functions in the Proliferation and Metastatic Potential of Breast Cancer Cells Mediated by ERK.

    Science.gov (United States)

    Zhang, Haitao; Zhou, Guo-Lei

    2016-05-13

    The actin-regulating protein CAP1 is implicated in the invasiveness of human cancers. However, the exact role remains elusive and controversial given lines of conflicting evidence. Moreover, a potential role in the proliferative transformation has largely been overlooked. Further establishing the role and dissecting underlying mechanisms are imperative before targeting CAP1 can become a possibility for cancer treatment. Here we report our findings that CAP1 exerts cell type-dependent functions in the invasiveness of breast cancer cells. Depletion of CAP1 in the metastatic MDA-MB-231 and BT-549 cancer cells stimulated the metastatic potential while it actually inhibited it in the non-metastatic MCF-7 cancer cells or in normal cells. Moreover, we demonstrate functions for CAP1 in cancer cell proliferation and anchorage-independent growth, again in a cell context-dependent manner. Importantly, we identify pivotal roles for the ERK-centered signaling in mediating both CAP1 functions. Phosphor mutants of CAP1 at the S307/S309 regulatory site had compromised rescue effects for both the invasiveness and proliferation in CAP1-knockdown cells, suggesting that CAP1 likely mediates upstream cell signals to control both functions. These novel mechanistic insights may ultimately open up avenues for strategies targeting CAP1 in the treatment of breast cancer, tailored for specific types of the highly diverse disease.

  5. Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF-κB Translocation in a Mechanism Independent of Plasmodium Killing

    Directory of Open Access Journals (Sweden)

    Mariana C. Souza

    2012-01-01

    Full Text Available Artemisinin and its derivates are an important class of antimalarial drug and are described to possess immunomodulatory activities. Few studies have addressed the effect of artesunate in the murine malaria model or its effect on host immune response during malaria infection. Herein, we study the effect of artesunate treatment and describe an auxiliary mechanism of artesunate in modulating the inflammatory response during experimental malaria infection in mice. Treatment with artesunate did not reduce significantly the parasitemia within 12 h, however, reduced BBB breakdown and TNF-α mRNA expression in the brain tissue of artesunate-treated mice. Conversely, mefloquine treatment was not able to alter clinical features. Notably, artesunate pretreatment failed to modulate the expression of LFA-1 in splenocytes stimulated with parasitized red blood cells (pRBCs in vitro; however, it abrogated the expression of ICAM-1 in pRBC-stimulated endothelial cells. Accordingly, a cytoadherence in vitro assay demonstrated that pRBCs did not adhere to artesunate-treated vascular endothelial cells. In addition, NF-κB nuclear translocation in endothelial cells stimulated with pRBCs was impaired by artesunate treatment. Our results suggest that artesunate is able to exert a protective effect against the P. berghei-induced inflammatory response by inhibiting NF-κB nuclear translocation and the subsequent expression of ICAM-1.

  6. Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF-κB Translocation in a Mechanism Independent of Plasmodium Killing

    Science.gov (United States)

    Souza, Mariana C.; Paixão, Flávio Henrique Marcolino; Ferraris, Fausto K.; Ribeiro, Isabela; Henriques, Maria das Graças M. O.

    2012-01-01

    Artemisinin and its derivates are an important class of antimalarial drug and are described to possess immunomodulatory activities. Few studies have addressed the effect of artesunate in the murine malaria model or its effect on host immune response during malaria infection. Herein, we study the effect of artesunate treatment and describe an auxiliary mechanism of artesunate in modulating the inflammatory response during experimental malaria infection in mice. Treatment with artesunate did not reduce significantly the parasitemia within 12 h, however, reduced BBB breakdown and TNF-α mRNA expression in the brain tissue of artesunate-treated mice. Conversely, mefloquine treatment was not able to alter clinical features. Notably, artesunate pretreatment failed to modulate the expression of LFA-1 in splenocytes stimulated with parasitized red blood cells (pRBCs) in vitro; however, it abrogated the expression of ICAM-1 in pRBC-stimulated endothelial cells. Accordingly, a cytoadherence in vitro assay demonstrated that pRBCs did not adhere to artesunate-treated vascular endothelial cells. In addition, NF-κB nuclear translocation in endothelial cells stimulated with pRBCs was impaired by artesunate treatment. Our results suggest that artesunate is able to exert a protective effect against the P. berghei-induced inflammatory response by inhibiting NF-κB nuclear translocation and the subsequent expression of ICAM-1. PMID:23097741

  7. Short-time QiBaoMeiRan Formula Treatment Exerts Estrogenic Activities without Side Effects on Reproductive Tissues in Immature Mice.

    Science.gov (United States)

    Xu, Ying; Ma, Xiao-ping; An, Jin-na; Zhang, Zi-jia; Ding, Jie; Qu, Ya-kun; Liu, Zhen-li; Lin, Na

    2015-12-08

    The Chinese herbal preparation QiBaoMeiRan formula (QBMR) displayed estrogenic effects in ovariectomized rats after long-term administration in a previous study. The uterus and vagina are negatively influenced by estrogens in hormone therapy. While QBMR is known to be a phytoestrogen, its estrogenic effects and safety on reproductive tissues after short-term administration and its mechanism via estrogen receptor (ER) pathway haven't been studied. Here, we characterized its estrogenic effects using immature mice together with in vitro studies for further molecular characterization. Immature mice were treated with QBMR at doses of 1.125, 2.25, and 4.5 g/kg for 7 days. 1.125 and 2.25 g/kg QBMR promoted the growth and development of uterus and vagina, and upregulated ERα and ERβ expression in reproductive tissues. QBMR had a stimulatory effect on proliferating cell nuclear antigen in vagina but not in uterus, and was without any influence on ki-67 antigen in uterus and vagina. QBMR significantly induced luciferase expression from the ERα/β-estrogen response element (ERE) luciferase reporter and upregulated ERα and ERβ expressions in MCF-7 cells, which were significantly inhibited by estrogen antagonist ICI182,780. This study demonstrated QBMR exerts estrogenic effects on reproductive tissues without side effects and through ER-ERE-dependent pathway.

  8. Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2.

    Science.gov (United States)

    Yu, Tao; Yang, Yanyan; Kwak, Yi-Seong; Song, Gwan Gyu; Kim, Mi-Yeon; Rhee, Man Hee; Cho, Jae Youl

    2017-04-01

    Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis factor-α/interferon-γ-treated synovial cells, and HEK293 cells transfected with various inducers of inflammation. G-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis factor-α and interleukin-1β. G-Rc also markedly suppressed the activation of TANK-binding kinase 1/IκB kinase ε/interferon regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. G-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase 1/IκB kinase ε/interferon regulatory factor-3 and p38/ATF-2 signaling.

  9. EPs® 7630 (Umckaloabo®), an extract from Pelargonium sidoides roots, exerts anti-influenza virus activity in vitro and in vivo.

    Science.gov (United States)

    Theisen, Linda L; Muller, Claude P

    2012-05-01

    A prodelphinidin-rich extract from Pelargonium sidoides DC, EPs® 7630 (Umckaloabo®), which is licensed to treat respiratory tract infections such as acute bronchitis, was investigated for its antiviral effects. EPs® 7630 showed dose-dependent anti-influenza activity at non-toxic concentrations against pandemic H1N1, oseltamivir-sensitive and -resistant seasonal H1N1, seasonal H3N2 and the laboratory H1N1 strain A/Puerto Rico/8/34, while it had no antiviral activity against adenovirus or measles virus. The extract inhibited an early step of influenza infection and impaired viral hemagglutination as well as neuraminidase activity. However, EPs® 7630 did not exhibit a direct virucidal effect, as virus preincubation (unlike cell preincubation) with the extract did not influence infectivity. Importantly, EPs® 7630 showed no propensity to resistance development in vitro. Analysis of EPs® 7630 constituents revealed that prodelphinidins represent the active principle. Chain length influenced antiviral activity, as monomers and dimers were less effective than oligo- and polymers. Importantly, gallocatechin and its stereoisomer epigallocatechin exert antiviral activity also in their monomeric form. In addition, EPs® 7630 administered by inhalation significantly improved survival, body weight and body temperature of influenza-infected mice, without obvious toxicity, demonstrating the benefit of EPs® 7630 in treatment of influenza.

  10. LUBAC-Recruited CYLD and A20 Regulate Gene Activation and Cell Death by Exerting Opposing Effects on Linear Ubiquitin in Signaling Complexes

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    Peter Draber

    2015-12-01

    Full Text Available Ubiquitination and deubiquitination are crucial for assembly and disassembly of signaling complexes. LUBAC-generated linear (M1 ubiquitin is important for signaling via various immune receptors. We show here that the deubiquitinases CYLD and A20, but not OTULIN, are recruited to the TNFR1- and NOD2-associated signaling complexes (TNF-RSC and NOD2-SC, at which they cooperate to limit gene activation. Whereas CYLD recruitment depends on its interaction with LUBAC, but not on LUBAC’s M1-chain-forming capacity, A20 recruitment requires this activity. Intriguingly, CYLD and A20 exert opposing effects on M1 chain stability in the TNF-RSC and NOD2-SC. While CYLD cleaves M1 chains, and thereby sensitizes cells to TNF-induced death, A20 binding to them prevents their removal and, consequently, inhibits cell death. Thus, CYLD and A20 cooperatively restrict gene activation and regulate cell death via their respective activities on M1 chains. Hence, the interplay between LUBAC, M1-ubiquitin, CYLD, and A20 is central for physiological signaling through innate immune receptors.

  11. O-linked β-N-acetylglucosamine During Hyperglycemia Exerts Both Anti-Inflammatory and Pro-Oxidative Properties in the Endothelial System

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    Angana Gupta Rajapakse

    2009-01-01

    Full Text Available Elevated cellular levels of protein O-linked β-N-acetylglucosamine (O-GlcNAc through hexosamine biosynthesis pathway (HBP are suggested to contribute to cardiovascular adverse effects under chronic hyperglycemic condition associated with oxidative stress and inflammation. Conversely, enhancing O-GlcNAc levels have also been demonstrated being protective against myocardial ischemia/reperfusion injury. We recently demonstrated that hyperglycemia increases oxidative stress and HBP flux in endothelial cells and enhances endothelial expression of vascular adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 in response to tumor necrosis factor-α (TNFα through oxidative stress rather than HBP pathway. Here we present further complementary data showing that enhancing O-GlcNAc levels by glucosamine does not mimic hyperglycemia's effect on TNFα-induced endothelial VCAM-1 and ICAM-1 expression. Glucosamine however inhibits ICAM-1 (not VCAM-1 expression and induces superoxide generation in the cells. The results further suggest that increased O-GlcNAc levels do not mediate the enhancing effect of hyperglycemia on the endothelial inflammatory responses to TNFα. In contrast, it exerts certain anti-inflammatory effects accompanied by pro-oxidative properties. Further work should delineate the exact role of HPB pathway in different aspects of cardiovascular functions, especially those of diabetic cardiovascular complications.

  12. Puerarin Exerts a Delayed Inhibitory Effect on the Proliferation of Cardiomyocytes Derived from Murine ES Cells via Slowing Progression through G2/M Phase

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    Xueying Luo

    2016-03-01

    Full Text Available Objective: Puerarin, which shows beneficial and protective effects on cardiovascular diseases, is the main isoflavone extracted from Pueraria lobata (kudzu root. The aim of this study was to investigate the effects of puerarin on in vitro myocardial proliferation and its underlying mechanism. Methods: Myocardial differentiation of transgenic embryonic stem (ES cells was performed by embryoid body-based differentiation method. The proliferation assay of cardiomyocytes (CMs derived from ES cells (ES-CMs was performed by EdU (5-Ethynyl-2'-deoxyuridine staining. Flow cytometry was employed to determine the cell cycle distribution and apoptosis of purified ES-CMs. Quantitative real-time PCR was utilized to study the transcription of genes related to cell cycle progression. Signaling pathways relating to proliferation were studied by western blot analysis and application of specific inhibitors. Results: Puerarin exerted a delayed inhibitory effect on the proliferation of ES-CMs at the early-stage differentiation. Meanwhile, puerarin slowed progression through G2/M phase without inducing apoptosis of ES-CMs. Further assays showed that puerarin up-regulated the transcription of Cyclin A2, Cyclin B1 and Cdk1 in ES-CMs. The ERK1/2 specific inhibitor PD0325901 and the PI3K specific inhibitor Wortmannin successfully reversed puerarin-induced up-regulation of Cdk1 but not Cyclin A2 and B1. Conclusion: These findings suggest that puerarin inhibits CM proliferation via slowing progression through G2/M phase during early-stage differentiation.

  13. Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase.

    Science.gov (United States)

    Wang, Chunhuai; Xiang, Ru; Zhang, Xiangzhong; Chen, Yunxian

    2015-09-01

    Doxycycline, a tetracycline-based antibiotic, has been reported to attenuate melanoma cell migration through inhibiting the focal adhesion kinase (FAK) signaling pathway. However, it remains to be elucidated whether doxycycline exerts this effect on leukemia cell migration. The present study aimed to examine the role of doxycycline in leukemia cell migration. The invasion capacities of the human leukemia cell lines KG1a (acute myelogenous leukemia) and K562 (chronic myelogenous leukemia) were evaluated using Matrigel® matrix‑coated Transwell® chamber assays; leukemic cell lines treated with doxycycline (1 µg/ml) or anti‑β1‑integrin antibodies were added to the upper chamber, while untreated cells were included as controls. Reverse transcription quantitative polymerase chain reaction was performed in order to further understand the influence of doxycycline treatment on the expression of FAK and gelatinases in the KG1a and K562 leukemic cell lines. In addition, FAK protein expression and phosphorylation were determined using western blot analysis in order to investigate the mechanism by which doxycycline inhibited leukemic cell migration. The results revealed that doxycycline treatment significantly attenuated the migration of KG1a and K562 cells, which was demonstrated to be associated with inhibition of the expression and phosphorylation of FAK. In addition, doxycycline treatment inhibited matrix metalloproteinase (MMP)‑2 and MMP‑9 expression. Furthermore, incubation with blocking anti‑β1‑integrin antibodies had an analogous inhibitory effect on leukemic cell migration to that of doxycycline. In conclusion, the results of the present study suggested that doxycycline attenuated leukemic cell migration through inhibiting the FAK signaling pathway. Therefore, doxycycline may have potential for use as a novel strategy for the treatment of leukemia.

  14. Cutting edge: TNFR-shedding by CD4+CD25+ regulatory T cells inhibits the induction of inflammatory mediators.

    NARCIS (Netherlands)

    Mierlo, G.J. van; Scherer, H.U.; Hameetman, M.; Morgan, M.E.; Flierman, R.; Huizinga, T.W.J.; Toes, R.E.

    2008-01-01

    CD4+CD25+ regulatory T (Treg) cells play an essential role in maintaining tolerance to self and nonself. In several models of T cell-mediated (auto) immunity, Treg cells exert protective effects by the inhibition of pathogenic T cell responses. In addition, Treg cells can modulate T cell-independent

  15. Just noticeable difference in perception of physical exertion during cycle exercise in young adult men and women.

    Science.gov (United States)

    Haile, Luke; Robertson, Robert J; Nagle, Elizabeth F; Krause, Maressa P; Gallagher, Michael; Ledezma, Christina M; Wisniewski, Kristofer S; Shafer, Alex B; Goss, Fredric L

    2013-04-01

    The purpose of this investigation was to describe the just noticeable difference (JND) in perceived exertion during cycle exercise. Males (n = 20) and females (n = 26) (21.4 ± 3.1 year) performed load-incremented cycle exercise to peak intensity. At the end of each minute, subjects rated their overall-body perceived exertion using the OMNI (0-10) rating of perceived exertion (RPE) scale. Individual regression derived the power output (PO) corresponding to RPE 5. This PO served as the standard stimulus (SS). On a separate occasion, four 5-min cycling bouts were performed with 5 min rest between bouts. During bouts 1 and 3 subjects cycled at the SS. During bouts 2 and 4 subjects adjusted the resistance to achieve a level of exertion just noticeably above/below the SS. The difference in final 30-s oxygen consumption (VO2) and PO between each JND bout and the previous SS were the above (JND-A) and below (JND-B) perceived exertion JNDs. JND-A and JND-B were compared between genders and between subjects exhibiting lower versus higher ventilatory threshold (VT) and VO(2PEAK) within genders for VO2 (l · min(-1), %VO(2PEAK)) and PO (W, %SS). JND-B was significantly (P < 0.05) greater than JND-A for VO2 and PO, when expressed in absolute (l · min(-1), W) and relative units (%VO(2PEAK), %SS). Males exhibited greater JND values than females in absolute, but not relative, units. Subjects with lower and higher VT and VO(2)PEAK exhibited similar JND values. The JND can serve as an effective tool to measure perceptual acuity and to determine individual ability to self-regulate prescribed exercise intensities.

  16. Active principles of Grindelia robusta exert antiinflammatory properties in a macrophage model.

    Science.gov (United States)

    La, Vu Dang; Lazzarin, Francesco; Ricci, Donata; Fraternale, Daniele; Genovese, Salvatore; Epifano, Francesco; Grenier, Daniel

    2010-11-01

    Plant extracts and/or secondary metabolites are receiving considerable attention as therapeutic agents for treating inflammatory diseases such as periodontitis, which affects the tooth supporting tissues. The aim of this study was to investigate the effect of a Grindelia robusta extract enriched in saponins and polyphenols on Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS)-induced inflammatory mediator (IL-6, TNF-a, RANTES, MCP-1, PGE(2) ) and matrix metalloproteinase (MMP-1, -3, -7, -8, -9, -13) secretion by macrophages. LPS induced a marked increase in the secretion of all inflammatory mediators and MMPs tested by macrophages, as determined by enzyme-linked immunosorbent assays. At non-cytotoxic concentrations, the G. robusta extract inhibited dose-dependently the secretion of IL-6, RANTES, MCP-1 and, to a lesser extent, PGE(2) and TNF-a. Such inhibition was also observed for MMP-1, -3, -7, -8, -9 and -13 secretion. This ability of G. robusta extract to reduce the LPS-induced secretion of inflammatory mediators and MMPs was associated with a reduction of nuclear factor-kappa B (NF-kB) p65 activation. The results suggest that G. robusta extract possesses an antiinflammatory therapeutic potential through its capacity to reduce the accumulation of inflammatory mediators and MMPs.

  17. Vinpocetine and piracetam exert antinociceptive effect in visceral pain model in mice.

    Science.gov (United States)

    Abdel Salam, Omar M E

    2006-01-01

    The effect of vinpocetine or piracetam on thermal and visceral pain was studied in mice. In the hot plate test, vinpocetine (0.9 and 1.8 mg/kg), but not piracetam, produced a reduction in nociceptive response. Vinpocetine (0.45-1.8 mg/kg, ip) or piracetam (75-300 mg/kg, ip) caused dose-dependent inhibition of the abdominal constrictions evoked by ip injection of acetic acid. The effect of vinpocetine or piracetam was markedly potentiated by co-administration of propranolol, guanethidine, atropine, naloxone, yohimbine or prazosin. The marked potentiation of antinociception occurred upon a co-administration of vinpocetine and baclofen (5 or 10 mg/kg). In contrast, piracetam antagonized antinociception caused by the low (5 mg/kg), but not the high (10 mg/kg) dose of baclofen. The antinociception caused by vinpocetine was reduced by sulpiride; while that of piracetam was enhanced by haloperidol or sulpiride. Either vinpocetine or piracetam enhanced antinociception caused by imipramine. The antinociceptive effects of vinpocetine or piracetam were blocked by prior administration of theophylline. Low doses of either vinpocetine or piracetam reduced immobility time in the Porsolt's forced-swimming test. This study indicates that vinpocetine and piracetam possess visceral antinociceptive properties. This effect depends on activation of adenosine receptors. Piracetam in addition inhibits GABA-mediated antinociception.

  18. Exertional-induced bronchoconstriction: Comparison between cardiopulmonary exercise test and methacholine challenging test

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    Mostafa Ghanei

    2015-01-01

    Full Text Available Introduction: Exertional-induced bronchoconstriction is a condition in which the physical activity causes constriction of airways in patients with airway hyper- responsiveness. In this study, we tried to study and evaluate any relationship between the findings of cardiopulmonary exercise testing (CPET and the response to methacholine challenge test (MCT in patients with dyspnea after activity. Materials and Methods: Thirty patients with complaints of dyspnea following activity referred to "Lung Clinic" of Baqiyatallah Hospital but not suffering from asthma were entered into the study. The subjects were excluded from the study if: Suffering from any other pulmonary diseases, smoking more than 1 cigarette a week in the last year, having a history of smoking more than 10 packets of cigarettes/year, having respiratory infection in the past 4 weeks, having abnormal chest X-ray or electrocardiogram, and cannot discontinue the use of medicines interfering with bronchial provocation. Baseline spirometry was performed for all the patients, and the values of forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, and FEV/FVC were recorded. The MCT and then the CPET were performed on all patients. Results: The mean VO 2 (volume oxygen in patients with positive methacholine test (20.45 mL/kg/min was significantly lower than patients with negative MCT (28.69 mL/kg/min (P = 0.000. Respiratory rates per minute (RR and minute ventilation in the group with positive MCT (38.85 and 1.636 L were significantly lower than the group with negative methacholine test (46.78 and 2.114 L (P < 0.05. Also, the O 2 pulse rate in the group with negative methacholine test (116.27 mL/beat was significantly higher than the group with positive methacholine test (84.26 mL/beat (P < 0.001. Conclusion: Pulmonary response to exercise in patients with positive methacholine test is insufficient. The dead space ventilation in these patients has increased. Also, dynamic

  19. Grouper TRIM13 exerts negative regulation of antiviral immune response against nodavirus.

    Science.gov (United States)

    Huang, Youhua; Yang, Min; Yu, Yepin; Yang, Ying; Zhou, Linli; Huang, Xiaohong; Qin, Qiwei

    2016-08-01

    -inflammatory factors. Together, our results firstly demonstrated that fish TRIM13 exerted negative regulation of antiviral response against nodavirus infection.

  20. Exertional Heat Illnesses and Environmental Conditions During High School Football Practices.

    Science.gov (United States)

    Tripp, Brady L; Eberman, Lindsey E; Smith, Michael Seth

    2015-10-01

    Guidelines for preventing exertional heat illnesses (EHIs) during extreme heat stress should be specific to regional environments, age, and sport and should be based on evidence of reducing the risk. Each year in the United States, over 1 million high school football players practice in the August heat; however, no published data describe the incidence of EHIs in these athletes. To describe the environmental conditions and incidence of EHIs during high school football practices over a 3-month period. Descriptive epidemiology study. For a 3-month period (August-October), athletic trainers at 12 high schools in North Central Florida recorded the practice time and length, environmental conditions (wet-bulb globe temperature), and incidences of EHIs in varsity football athletes. Athletes suffered 57 total EHIs during 29,759 athlete-exposures (AEs) for the 3-month data collection period (rate = 1.92/1000 AEs). August accounted for the majority of all EHIs, with 82.5% (47/57) and the highest rate (4.35/1000 AEs). Of total heat illnesses, heat cramps accounted for 70.2% (40/57), heat exhaustion 22.8% (13/57), and heat syncope 7.0% (4/57). The odds ratio indicated that athletes in August practices that lasted longer than the recommended 3 hours were 9.84 times more likely to suffer a heat illness than those in practices lasting ≤3 hours. The highest rate of EHIs was during August. Practices in August that exceeded the recommended 3 hours were associated with a greater risk of heat illnesses. The overall rate of EHIs was lower for the high school football athletes observed in the study compared with that reported for collegiate football athletes in the region. The low rates of EHIs recorded suggest that the prevention guidelines employed by sports medicine teams are appropriate for the region and population. Team physicians and athletic trainers should employ evidence-based, region- and population-specific EHI prevention guidelines. Sports medicine teams, coaches, and

  1. Low Prevalence of Periodontitis in Acromegaly: Growth Hormone May Exert a Protective Effect

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    Hülya Serinsöz

    2015-06-01

    Full Text Available Purpose: To evaluate bone mineral density (BMD measurements and the presence of periodontitis in patients with acromegaly, as well as to inquire the impact of interfering factors. Material and Method: Forty-seven acromegalic patients with any accompanying condition known to affect calcium-bone metabolism and 60 age-matched healthy controls were included. Age, gender, duration and activity of acromegaly, past-present therapy options, pituitary hormone profiles, replacement therapies, and the results of periodontal analysis were recorded. Results: Eighteen patients were male (38.3%, 29 were female (61.7%. The mean age of the patients was 46.6±11.5 years, twenty-five (53.1% had active, 22 (46.8% had inactive acromegaly. The latter were older and had longer disease duration (p=0.04, p=0.003, respectively. Serum calcium and phosphorus levels, 24-hour urinary calcium excretion and BMD at the lumbar spine and femur neck insignificantly associated with disease activity (p>0.05. Osteoporosis was detected in 6 patients (12.76%. Periodontitis and advanced periodontitis were more common in control group (66.7% vs. 44.7%, (43.3% vs. 12.8% (p=0.022, p=0.0001, respectively. There was no difference in chronic periodontitis and severity between active and inactive groups (48% vs. 40.9%; p=0.279. No difference was noted in other study parameters, as well. Repeated measures analysis of variance demonstrated statistically insignificant distribution between GH change in time and periodontitis subgroups. Discussion: We demonstrated that acromegaly exerted no clear negative impact on vertebral BMD in the absence of overt hypogonadism. Regardless of disease activity, acromegaly cases exhibited lower rates of periodontitis with less severity which remained unchanged in the presence of accompanying metabolic disorders known to have negative impact on periodontal tissue. Chronic exposure to excess GH may have a protective role against periodontitis. Turk Jem 2015; 19: 42-48

  2. Is there a link between exertional heat stroke and susceptibility to malignant hyperthermia?

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    Emmanuel Sagui

    Full Text Available The identification of a predisposition toward malignant hyperthermia (MH as a risk factor for exertional heat stroke (EHS remains a matter of debate. Such a predisposition indicates a causal role for MH susceptibility (MHS after EHS in certain national recommendations and has led to the use of an in vitro contracture test (IVCT to identify the MHS trait in selected or unselected EHS patients. The aim of this study was to determine whether the MHS trait is associated with EHS.EHS subjects in the French Armed Forces were routinely examined for MHS after experiencing an EHS episode. This retrospective study compared the features of IVCT-diagnosed MHS (iMHS EHS subjects with those of MH-normal EHS patients and MH patients during the 2004-2010 period. MHS status was assessed using the European protocol.During the study period, 466 subjects (median age 25 years; 31 women underwent MHS status investigation following an EHS episode. None of the subjects reported previous MH events. An IVCT was performed in 454 cases and was diagnostic of MHS in 45.6% of the study population, of MH susceptibility to halothane in 18.5%, of MH susceptibility to caffeine in 9.9%, and of MH susceptibility to halothane and caffeine in 17.2%. There were no differences in the clinical features, biological features or outcomes of iMHS EHS subjects compared with those of MH-normal or caffeine or halothane MHS subjects without known prior EHS episode. The recurrence rate was 12.7% and was not associated with MH status or any clinical or biological features. iMHS EHS patients exhibited a significantly less informative IVCT response than MH patients.The unexpected high prevalence of the MHS trait after EHS suggested a latent disturbance of calcium homeostasis that accounted for the positive IVCT results. This study did not determine whether EHS patients have an increased risk of MH, and it could not determine whether MH susceptibility is a risk factor for EHS.

  3. Effect of extremely weak pulsed magnetic field type Bemer 3000 on ratings of perceived exertion

    Directory of Open Access Journals (Sweden)

    D Gazurek

    2008-06-01

    Full Text Available The aim of this study was to examine whether is an influence of the exposition on different inductions of magnetic fields on rating of perceived exertion during 10 min long standardised physical cycloergometer exercise. The investigation was performed in 40 healthy, non-smoking, fit men, mean age 202. The participants were randomly attributed to 4 groups, each including 10 subjects. The first one (group E18 consisted of subjects exposed to the magnetic field with the intensity of 18 μT, the second one (group E64 exposed to the magnetic field with the intensity of 64 μT. Two control groups were formed to accompany these exposed to the magnetic field. In these placebo groups (S-T subjects were not exposed to the magnetic field (so called false therapy, „sham treatment”. The study consisted of 4 steps: pilot study, the first endurance test, exposure to the magnetic field, the second endurance test. The aim of the pilot study was to define subjective feelings of the participant during the effort, his reaction to the effort and also practical familiarization with the character and rules of the endurance test and Borg scale interpretation during 10 min of endurance cycloergometer test. The first endurance test was performed two days after the pilot study with the same rules and its goal was to measure the level of tiredness according to the Borg scale during 10 min long standardised physical effort. The second endurance test was performed according to the same rules as the first one and its goal was to analyse the effect of 20 exposures to the magnetic field with the intensity of 18 and 64 μT repeated daily on the perception of tiredness increase as expressed in the Borg scale when performing 10 min long standardised physical effort. In subjects exposed to 18 μT magnetic field neither changes in the perception of fatigue nor changes in the heart rate at particular levels of the Borg scale have been observed. When compared with both control

  4. Preliminary investigation of cardiopulmonary function in stroke patients with stable heart failure and exertional dyspnea

    Science.gov (United States)

    Liaw, Mei-Yun; Wang, Lin-Yi; Pong, Ya-Ping; Tsai, Yu-Chin; Huang, Yu-Chi; Yang, Tsung-Hsun; Lin, Meng-Chih

    2016-01-01

    Abstract The aim of this study was to investigate the relationships between pulmonary function, respiratory muscle strength, perceived dyspnea, degree of fatigue, and activity of daily living with motor function and neurological status in stroke patients with stable congestive heart failure (CHF). This was a cohort study in a tertiary care medical center. Stroke patients with CHF and exertional dyspnea (New York Heart Association class I–III) were recruited. The baseline characteristics included duration of disease, Brunnstrom stage, spirometry, resting heart rate, resting oxyhemoglobin saturation (SpO2), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), Borg scale, fatigue scale, and Barthel index. A total of 47 stroke patients (24 males, 23 females, mean age 65.9 ± 11.5 years) were included. The average Brunnstrom stages of affected limbs were 3.6 ± 1.3 over the proximal parts and 3.5 ± 1.4 over the distal parts of upper limbs, and 3.9 ± 0.9 over lower limbs. The average forced vital capacity (FVC) was 2.0 ± 0.8 L, with a predicted FVC% of 67.9 ± 18.8%, forced expiratory volume in the first second (FEV1) of 1.6 ± 0.7 L, predicted FEV1% of 70.6 ± 20.1%, FEV1/FVC of 84.2 ± 10.5%, and maximum mid-expiratory flow of 65.4 ± 29.5%. The average MIP and MEP were −52.9 ± 33.3 cmH2O and 60.8 ± 29.0 cmH2O, respectively. The Borg scale was 1.5 ± 0.8. MIP was negatively associated with the average Brunnstrom stage of the proximal (r = −0.318, P lower extremities (r = −0.288, P lower extremities (r = −0.311, P limbs. FVC was more strongly associated with MIP and MEP than predicted FVC%. FEV1/FVC may be used as a reference for the pulmonary dysfunction. PMID:27749577

  5. Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats.

    Science.gov (United States)

    Semaming, Yoswaris; Kumfu, Sirinart; Pannangpetch, Patchareewan; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2014-10-01

    Oxidative stress has been shown to play an important role in the pathogenesis of diabetes-induced cardiac dysfunction. Protocatechuic acid (PCA) is a phenolic compound, a main metabolite of anthocyanin, which has been reported to display various pharmacological properties. We proposed the hypothesis that PCA exerts cardioprotection in type 1 diabetic (T1DM) rats. T1DM was induced in male Sprague-Dawley rats by a single i.p. injection of 50 mg/kg streptozotocin (STZ) and groups of these animals received the following treatments for 12 weeks: i) oral administration of vehicle, ii) oral administration of PCA at a dose of 50  mg/kg per day, iii) oral administration of PCA at a dose of 100 mg/kg per day, iv) s.c. injection of insulin at a dose of 4 U/kg per day, and v) a combination of PCA, 100 mg/kg per day and insulin, 4 U/kg per day. Metabolic parameters, results from echocardiography, and heart rate variability were monitored every 4 weeks, and the HbA1c, cardiac malondialdehyde (MDA), cardiac mitochondrial function, and cardiac BAX/BCL2 expression were evaluated at the end of treatment. PCA, insulin, and combined drug treatments significantly improved metabolic parameters and cardiac function as shown by increased percentage fractional shortening and percentage left ventricular ejection fraction and decreased low-frequency:high-frequency ratio in T1DM rats. Moreover, all treatments significantly decreased plasma HbA1c and cardiac MDA levels, improved cardiac mitochondrial function, and increased BCL2 expression. Our results demonstrated for the first time, to our knowledge, the efficacy of PCA in improving cardiac function and cardiac autonomic balance, preventing cardiac mitochondrial dysfunction, and increasing anti-apoptotic protein in STZ-induced T1DM rats. Thus, PCA possesses a potential cardioprotective effect and could restore cardiac function when combined with insulin treatment. These findings indicated that supplementation with PCA might be

  6. SALIVARY CORTISOL RESPONSES AND PERCEIVED EXERTION DURING HIGH INTENSITY AND LOW INTENSITY BOUTS OF RESISTANCE EXERCISE

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    Alison D. Egan

    2004-03-01

    Full Text Available The purpose of this study was to measure the salivary cortisol response to different intensities of resistance exercise. In addition, we wanted to determine the reliability of the session rating of perceived exertion (RPE scale to monitor resistance exercise intensity. Subjects (8 men, 9 women completed 2 trials of acute resistance training bouts in a counterbalanced design. The high intensity resistance exercise protocol consisted of six, ten-repetition sets using 75% of one repetition maximum (RM on a Smith machine squat and bench press exercise (12 sets total. The low intensity resistance exercise protocol consisted of three, ten-repetition sets at 30% of 1RM of the same exercises as the high intensity protocol. Both exercise bouts were performed with 2 minutes of rest between each exercise and sessions were repeated to test reliability of the measures. The order of the exercise bouts was randomized with least 72 hours between each session. Saliva samples were obtained immediately before, immediately after and 30 mins following each resistance exercise bout. RPE measures were obtained using Borg's CR-10 scale following each set. Also, the session RPE for the entire exercise session was obtained 30 minutes following completion of the session. There was a significant 97% increase in the level of salivary cortisol immediately following the high intensity exercise session (P<0.05. There was also a significant difference in salivary cortisol of 145% between the low intensity and high intensity exercise session immediately post-exercise (P<0.05. The low intensity exercise did not result in any significant changes in cortisol levels. There was also a significant difference between the session RPE values for the different intensity levels (high intensity 7.1 vs. low intensity 1.9 (P<0.05. The intraclass correlation coefficient for the session RPE measure was 0.95. It was concluded that the session RPE method is a valid and reliable method of

  7. Epigenetic memory of oxidative stress: does nephrilin exert its protective effects via Rac1?

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    Mascarenhas DD

    2017-07-01

    Full Text Available Desmond D Mascarenhas,1,2 David N Herndon,3 Istvan Arany4 1Mayflower Organization for Research & Education, Sunnyvale, CA, 2Transporin, Inc., Sunnyvale, CA, 3Department of Surgery, The University of Texas Medical Branch, and Shriners Hospitals for Children, Galveston, TX, 4Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, USA Aim: Nephrilin peptide, a designed inhibitor of Rictor complex (mTORC2, exerts pleiotropic protective effects in metabolic, xenobiotic and traumatic stress models. Stress can generate enduring epigenetic changes in gene function. In this work we examine the possibility that nephrilin treatment protects against acute and enduring global changes in oxidative metabolism, with a focus on the Rictor-complex-mediated activation of Rac1, a subunit of NADPH oxidase (Nox via PKCs, Prex1 and p66shc. Methods: Given the wide range of animal models in which nephrilin peptide has previously demonstrated effectiveness in vivo, we chose three different experimental systems for this investigation: dermal fibroblasts, renal proximal tubule epithelial cells (PTECs, and kidney tissue and urine from an animal model of burn trauma in which nephrilin was previously shown to prevent loss of kidney function. Results: (1 Nephrilin protects dermal fibroblasts from loss of viability and collagen synthesis after ultraviolet A (UV-A or H2O2 insult. (2 Nephrilin reduces reactive oxygen species (ROS formation by H2O2–treated (PTECs with or without nicotine pretreatment. Using RNA arrays and pathway analysis we demonstrate that nicotine and H2O2-treated PTECs specifically induced Rac1 gene networks in these cells. (3 Using kidney tissue and urine from the burn trauma model we demonstrate significant elevations of [a] 8-aminoprostane in urine; [b] kidney tissue histone modification and DNA methylation; and [c] post-transcriptional phosphorylation events consistent with Rac1 activation in

  8. Anger inhibition and pain: conceptualizations, evidence and new directions.

    Science.gov (United States)

    Burns, John W; Quartana, Phillip J; Bruehl, Stephen

    2008-06-01

    Anger and how anger is regulated appear to affect acute and chronic pain intensity. The inhibition of anger (anger-in), in particular, has received much attention, and it is widely believed that suppressing or inhibiting the verbal or physical expression of anger is related to increased pain severity. We examine theoretical accounts for expecting that anger inhibition should affect pain, and review evidence for this claim. We suggest that the evidence for a link between trait anger-in (the self-reported tendency to inhibit anger expression when angry) and acute and chronic pain severity is quite limited owing to a number of factors including a inadequate definition of trait anger-in embodied in the popular anger-in subscale of Spielberger's Anger Expression Inventory, and a strong overlap between trait anger-in scores and measures of general negative affect (NA). We argue that in order to determine whether something unique to the process of anger inhibition exerts direct effects on subsequent pain intensity, new conceptualizations and approaches are needed that go beyond self-report assessments of trait anger-in. We present one model of anger inhibition and pain that adopts elements of Wegner's ironic process theory of thought suppression. Findings from this emerging research paradigm indicate that state anger suppression (suppression manipulated in the laboratory) may indeed affect sensitivity to subsequent painful stimuli, and we outline potentially productive avenues of future inquiry that build on this model. We conclude that although studies employing correlational designs and self-reports of trait anger-in have not upheld the claim that anger inhibition affects pain severity, evidence from studies using new models suggests that actually inhibiting anger expression during a provocative event may increase perceived pain at a later time.

  9. Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-κB and Jak2-Stat3 Signaling Pathways.

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    Fangjiao Song

    Full Text Available Microglial-mediated neuroinflammation has been established as playing a vital role in pathogenesis of neurodegenerative disorders. Thus, rational regulation of microglia functions to inhibit inflammation injury may be a logical and promising approach to neurodegenerative disease therapy. The purposes of the present study were to explore the neuroprotective effects and potential molecular mechanism of Schizandrin A (Sch A, a lignin compound isolated from Schisandra chinesnesis. Our observations showed that Sch A could significantly down-regulate the increased production of nitric oxide (NO, tumor necrosis factor (TNF-α and interleukin (IL-6 induced by lipopolysaccharide (LPS both in BV-2 cells and primary microglia cells. Moreover, Sch A exerted obvious neuroprotective effects against inflammatory injury in neurons when exposed to microglia-conditioned medium. Investigations of the mechanism showed the anti-inflammatory effect of Sch A involved the inhibition of inducible nitric oxide synthase (iNOS and cyclooxygenase 2 (COX-2 expression levels and inhibition of the LPS-induced TRAF6-IKKβ-NF-κB pathway. Furthermore, inhibition of Jak2-Stat3 pathway activation and Stat3 nuclear translocation also was observed. In conclusion, SchA can exert anti-inflammatory and neuroprotective effects by alleviating microglia-mediated neuroinflammation injury through inhibiting the TRAF6-IKKβ-NF-κB and Jak2-Stat3 signaling pathways.

  10. Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-κB and Jak2-Stat3 Signaling Pathways

    Science.gov (United States)

    Song, Fangjiao; Zeng, Kewu; Liao, Lixi; Yu, Qian; Tu, Pengfei; Wang, Xuemei

    2016-01-01

    Microglial-mediated neuroinflammation has been established as playing a vital role in pathogenesis of neurodegenerative disorders. Thus, rational regulation of microglia functions to inhibit inflammation injury may be a logical and promising approach to neurodegenerative disease therapy. The purposes of the present study were to explore the neuroprotective effects and potential molecular mechanism of Schizandrin A (Sch A), a lignin compound isolated from Schisandra chinesnesis. Our observations showed that Sch A could significantly down-regulate the increased production of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin (IL)-6 induced by lipopolysaccharide (LPS) both in BV-2 cells and primary microglia cells. Moreover, Sch A exerted obvious neuroprotective effects against inflammatory injury in neurons when exposed to microglia-conditioned medium. Investigations of the mechanism showed the anti-inflammatory effect of Sch A involved the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression levels and inhibition of the LPS-induced TRAF6-IKKβ-NF-κB pathway. Furthermore, inhibition of Jak2-Stat3 pathway activation and Stat3 nuclear translocation also was observed. In conclusion, SchA can exert anti-inflammatory and neuroprotective effects by alleviating microglia-mediated neuroinflammation injury through inhibiting the TRAF6-IKKβ-NF-κB and Jak2-Stat3 signaling pathways. PMID:26919063

  11. Citral exerts its antifungal activity against Penicillium digitatum by affecting the mitochondrial morphology and function.

    Science.gov (United States)

    Zheng, Shiju; Jing, Guoxing; Wang, Xiao; Ouyang, Qiuli; Jia, Lei; Tao, Nengguo

    2015-07-01

    This work investigated the effect of citral on the mitochondrial morphology and function of Penicillium digitatum. Citral at concentrations of 2.0 or 4.0 μL/mL strongly damaged mitochondria of test pathogen by causing the loss of matrix and increase of irregular mitochondria. The deformation extent of the mitochondria of P. digitatum enhanced with increasing concentrations of citral, as evidenced by a decrease in intracellular ATP content and an increase in extracellular ATP content of P. digitatum cells. Oxygen consumption showed that citral resulted in an inhibition in the tricarboxylic acid cycle (TCA) pathway of P. digitatum cells, induced a decrease in activities of citrate synthetase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinodehydrogenase and the content of citric acid, while enhancing the activity of malic dehydrogenase in P. digitatum cells. Our present results indicated that citral could damage the mitochondrial membrane permeability and disrupt the TCA pathway of P. digitatum.

  12. Restoration of Tidal Flow to Impounded Salt Marsh Exerts Mixed Effect on Leaf Litter Decomposition

    Science.gov (United States)

    Henry, B. A.; Schade, J. D.; Foreman, K.

    2015-12-01

    Salt marsh impoundments (e.g. roads, levees) disconnect marshes from ocean tides, which impairs ecosystem services and often promotes invasive species. Numerous restoration projects now focus on removing impoundments. Leaf litter decomposition is a central process in salt marsh carbon and nutrient cycles, and this study investigated the extent to which marsh restoration alters litter decomposition rates. We considered three environmental factors that can potentially change during restoration: salinity, tidal regime, and dominant plant species. A one-month field experiment (Cape Cod, MA) measured decay of litter bags in impounded, restored, and natural marshes under ambient conditions. A two-week lab experiment measured litter decay in controlled incubations under experimental treatments for salinity (1ppt and 30 ppt), tidal regime (inundated and 12 hr wet-dry cycles), and plant species (native Spartina alterniflora and invasive Phragmites australis). S. alterniflora decomposed faster in situ than P. australis (14±1.0% mass loss versus 0.74±0.69%). Corroborating this difference in decomposition, S. alterniflora supported greater microbial respiration during lab incubation, measured as CO2 flux from leaf litter and biological oxygen demand of water containing leached organic matter (OM). However, nutrient analysis of plant tissue and leached OM show P. australis released more nitrogen than S. alterniflora. Low salinity treatments in both lab and field experiments decayed more rapidly than high salinity treatments, suggesting that salinity inhibited microbial activity. Manipulation of inundation regime did not affect decomposition. These findings suggest the reintroduction of tidal flow to an impounded salt marsh can have mixed effects; recolonization by the native cordgrass could supply labile OM to sediment and slow carbon sequestration, while an increase in salinity might inhibit decomposition and accelerate sequestration.

  13. Imetelstat (a telomerase antagonist) exerts off‑target effects on the cytoskeleton.

    Science.gov (United States)

    Mender, Ilgen; Senturk, Serif; Ozgunes, Nuriman; Akcali, K Can; Kletsas, Dimitris; Gryaznov, Sergei; Can, Alp; Shay, Jerry W; Dikmen, Z Gunnur

    2013-05-01

    Telomerase is a cellular ribonucleoprotein reverse transcriptase that plays a crucial role in telomere maintenance. This enzyme is expressed in approximately 90% of human tumors, but not in the majority of normal somatic cells. imetelstat sodium (GRN163L), is a 13-mer oligonucleotide N3'→P5' thio-phosphoramidate lipid conjugate, which represents the latest generation of telomerase inhibitors targeting the template region of the human functional telomerase RNA (hTR) subunit. In preclinical trials, this compound has been found to inhibit telomerase activity in multiple cancer cell lines, as well as in vivo xenograft mouse models. Currently, GRN163L is being investigated in several clinical trials, including a phase II human non‑small cell lung cancer clinical trial, in a maintenance setting following standard doublet chemotherapy. In addition to the inhibition of telomerase activity in cancer cell lines, GRN163L causes morphological cell rounding changes, independent of hTR expression or telomere length. This leads to the loss of cell adhesion properties; however, the mechanism underlying this effect is not yet fully understood. In the present study, we observed that GRN163L treatment leads to the loss of adhesion in A549 lung cancer cells, due to decreased E-cadherin expression, leading to the disruption of the cytoskeleton through the alteration of actin, tubulin and intermediate filament organization. Consequently, the less adherent cancer cells initially cease to proliferate and are arrested in the G1 phase of the cell cycle, accompanied by decreased matrix metalloproteinase-2 (MMP-2) expression. These effects of GRN163L are independent of its telomerase catalytic activity and may increase the therapeutic efficacy of GRN163L by decreasing the adhesion, proliferation and metastatic potential of cancer cells in vivo.

  14. Punicalagin exerts protective effect against high glucose-induced cellular stress and neural tube defects.

    Science.gov (United States)

    Zhong, Jianxiang; Reece, E Albert; Yang, Peixin

    2015-11-13

    Maternal diabetes-induced birth defects remain a significant health problem. Studying the effect of natural compounds with antioxidant properties and minimal toxicities on diabetic embryopathy may lead to the development of new and safe dietary supplements. Punicalagin is a primary polyphenol found in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumorigenic properties, suggesting a protective effect of punicalagin on diabetic embryopathy. Here, we examined whether punicalagin could reduce high glucose-induced neural tube defects (NTDs), and if this rescue occurs through blockage of cellular stress and caspase activation. Embryonic day 8.5 (E8.5) mouse embryos were cultured for 24 or 36 h with normal (5 mM) glucose or high glucose (16.7 mM), in presence or absence of 10 or 20 μM punicalagin. 10 μM punicalagin slightly reduced NTD formation under high glucose conditions; however, 20 μM punicalagin significantly inhibited high glucose-induced NTD formation. Punicalagin suppressed high glucose-induced lipid peroxidation marker 4-hydroxynonenal, nitrotyrosine-modified proteins, and lipid peroxides. Moreover, punicalagin abrogated endoplasmic reticulum stress by inhibiting phosphorylated protein kinase ribonucleic acid (RNA)-like ER kinase (p-PERK), phosphorylated inositol-requiring protein-1α (p-IRE1α), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP) and x-box binding protein 1 (XBP1) mRNA splicing. Additionally, punicalagin suppressed high glucose-induced caspase 3 and caspase 8 cleavage. Punicalagin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation. These observations suggest punicalagin supplements could mitigate the teratogenic effects of hyperglycemia in the developing embryo, and possibly prevent diabetes-induced NTDs.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Huei Chu Kao

    Full Text Available 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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Neuropeptide Y inhibits hippocampal seizures and wet dog shakes

    DEFF Research Database (Denmark)

    Woldbye, D P; Madsen, T M; Larsen, P J

    1996-01-01

    The effects of intracerebroventricular neuropeptide Y (NPY) or somatostatin were studied upon hippocampal EEG seizures elicited by electrical stimulation of the rat dentate gyrus or subiculum. At doses of 6 and 12 nmol, the latter dose being more effective, NPY reduced the primary afterdischarge...... effects in the dentate gyrus and subiculum, but also in areas to which epileptiform EEG activity spreads before reverberating. In addition, NPY strongly reduced seizure-related 'wet dog shakes' (WDS). This is consistent with previous studies showing that the dentate gyrus is essential for the generation...... of WDS. However, NPY inhibited WDS even when 1.ADDs were evoked which did not differ from those of vehicle rats, indicating extra-dentate inhibition by NPY as well. No effects were seen with somatostatin. These results show that NPY exerts antiepileptiform effects in vivo, suggesting that increased NPY...

  19. D-ribose inhibits DNA repair synthesis in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Zunica, G.; Marini, M.; Brunelli, M.A.; Chiricolo, M.; Franceschi, C.

    1986-07-31

    D-ribose is cytotoxic for quiescent human lymphocytes and severely inhibits their PHA-induced proliferation at concentrations (25-50 mM) at which other simple sugars are ineffective. In order to explain these effects, DNA repair synthesis was evaluated in PHA-stimulated human lymphocytes treated with hydroxyurea and irradiated. D-ribose, in contrast to other reducing sugars, did not induce repair synthesis and therefore did not apparently damage DNA in a direct way, although it markedly inhibited gamma ray-induced repair. Taking into account that lymphocytes must rejoin physiologically-formed DNA strand breaks in order to enter the cell cycle, we suggest that D-ribose exerts its cytotoxic activity by interfering with metabolic pathways critical for the repair of DNA breaks.

  20. The Effect of Oxidation on Berberine-Mediated CYP1 Inhibition: Oxidation Behavior and Metabolite-Mediated Inhibition.

    Science.gov (United States)

    Lo, Sheng-Nan; Shen, Chien-Chang; Chang, Chia-Yu; Tsai, Keng-Chang; Huang, Chiung-Chiao; Wu, Tian-Shung; Ueng, Yune-Fang

    2015-07-01

    The protoberberine alkaloid berberine carries methylenedioxy moiety and exerts a variety of pharmacological effects, such as anti-inflammation and lipid-lowering effects. Berberine causes potent CYP1B1 inhibition, whereas CYP1A2 shows resistance to the inhibition. To reveal the influence of oxidative metabolism on CYP1 inhibition by berberine, berberine oxidation and the metabolite-mediated inhibition were determined. After NADPH-fortified preincubation of berberine with P450, the inhibition of CYP1A1 and CYP1B1 variants (CYP1B1.1, CYP1B1.3, and CYP1B1.4) by berberine was not enhanced, and CYP1A2 remained resistant. Demethyleneberberine was identified as the most abundant metabolite of CYP1A1- and CYP1B1-catalyzed oxidations, and thalifendine was generated at a relatively low rate. CYP1A1-catalyzed berberine oxidation had the highest maximal velocity (V max) and exhibited positive cooperativity, suggesting the assistance of substrate binding when the first substrate was present. In contrast, the demethylenation by CYP1B1 showed the property of substrate inhibition. CYP1B1-catalyzed berberine oxidation had low K m values, but it had V max values less than 8% of those of CYP1A1. The dissociation constants generated from the binding spectrum and fluorescence quenching suggested that the low K m values of CYP1B1-catalyzed oxidation might include more than the rate constants describing berberine binding. The natural protoberberine/berberine fmetabolites with methylenedioxy ring-opening (palmatine, jatrorrhizine, and demethyleneberberine) and the demethylation (thalifendine and berberrubine) caused weak CYP1 inhibition. These results demonstrated that berberine was not efficiently oxidized by CYP1B1, and metabolism-dependent irreversible inactivation was minimal. Metabolites of berberine caused a relatively weak inhibition of CYP1.

  1. Tumour growth inhibition and anti-angiogenic effects using curcumin correspond to combined PDE2 and PDE4 inhibition.

    Science.gov (United States)

    Abusnina, Abdurazzag; Keravis, Thérèse; Zhou, Qingwei; Justiniano, Hélène; Lobstein, Annelise; Lugnier, Claire

    2015-02-01

    Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis by stimulating endothelial cells. Increase in cyclic AMP (cAMP) level inhibits VEGF-induced endothelial cell proliferation and migration. Cyclic nucleotide phosphodiesterases (PDEs), which specifically hydrolyse cyclic nucleotides, are critical in the regulation of this signal transduction. We have previously reported that PDE2 and PDE4 up-regulations in human umbilical vein endothelial cells (HUVECs) are implicated in VEGF-induced angiogenesis and that inhibition of PDE2 and PDE4 activities prevents the development of the in vitro angiogenesis by increasing cAMP level, as well as the in vivo chicken embryo angiogenesis. We have also shown that polyphenols are able to inhibit PDEs. The curcumin having anti-cancer properties, the present study investigated whether PDE2 and PDE4 inhibitors and curcumin could have similar in vivo anti-tumour properties and whether the anti-angiogenic effects of curcumin are mediated by PDEs. Both PDE2/PDE4 inhibitor association and curcumin significantly inhibited in vivo tumour growth in C57BL/6N mice. In vitro, curcumin inhibited basal and VEGF-stimulated HUVEC proliferation and migration and delayed cell cycle progression at G0/G1, similarly to the combination of selective PDE2 and PDE4 inhibitors. cAMP levels in HUVECs were significantly increased by curcumin, similarly to rolipram (PDE4 inhibitor) and BAY-60-550 (PDE2 inhibitor) association, indicating cAMP-PDE inhibitions. Moreover, curcumin was able to inhibit VEGF-induced cAMP-PDE activity without acting on cGMP-PDE activity and to modulate PDE2 and PDE4 expressions in HUVECs. The present results suggest that curcumin exerts its in vitro anti-angiogenic and in vivo anti-tumour properties through combined PDE2 and PDE4 inhibition.

  2. Comparison between perceived exertion threshold and indicators of maximal lactate steady state in intermittent exercise

    Directory of Open Access Journals (Sweden)

    Herbert Gustavo Simões

    2007-12-01

    Full Text Available O limiar de esforço percebido contínuo (LEPc pode ser considerado como ponto de transição metabólica entre os domínios intenso e severo, pois se relaciona com a potência crítica. Dessa forma, os objetivos do presente estudo foram: (1 verifi car a possibilidade de estimativa do LEP e de um indicador de máximo estado estável de lactato em exercício intermitente (LEPi e MEELINDIC, (2 comparar o LEPi e MEELINDIC com o máximo estado estável de lactato intermitente (MEELi, e (3 verifi car a relação entre a PSE e as respostas de lactato sangüíneo ([La] em esforços intermitentes de alta intensidade. Dez participantes foram submetidos a sessões de familiarização, teste de esforço progressivo, testes preditivos intermitentes e determinação do MEELi. O LEPi e o MEELINDIC foram estimados a partir dos testes preditivos, e o MEELi foi determinado a partir de testes de 30 minutos. As correlações entre as taxas de aumento da PSE e [La] (r=0,77, e os valores absolutos de PSE e [La] (r=0,78 foram moderadas. Os altos valores de R2 das taxas de aumento da PSE e [La] e das regressões lineares para a estimativa do LEPi e do MEELINDIC sugerem que essas variáveis podem ser estimadas de forma acurada. As intensidades do LEPi, MEELINDIC e MEELi não foram diferentes entre si. O LEPi e MEELINDIC apresentaram altas correlações com o MEELi (r=0,90 e r=0,80, respectivamente. Portanto, a relação entre a PSE e [La] é moderada, e tanto o LEPi quanto o MEELINDIC podem ser estimados e utilizados como indicadores de capacidade aeróbia. ABSTRACT The continuous perceived exertion threshold (PETc is considered as a metabolic transition point between the heavy and severe domain, since it is related with critical power. Thus, the aims of this study were: (1 to verify the possibility to estimate PET and maximal lactate steady state index in intermittent exercises (PETi and MLSSINDEX, (2 compare the PETi and MLSSINDEX with intermittent exercise maximal

  3. Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

    Science.gov (United States)

    Wang, Ye; Yang, Qi-Wei; Yang, Qing; Zhou, Tie; Shi, Min-Feng; Sun, Chen-Xia; Gao, Xiu-Xia; Cheng, Yan-Qiong; Cui, Xin-Gang; Sun, Ying-Hao

    2017-01-01

    Disordered copper metabolism plays a critical role in the development of various cancers. As a nanomedicine containing copper, cuprous oxide nanoparticles (CONPs) exert ideal antitumor pharmacological effects in vitro and in vivo. Prostate cancer is a frequently diagnosed male malignancy prone to relapse, and castration resistance is the main reason for endocrine therapy failure. However, whether CONPs have the potential to treat castration-resistant prostate cancer is still unknown. Here, using the castration-resistant PC-3 human prostate cancer cell line as a model, we report that CONPs can selectively induce apoptosis and inhibit the proliferation of cancer cells in vitro and in vivo without affecting normal prostate epithelial cells. CONPs can also attenuate the stemness of cancer cells and inhibit the Wnt signaling pathway, both of which highlight the great potential of CONPs as a new clinical castration-resistant prostate cancer therapy.

  4. The relationship between biomechanical-anthropometrical parameters and the force exerted on the head when heading free kicks in soccer.

    Science.gov (United States)

    Teymouri, Meghdad; Sadeghi, Heydar; Nabaei, Amir; Kasaeian, Amir

    2012-01-01

    Soccer is a contact sport in which the players are frequently faced with the risk of injury. It has been shown that the force exerted on the head during heading can be as much as 500-1200 Newton (N). The main objective of this study was to determine whether there was any relationship between the force exerted on the head and several biomechanical and anthropometrical parameters related to heading free kicks. A total of 16 semi-professional soccer players with at least 5 years experience participated in this study. The mean age, height, and weight of the study participants were 21.36 ± 5.67, 178 ± 5.99 cm, and 70.55 ± 8.55 kg, respectively. To measure the force exerted on the heads of the players, a pressure gauge was installed on their foreheads. Each participant was asked to defend the ball using the heading technique three times. A camera with a sampling frequency of 150 frames per second was used to record the moment of impact between the ball and head during each heading event. For each participant and replicate, the ball and head velocity (m/s) as well as the angular body changes (degrees) were calculated using MATLAB and AutoCAD softwares, respectively. Descriptive statistics, including means and standard deviations were used to describe the data. Pearson correlation coefficient (alpha = 0.05) was used to examine potential relationships between the variables of interest. Significant correlations existed between the force exerted on the head during heading, participant age, body mass, body fat percentage, and head perimeter (P heading, such as age and head perimeter. Therefore, it was concluded that these variables should be considered when teaching and practicing the heading technique with players of different ages and anthropometric sizes.

  5. Sickle Cell Trait and Fatal Exertional Heat Illness: Implications for Exercise-Related Death of Young Ddults

    Science.gov (United States)

    2008-10-22

    not require identification of Hb AS since current diagnosis and treatment do not differ by hemoglobin type. 4. The effect of our intervention on...athletes who utilize ordinary weather reports? Alpha- Thalassemia Protects Against Exertional Mortality with Sickle Cell Trait • 30% of African...Americans have alpha- thalassemia (2-3 alpha genes instead of 4). In those with sickle cell trait the main effect is to lower the Hb S fraction below 36

  6. 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…

  7. Potentiation of latent inhibition.

    Science.gov (United States)

    Rodriguez, Gabriel; Hall, Geoffrey

    2008-07-01

    Rats were given exposure either to an odor (almond) or a compound of odor plus taste (almond plus saline), prior to training in which the odor served as the conditioned stimulus. It was found, for both appetitive and aversive procedures, that conditioning was retarded by preexposure (a latent inhibition effect), and the extent of the retardation was greater in rats preexposed to the compound (i.e., latent inhibition to the odor was potentiated by the presence of the taste). In contrast, the presence of the taste during conditioning itself overshadowed learning about the odor. We argue that the presence of the salient taste in compound with the odor enhances the rate of associative learning, producing a rapid loss in the associability of the odor. This loss of associability will generate both overshadowing and the potentiation of latent inhibition that is observed after preexposure to the compound.

  8. BCL3 exerts an oncogenic function by regulating STAT3 in human cervical cancer

    Directory of Open Access Journals (Sweden)

    Zhao H

    2016-10-01

    Full Text Available Hu Zhao,1 Wuliang Wang,1 Qinghe Zhao,1 Guiming Hu,2 Kehong Deng,1 Yuling Liu1 1Department of Gynecology and Obstetrics, 2Department of Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Aberrant expression of oncogenes and/or tumor suppressors play a fundamental effect on the pathogenesis and tumorigenicity of cervical cancer (CC. B-cell CLL/lymphoma 3 (BCL3 was previously found to be a putative proto-oncogene in human cancers and regulated signal transducer and activator of transcription 3 (STAT3, a critical oncogene, in CC cell line. However, its expression status, clinical significance and biological functions in CC remain largely unclear. The expressions of BCL3 and STAT3 in CC specimens were determined by immunohistochemistry. MTT, colony formation assays and flow cytometry analysis were carried out to test proliferation and cell cycle of CC cells. Here, the levels of BCL3 were overexpressed in CC compared to adjacent cervical tissues. Furthermore, high levels of BCL3 protein were confirmed by immunoblotting in CC cells as compared with normal cervical epithelial cells. The positive expression of BCL3 was correlated with adverse prognostic features and reduced survival rate. In addition, BCL3 regulated STAT3 abundance in CC cells. STAT3 was found to be upregulated and positively correlated with BCL3 expression in CC specimens. BCL3 overexpression resulted in prominent increased proliferation and cell cycle progression in Hela cells. By contrast, inhibition of BCL3 in CaSki cells remarkably suppressed proliferative ability and cell cycle progression. In vivo studies showed that knockdown of BCL3 inhibited tumor growth of CC in mice xenograft model. Notably, we confirmed that STAT3 mediated the oncogenic roles of BCL3 in CC. In conclusion, we suggest that BCL3 serves as an oncogene in CC by modulating proliferation and cell cycle progression, and its oncogenic effect is

  9. Age and sex differences of controlled force exertion measured by a computer-generated sinusoidal target-pursuit system.

    Science.gov (United States)

    Nagasawa, Yoshinori; Demura, Shinichi

    2009-06-01

    This study examined age and sex differences of controlled force exertion in 207 males and 249 females aged 15 to 86 years. The subjects matched the submaximal grip strength of their dominant hand to changing demand values, appearing as a sinusoidal waveform on the display of a personal computer. The total difference (%) between the demand value and the grip exertion value for 25 sec was used as an evaluation parameter. Significant linear regressions were identified, but there was no significant difference in the rate of increase of both sexes. Analysis of variance showed insignificant differences among the means of both sexes, except for those of the 20-24yr-old group, and the differences between means of subjects greater than 50 years of age and 20 years of age increased in both sexes. Individual differences were almost the same in both sexes. The errors in controlled force exertion did not show a significant sex difference and tended to increase with age in both sexes. However, their rates of increase were significant only after 50 years of age.

  10. Measurement of plasma momentum exerted on target by a small helicon plasma thruster and comparison with direct thrust measurement.

    Science.gov (United States)

    Takahashi, Kazunori; Komuro, Atsushi; Ando, Akira

    2015-02-01

    Momentum, i.e., force, exerted from a small helicon plasma thruster to a target plate is measured simultaneously with a direct thrust measurement using a thrust balance. The calibration coefficient relating a target displacement to a steady-state force is obtained by supplying a dc to a calibration coil mounted on the target, where a force acting to a small permanent magnet located near the coil is directly measured by using a load cell. As the force exerted by the plasma flow to the target plate is in good agreement with the directly measured thrust, the validity of the target technique is demonstrated under the present operating conditions, where the thruster is operated in steady-state. Furthermore, a calibration coefficient relating a swing amplitude of the target to an impulse bit is also obtained by pulsing the calibration coil current. The force exerted by the pulsed plasma, which is estimated from the measured impulse bit and the pulse width, is also in good agreement with that obtained for the steady-state operation; hence, the thrust assessment of the helicon plasma thruster by the target is validated for both the steady-state and pulsed operations.

  11. Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

    OpenAIRE

    Hye Joo Kim; Seong Hwan Kim; Jung-Mi Yun

    2012-01-01

    Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway. In this...

  12. Eruberin A, a Natural Flavanol Glycoside, Exerts Anti-Fibrotic Action on Pancreatic Stellate Cells

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    Siu Wai Tsang

    2015-07-01

    Full Text Available Background: Eruberin A (2, 3-dehydroflavonoid, a flavanol glycoside isolated from Pronephrium penangianum, has been used as a blood-nourishing folk medicine for centuries; however, it indeed possesses a variety of other health-promoting benefits including anti-fibrotic bioactivity. Activation of pancreatic stellate cells (PSCs is the key initiating step in pancreatic fibrosis, which is a characteristic feature associated with chronic pancreatitis and pancreatic adenocarcinoma. Methods: The anti-fibrotic effect of eruberin A and the underlying mechanisms of its anti-fibrotic action in LTC-14 cells, which retained essential characteristics and morphological features of primary PSCs, were examined by means of real-time polymerase chain reactions, Western blotting and immunostaining. Results: The application of eruberin A (20 µg/ml effectively inhibited the expression levels of fibrotic mediators namely alpha-smooth muscle actin, fibronectin and type I-collagen, so as the sonic hedgehog signaling pathway components post transforming growth factor-beta (5 ng/ml stimulation. Eruberin A treatment also led to a notable decrease in the activation of nuclear factor-kappaB (NF-κB and the phosphorylation of phosphoinositide 3-kinase (PI3K/serine-threonine kinase (AKT. Conclusion: Our results demonstrated that eruberin A significantly suppressed the expression levels of fibrotic mediators in PSCs, and we suggest that its anti-fibrotic mechanism was associated with an attenuation of the PI3K/AKT/NF-κB signaling pathway.

  13. Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction

    Directory of Open Access Journals (Sweden)

    María Roel

    2015-07-01

    Full Text Available The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1 on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities.