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  1. NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

    International Nuclear Information System (INIS)

    Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta; Turski, Waldemar A.

    2007-01-01

    Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects of both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures

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

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    Frank N.M. Twisk

    2018-04-01

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

  3. The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

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    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

  4. The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

    International Nuclear Information System (INIS)

    Liu, Tong; Yu, Rong; Jin, Shao-Bo; Han, Liwei; Lendahl, Urban; Zhao, Jian; Nistér, Monica

    2013-01-01

    Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion

  5. Antagonistic activity exerted in vitro and in vivo by Lactobacillus casei (strain GG) against Salmonella typhimurium C5 infection.

    Science.gov (United States)

    Hudault, S; Liévin, V; Bernet-Camard, M F; Servin, A L

    1997-02-01

    The aim of this study was to compare the antagonistic properties of Lactobacillus casei GG exerted in vitro against Salmonella typhimurium C5 in a cellular model, cultured enterocyte-like Caco-2 cells, to those exerted in vivo in an animal model, C3H/He/Oujco mice. Our results show that a 1-h contact between the invading strain C5 and either the culture or the supernatant of L. casei GG impeded the invasion by the Salmonella strain in Caco-2 cells, without modifying the viability of the strain. After neutralization at pH 7, no inhibition of the invasion by C5 was observed. The antagonistic activity of L. casei GG was examined in C3H/He/Oujco mice orally infected with C5 as follows: (i) L. casei GG was given daily to conventional animals as a probiotic, and (ii) it was given once to germ-free animals in order to study the effect of the population of L. casei GG established in the different segments of the gut. In vivo experiments show that after a single challenge with C5, this strain survives and persists at a higher level in the feces of the untreated conventional mice than in those of the treated group. In L. casei GG germ-free mice, establishment of L. casei GG in the gut significantly delayed the occurrence of 100% mortality of the animals (15 days after C5 challenge versus 9 days in germ-free mice [P L. casei GG population level in the gut dramatically decreased in these animals.

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

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    Ying An

    2011-01-01

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

  7. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity.

    Science.gov (United States)

    Mueller, Michaela; Thorell, Anders; Claudel, Thierry; Jha, Pooja; Koefeler, Harald; Lackner, Carolin; Hoesel, Bastian; Fauler, Guenter; Stojakovic, Tatjana; Einarsson, Curt; Marschall, Hanns-Ulrich; Trauner, Michael

    2015-06-01

    Bile acids (BAs) are major regulators of hepatic BA and lipid metabolism but their mechanisms of action in non-alcoholic fatty liver disease (NAFLD) are still poorly understood. Here we aimed to explore the molecular and biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross-talk between liver and visceral white adipose tissue (vWAT) regarding BA and cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD patients. In this randomized controlled pharmacodynamic study, we analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese patients receiving UDCA (20 mg/kg/day) or no treatment three weeks prior to bariatric surgery. Short term UDCA administration stimulated BA synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X receptor (FXR) activation, resulting in cholesterol 7α-hydroxylase induction mirrored by elevated C4 and 7α-hydroxycholesterol. Enhanced BA formation depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the liver, thereby increasing hepatic triglyceride content. In addition, induced SCD activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic and more lipogenic monounsaturated fatty acids such as oleic acid. These data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces neutral lipid accumulation in both liver and vWAT. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. Meta-diamide insecticides acting on distinct sites of RDL GABA receptor from those for conventional noncompetitive antagonists.

    Science.gov (United States)

    Nakao, Toshifumi; Banba, Shinich; Nomura, Michikazu; Hirase, Kangetsu

    2013-04-01

    The RDL GABA receptor is an attractive target of insecticides. Here we demonstrate that meta-diamides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] are a distinct class of RDL GABA receptor antagonists showing high insecticidal activity against Spodoptera litura. We also suggest that the mode of action of the meta-diamides is distinct from that of conventional noncompetitive antagonists (NCAs), such as fipronil, picrotoxin, lindane, dieldrin, and α-endosulfan. Using a membrane potential assay, we examined the effects of the meta-diamide 3-benzamido-N-(2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide (meta-diamide 7) and NCAs on mutant Drosophila RDL GABA receptors expressed in Drosophila Mel-2 cells. NCAs had little or no inhibitory activity against at least one of the three mutant receptors (A2'S, A2'G, and A2'N), which were reported to confer resistance to NCAs. In contrast, meta-diamide 7 inhibited all three A2' mutant receptors, at levels comparable to its activity with the wild-type receptor. Furthermore, the A2'S·T6'V mutation almost abolished the inhibitory effects of all NCAs. However, meta-diamide 7 inhibited the A2'S・T6'S mutant receptor at the same level as its activity with the wild-type receptor. In contrast, a G336M mutation in the third transmembrane domain of the RDL GABA receptor abolished the inhibitory activities of meta-diamide 7, although the G336M mutation had little effect on the inhibitory activities of conventional NCAs. Molecular modeling studies also suggested that the binding site of meta-diamides was different from those of NCAs. Meta-diamide insecticides are expected to be prominent insecticides effective against A2' mutant RDL GABA receptors with a different mode of action. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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    Mojca Frank-Bertoncelj

    2018-01-01

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

  10. Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators

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    Andres D. Ramirez

    2013-12-01

    Full Text Available Dual orexin receptor antagonists (DORAs are a potential treatment for insomnia that function by blocking both the orexin 1 and orexin 2 receptors. The objective of the current study was to further confirm the impact of therapeutic mechanisms targeting insomnia on locomotor coordination and ethanol interaction using DORAs and gamma-aminobutyric acid (GABA-A receptor modulators of distinct chemical structure and pharmacologic properties in the context of sleep-promoting potential. The current study compared rat motor co-ordination after administration of DORAs, DORA-12 and almorexant, and GABA-A receptor modulators, zolpidem, eszopiclone and diazepam, alone or each in combination with ethanol. Motor performance was assessed by measuring time spent walking on a rotarod apparatus. Zolpidem, eszopiclone and diazepam (0.3–30 mg/kg administered orally [PO] impaired rotarod performance in a dose-dependent manner. Furthermore, all three GABA-A receptor modulators potentiated ethanol- (0.25–1.25 g/kg induced impairment on the rotarod. By contrast, neither DORA-12 (10–100 mg/kg, PO nor almorexant (30–300 mg/kg, PO impaired motor performance alone or in combination with ethanol. In addition, distinct differences in sleep architecture were observed between ethanol, GABA-A receptor modulators (zolpidem, eszopiclone and diazepam and DORA-12 in electroencephalogram studies in rats. These findings provide further evidence that orexin receptor antagonists have an improved motor side-effect profile compared with currently available sleep-promoting agents based on preclinical data and strengthen the rationale for further evaluation of these agents in clinical development.

  11. Exerting Capacity.

    Science.gov (United States)

    Leger, J Michael; Phillips, Carolyn A

    2017-05-01

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

  12. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells

    International Nuclear Information System (INIS)

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2015-01-01

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl + K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5

  13. Differential Alterations in Excitatory and Inhibitory Networks Involving Dentate Granule Cells Following Chronic Treatment with Distinct Classes of NMDAR Antagonists in Hippocampal Slice Cultures

    Science.gov (United States)

    2010-03-08

    Rev. 8-98) Prescribed by ANSI Std Z39-18 Copyright Statement The author herby certitles thaI the use of any copyrighted material in the thesis...synaptic Ras-GTPase activating protein TBI: traumatic brain injury TeNT: tetanus toxin TLE: temporal lobe epilepsy TEA : tetraethylammonium TTX...antagonist QX-314 non membrane permeable sodium channel blocker TEA Kv channel blocker XVI XVII List of compounds and their pharmacological actions

  14. The MAPKERK-1,2 pathway integrates distinct and antagonistic signals from TGF alpha and FGF7 in morphogenesis of mouse mammary epithelium

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    Fata, Jimmie E; Mori, Hidetoshi; Ewald, Andrew J; Zhang, Hui; Yao, Evelyn; Werb, Zena; Bissell, Mina J

    2006-10-03

    Transforming growth factor-{alpha} (TGF{alpha}) and fibroblast growth factor-7 (FGF7) exhibit distinct expression patterns in the mammary gland. Both factors signal through mitogen-activated kinase/extracellular regulated kinase-1,2 (MAPK{sup ERK1,2}); however, their unique and/or combined contributions to mammary morphogenesis have not been examined. In ex vivo mammary explants, we show that a sustained activation of MAPK{sup ERK1,2} for 1 h, induced by TGF{alpha}, was necessary and sufficient to initiate branching morphogenesis, whereas a transient activation (15 min) of MAPK{sup ERK1,2}, induced by FGF7, led to growth without branching. Unlike TGF{alpha}, FGF7 promoted sustained proliferation as well as ectopic localization of, and increase in, keratin-6 expressing cells. The response of the explants to FGF10 was similar to that to FGF7. Simultaneous stimulation by FGF7 and TGF{alpha} indicated that the FGF7-induced MAPK{sup ERK1,2} signaling and associated phenotypes were dominant: FGF7 may prevent branching by suppression of two necessary TGF{alpha}-induced morphogenetic effectors, matrix metalloproteinase-3 (MMP-3/stromelysin-1), and fibronectin. Our findings indicate that expression of morphogenetic effectors, proliferation, and cell-type decisions during mammary organoid morphogenesis are intimately dependent on the duration of activation of MAPK{sup ERK1,2} activation.

  15. Perspectives on Exertional Rhabdomyolysis.

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

    2017-03-01

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

  16. Exertional dyspnoea in obesity

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    Vipa Bernhardt

    2016-12-01

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

  17. Exertional Rhabdomyolysis after Spinning.

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    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.

  18. Exertional Rhabdomyolysis after Spinning

    OpenAIRE

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

    2016-01-01

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

  19. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels

    2015-01-01

    to the local temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific GABAAR antagonists are essential tools for physiological and pharmacological elucidation of the different type of GABAAR inhibition. However, distinct selectivity among the receptor subtypes (populations) has been shown...... antagonists have been essential in defining the tonic current but both remaining issues concerning the GABAARs involved and the therapeutic possibilities of modulating tonic inhibition underline the need for GABAAR antagonists with improved selectivity....

  20. Distinct DNA-binding surfaces in the ATPase and linker domains of MutLγ determine its substrate specificities and exert separable functions in meiotic recombination and mismatch repair.

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    Corentin Claeys Bouuaert

    2017-05-01

    Full Text Available Mlh1-Mlh3 (MutLγ is a mismatch repair factor with a central role in formation of meiotic crossovers, presumably through resolution of double Holliday junctions. MutLγ has DNA-binding, nuclease, and ATPase activities, but how these relate to one another and to in vivo functions are unclear. Here, we combine biochemical and genetic analyses to characterize Saccharomyces cerevisiae MutLγ. Limited proteolysis and atomic force microscopy showed that purified recombinant MutLγ undergoes ATP-driven conformational changes. In vitro, MutLγ displayed separable DNA-binding activities toward Holliday junctions (HJ and, surprisingly, single-stranded DNA (ssDNA, which was not predicted from current models. MutLγ bound DNA cooperatively, could bind multiple substrates simultaneously, and formed higher-order complexes. FeBABE hydroxyl radical footprinting indicated that the DNA-binding interfaces of MutLγ for ssDNA and HJ substrates only partially overlap. Most contacts with HJ substrates were located in the linker regions of MutLγ, whereas ssDNA contacts mapped within linker regions as well as the N-terminal ATPase domains. Using yeast genetic assays for mismatch repair and meiotic recombination, we found that mutations within different DNA-binding surfaces exert separable effects in vivo. For example, mutations within the Mlh1 linker conferred little or no meiotic phenotype but led to mismatch repair deficiency. Interestingly, mutations in the N-terminal domain of Mlh1 caused a stronger meiotic defect than mlh1Δ, suggesting that the mutant proteins retain an activity that interferes with alternative recombination pathways. Furthermore, mlh3Δ caused more chromosome missegregation than mlh1Δ, whereas mlh1Δ but not mlh3Δ partially alleviated meiotic defects of msh5Δ mutants. These findings illustrate functional differences between Mlh1 and Mlh3 during meiosis and suggest that their absence impinges on chromosome segregation not only via reduced

  1. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl{sup +} K562 and Jak2(V617F){sup +} HEL Leukemia Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Axel [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany); Borghouts, Corina [Ganymed Pharmaceuticals AG, Mainz 55131 (Germany); Brendel, Christian [Boston Children’s Hospital, Division of Hematology/Oncology, Boston, MA 02115 (United States); Moriggl, Richard [Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna 1090 (Austria); Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd, E-mail: Groner@em.uni-frankfurt.de [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany)

    2015-03-19

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl{sup +} K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells

  2. ACTH antagonists

    Directory of Open Access Journals (Sweden)

    Adrian John Clark

    2016-08-01

    Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

  3. Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative

    International Nuclear Information System (INIS)

    Singh, L.; Donald, A.E.; Foster, A.C.; Hutson, P.H.; Iversen, L.L.; Iversen, S.D.; Kemp, J.A.; Leeson, P.D.; Marshall, G.R.; Oles, R.J.; Priestley, T.; Thorn, L.; Tricklebank, M.D.; Vass, C.A.; Williams, B.J.

    1990-01-01

    The antagonist effect of ±-3-amino-1-hydroxypyrrolid-2-one (HA-966) at the N-methyl-D-aspartate (NMDA) receptor occurs through a selective interaction with the glycine modulatory site within the receptor complex. When the enantiomers of ±-HA-966 were resolved, the (R)-(+)-enantiomer was found to be a selective glycine/NMDA receptor antagonist, a property that accounts for its anticonvulsant activity in vivo. In contrast, the (S)-(-)-enantiomer was only weakly active as an NMDA-receptor antagonist, but nevertheless it possessed a marked sedative and muscle relaxant action in vivo. In radioligand binding experiments, (+)-HA-966 inhibited strychnine-insensitive [ 3 H]glycine binding to rat cerebral cortex synaptic membranes with an IC 50 of 12.5 μM, whereas (-)-HA-966 had an IC 50 value of 339 μM. In mice, (+)-HA-966 antagonized sound and N-methyl-DL-aspartic acid (NMDLA)-induced seizures. The coadministration of D-serine dose-dependently antagonized the anticonvulsant effect of a submaximal dose of (+)-HA-966 against NMDLA-induced seizures. The sedative/ataxic effect of racemic HA-966 was mainly attributable to the (-)-enantiomer. It is suggested that, as in the case of the sedative γ-butyrolactone, disruption of striatal dopaminergic mechanisms may be responsible for this action

  4. When exercise causes exertional rhabdomyolysis.

    Science.gov (United States)

    Furman, Janet

    2015-04-01

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

  5. Does mental exertion alter maximal muscle activation?

    Directory of Open Access Journals (Sweden)

    Vianney eRozand

    2014-09-01

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

  6. Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms.

    Science.gov (United States)

    Achterberg, E J Marijke; Trezza, Viviana; Siviy, Stephen M; Schrama, Laurens; Schoffelmeer, Anton N M; Vanderschuren, Louk J M J

    2014-04-01

    Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems involved in reward and motivation. Interestingly, psychostimulant drugs, such as amphetamine and cocaine, profoundly suppress social play, but the neural mechanisms underlying these effects remain to be elucidated. In this study, we investigated the pharmacological underpinnings of amphetamine- and cocaine-induced suppression of social play behavior in rats. The play-suppressant effects of amphetamine were antagonized by the alpha-2 adrenoreceptor antagonist RX821002 but not by the dopamine receptor antagonist alpha-flupenthixol. Remarkably, the effects of cocaine on social play were not antagonized by alpha-2 noradrenergic, dopaminergic, or serotonergic receptor antagonists, administered either alone or in combination. The effects of a subeffective dose of cocaine were enhanced by a combination of subeffective doses of the serotonin reuptake inhibitor fluoxetine, the dopamine reuptake inhibitor GBR12909, and the noradrenaline reuptake inhibitor atomoxetine. Amphetamine, like methylphenidate, exerts its play-suppressant effect through alpha-2 noradrenergic receptors. On the other hand, cocaine reduces social play by simultaneous increases in dopamine, noradrenaline, and serotonin neurotransmission. In conclusion, psychostimulant drugs with different pharmacological profiles suppress social play behavior through distinct mechanisms. These data contribute to our understanding of the neural mechanisms of social behavior during an important developmental period, and of the deleterious effects of psychostimulant exposure thereon.

  7. Distinctive Citizenship

    DEFF Research Database (Denmark)

    Kaur, Ravinder

    2009-01-01

    The refugee, in India's Partition history, appears as an enigmatic construct - part pitiful, part heroic, though mostly shorn of agency - representing the surface of the human tragedy of Partition. Yet this archetype masks the undercurrent of social distinctions that produced hierarchies of post...

  8. 1,4,2-Benzo/pyridodithiazine 1,1-dioxides structurally related to the ATP-sensitive potassium channel openers 1,2,4-Benzo/pyridothiadiazine 1,1-dioxides exert a myorelaxant activity linked to a distinct mechanism of action.

    Science.gov (United States)

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

    2013-04-25

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

  9. Dual antagonists of integrins.

    Science.gov (United States)

    Nadrah, K; Dolenc, M Sollner

    2005-01-01

    The roles of integrins in pathologies have been studied intensively and only partially explained. This has resulted in the development of several nanomolar antagonists to certain integrins. In most cases, the aim was to produce compounds which are highly selective towards specific integrins. This paradigm has recently shifted a little. Targeting two or more integrins with one compound has become a very attractive concept, especially since it has become clear that several severe disorders, such as pathological angiogenesis, cannot be treated just with highly specific integrin antagonists. This review is aimed to elucidate some aspects regarding the design of drugs with dual activity towards integrins. Integrin structure and tissue distribution will first be described, in order to provide the basis for their functions in various pathologies which will follow. Inhibitors of several pairs of integrins will be described.

  10. Distinct neural control of intrinsic and extrinsic muscles of the hand during single finger pressing.

    Science.gov (United States)

    Dupan, Sigrid S G; Stegeman, Dick F; Maas, Huub

    2018-06-01

    Single finger force tasks lead to unintended activation of the non-instructed fingers, commonly referred to as enslaving. Both neural and mechanical factors have been associated with this absence of finger individuality. This study investigates the amplitude modulation of both intrinsic and extrinsic finger muscles during single finger isometric force tasks. Twelve participants performed single finger flexion presses at 20% of maximum voluntary contraction, while simultaneously the electromyographic activity of several intrinsic and extrinsic muscles associated with all four fingers was recorded using 8 electrode pairs in the hand and two 30-electrode grids on the lower arm. The forces exerted by each of the fingers, in both flexion and extension direction, were recorded with individual force sensors. This study shows distinct activation patterns in intrinsic and extrinsic hand muscles. Intrinsic muscles exhibited individuation, where the agonistic and antagonistic muscles associated with the instructed fingers showed the highest activation. This activation in both agonistic and antagonistic muscles appears to facilitate finger stabilisation during the isometric force task. Extrinsic muscles show an activation independent from instructed finger in both agonistic and antagonistic muscles, which appears to be associated with stabilisation of the wrist, with an additional finger-dependent modulation only present in the agonistic extrinsic muscles. These results indicate distinct muscle patterns in intrinsic and extrinsic hand muscles during single finger isometric force pressing. We conclude that the finger specific activation of intrinsic muscles is not sufficient to fully counteract enslaving caused by the broad activation of the extrinsic muscles. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Pulmonary antioxidants exert differential protective effects against ...

    Indian Academy of Sciences (India)

    Unknown

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

  12. Sevoflurane improves gaseous exchange and exerts protective ...

    African Journals Online (AJOL)

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

  13. Exertional Heat Illness and Human Gene Expression

    National Research Council Canada - National Science Library

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

    2007-01-01

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

  14. Sevoflurane improves gaseous exchange and exerts protective ...

    African Journals Online (AJOL)

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

  15. An Antagonistic Dialogue about Chaordic Systems Thinking: Part I

    Science.gov (United States)

    Wafler, Toni

    2004-01-01

    This paper explores the added value of chaordic systems Thinking for organizational renewal, which is defined as transformation instead of reformation. The exploration is presented in the form of an antagonistic dialogue between two "voices," which develop commentaries from distinct theoretical inspirations, namely chaordic systems thinking (CST)…

  16. Medicinal Chemistry of Competitive Kainate Receptor Antagonists

    Science.gov (United States)

    2010-01-01

    Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1−5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure−activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field. PMID:22778857

  17. Naloxone : actions of an antagonist

    NARCIS (Netherlands)

    Dorp, Eveline Louise Arianna van

    2009-01-01

    The opioid antagonist naloxone has a special place in pharmacology – it has no intrinsic action of its own, but it is able to save lives in the case of life threatening side-effects caused by other drugs. Naloxone is an antagonist for all opioid receptors, but most specifically for the μ-opioid

  18. Design Strategies for Balancing Exertion Games

    DEFF Research Database (Denmark)

    Jensen, Mads Møller; Grønbæk, Kaj

    2016-01-01

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

  19. Carbon adaptation influence the antagonistic ability of ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... INTRODUCTION. The use of antagonistic bacteria to control soil-borne ... plant was used to evaluate the antifungal activities of antagonistic bacteria. ..... antagonistic bacteria and cloning of its phenazine carboxylic acid genes.

  20. 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...

  1. ANTAGONISTIC POTENTIAL OF FLUORESCENT Pseudomonas ...

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    GROWTH OF TOMATO CHALLENGED WITH PHTOPATHOGENS ... This study focused on the antagonistic potential of fluorescent Pseudomonas in vitro, and its inoculation effect on growth .... the 5 days old culture in starch agar with Lugol's.

  2. Isolation of Fully Human Antagonistic RON Antibodies Showing Efficient Block of Downstream Signaling and Cell Migration1

    Science.gov (United States)

    Gunes, Zeynep; Zucconi, Adriana; Cioce, Mario; Meola, Annalisa; Pezzanera, Monica; Acali, Stefano; Zampaglione, Immacolata; De Pratti, Valeria; Bova, Luca; Talamo, Fabio; Demartis, Anna; Monaci, Paolo; La Monica, Nicola; Ciliberto, Gennaro; Vitelli, Alessandra

    2011-01-01

    RON belongs to the c-MET family of receptor tyrosine kinases. As its well-known family member MET, RON and its ligand macrophage-stimulating protein have been implicated in the progression and metastasis of tumors and have been shown to be overexpressed in cancer. We generated and tested a large number of human monoclonal antibodies (mAbs) against human RON. Our screening yielded three high-affinity antibodies that efficiently block ligand-dependent intracellular AKT and MAPK signaling. This effect correlates with the strong reduction of ligand-activated migration of T47D breast cancer cell line. By cross-competition experiments, we showed that the antagonistic antibodies fall into three distinct epitope regions of the RON extracellular Sema domain. Notably, no inhibition of tumor growth was observed in different epithelial tumor xenografts in nude mice with any of the antibodies. These results suggest that distinct properties beside ligand antagonism are required for anti-RON mAbs to exert antitumor effects in vivo. PMID:21286376

  3. Arachidonic and oleic acid exert distinct effects on the DNA methylome

    DEFF Research Database (Denmark)

    Silva-Martínez, Guillermo A.; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda

    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....... 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...

  4. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  5. Specific cerebral heat shock proteins and histamine receptor cross-talking mechanisms promote distinct lead-dependent neurotoxic responses in teleosts

    International Nuclear Information System (INIS)

    Giusi, Giuseppina; Alo, Raffaella; Crudo, Michele; Facciolo, Rosa Maria; Canonaco, Marcello

    2008-01-01

    Recent interests are beginning to be directed towards toxic neurobiological dysfunctions caused by lead (Pb) in aquatic vertebrates. In the present work, treatment with a maximum acceptable toxic concentration of this heavy metal was responsible for highly significant (p 2 R) antagonist cimetidine (Cim), as shown by the very robust (p 3 R) thioperamide (Thio), instead, blocked Pb-dependent up-regulatory trends of both chaperones in mostly hypothalamic areas. Moreover, intense neuronal damages of the above brain regions coincided with altered expressions of HSP70 and HSP90 when treated only with Cim. Overall these first results show that distinct H n R are able to exert a net neuroprotective role arising from their interaction with chaperones in fish exposed to Pb-dependent stressful conditions making this a potentially key interaction especially for T. pavo, aquatic species which plays an important ecological role towards the survival of other commercially vital fishes

  6. Traction forces exerted by epithelial cell sheets

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  7. [Leukotriene antagonists: a new approach in the treatment of asthma].

    Science.gov (United States)

    Devillier, P; Bessard, G; Advenier, C

    1997-06-01

    Inflammation plays an essential role in the genesis of airflow obstruction and bronchial hyper-reactivity in the early stages of clinical asthma. The treatment of bronchial inflammation has become an essential element in the therapeutic strategy and principally rests on inhaled glucocorticoids. Amongst a number of inflammatory mediators leukotrienes occupy a privileged place by the power of their inflammatory and constrictor effects on bronchial smooth muscles. These properties have justified the clinical development of inhibitors of their synthesis and of specific antagonists to their receptors. Leukotriene antagonists are specific for a sub type of leukotriene receptors C4, D4 and E4 which is implicated in the majority of the bronchial constrictor and inflammatory effects of leukotrienes. The antagonists of Cys-LT1 receptor but also the inhibitors of the leukotriene synthesis exert an additive bronchodilator effect to those of B2 stimulants confirming an efficacious protection vis a vis bronchial provocation tests and above all they improve the clinical scores, lung function and also enable a decrease in the consumption of beta 2 agonists. The marketing of these products represents a major event because it corresponds to the advent of a new therapeutic class. The ease of administration by the oral route, their demonstrated efficacy and their good tolerance profile (in particular for ICI 204.219, and antagonists to Cys-LT1 receptors) are elements which foresee a success for this new asthmatic treatment. However numerous studies, notably comparative studies vis a vis reference treatments will be necessary to define their place in the strategic approach to the treatment of asthma.

  8. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  10. Quantum Distinction: Quantum Distinctiones!

    OpenAIRE

    Zeps, Dainis

    2009-01-01

    10 pages; How many distinctions, in Latin, quantum distinctiones. We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking) should be equated with subject of physics (that of nature). For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinct...

  11. Muscarinic Receptor Agonists and Antagonists

    Directory of Open Access Journals (Sweden)

    David R. Kelly

    2001-02-01

    Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

  12. Antagonistic neural networks underlying differentiated leadership roles

    Science.gov (United States)

    Boyatzis, Richard E.; Rochford, Kylie; Jack, Anthony I.

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks – the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success. PMID:24624074

  13. Antagonistic Neural Networks Underlying Differentiated Leadership Roles

    Directory of Open Access Journals (Sweden)

    Richard Eleftherios Boyatzis

    2014-03-01

    Full Text Available The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950’s. Recent research in neuroscience suggests that the division between task oriented and socio-emotional oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks -- the Task Positive Network (TPN and the Default Mode Network (DMN. Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  14. Antagonistic neural networks underlying differentiated leadership roles.

    Science.gov (United States)

    Boyatzis, Richard E; Rochford, Kylie; Jack, Anthony I

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks - the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  15. Effects of TNF antagonists on immune and neuroendocrine system

    Directory of Open Access Journals (Sweden)

    M. Cutolo

    2011-09-01

    Full Text Available In the article, the literature on the effects of TNFa-antagonists (etanercept, infliximab and adalimumab on the immune system is reviewed. These biologic agents are employed in chronic inflammatory diseases such as rheumatoid arthritis, seronegative spondyloarthritides, as well as psoriasis and Crohn’s disease. The differences of these drugs, testified by the different effects on the immune response, are discussed. These molecules exert their effect through cytokine inhibition, but they present striking differences since they can modulate macrophage activity, T cells apoptosis, leukocyte migration, and angiogenesis to a different degree. Some studies showed that these agents also affect the hypothalamo- pituitary-adrenal axis. The potential immunogenicity of these biologic agents is also discussed.

  16. Antidepressant activity of the adenosine A2A receptor antagonist, istradefylline (KW-6002) on learned helplessness in rats.

    Science.gov (United States)

    Yamada, Koji; Kobayashi, Minoru; Shiozaki, Shizuo; Ohta, Teruko; Mori, Akihisa; Jenner, Peter; Kanda, Tomoyuki

    2014-07-01

    Istradefylline, an adenosine A2A receptor antagonist, improves motor function in animal models of Parkinson's disease (PD) and in patients with PD. In addition, some A2A antagonists exert antidepressant-like activity in rodent models of depression, such as the forced swim and the tail suspension tests. We have investigated the effect of istradefylline on depression-like behaviors using the rat learned helplessness (LH) model. Acute, as well as chronic, oral administration of istradefylline significantly improved the inescapable shock (IES)-induced escape deficit with a degree of efficacy comparable to chronic treatment with the tricyclic antidepressant desipramine and the selective serotonin (5-HT) reuptake inhibitor, fluoxetine. Both the A1/A2A receptor nonspecific antagonist theophylline and the moderately selective antagonist CGS15943, but not the A1 selective antagonist DPCPX, ameliorated the IES-induced escape deficit. The enhancement of escape response by istradefylline was reversed by a local injection of the A2A specific agonist CGS21680 either into the nucleus accumbens, the caudate-putamen, or the paraventricular nucleus of the hypothalamus, but not by the A1 specific agonist R-PIA into the nucleus accumbens. Moreover, neither the 5-HT2A/2C receptor antagonist methysergide or the adrenergic α 2 antagonist yohimbine, nor the β-adrenergic antagonist propranolol, affected the improvement of escape response induced by istradefylline. Istradefylline exerts antidepressant-like effects via modulation of A2A receptor activity which is independent of monoaminergic transmission in the brain. Istradefylline may represent a novel treatment option for depression in PD as well as for the motor symptoms.

  17. Picrotoxin-induced seizures modified by morphine and opiate antagonists.

    Science.gov (United States)

    Thomas, J; Nores, W L; Kenigs, V; Olson, G A; Olson, R D

    1993-07-01

    The effects of naloxone, Tyr-MIF-1, and MIF-1 on morphine-mediated changes in susceptibility to picrotoxin-induced seizures were studied. Rats were pretreated with naloxone, MIF-1, Tyr-MIF-1, or saline. At 15-min intervals, they received a second pretreatment of morphine or saline and then were tested for seizures following a convulsant dose of picrotoxin. Several parameters of specific categories of seizures were scored. Morphine increased the number of focal seizure episodes, duration of postseizure akinesis, and incidence of generalized clonic seizures. Naloxone tended to block the morphine-mediated changes in susceptibility. Tyr-MIF-1 had effects similar to naloxone on duration of postseizure immobility but tended to potentiate the effects of morphine on focal seizure episodes. The effects of morphine and the opiate antagonists on focal seizure episodes and postseizure duration suggest the general involvement of several types of opiate receptors in these picrotoxin-induced behaviors. However, the observation of antagonistic effects for Tyr-MIF-1 on immobility but agonistic effects for focal seizures suggests that the type of effect exerted by opiate agents may depend upon other neuronal variables.

  18. Discovery and mapping of an intracellular antagonist binding site at the chemokine receptor CCR2

    DEFF Research Database (Denmark)

    Zweemer, Annelien J M; Bunnik, Julia; Veenhuizen, Margo

    2014-01-01

    be divided into two groups with most likely two topographically distinct binding sites. The aim of the current study was to identify the binding site of one such group of ligands, exemplified by three allosteric antagonists, CCR2-RA-[R], JNJ-27141491, and SD-24. We first used a chimeric CCR2/CCR5 receptor...

  19. Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes

    Science.gov (United States)

    Block, Linda; Jörneberg, Per; Björklund, Ulrika; Westerlund, Anna; Biber, Björn; Hansson, Elisabeth

    2013-01-01

    Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na+ channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, bupivacaine exerts an influence on the Ca2+ signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca2+ signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist. PMID:24083665

  20. Interleukin-1 antagonists for diabetes

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, Thomas

    2013-01-01

    pathways. The testing of specific anti-inflammatory biologics targeting single pro-inflammatory cytokines has provided clinical proof-of-concept. EXPERT OPINION: IL-1 antagonists have so far failed to meet primary end points in recent-onset type 1 diabetes in Phase IIa, and promising Phase I and IIa trials......INTRODUCTION: Diabetes is a currently incurable, epidemically growing global health concern. Contemporary symptomatic treatment targets acute and chronic metabolic consequences of relative or absolute insulin deficiency. Intensive multifactorial therapy is required to attenuate morbidity...... and mortality from late micro- and macrovascular complications, and despite current best clinical practice diabetes is still associated with shortened lifespan. There is an unmet need for interventions targeting pathogenetic mechanisms in diabetes, and the market for such therapies is huge. AREAS COVERED...

  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. 20 CFR 404.1567 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

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

  3. 20 CFR 416.967 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Exertional headache and coronary ischemia despite normal electrocardiographic stress testing.

    Science.gov (United States)

    Cutrer, F Michael; Huerter, Karina

    2006-01-01

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

  6. Antagonistic Phenomena in Network Dynamics

    Science.gov (United States)

    Motter, Adilson E.; Timme, Marc

    2018-03-01

    Recent research on the network modeling of complex systems has led to a convenient representation of numerous natural, social, and engineered systems that are now recognized as networks of interacting parts. Such systems can exhibit a wealth of phenomena that not only cannot be anticipated from merely examining their parts, as per the textbook definition of complexity, but also challenge intuition even when considered in the context of what is now known in network science. Here, we review the recent literature on two major classes of such phenomena that have far-reaching implications: (a) antagonistic responses to changes of states or parameters and (b) coexistence of seemingly incongruous behaviors or properties - both deriving from the collective and inherently decentralized nature of the dynamics. They include effects as diverse as negative compressibility in engineered materials, rescue interactions in biological networks, negative resistance in fluid networks, and the Braess paradox occurring across transport and supply networks. They also include remote synchronization, chimera states, and the converse of symmetry breaking in brain, power-grid, and oscillator networks as well as remote control in biological and bioinspired systems. By offering a unified view of these various scenarios, we suggest that they are representative of a yet broader class of unprecedented network phenomena that ought to be revealed and explained by future research.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  8. Structural determinants for antagonist pharmacology that distinguish the rho1 GABAC receptor from GABAA receptors.

    Science.gov (United States)

    Zhang, Jianliang; Xue, Fenqin; Chang, Yongchang

    2008-10-01

    GABA receptor (GABAR) types C (GABACR) and A (GABAAR) are both GABA-gated chloride channels that are distinguished by their distinct competitive antagonist properties. The structural mechanism underlying these distinct properties is not well understood. In this study, using previously identified binding residues as a guide, we made individual or combined mutations of nine binding residues in the rho1 GABACR subunit to their counterparts in the alpha1beta2gamma2 GABAAR or reverse mutations in alpha1 or beta2 subunits. The mutants were expressed in Xenopus laevis oocytes and tested for sensitivities of GABA-induced currents to the GABAA and GABAC receptor antagonists. The results revealed that bicuculline insensitivity of the rho1 GABACR was mainly determined by Tyr106, Phe138 and Phe240 residues. Gabazine insensitivity of the rho1 GABACR was highly dependent on Tyr102, Tyr106, and Phe138. The sensitivity of the rho1 GABACR to 3-aminopropyl-phosphonic acid and its analog 3-aminopropyl-(methyl)phosphinic acid mainly depended on residues Tyr102, Val140, FYS240-242, and Phe138. Thus, the residues Tyr102, Tyr106, Phe138, and Phe240 in the rho1 GABACR are major determinants for its antagonist properties distinct from those in the GABAAR. In addition, Val140 in the GABACR contributes to 3-APA binding. In conclusion, we have identified the key structural elements underlying distinct antagonist properties for the GABACR. The mechanistic insights were further extended and discussed in the context of antagonists docking to the homology models of GABAA or GABAC receptors.

  9. Microbial Herd Protection Mediated by Antagonistic Interaction in Polymicrobial Communities

    Science.gov (United States)

    Wong, Megan J. Q.; Liang, Xiaoye; Smart, Matt; Tang, Le; Moore, Richard; Ingalls, Brian

    2016-01-01

    ABSTRACT In host and natural environments, microbes often exist in complex multispecies communities. The molecular mechanisms through which such communities develop and persist, despite significant antagonistic interactions between species, are not well understood. The type VI secretion system (T6SS) is a lethal weapon commonly employed by Gram-negative bacteria to inhibit neighboring species through the delivery of toxic effectors. It is well established that intraspecies protection is conferred by immunity proteins that neutralize effector toxicities. In contrast, the mechanisms for interspecies protection are not clear. Here we use two T6SS-active antagonistic bacterial species, Aeromonas hydrophila and Vibrio cholerae, to demonstrate that interspecies protection is dependent on effectors. A. hydrophila and V. cholerae do not share conserved immunity genes but could coexist equally in a mixture. However, mutants lacking the T6SS or effectors were effectively eliminated by the competing wild-type strain. Time-lapse microscopic analyses showed that mutually lethal interactions drive the segregation of mixed species into distinct single-species clusters by eliminating interspersed single cells. Cluster formation provides herd protection by abolishing lethal interactions inside each cluster and restricting the interactions to the boundary. Using an agent-based modeling approach, we simulated the antagonistic interactions of two hypothetical species. The resulting simulations recapitulated our experimental observations. These results provide mechanistic insights regarding the general role of microbial weapons in determining the structures of complex multispecies communities. IMPORTANCE Investigating the warfare of microbes allows us to better understand the ecological relationships in complex microbial communities such as the human microbiota. Here we use the T6SS, a deadly bacterial weapon, as a model to demonstrate the importance of lethal interactions in

  10. Microbial herd protection mediated by antagonistic interaction in polymicrobial communities.

    Science.gov (United States)

    Wong, Megan; Liang, Xiaoye; Smart, Matt; Tang, Le; Moore, Richard; Ingalls, Brian; Dong, Tao G

    2016-09-16

    In the host and natural environments, microbes often exist in complex multispecies communities. The molecular mechanisms through which such communities develop and persist - despite significant antagonistic interactions between species - are not well understood. The type VI secretion system (T6SS) is a lethal weapon commonly employed by Gram-negative bacteria to inhibit neighboring species through delivery of toxic effectors. It is well established that intra-species protection is conferred by immunity proteins that neutralize effector toxicities. By contrast, the mechanisms for interspecies protection are not clear. Here we use two T6SS active antagonistic bacteria, Aeromonas hydrophila (AH) and Vibrio cholerae (VC), to demonstrate that interspecies protection is dependent on effectors. AH and VC do not share conserved immunity genes but could equally co-exist in a mixture. However, mutants lacking the T6SS or effectors were effectively eliminated by the other competing wild type. Time-lapse microscopy analyses show that mutually lethal interactions drive the segregation of mixed species into distinct single-species clusters by eliminating interspersed single cells. Cluster formation provides herd protection by abolishing lethal interaction inside each cluster and restricting it to the boundary. Using an agent-based modeling approach, we simulated the antagonistic interactions of two hypothetical species. The resulting simulations recapitulate our experimental observation. These results provide mechanistic insights for the general role of microbial weapons in determining the structures of complex multispecies communities. Investigating the warfare of microbes allows us to better understand the ecological relationships in complex microbial communities such as the human microbiota. Here we use the T6SS, a deadly bacterial weapon, as a model to demonstrate the importance of lethal interactions in determining community structures and exchange of genetic materials

  11. Do placebo expectations influence perceived exertion during physical exercise?

    Directory of Open Access Journals (Sweden)

    Hendrik Mothes

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

  12. 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.

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

    Science.gov (United States)

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

    2016-09-01

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

  14. Calcium antagonists for aneurysmal subarachnoid haemorrhage

    NARCIS (Netherlands)

    Dorhout Mees, S. M.; Rinkel, G. J. E.; Feigin, V. L.; Algra, A.; van den Bergh, W. M.; Vermeulen, M.; van Gijn, J.

    2007-01-01

    BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm probably is a contributing factor. Experimental studies have suggested that calcium antagonists can prevent or reverse

  15. Functional antagonistic properties of clozapine at the 5-HT3 receptor.

    Science.gov (United States)

    Hermann, B; Wetzel, C H; Pestel, E; Zieglgänsberger, W; Holsboer, F; Rupprecht, R

    1996-08-23

    The atypical neuroleptic clozapine is thought to exert its psychopharmacological actions through a variety of neurotransmitter receptors. It binds preferentially to D4 and 5-HT2 receptors; however, little is known on it's interaction with the 5-HT3 receptor. Using a cell line stably expressing the 5-HT3 receptor, whole-cell voltage-clamp analysis revealed functional antagonistic properties of clozapine at low nanomolar concentrations in view of a binding affinity in the upper nanomolar range. Because the concentration of clozapine required for an interaction with the 5-HT3 receptor can be achieved with therapeutical doses, functional antagonistic properties at this ligand-gated ion channel may contribute to its unique psychopharmacological profile.

  16. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  17. MIBE acts as antagonist ligand of both estrogen receptor α and GPER in breast cancer cells.

    Science.gov (United States)

    Lappano, Rosamaria; Santolla, Maria Francesca; Pupo, Marco; Sinicropi, Maria Stefania; Caruso, Anna; Rosano, Camillo; Maggiolini, Marcello

    2012-01-17

    The multiple biological responses to estrogens are mainly mediated by the classical estrogen receptors ERα and ERβ, which act as ligand-activated transcription factors. ERα exerts a main role in the development of breast cancer; therefore, the ER antagonist tamoxifen has been widely used although its effectiveness is limited by de novo and acquired resistance. Recently, GPR30/GPER, a member of the seven-transmembrane G protein-coupled receptor family, has been implicated in mediating the effects of estrogens in various normal and cancer cells. In particular, GPER triggered gene expression and proliferative responses induced by estrogens and even ER antagonists in hormone-sensitive tumor cells. Likewise, additional ER ligands showed the ability to bind to GPER eliciting promiscuous and, in some cases, opposite actions through the two receptors. We synthesized a novel compound (ethyl 3-[5-(2-ethoxycarbonyl-1-methylvinyloxy)-1-methyl-1H-indol-3-yl]but-2-enoate), referred to as MIBE, and investigated its properties elicited through ERα and GPER in breast cancer cells. Molecular modeling, binding experiments and functional assays were performed in order to evaluate the biological action exerted by MIBE through ERα and GPER in MCF7 and SkBr3 breast cancer cells. MIBE displayed the ability to act as an antagonist ligand for ERα and GPER as it elicited inhibitory effects on gene transcription and growth effects by binding to both receptors in breast cancer cells. Moreover, GPER was required for epidermal growth factor receptor (EGFR) and ERK activation by EGF as ascertained by using MIBE and performing gene silencing experiments. Our findings provide novel insights on the functional cross-talk between GPER and EGFR signaling. Furthermore, the exclusive antagonistic activity exerted by MIBE on ERα and GPER could represent an innovative pharmacological approach targeting breast carcinomas which express one or both receptors at the beginning and/or during tumor

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Viability of D283 medulloblastoma cells treated with a histone deacetylase inhibitor combined with bombesin receptor antagonists.

    Science.gov (United States)

    Jaeger, Mariane; Ghisleni, Eduarda C; Fratini, Lívia; Brunetto, Algemir L; Gregianin, Lauro José; Brunetto, André T; Schwartsmann, Gilberto; de Farias, Caroline B; Roesler, Rafael

    2016-01-01

    Medulloblastoma (MB) comprises four distinct molecular subgroups, and survival remains particularly poor in patients with Group 3 tumors. Mutations and copy number variations result in altered epigenetic regulation of gene expression in Group 3 MB. Histone deacetylase inhibitors (HDACi) reduce proliferation, promote cell death and neuronal differentiation, and increase sensitivity to radiation and chemotherapy in experimental MB. Bombesin receptor antagonists potentiate the antiproliferative effects of HDACi in lung cancer cells and show promise as experimental therapies for several human cancers. Here, we examined the viability of D283 cells, which belong to Group 3 MB, treated with an HDACi alone or combined with bombesin receptor antagonists. D283 MB cells were treated with different doses of the HDACi sodium butyrate (NaB), the neuromedin B receptor (NMBR) antagonist BIM-23127, the gastrin releasing peptide receptor (GRPR) antagonist RC-3095, or combinations of NaB with each receptor antagonist. Cell viability was examined by cell counting. NaB alone or combined with receptor antagonists reduced cell viability at all doses tested. BIM-23127 alone did not affect cell viability, whereas RC-3095 at an intermediate dose significantly increased cell number. Although HDACi are promising agents to inhibit MB growth, the present results provide preliminary evidence that combining HDACi with bombesin receptor antagonists is not an effective strategy to improve the effects of HDACi against MB cells.

  1. Factors associated with high physical exertion during manual lifting

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  2. NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.

    Science.gov (United States)

    Moore, N A; Blackman, A; Awere, S; Leander, J D

    1993-06-11

    In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.

  3. Influence of permittivity on gradient force exerted on Mie spheres.

    Science.gov (United States)

    Chen, Jun; Li, Kaikai; Li, Xiao

    2018-04-01

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

  4. Exertional Heat Illness among Secondary School Athletes: Statewide Policy Implications

    Science.gov (United States)

    Rodgers, Jill; Slota, Peggy; Zamboni, Beth

    2018-01-01

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

  5. 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...

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2015-06-01

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

  8. Forces exerted by jumping children: A pilot study

    NARCIS (Netherlands)

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

    1998-01-01

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

  9. Mind the gap : probing exertion experience with experiential design landscapes

    NARCIS (Netherlands)

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

    2016-01-01

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

  10. 20 CFR 220.132 - Physical exertion requirements.

    Science.gov (United States)

    2010-04-01

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

  11. Behavioral Effects of Systemic, Infralimbic and Prelimbic Injections of a Serotonin 5-HT2A Antagonist in Carioca High- and Low-Conditioned Freezing Rats

    Directory of Open Access Journals (Sweden)

    Laura A. León

    2017-07-01

    Full Text Available The role of serotonin (5-hydroxytryptamine [5-HT] and 5-HT2A receptors in anxiety has been extensively studied, mostly without considering individual differences in trait anxiety. Our laboratory developed two lines of animals that are bred for high and low freezing responses to contextual cues that are previously associated with footshock (Carioca High-conditioned Freezing [CHF] and Carioca Low-conditioned Freezing [CLF]. The present study investigated whether ketanserin, a preferential 5-HT2A receptor blocker, exerts distinct anxiety-like profiles in these two lines of animals. In the first experiment, the animals received a systemic injection of ketanserin and were exposed to the elevated plus maze (EPM. In the second experiment, these two lines of animals received microinjections of ketanserin in the infralimbic (IL and prelimbic (PL cortices and were exposed to either the EPM or a contextual fear conditioning paradigm. The two rat lines exhibited bidirectional effects on anxiety-like behavior in the EPM and opposite responses to ketanserin. Both systemic and intra-IL cortex injections of ketanserin exerted anxiolytic-like effects in CHF rats but anxiogenic-like effects in CLF rats. Microinjections of ketanserin in the PL cortex also exerted anxiolytic-like effects in CHF rats but had no effect in CLF rats. These results suggest that the behavioral effects of 5-HT2A receptor antagonism might depend on genetic variability associated with baseline reactions to threatening situations and 5-HT2A receptor expression in the IL and PL cortices.Highlights-CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.-CHF rats have a more “anxious” phenotype than CLF rats in the EPM.-The 5-HT2A receptor antagonist ketanserin had opposite behavioral effects in CHF and CLF rats.-Systemic and IL injections either decreased (CHF or increased (CLF anxiety-like behavior.-PL injections either decreased (CHF anxiety

  12. Antagonistic properties of microogranisms associated with cassava ...

    African Journals Online (AJOL)

    The antagonistic properties of indigenous microflora from cassava starch, flour and grated cassava were investigated using the conventional streak, novel ring and well diffusion methods. Antagonism was measured by zone of inhibition between the fungal plug and bacterial streak/ring. Bacillus species were more effective ...

  13. Carbon adaptation influence the antagonistic ability of ...

    African Journals Online (AJOL)

    Influences of carbon adaptation on antagonistic activities of three Pseudomonas aeruginosa strains V4, V7 and V10 against Fusarium oxysporum f. sp. melonis were determined in this study. Results from this study showed that the P. aeruginosa strains and their adapted strains significantly inhibited the growth of mycelium ...

  14. Small molecule antagonists of integrin receptors.

    Science.gov (United States)

    Perdih, A; Dolenc, M Sollner

    2010-01-01

    The complex and widespread family of integrin receptors is involved in numerous physiological processes, such as tissue remodeling, angiogenesis, development of the immune response and homeostasis. In addition, their key role has been elucidated in important pathological disorders such as cancer, cardiovascular diseases, osteoporosis, autoimmune and inflammatory diseases and in the pathogenesis of infectious diseases, making them highly important targets for modern drug design campaigns. In this review we seek to present a concise overview of the small molecule antagonists of this diverse and highly complex receptor family. Integrin antagonists are classified according to the targeted integrin receptor and are discussed in four sections. First we present the fibrinogen alpha(IIb)beta3 and the vitronectin alpha (V)beta(3) receptor antagonists. The remaining selective integrin antagonists are examined in the third section. The final section is dedicated to molecules with dual or multiple integrin activity. In addition, the use of antibodies and peptidomimetic approaches to modulate the integrin receptors are discussed, as well providing the reader with an overall appreciation of the field.

  15. Pharmacology of JB-9315, a new selective histamine H2-receptor antagonist.

    Science.gov (United States)

    Palacios, B; Montero, M J; Sevilla, M A; San Román, L

    1998-02-01

    1. The histamine H2-receptor antagonistic activity and antisecretory and antiulcer effects of JB-9315 were studied in comparison with the standard H2 blocker ranitidine. 2. In vitro, JB-9315 is a competitive antagonist of histamine H2 receptors in the isolated, spontaneously beating guinea-pig right atrium, with a pA2 value of 7.30 relative to a value of 7.36 for ranitidine. JB-9315 was specific for the histamine H2 receptor because, at high concentration, it did not affect histamine- or acetylcholine-induced contractions in guinea-pig isolated ileum or rat isolated duodenum, respectively. 3. JB-9315 dose dependently inhibited histamine-, pentagastrin- or carbachol-stimulated acid secretion and basal secretion in the perfused stomach preparation of the anesthetized rat. In the pylorus-ligated rat after intraperitoneal administration, total acid output over 4 h was inhibited by JB-9315 with an ID50 of 32.8 mg/kg, confirming its H2-receptor antagonist properties. 4. JB-9315 showed antiulcer activity against cold stress plus indomethacin-induced lesions with an ID50 of 6.8 mg/kg. 5. JB-9315, 50 and 100 mg/kg, inhibited macroscopic gastric hemorrhagic lesions induced by ethanol. In contrast, ranitidine (50 mg/kg) failed to reduce these lesions. 6. These results indicate that JB-9315 is a new antiulcer drug that exerts a cytoprotective effect in addition to its gastric antisecretory activity.

  16. Touch communicates distinct emotions.

    Science.gov (United States)

    Hertenstein, Matthew J; Keltner, Dacher; App, Betsy; Bulleit, Brittany A; Jaskolka, Ariane R

    2006-08-01

    The study of emotional signaling has focused almost exclusively on the face and voice. In 2 studies, the authors investigated whether people can identify emotions from the experience of being touched by a stranger on the arm (without seeing the touch). In the 3rd study, they investigated whether observers can identify emotions from watching someone being touched on the arm. Two kinds of evidence suggest that humans can communicate numerous emotions with touch. First, participants in the United States (Study 1) and Spain (Study 2) could decode anger, fear, disgust, love, gratitude, and sympathy via touch at much-better-than-chance levels. Second, fine-grained coding documented specific touch behaviors associated with different emotions. In Study 3, the authors provide evidence that participants can accurately decode distinct emotions by merely watching others communicate via touch. The findings are discussed in terms of their contributions to affective science and the evolution of altruism and cooperation. (c) 2006 APA, all rights reserved

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

    Science.gov (United States)

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

    1992-11-01

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

  18. Pressure exerted by a vesicle on a surface

    International Nuclear Information System (INIS)

    Owczarek, A L; Prellberg, T

    2014-01-01

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

  19. antagonistic effect of native bacillus isolates against black root rot

    African Journals Online (AJOL)

    ACSS

    A number of fungi and bacteria are known to be very effective .... Round. Convex. Smooth. Wrinkled. Slow. BS024. Irregular and spreading. Flat. Wavy .... Antibiotic effect of bacterial antagonist ..... antagonistic Bacillus and Trichoderma isolates ...

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

    Science.gov (United States)

    Colman, Gregory; Dave, Dhaval

    2013-09-01

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

  1. Highly potent antagonists of luteinizing hormone-releasing hormone free of edematogenic effects.

    Science.gov (United States)

    Bajusz, S; Kovacs, M; Gazdag, M; Bokser, L; Karashima, T; Csernus, V J; Janaky, T; Guoth, J; Schally, A V

    1988-03-01

    To eliminate the undesirable edematogenic effect of the luteinizing hormone-releasing hormone (LH-RH) antagonists containing basic D amino acids at position 6, exemplified by [Ac-D-Phe(pCl)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH [Phe(pCl) indicates 4-chlorophenylalanine], analogs with D-ureidoalkyl amino acids such as D-citrulline (D-Cit) or D-homocitrulline (D-Hci) at position 6 were synthesized and tested in several systems in vitro and in vivo. HPLC analysis revealed that the overall hydrophobicity of the D-Cit/D-Hci6 analogs was similar to that of the basic D-Arg6 antagonists. In vitro, most of the analogs completely inhibited LH-RH-mediated luteinizing hormone release in perfused rat pituitary cell systems at an antagonist to LH-RH molar ratio of 5:1. In vivo, the most active peptides, [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Trp3,D-Cit6,D-Ala10]LH-RH [Nal(2) indicates 3-(2-naphthyl)alanine] and its D-Hci6 analog, caused 100% inhibition of ovulation in cycling rats in doses of 3 micrograms and suppressed the luteinizing hormone level in ovariectomized female rats for 47 hr when administered at doses of 25 micrograms. Characteristically, these peptides did not exert any edematogenic effects even at 1.5 mg/kg. These properties of the D-Cit/D-Hci6 antagonists may make them useful clinically.

  2. Antagonist targeting microRNA-155 protects against lithium-pilocarpine-induced status epilepticus in C57BL/6 mice by activating brain-derived neurotrophic factor

    Directory of Open Access Journals (Sweden)

    Zhengxu eCai

    2016-05-01

    Full Text Available Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155 could serve as a promising treatment of mesial temporal lobe epilepsy (MTLE. In the current study, the therapeutic potential of miR-155 antagonist against TLE was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG recordings. The expression of brain-derived neurotrophic factor (BDNF and its association with miR-155 were also assessed with a series of experiments. Our results showed that level of miR-155 was significantly up-regulated after induction of TLE model. Based on the results of EEG and behavior analyses, seizures in mice were alleviated by miR-155 antagonist. Moreover, administration of miR-155 antagonist also significantly increased the level of BDNF. The results of dual luciferase assay and western blotting showed that miR-155 antagonist exerted its action on status epilepticus by directly regulating the activity of BDNF. Taken all the information together, our results demonstrated that miR-155 antagonist might firstly induce the expression of BDNF, which then contributed to the alleviation of epilepsy in the current study.

  3. Antagonistic parent-offspring co-adaptation.

    Directory of Open Access Journals (Sweden)

    Mathias Kölliker

    2010-01-01

    Full Text Available In species across taxa, offspring have means to influence parental investment (PI. PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear.In contrast to previous theory that largely uses a static approach to predict how "offspring individuals" and "parental individuals" should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents.We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.

  4. Pharmacological analysis of calcium antagonist receptors

    International Nuclear Information System (INIS)

    Reynolds, I.J.

    1987-01-01

    This work focuses on two aspects of the action of calcium antagonist drugs, namely, the interaction of drugs with receptors for verapamil-like calcium antagonists, and the interactions of drugs with voltage-sensitive calcium fluxes in rat brain synaptosomes. From binding studies I have found that the ligand of choice for labeling the verapamil receptor is (-)[ 3 H]desmethoxy-verapamil. This drug labels potently, reversibly and stereoselectively two receptors in membranes prepared from rat brain and rabbit skeletal muscle tissues. In equilibrium studies dihydropyridine calcium antagonists interact in a non-competitive fashion, while many non-DHPs are apparently competitive. In-depth kinetic studies in skeletal muscle membranes indicate that the two receptors are linked in a negative heterotropic fashion, and that low-affinity binding of (-) [ 3 H]desmethoxy-verapamil may be to the diltiazem receptor. However, these studies were not able to distinguish between the hypothesis that diltiazem binds to spatially separate, allosterically coupled receptors, and the hypothesis that diltiazem binds to a subsite of the verapamil receptor

  5. Measurements of the Exerted Pressure by Pelvic Circumferential Compression Devices

    Science.gov (United States)

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

    2010-01-01

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

  6. The effects of superset configuration on kinetic, kinematic, and perceived exertion in the barbell bench press.

    Science.gov (United States)

    Weakley, Jonathon Js; Till, Kevin; Read, Dale B; Phibbs, Padraic J; Roe, Gregory; Darrall-Jones, Joshua; Jones, Ben L

    2017-08-04

    Training that is efficient and effective is of great importance to an athlete. One method of improving efficiency is by incorporating supersets into resistance training routines. However, the structuring of supersets is still unexplored. Therefore, the purpose of this study was to assess the effects of agonist-antagonist (A-A), alternate peripheral (A-P), and similar biomechanical (SB) superset configurations on rate of perceived exertion (RPE), kinetic and kinematic changes during the bench press. 10 subjects performed resistance training protocols in a randomized-crossover design, with magnitude-based inferences assessing changes/differences within and between protocols. Changes in RPE were very likely and almost certainly greater in the A-P and SB protocols when compared with the A-A, while all superset protocols had very likely to almost certain reductions in mean velocity and power from baseline. Reductions in mean velocity and power were almost certainly greater in the SB protocol, with differences between the A-A and A-P protocols being unclear. Decreases in peak force were likely and almost certain in the A-A and SB protocols respectively, with changes in A-P being unclear. Differences between these protocols showed likely greater decreases in SB peak forces when compared to A-A, with all other superset comparisons being unclear. This study demonstrates the importance of exercise selection when incorporating supersets into a training routine. It is suggested that the practitioner uses A-A supersets when aiming to improve training efficiency and minimize reductions in kinetic and kinematic output of the agonist musculature while completing the barbell bench press.

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

    Science.gov (United States)

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

    2017-01-01

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

  8. The pressure exerted by a confined ideal gas

    International Nuclear Information System (INIS)

    Pang Hai; Dai Wusheng; Xie Mi

    2011-01-01

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

  9. Leg 201Tl-SPECT in chronic exertional compartment syndrome

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  10. 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.

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

    Science.gov (United States)

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

    2015-09-01

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

  12. Combination decongestion therapy in hospitalized heart failure: loop diuretics, mineralocorticoid receptor antagonists and vasopressin antagonists.

    Science.gov (United States)

    Vaduganathan, Muthiah; Mentz, Robert J; Greene, Stephen J; Senni, Michele; Sato, Naoki; Nodari, Savina; Butler, Javed; Gheorghiade, Mihai

    2015-01-01

    Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.

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

    Directory of Open Access Journals (Sweden)

    Juan Del Coso

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

  14. Antagonist effects of calcium on borosilicate glass alteration

    Energy Technology Data Exchange (ETDEWEB)

    Mercado-Depierre, S. [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France); Angeli, F., E-mail: frederic.angeli@cea.fr [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France); Frizon, F. [CEA Marcoule, DTCD SECM LP2C, 30207 Bagnols sur Cèze (France); Gin, S. [CEA Marcoule, DTCD SPDE LCLT, 30207 Bagnols sur Cèze (France)

    2013-10-15

    Graphical abstract: Display Omitted -- Highlights: •Kinetic study of glass alteration is investigated in calcium-enriched solutions. •New insights into silicon–calcium interactions in glass/cement systems are proposed. •Glass alteration is controlled by pH, Ca concentration and reaction progress. •Evidence of antagonist effects according to the importance of these parameters. -- Abstract: Numerous studies have been conducted on glass and cement durability in contact with water, but very little work to date has focused directly on interactions between the two materials. These interactions are mostly controlled by silicon–calcium reactivity. However, the physical and chemical processes involved remain insufficiently understood to predict the evolution of coupled glass–cement systems used in several industrial applications. Results are reported from borosilicate glass alteration in calcium-rich solutions. Our data show that four distinct behaviors can be expected according to the relative importance of three key parameters: the pH, the reaction progress (short- or long-term alteration) and the calcium concentration. Glass alteration is thus controlled by specific mechanisms depending on the solution chemistry: calcium complexation at the glass surface, precipitation of calcium silicate hydrates (C–S–H) or calcium incorporation in the altered layer. These findings highlight the impact of silicon–calcium interactions on glass durability and open the way for a better understanding of glass–cement mixing in civil engineering applications as well as in nuclear waste storage.

  15. Antagonist effects of calcium on borosilicate glass alteration

    International Nuclear Information System (INIS)

    Mercado-Depierre, S.; Angeli, F.; Frizon, F.; Gin, S.

    2013-01-01

    Graphical abstract: Display Omitted -- Highlights: •Kinetic study of glass alteration is investigated in calcium-enriched solutions. •New insights into silicon–calcium interactions in glass/cement systems are proposed. •Glass alteration is controlled by pH, Ca concentration and reaction progress. •Evidence of antagonist effects according to the importance of these parameters. -- Abstract: Numerous studies have been conducted on glass and cement durability in contact with water, but very little work to date has focused directly on interactions between the two materials. These interactions are mostly controlled by silicon–calcium reactivity. However, the physical and chemical processes involved remain insufficiently understood to predict the evolution of coupled glass–cement systems used in several industrial applications. Results are reported from borosilicate glass alteration in calcium-rich solutions. Our data show that four distinct behaviors can be expected according to the relative importance of three key parameters: the pH, the reaction progress (short- or long-term alteration) and the calcium concentration. Glass alteration is thus controlled by specific mechanisms depending on the solution chemistry: calcium complexation at the glass surface, precipitation of calcium silicate hydrates (C–S–H) or calcium incorporation in the altered layer. These findings highlight the impact of silicon–calcium interactions on glass durability and open the way for a better understanding of glass–cement mixing in civil engineering applications as well as in nuclear waste storage

  16. Dopamine receptors play distinct roles in sexual behavior expression of rats with a different sexual motivational tone.

    Science.gov (United States)

    Guadarrama-Bazante, Irma L; Canseco-Alba, Ana; Rodríguez-Manzo, Gabriela

    2014-10-01

    Dopamine (DA) plays a central role in the expression of male sexual behavior. The effects of DA-enhancing drugs on copulation seem to vary depending on the dose of the agonist used, the type of DA receptor activated, and the sexual condition of the animals. The aim of the present study was to carry out a systematic analysis of the effects of dopaminergic agonists on the expression of male sexual behavior by sexually competent rats in different sexual motivational states, that is when sexually active (sexually experienced) and when temporarily inhibited (sexually exhausted). To this end, the same doses of the nonselective DA receptor agonist apomorphine, the selective D2-like DA receptor agonist quinpirole, and the selective D1-like DA receptor agonist SKF38393 were injected intraperitoneally to sexually experienced or sexually exhausted male rats and their sexual behavior was recorded. Low apomorphine doses induced expression of sexual behavior in sexually satiated rats, but only reduced the intromission latency of sexually experienced rats. SKF38393 facilitated the expression of sexual behavior by sexually exhausted rats, but not that of sexually experienced males and quinpirole did not exert an effect in both types of animal. In line with these results, the apomorphine-induced reversal of sexual exhaustion was blocked by the D1-like receptor antagonist SCH23390. The data suggest that DA receptors play distinct roles in the expression of sexual behavior by male rats depending on their motivational state and that activation of D1-like receptors promotes the expression of sexual behavior in satiated rats.

  17. Characteristics of patients with chronic exertional compartment syndrome.

    Science.gov (United States)

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

    2013-10-01

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

  18. Traction Stresses Exerted by Adherent Cells: From Angiogenesis to Metastasis

    Science.gov (United States)

    Reinhart-King, Cynthia

    2010-03-01

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

  19. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  20. Sexually antagonistic selection in human male homosexuality.

    Directory of Open Access Journals (Sweden)

    Andrea Camperio Ciani

    Full Text Available Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness, accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait.

  1. Hypocretin antagonists in insomnia treatment and beyond.

    Science.gov (United States)

    Ruoff, Chad; Cao, Michelle; Guilleminault, Christian

    2011-01-01

    Hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep through stabilization of sleep promoting GABAergic and wake promoting cholinergic/monoaminergic neural pathways. Hypocretin also influences other physiologic processes such as metabolism, appetite, learning and memory, reward and addiction, and ventilatory drive. The discovery of hypocretin and its effect upon the sleep-wake cycle has led to the development of a new class of pharmacologic agents that antagonize the physiologic effects of hypocretin (i.e. hypocretin antagonists). Further investigation of these agents may lead to novel therapies for insomnia without the side-effect profile of currently available hypnotics (e.g. impaired cognition, confusional arousals, and motor balance difficulties). However, antagonizing a system that regulates the sleep-wake cycle while also influencing non-sleep physiologic processes may create an entirely different but equally concerning side-effect profile such as transient loss of muscle tone (i.e. cataplexy) and a dampened respiratory drive. In this review, we will discuss the discovery of hypocretin and its receptors, hypocretin and the sleep-wake cycle, hypocretin antagonists in the treatment of insomnia, and other implicated functions of the hypocretin system.

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

    Science.gov (United States)

    Gabbard, Carl

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

  3. History of the 'geste antagoniste' sign in cervical dystonia.

    Science.gov (United States)

    Poisson, A; Krack, P; Thobois, S; Loiraud, C; Serra, G; Vial, C; Broussolle, E

    2012-08-01

    The geste antagoniste is a voluntary maneuver that temporarily reduces the severity of dystonic posture or movements. It is a classical feature of focal and particularly cervical dystonia. However, the precise historical aspects of geste antagoniste still remain obscure. The goals of this review were (1) to clarify the origin of the geste antagoniste sign; (2) to identify the factors that led to its diffusion in the international literature; (3) to follow the evolution of that term across the twentieth century. We used medical and neurological French, German and English literature of the late nineteenth and early twentieth centuries, and the PubMed database by entering the terms geste antagoniste, antagonistic gesture and sensory trick. The geste antagoniste sign is a legacy of the Paris Neurological School of the end of the nineteenth century. The term was introduced by Meige and Feindel in their 1902 book on tics, written in the vein of their master, Brissaud, who first described this sign in 1893. The almost immediate translations of this book by Giese into German and Kinnier Wilson into English contributed to the rapid spreading of the term geste antagoniste, which is still in use worldwide today. The term antagonistic gesture is the translation proposed by Kinnier Wilson, which also led to the use of the term geste antagonistique. The geste antagoniste sign has long been considered a solid argument for the psychogenic origins of dystonia until the 1980s when Marsden made strong arguments for its organic nature.

  4. Distinction

    OpenAIRE

    2010-01-01

    Pr Serge Haroche La Médaille d’or 2009 du CNRS est décernée au Pr Serge Haroche, titulaire de la chaire de Physique quantique depuis 2001. Serge Haroche est spécialiste de physique atomique et d’optique quantique. Il est l’un des fondateurs de l’électrodynamique quantique en cavité, domaine qui permet, par des expériences conceptuellement simples, d’éclairer les fondements de la théorie quantique et de réaliser des prototypes de systèmes de traitement quantique de l’information. Serge Haroche...

  5. The Attractiveness of Opposites: Agonists and Antagonists.

    LENUS (Irish Health Repository)

    O'Brien, Tony

    2015-02-02

    ABSTRACT Opioid-induced bowel dysfunction, of which constipation is the most common aspect, is a major limiting factor in the use of opioids for pain management. The availability of an oral, long-acting formulation of oxycodone and naloxone represents a highly significant development in pain management. The combination of an opioid analgesic with an opioid antagonist offers reliable pain control with a significant reduction in the burden of opioid-induced constipation. This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http:\\/\\/www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.

  6. Antiallergic effects of H1-receptor antagonists.

    Science.gov (United States)

    Baroody, F M; Naclerio, R M

    2000-01-01

    The primary mechanism of antihistamine action in the treatment of allergic diseases is believed to be competitive antagonism of histamine binding to cellular receptors (specifically, the H1-receptors), which are present on nerve endings, smooth muscles, and glandular cells. This notion is supported by the fact that structurally unrelated drugs antagonize the H1-receptor and provide clinical benefit. However, H1-receptor antagonism may not be their sole mechanism of action in treating allergic rhinitis. On the basis of in vitro and animal experiments, drugs classified as H1-receptor antagonists have long been recognized to have additional pharmacological properties. Most first-generation H1-antihistamines have anticholinergic, sedative, local anaesthetic, and anti-5-HT effects, which might favourably affect the symptoms of the allergic response but also contribute to side-effects. These additional properties are not uniformly distributed among drugs classified as H1-receptor antagonists. Azatadine, for example, inhibits in vitro IgE-mediated histamine and leukotriene (LT) release from mast cells and basophils. In human challenge models, terfenadine, azatadine, and loratadine reduce IgE-mediated histamine release. Cetirizine reduces eosinophilic infiltration at the site of antigen challenge in the skin, but not the nose. In a nasal antigen challenge model, cetirizine pretreatment did not affect the levels of histamine and prostaglandin D2 recovered in postchallenge lavages, whereas the levels of albumin, N-tosyl-L-arginine methyl ester (TAME) esterase activity, and LTs were reduced. Terfenadine, cetirizine, and loratadine blocked allergen-induced hyperresponsiveness to methacholine. In view of the complexity of the pathophysiology of allergy, a number of H1 antagonists with additional properties are currently under development for allergic diseases. Mizolastine, a new H1-receptor antagonist, has been shown to have additional actions that should help reduce the

  7. Association between work engagement and perceived exertion among healthcare workers

    Directory of Open Access Journals (Sweden)

    Rodrigo Luiz Carregaro

    Full Text Available INTRODUCTION: Complaints and musculoskeletal discomforts are common manifestations of individuals affected by work-related disorders (WRMD, and the influence of individual and/or psychosocial risk factors may play a significant role in WRMD development. OBJECTIVE: To evaluate and to compare work engagement (WE and ratings of perceived exertion (RPE and to assess the association between indexes of WE and RPE among healthcare workers. MATERIALS AND METHODS: Seventeen female subjects (36 ± 11 years, 1.58 ± 0.06 m and 59 ± 9 kg participated, all officially employed on a nonprofit agency. The Nordic Questionnaire was used to evaluate musculoskeletal complaints and the Borg Scale used to evaluate the RPE. The Utrecht Work Engagement Scale quantified WE (vigor, dedication and absorption domains. Participants were divided into two groups, according to their sectors: healthcare clinics and institution for the elderly. The independent student t test was used to verify differences between groups and the chi-square test to verify associations between variables. RESULTS: All subjects reported musculoskeletal complaints, mainly in the low back (58%. RPE did not differ between groups, while in the vigor, it was found a significant statistically difference (p = 0.035. An association between RPE and vigor and RPE and dedication was establish (p = 0.02 and p = 0.036, respectively. CONCLUSION: The association between WE and RPE suggests that workers with lower indexes of vigor and dedication may perceive greater physical demand, which can be imposed by work demands.

  8. Exertional Rhabdomyolysis after an Extreme Conditioning Competition: A Case Report

    Directory of Open Access Journals (Sweden)

    Ramires Alsamir Tibana

    2018-04-01

    Full Text Available This case report describes an instance of exercise-induced rhabdomyolysis caused by an extreme conditioning program (ECP competition. A 35-year-old female presented with abdominal pain and soreness, which began one day after she completed two days of ECPcompetition composed of five workouts. Three days after competition, creatine kinase (CK was 77,590 U/L accompanied by myalgia and abnormal liver function tests, while renal function was normal and this resulted in a diagnosis of rhabdomyolysis. A follow-up examination revealed that her serum level of CK was still elevated to 3034 U/L on day 10 and 1257 U/L on day 25 following the ECP competition. The subject reported myalgia even up to 25 days after the ECP competition. Exertional rhabdomyolysis can be observed in ECP athletes following competition and highlights a dangerous condition, which may be increasing in recent years due to the massive expansion of ECP popularity and a growing number of competitions. Future research should investigate the causes of rhabdomyolysis that occur as a result of ECP, especially training methods and/or tasks developed specifically for these competitions.

  9. Metallic nanomaterials formed by exerting large plastic strains

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  10. Synthetic oligorotaxanes exert high forces when folding under mechanical load

    Science.gov (United States)

    Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

    2018-01-01

    Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

  11. Petiveria alliacea exerts mnemonic and learning effects on rats.

    Science.gov (United States)

    Silva, Mallone Lopes; Luz, Diandra Araújo; Paixão, Thiago Portal da; Silva, João Paulo Bastos; Belém-Filho, Ivaldo Jesus Almeida; Fernandes, Luanna Melo Pereira; Gonçalves, Ana Cristina Baetas; Fontes-Júnior, Enéas Andrade; de Andrade, Marciene Ataíde; Maia, Cristiane Socorro Ferraz

    2015-07-01

    Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub native to the Amazon region and other tropical areas such as Central America and the Caribbean. Popularly known as mucuracaá, P. alliacea is used in the folk medicine for a broad variety of therapeutic purpose and also in religious ceremonies by slaves as a sedative, which highlights its properties on the Central Nervous System (CNS). The present study evaluated the effects of the P. alliacea leaves hydroalcoholic extract (PaLHE) on the cognition, including learning and memory. Three-month-old male and female Wistar rats (n=8-10/group) were administered with 900mg/kg of PaLHE. The behavioral assays included Step-down Inhibitory avoidance (IA) and Morris Water Maze (MWM) tests. Consistent with our previous reports, P. alliacea improved long-term memory. It also exerted previously unreported effects on short-term and spatial memory improvement, and increased learning in the tasks. The P. alliacea extract elicited mnemonic effects and improved the learning process in both IA and MWM tests. Our results highlight the importance of further studies in order to identify the active substances of the PaLHE and investigate the pharmacological mechanisms that underlies the reported effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Antagonistic activity of marine sponges associated Actinobacteria

    Directory of Open Access Journals (Sweden)

    Selvakumar Dharmaraj

    2016-06-01

    Full Text Available Objective: To focus on the isolation and preliminary characterization of marine sponges associated Actinobacteria particularly Streptomyces species and also their antagonistic activities against bacterial and fungal pathogens. Methods: The sponges were collected from Kovalam and Vizhinjam port of south-west coast of Kerala, India. Isolation of strains was carried out from sponge extracts using international Streptomyces project media. For preliminary identification of the strains, morphological (mycelial colouration, soluble pigments, melanoid pigmentation, spore morphology, nutritional uptake (carbon utilisation, amonoacids influence, sodium chloride tolerance, physiological (pH, temperature and chemotaxonomical characterization were done. Antimicrobial studies were also carried out for the selected strains. Results: With the help of the spicule structures, the collected marine sponges were identified as Callyspongia diffusa, Mycale mytilorum, Tedania anhelans and Dysidea fragilis. Nearly 94 strains were primarily isolated from these sponges and further they were sub-cultured using international Streptomyces project media. The strains exhibited different mycelial colouration (aerial and substrate, soluble and melanoid pigmentations. The strains possessed three types of sporophore morphology namely rectus flexibilis, spiral and retinaculiaperti. Among the 94 isolates, seven exhibited antibacterial and antifungal activities with maximal zone of inhibition of 30 mm. The nutritional, physiological and chemotaxonomical characteristic study helped in the conventional identification of the seven strains and they all suggest that the strains to be grouped under the genus Streptomyces. Conclusions: The present study clearly helps in the preliminary identification of the isolates associated with marine sponges. Antagonistic activities prove the production of antimicrobial metabolites against the pathogens. Marine sponges associated Streptomyces are

  13. Assay method for organic calcium antagonist drugs and a kit for such an assay

    International Nuclear Information System (INIS)

    Snyder, S. H.; Gould, R. J.

    1985-01-01

    A method for measuring the level of organic calcium antagonist drug in a body fluid comprises preparing a mixture of a radioactive calcium antagonist drug, a body fluid containing a calcium antagonist drug and a calcium antagonist receptor material, measuring the radioactivity of the radioactive calcium antagonist drug bound to said calcium antagonist receptor material and deriving the concentration of the calcium antagonist drug in the body fluid from a standard curve indicating the concentration of calcium antagonist drug versus inhibition of binding of said radioactive calcium antagonist drug to said receptor sites caused by the calcium antagonist drug in said body fluid. A kit for measuring the level of an organic calcium drug comprises a receptacle containing a radioactive calcium antagonist drug, a calcium antagonist receptor material and a standard amount of a nonradioactive calcium antagonist drug

  14. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

    DEFF Research Database (Denmark)

    Tricoci, Pierluigi; Huang, Zhen; Held, Claes

    2012-01-01

    Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.......Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation....

  15. Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

    Science.gov (United States)

    Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

    2009-11-01

    To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

  16. Antagonistic and Bargaining Games in Optimal Marketing Decisions

    Science.gov (United States)

    Lipovetsky, S.

    2007-01-01

    Game theory approaches to find optimal marketing decisions are considered. Antagonistic games with and without complete information, and non-antagonistic games techniques are applied to paired comparison, ranking, or rating data for a firm and its competitors in the market. Mix strategy, equilibrium in bi-matrix games, bargaining models with…

  17. Vitamin K antagonist use and mortality in dialysis patients

    NARCIS (Netherlands)

    Voskamp, Pauline W.M.; Rookmaaker, Maarten B.; Verhaar, Marianne C.; Dekker, Friedo W.; Ocak, Gurbey

    2018-01-01

    Background. The risk-benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc

  18. Evaluation of antagonistic fungi against charcoal rot of sunflower ...

    African Journals Online (AJOL)

    In vitro, sensitivity of Macrophomina phaseolina (Tassi) Goid determined through inhibition zone technique to various antagonistic fungi viz., Aspergillus niger, Aspergillus flavus, Trichoderma viride, Trichoderma harzianum and Penicillium capsulatum amended into PDA medium. All the antagonists reduced the colony ...

  19. Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat

    Directory of Open Access Journals (Sweden)

    Alireza Komaki

    2014-07-01

    Full Text Available Introduction: Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP injection of cannabinoid CB1 receptor antagonist (AM251 in the presence of alpha-1 adrenergic antagonist (Prazosin on rat behavior in the EPM. Methods: In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg, Prazosin (0.3 mg/kg and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg. Results: Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Discussion: Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

  20. Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat.

    Science.gov (United States)

    Komaki, Alireza; Abdollahzadeh, Fatemeh; Sarihi, Abdolrahman; Shahidi, Siamak; Salehi, Iraj

    2014-01-01

    Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP) injection of cannabinoid CB1 receptor antagonist (AM251) in the presence of alpha-1 adrenergic antagonist (Prazosin) on rat behavior in the EPM. In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg), Prazosin (0.3 mg/kg) and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg). Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

  1. Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

    Science.gov (United States)

    Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

    2012-01-01

    Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

  2. Kinetic properties of 'dual' orexin receptor antagonists at OX1R and OX2R orexin receptors.

    Directory of Open Access Journals (Sweden)

    Gabrielle Elizabeth Callander

    2013-12-01

    Full Text Available Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. Both efficacy and safety are crucial in clinical settings and thorough investigations of pharmacokinetics and pharmacodynamics can predict contributing factors such as duration of action and undesirable effects. To this end, we studied the interactions between various ‘dual’ orexin receptor antagonists and the orexin receptors, OX1R and OX2R, over time using saturation and competition radioligand binding with [3H]-BBAC ((S-N-([1,1'-biphenyl]-2-yl-1-(2-((1-methyl-1H-benzo[d]imidazol-2-ylthioacetylpyrrolidine-2-carboxamide. In addition, the kinetics of these compounds were investigated in cells expressing human, mouse and rat OX1R and OX2R using FLIPR® assays for calcium accumulation. We demonstrate that almorexant reaches equilibrium very slowly at OX2R, whereas SB-649868, suvorexant and filorexant may take hours to reach steady state at both orexin receptors. By contrast, compounds such as BBAC or the selective OX2R antagonist IPSU ((2-((1H-Indol-3-ylmethyl-9-(4-methoxypyrimidin-2-yl-2,9-diazaspiro[5.5]undecan-1-one bind rapidly and reach equilibrium very quickly in both binding and / or functional assays. Overall, the dual antagonists tested here tend to be rather unselective under non-equilibrium conditions and reach equilibrium very slowly. Once equilibrium is reached, each ligand demonstrates a selectivity profile that is however, distinct from the non-equilibrium condition. The slow kinetics of the dual antagonists tested suggest that in vitro receptor occupancy may be longer lasting than would be predicted. This raises questions as to whether pharmacokinetic studies measuring plasma or brain levels of these antagonists are accurate reflections of receptor occupancy in vivo.

  3. Common influences of non-competitive NMDA receptor antagonists on the consolidation and reconsolidation of cocaine-cue memory.

    Science.gov (United States)

    Alaghband, Yasaman; Marshall, John F

    2013-04-01

    Environmental stimuli or contexts previously associated with rewarding drugs contribute importantly to relapse among addicts, and research has focused on neurobiological processes maintaining those memories. Much research shows contributions of cell surface receptors and intracellular signaling pathways in maintaining associations between rewarding drugs (e.g., cocaine) and concurrent cues/contexts; these memories can be degraded at the time of their retrieval through reconsolidation interference. Much less studied is the consolidation of drug-cue memories during their acquisition. The present experiments use the cocaine-conditioned place preference (CPP) paradigm in rats to directly compare, in a consistent setting, the effects of N-methyl-D-aspartate (NMDA) glutamate receptor antagonists MK-801 and memantine on the consolidation and reconsolidation of cocaine-cue memories. For the consolidation studies, animals were systemically administered MK-801 or memantine immediately following training sessions. To investigate the effects of these NMDA receptor antagonists on the retention of previously established cocaine-cue memories, animals were systemically administered MK-801 or memantine immediately after memory retrieval. Animals given either NMDA receptor antagonist immediately following training sessions did not establish a preference for the cocaine-paired compartment. Post-retrieval administration of either NMDA receptor antagonist attenuated the animals' preference for the cocaine-paired compartment. Furthermore, animals given NMDA receptor antagonists post-retrieval showed a blunted response to cocaine-primed reinstatement. Using two distinct NMDA receptor antagonists in a common setting, these findings demonstrate that NMDA receptor-dependent processes contribute both to the consolidation and reconsolidation of cocaine-cue memories, and they point to the potential utility of treatments that interfere with drug-cue memory reconsolidation.

  4. Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells

    International Nuclear Information System (INIS)

    Sansoni, P.; Silverman, E.D.; Khan, M.M.; Melmon, K.L.; Engleman, E.G.

    1985-01-01

    One mechanism of histamine-mediated inhibition of the immune response in man is to activate T suppressor cells that bear the Leu 2 (OKT8) marker. The current study was undertaken to characterize the histamine-induced suppressor cell using a monoclonal antibody (9.3) shown previously to distinguish cytotoxic T cells from antigen-specific suppressor T cells. Leu 2+ cells isolated from peripheral blood were further separated with antibody 9.3 into Leu 2+, 9.3+, and Leu 2+, 9.3- subsets and each subset was incubated with different concentrations of histamine before determining their ability to suppress immune responses in vitro. The results indicate that the Leu 2+, 9.3- subpopulation includes all histamine-induced suppressor cells, that 10(-4) M histamine is the optimal concentration for suppressor cell induction, and that exposure of Leu 2+, 9.3- cells to histamine for 30 s is sufficient to initiate the induction process. After treatment with histamine these cells inhibit both phytohemagglutinin-induced T cell proliferation and pokeweed mitogen-induced B cell differentiation. The suppression of phytohemagglutinin-induced proliferation was resistant to x-irradiation with 1,200 rad, either before or after histamine exposure, suggesting that Leu 2+, 9.3- cells need not proliferate to become suppressor cells or exert suppression. Moreover, suppression by these cells was not due to altered kinetics of the response. Finally, a histamine type 2 receptor antagonist (cimetidine) but not a type 1 receptor antagonist (mepyramine) blocked the induction of suppressor cells. On the basis of these results and our previous studies of antigen specific suppressor cells, we conclude that Leu 2+ suppressor cells in man are derived from a precursor pool that is phenotypically distinct from cells that can differentiate into cytotoxic T cells

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

    Science.gov (United States)

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

    2015-11-01

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

  6. Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis.

    Science.gov (United States)

    von Rüden, E-L; Avemary, J; Zellinger, C; Algermissen, D; Bock, P; Beineke, A; Baumgärtner, W; Stein, V M; Tipold, A; Potschka, H

    2012-08-01

    Despite knowledge about the impact of brain inflammation on hippocampal neurogenesis, data on the influence of virus encephalitis on dentate granule cell neurogenesis are so far limited. Canine distemper is considered an interesting model of virus encephalitis, which can be associated with a chronic progressing disease course and can cause symptomatic seizures. To determine the impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we compared post-mortem tissue from dogs with infection with and without seizures, from epileptic dogs with non-viral aetiology and from dogs without central nervous system diseases. The majority of animals with infection and with epilepsy of non-viral aetiology exhibited neuronal progenitor numbers below the age average in controls. Virus infection with and without seizures significantly decreased the mean number of neuronal progenitor cells by 43% and 76% as compared to age-matched controls. Ki-67 labelling demonstrated that hippocampal cell proliferation was neither affected by infection nor by epilepsy of non-viral aetiology. Analysis of CDV infection in cells expressing caspase-3, doublecortin or Ki-67 indicated that infection of neuronal progenitor cells is extremely rare and suggests that infection might damage non-differentiated progenitor cells, hamper neuronal differentiation and promote glial differentiation. A high inter-individual variance in the number of lectin-reactive microglial cells was evident in dogs with distemper infection. Statistical analyses did not reveal a correlation between the number of lectin-reactive microglia cells and neuronal progenitor cells. Our data demonstrate that virus encephalitis with and without seizures can exert detrimental effects on hippocampal neurogenesis, which might contribute to long-term consequences of the disease. The lack of a significant impact of distemper virus on Ki-67-labelled cells indicates that the infection affected neuronal differentiation and

  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. 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.

  9. NMDA receptor antagonist-enhanced high frequency oscillations: are they generated broadly or regionally specific?

    Science.gov (United States)

    Olszewski, Maciej; Dolowa, Wioleta; Matulewicz, Pawel; Kasicki, Stefan; Hunt, Mark J

    2013-12-01

    Systemic administration of NMDA receptor antagonists, used to model schizophrenia, increase the power of high-frequency oscillations (130-180Hz, HFO) in a variety of neuroanatomical and functionally distinct brain regions. However, it is unclear whether HFO are independently and locally generated or instead spread from a distant source. To address this issue, we used local infusion of tetrodotoxin (TTX) to distinct brain areas to determine how accurately HFO recorded after injection of NMDAR antagonists reflect the activity actually generated at the electrode tip. Changes in power were evaluated in local field potentials (LFPs) recorded from the nucleus accumbens (NAc), prefrontal cortex and caudate and in electrocorticograms (ECoGs) from visual and frontal areas. HFO recorded in frontal and visual cortices (ECoGs) or in the prefrontal cortex, caudate (LFPs) co-varied in power and frequency with observed changes in the NAc. TTX infusion to the NAc immediately and profoundly reduced the power of accumbal HFO which correlated with changes in HFO recorded in distant cortical sites. In contrast, TTX infusion to the prefrontal cortex did not change HFO power recorded locally, although gamma power was reduced. A very similar result was found after TTX infusion to the caudate. These findings raise the possibility that the NAc is an important neural generator. Our data also support existing studies challenging the idea that high frequencies recorded in LFPs are necessarily generated at the recording site. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  10. Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

    NARCIS (Netherlands)

    R. de Wit (Ronald)

    2003-01-01

    textabstractThe advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients

  11. Defining poverty as distinctively human

    Directory of Open Access Journals (Sweden)

    H.P.P. Lötter

    2007-05-01

    Full Text Available While it is relatively easy for most people to identify human beings suffering from poverty, it is rather more difficult to come to a proper understanding of poverty. In this article the author wants to deepen our understanding of poverty by interpreting the conventional definitions of poverty in a new light. The article starts with a defence of a claim that poverty is a concept uniquely applicable to humans. It then present a critical discussion of the distinction between absolute and relative poverty and it is then argued that a revision of this distinction can provide general standards applicable to humans everywhere.

  12. Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

    Directory of Open Access Journals (Sweden)

    Andrew John Dudley Nelson

    2013-05-01

    Full Text Available Repeated exposure to the psychostimulant amphetamine has been shown to disrupt goal-directed instrumental actions and promote the early and abnormal development of goal-insensitive habitual responding (Nelson and Killcross, 2006. To investigate the neuropharmacological specificity of this effect as well as restore goal-directed responding in animals with pre-training amphetamine exposure, animals were treated with the non-selective dopamine antagonist α-flupenthixol, the selective D1 antagonist SCH 23390 or the selective D2 antagonist eticlopride, prior to instrumental training (3 sessions. Subsequently, the reinforcer was paired with LiCL-induced gastric-malaise and animals were given a test of goal-sensitivity both in extinction and reacquisition. The effect of these dopaminergic antagonists on the sensitivity of lever press performance to outcome devaluation was assessed in animals with pre-training exposure to amphetamine (Experiments 1a-1c or in non-sensitized animals (Experiment 2. Both α-flupenthixol and SCH23390 reversed accelerated habit formation following amphetamine sensitization. However, eticlopride appeared to enhance this effect and render instrumental performance compulsive as these animals were unable to inhibit responding both in extinction and reacquisition, even though a consumption test confirmed they had acquired an aversion to the reinforcer. These findings demonstrate that amphetamine induced-disruption of goal-directed behaviour is mediated by activity at distinct dopamine receptor subtypes and may represent a putative model of the neurochemical processes involved in the loss of voluntary control over behaviour.

  13. The Antidepressant 5-HT2A Receptor Antagonists Pizotifen and Cyproheptadine Inhibit Serotonin-Enhanced Platelet Function

    Science.gov (United States)

    Lin, Olivia A.; Karim, Zubair A.; Vemana, Hari Priya; Espinosa, Enma V. P.; Khasawneh, Fadi T.

    2014-01-01

    There is considerable interest in defining new agents or targets for antithrombotic purposes. The 5-HT2A receptor is a G-protein coupled receptor (GPCR) expressed on many cell types, and a known therapeutic target for many disease states. This serotonin receptor is also known to regulate platelet function. Thus, in our FDA-approved drug repurposing efforts, we investigated the antiplatelet activity of cyproheptadine and pizotifen, two antidepressant 5-HT2A Receptor antagonists. Our results revealed that cyproheptadine and pizotifen reversed serotonin-enhanced ADP-induced platelet aggregation in vitro and ex vivo. And the inhibitory effects of these two agents were found to be similar to that of EMD 281014, a 5-HT2A Receptor antagonist under development. In separate experiments, our studies revealed that these 5-HT2A receptor antagonists have the capacity to reduce serotonin-enhanced ADP-induced elevation in intracellular calcium levels and tyrosine phosphorylation. Using flow cytometry, we also observed that cyproheptadine, pizotifen, and EMD 281014 inhibited serotonin-enhanced ADP-induced phosphatidylserine (PS) exposure, P-selectin expression, and glycoprotein IIb-IIIa activation. Furthermore, using a carotid artery thrombosis model, these agents prolonged the time for thrombotic occlusion in mice in vivo. Finally, the tail-bleeding time was investigated to assess the effect of cyproheptadine and pizotifen on hemostasis. Our findings indicated prolonged bleeding time in both cyproheptadine- and pizotifen-treated mice. Notably, the increases in occlusion and bleeding times associated with these two agents were comparable to that of EMD 281014, and to clopidogrel, a commonly used antiplatelet drug, again, in a fashion comparable to clopidogrel and EMD 281014. Collectively, our data indicate that the antidepressant 5-HT2A antagonists, cyproheptadine and pizotifen do exert antiplatelet and thromboprotective effects, but similar to clopidogrel and EMD 281014, their

  14. Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats.

    Science.gov (United States)

    Kawaura, Kazuaki; Ogata, Yukino; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2016-04-01

    We investigated whether tipepidine exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone (ACTH)-treated rats, which is known as a treatment-resistant depression model, and we studied the pharmacological mechanisms of the effects of tipepidine. Male Wistar rats (5-7 weeks old) were used in this study. Tipepidine (20 and 40 mg/kg, i.p.) decreased the immobility time in the forced swimming test in ACTH-treated rats. The anti-immobility effect of tipepidine was blocked by a catecholamine-depleting agent, alpha-methyl-p-tyrosine (300 mg/kg, s.c.), but not by a serotonin-depleting agent, p-chlorophenylalanine. The anti-immobility effect of tipepidine was also blocked by a dopamine D1 receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) and an adrenaline α2 receptor antagonist, yohimbine (2 mg/kg, i.p.). In microdialysis technique, tipepidine (40 mg/kg, i.p.) increased the extracellular dopamine level of the nucleus accumbens (NAc) in ACTH-treated rats. These results suggest that tipepidine exerts an antidepressant-like effect in the forced swimming test in ACTH-treated rats, and that the effect of tipepidine is mediated by the stimulation of dopamine D1 receptors and adrenaline α2 receptors. The results also suggest that an increase in the extracellular dopamine level in the NAc may be involved in the antidepressant-like effect of tipepidine in ACTH-treated rats. Copyright © 2016. Published by Elsevier B.V.

  15. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar

    2016-05-01

    Full Text Available With the very recent market approval of pitolisant (Wakix®, the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  16. P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

    Science.gov (United States)

    Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

    2015-09-01

    279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Antagonism of acetylcholine by adrenaline antagonists

    Science.gov (United States)

    Benfey, B. G.; Grillo, S. A.

    1963-01-01

    Phenoxybenzamine antagonized the inhibitory action of acetylcholine on the guinea-pig isolated atrium. The antagonism was slow in onset, very slowly reversible, and could be overcome by increased concentrations of acetylcholine. In contrast, atropine inhibited the action of acetylcholine quickly, and the effect disappeared soon after withdrawal. The pA10 of phenoxybenzamine (2 hr of contact) was 6.8, and that of atropine (30 min of contact) was 8.4. In the presence of atropine phenoxybenzamine did not exert a slowly reversible antagonism, and the dose-ratio of acetylcholine returned to normal soon after withdrawal of both drugs. Phenoxybenzamine also antagonized acetylcholine in the guinea-pig isolated ileum, but with higher concentrations acetylcholine did not overcome the antagonism. The pA10 (60 min of contact) was 6.6. The pA10 of chlorpromazine in the atrium (2 hr of contact) and ileum (60 min of contact) was 5.9. Phentolamine, 2-diethylaminomethylbenzo-1,4-dioxan hydrochloride (883 F), and yohimbine antagonized acetylcholine in the atrium and ileum but required higher concentrations than chlorpromazine. PMID:13967429

  18. Emotional stimuli exert parallel effects on attention and memory.

    Science.gov (United States)

    Talmi, Deborah; Ziegler, Marilyne; Hawksworth, Jade; Lalani, Safina; Herman, C Peter; Moscovitch, Morris

    2013-01-01

    Because emotional and neutral stimuli typically differ on non-emotional dimensions, it has been difficult to determine conclusively which factors underlie the ability of emotional stimuli to enhance immediate long-term memory. Here we induced arousal by varying participants' goals, a method that removes many potential confounds between emotional and non-emotional items. Hungry and sated participants encoded food and clothing images under divided attention conditions. Sated participants attended to and recalled food and clothing images equivalently. Hungry participants performed worse on the concurrent tone-discrimination task when they viewed food relative to clothing images, suggesting enhanced attention to food images, and they recalled more food than clothing images. A follow-up regression analysis of the factors predicting memory for individual pictures revealed that food images had parallel effects on attention and memory in hungry participants, so that enhanced attention to food images did not predict their enhanced memory. We suggest that immediate long-term memory for food is enhanced in the hungry state because hunger leads to more distinctive processing of food images rendering them more accessible during retrieval.

  19. A SELECTIVE ANTAGONIST OF MINERALOCORTICOID RECEPTOR EPLERENONE IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    B. B. Gegenava

    2015-01-01

    Full Text Available The role of aldosterone in pathophysiological processes is considered. The effects of the selective antagonist of mineralocorticoid receptor eplerenone are analyzed. The advantages of eplerenone compared with spironolactone are discussed.

  20. Characterization and design of antagonistic shape memory alloy actuators

    International Nuclear Information System (INIS)

    Georges, T; Brailovski, V; Terriault, P

    2012-01-01

    Antagonistic shape memory actuators use opposing shape memory alloy (SMA) elements to create devices capable of producing differential motion paths and two-way mechanical work in a very efficient manner. There is no requirement for additional bias elements to ‘re-arm’ the actuators and allow repetitive actuation. The work generation potential of antagonistic shape memory actuators is determined by specific SMA element characteristics and their assembly conditions. In this study, the selected SMA wires are assembled in antagonistic configuration and characterized using a dedicated test bench to evaluate their stress–strain characteristics as a function of the number of cycles. Using these functional characteristics, a so-called ‘working envelope’ is built to assist in the design of such an actuator. Finally, the test bench is used to simulate a real application of an antagonistic actuator (case study). (paper)

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

    Dahl, Morten; Hansen, Philip; Stål, Per

    2011-01-01

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

  3. 5-HT7 Receptor Antagonists with an Unprecedented Selectivity Profile.

    Science.gov (United States)

    Ates, Ali; Burssens, Pierre; Lorthioir, Olivier; Lo Brutto, Patrick; Dehon, Gwenael; Keyaerts, Jean; Coloretti, Francis; Lallemand, Bénédicte; Verbois, Valérie; Gillard, Michel; Vermeiren, Céline

    2018-04-23

    Selective leads: In this study, we generated a new series of serotonin 5-HT 7 receptor antagonists. Their synthesis, structure-activity relationships, and selectivity profiles are reported. This series includes 5-HT 7 antagonists with unprecedented high selectivity for the 5-HT 7 receptor, setting the stage for lead optimization of drugs acting on a range of neurological targets. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Feline immunodeficiency virus envelope glycoproteins antagonize tetherin through a distinctive mechanism that requires virion incorporation.

    Science.gov (United States)

    Morrison, James H; Guevara, Rebekah B; Marcano, Adriana C; Saenz, Dyana T; Fadel, Hind J; Rogstad, Daniel K; Poeschla, Eric M

    2014-03-01

    BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins of species representing both branches of the order Carnivora. Comparison of tiger and cat (Feliformia) to dog and ferret (Caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineage (19 of 27 amino acids, including the dual tyrosine motif). Alpha interferon (IFN-α) induced tetherin and blocked feline immunodeficiency virus (FIV) replication in lymphoid and nonlymphoid feline cells. Budding of bald FIV and HIV particles was blocked by carnivore tetherins. However, infectious FIV particles were resistant, and spreading FIV replication was uninhibited. Antagonism mapped to the envelope glycoprotein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in contrast to known antagonists, did not rescue noncognate particles. Also unlike the primate lentiviral antagonists, but similar to the Ebola virus glycoprotein, FIV Env did not reduce intracellular or cell surface tetherin levels. Furthermore, FIV-enveloped FIV particles actually required tetherin for optimal release from cells. The results show that FIV Envs mediate a distinctive tetherin evasion. Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires functional virion incorporation of Env, and it shields the budding particle without downregulating plasma membrane tetherin. Moreover, FIV has evolved dependence on this protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env(-) particles do not. HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and the filovirus Ebola use their envelope (Env) glycoproteins for this purpose. It turns out that the FIV tetherin antagonist is

  5. Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Chien, Ellen Y.T.; Liu, Wei; Zhao, Qiang; Katritch, Vsevolod; Han, Gye Won; Hanson, Michael A.; Shi, Lei; Newman, Amy Hauck; Javitch, Jonathan A.; Cherezov, Vadim; Stevens, Raymond C. (Cornell); (Scripps); (NIDA); (Columbia); (UCSD); (Receptos)

    2010-11-30

    Dopamine modulates movement, cognition, and emotion through activation of dopamine G protein-coupled receptors in the brain. The crystal structure of the human dopamine D3 receptor (D3R) in complex with the small molecule D2R/D3R-specific antagonist eticlopride reveals important features of the ligand binding pocket and extracellular loops. On the intracellular side of the receptor, a locked conformation of the ionic lock and two distinctly different conformations of intracellular loop 2 are observed. Docking of R-22, a D3R-selective antagonist, reveals an extracellular extension of the eticlopride binding site that comprises a second binding pocket for the aryl amide of R-22, which differs between the highly homologous D2R and D3R. This difference provides direction to the design of D3R-selective agents for treating drug abuse and other neuropsychiatric indications.

  6. Exploring the binding energy profiles of full agonists, partial agonists, and antagonists of the α7 nicotinic acetylcholine receptor.

    Science.gov (United States)

    Tabassum, Nargis; Ma, Qianyun; Wu, Guanzhao; Jiang, Tao; Yu, Rilei

    2017-09-01

    Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are important drug targets for the treatment of neurological diseases. However, the precise determinants of the binding efficacies of ligands for these receptors are unclear. Therefore, in this study, the binding energy profiles of various ligands (full agonists, partial agonists, and antagonists) were quantified by docking those ligands with structural ensembles of the α7 nAChR exhibiting different degrees of C-loop closure. This approximate treatment of interactions suggested that full agonists, partial agonists, and antagonists of the α7 nAChR possess distinctive binding energy profiles. Results from docking revealed that ligand binding efficacy may be related to the capacity of the ligand to stabilize conformational states with a closed C loop.

  7. On the Distinct Effects of Left-Wing and Right-Wing Populism on Democratic Quality

    OpenAIRE

    Huber, Robert A.; Schimpf, Christian H.

    2017-01-01

    This study examines the differences and commonalities of how populist parties of the left and right relate to democracy. The focus is narrowed to the relationship between these parties and two aspects of democratic quality, minority rights and mutual constraints. Our argument is twofold: first, we contend that populist parties can exert distinct influences on minority rights, depending on whether they are left-wing or right-wing populist parties. Second, by contrast, we propose that the assoc...

  8. Presidential address: distinction or extinction.

    Science.gov (United States)

    Pressman, Barry D

    2008-10-01

    Despite its continuing scientific successes in imaging, radiology as a specialty is faced with a very difficult and competitive environment. Nonradiologists are more and more interested in vertically integrating imaging into their practices, while teleradiology and picture archiving and communication systems are resulting in the greater isolation of radiologists. Commoditization is a realistic and devastating threat to the survival and professionalism of the specialty. To remain viable as a specialty, radiologists must elevate their practice by subspecializing, becoming more involved with clinical care, and actively interacting with patients and referring clinicians. Distinction will prevent extinction.

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

    Science.gov (United States)

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

    2016-10-01

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

  10. Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia

    Science.gov (United States)

    Broussolle, Emmanuel; Laurencin, Chloé; Bernard, Emilien; Thobois, Stéphane; Danaila, Teodor; Krack, Paul

    2015-01-01

    Background Geste antagoniste, or sensory trick, is a voluntary maneuver that temporarily reduces the severity of dystonic postures or movements. We present a historical review of early reports and illustrations of geste antagoniste. Results In 1894, Brissaud described this phenomenon in Paris in patients with torticollis. He noted that a violent muscular contraction could be reversed by a minor voluntary action. He considered the improvement obtained by what he called “simple mannerisms, childish behaviour or fake pathological movements” was proof of the psychogenic origin of what he named mental torticollis. This concept was supported by photographical illustrations of the patients. The term geste antagoniste was used by Brissaud’s pupils, Meige and Feindel, in their 1902 monograph on movement disorders. Other reports and illustrations of this sign were published in Europe between 1894 and 1906. Although not mentioned explicitly, geste antagoniste was also illustrated in a case report of generalized dystonia in Oppenheim’s 1911 seminal description of dystonia musculorum deformans in Berlin. Discussion Brissaud-Meige’s misinterpretation of the geste antagoniste unfortunately anchored the psychogenic origin of dystonia for decades. In New York, Herz brought dystonia back into the realm of organic neurology in 1944. Thereafter, it was given prominence by other authors, notably Fahn and Marsden in the 1970–1980s. Nowadays, neurologists routinely investigate for geste antagoniste when a dystonic syndrome is suspected, because it provides a further argument in favor of dystonia. The term alleviating maneuver was proposed in 2014 to replace sensory trick or geste antagoniste. This major sign is now part of the motor phenomenology of the 2013 Movement Disorder Society’s classification of dystonia. PMID:26417535

  11. Characterization of the discriminative stimulus produced by the dopamine antagonist tiapride.

    Science.gov (United States)

    Cohen, C; Sanger, D J; Perrault, G

    1997-11-01

    The ability of tiapride, a selective D2/D3 dopamine receptor antagonist, to exert discriminative stimulus control of responding was investigated by training rats to discriminate this drug (30 mg/kg) from saline in a two-lever, food-reinforcement procedure. Acquisition of tiapride discrimination required a relatively lengthy training period (mean of 76 sessions) but stable performance was maintained throughout the 18- month study. The dose of tiapride eliciting 50% tiapride-lever choice (ED50) was 2.2 mg/kg. After determination of the dose-effect curve with tiapride, substitution tests with several dopamine antagonists and other reference compounds were performed. All dopamine antagonists, including amisulpride (ED50 4 mg/kg), sulpiride (18 mg/kg), sultopride (1.5 mg/kg), clebopride (0.13 mg/kg), raclopride (0.16 mg/kg), metoclopramide (1.4 mg/kg), remoxipride (4.8 mg/kg), pimozide (2.7 mg/kg), thioridazine (3.4 mg/kg), olanzapine (0.97 mg/kg), chlorpromazine (1.9 mg/kg), risperidone (0.22 mg/kg) and haloperidol (0.14 mg/kg), except clozapine (>10 mg/kg), produced dose-dependent substitution for tiapride. Tiapride-like stimulus effects were observed at doses that decreased response rates. However, ED50 values for substitution by tiapride, amisulpride, sulpiride, sultopride, pimozide, clebopride and thioridazine were lower than ED50 values for decreasing responding. Additional studies were conducted to evaluate the ability of direct and indirect dopamine agonists to attenuate the tiapride discriminative stimulus. Pretreatment with d-amphetamine and nomifensine antagonized the discriminative stimulus effects of tiapride. Quinpirole, 7-OH-DPAT, bromocriptine and apomorphine partially blocked the stimulus effects of tiapride whereas SKF 38393 did not affect the discrimination. These results from substitution and antagonism tests indicated that the discriminative effects of tiapride are mediated by activity at D2/D3 dopamine receptors.

  12. Structural and energetic effects of A2A adenosine receptor mutations on agonist and antagonist binding.

    Directory of Open Access Journals (Sweden)

    Henrik Keränen

    Full Text Available To predict structural and energetic effects of point mutations on ligand binding is of considerable interest in biochemistry and pharmacology. This is not only useful in connection with site-directed mutagenesis experiments, but could also allow interpretation and prediction of individual responses to drug treatment. For G-protein coupled receptors systematic mutagenesis has provided the major part of functional data as structural information until recently has been very limited. For the pharmacologically important A(2A adenosine receptor, extensive site-directed mutagenesis data on agonist and antagonist binding is available and crystal structures of both types of complexes have been determined. Here, we employ a computational strategy, based on molecular dynamics free energy simulations, to rationalize and interpret available alanine-scanning experiments for both agonist and antagonist binding to this receptor. These computer simulations show excellent agreement with the experimental data and, most importantly, reveal the molecular details behind the observed effects which are often not immediately evident from the crystal structures. The work further provides a distinct validation of the computational strategy used to assess effects of point-mutations on ligand binding. It also highlights the importance of considering not only protein-ligand interactions but also those mediated by solvent water molecules, in ligand design projects.

  13. Antagonistic effect of chosen lactic acid bacteria strains on Salmonella species in meat and fermented sausages.

    Science.gov (United States)

    Gomółka-Pawlicka, M; Uradziński, J

    2003-01-01

    The aim of this study was to determine of influence of 15 strains of lactic acid bacteria on the growth of 7 Salmonella spp. strains in model set-ups, and in meat and ripened fermented sausages. The investigations were performed within the framework of three alternate stages which differed in respect to the products studied, the number of Lactobacillus spp. strains and, partly, methodological approach. The ratio between lactic acid bacteria and Salmonella strains studied was, depending on the alternate, 1:1, 1:2 and 2:1, respectively. The investigations also covered the water activity (a(w)) and pH of the tested products. The results obtained are shown in 12 figures and suggest that all the lactic acid bacteria strains used within the framework of the model set-ups showed antagonistic effect on all the Salmonella spp. strains. However, these abilities were not observed with respect to some lactic acid bacteria strains in meat and fermented sausage. The temperature and length of the incubation period of sausages, but not a(w) and pH, were found to have a distinct influence on the antagonistic interaction between the bacteria.

  14. Pituitary adenylate cyclase activating polypeptide (PACAP signalling exerts chondrogenesis promoting and protecting effects: implication of calcineurin as a downstream target.

    Directory of Open Access Journals (Sweden)

    Tamás Juhász

    Full Text Available Pituitary adenylate cyclase activating polypeptide (PACAP is an important neurotrophic factor influencing differentiation of neuronal elements and exerting protecting role during traumatic injuries or inflammatory processes of the central nervous system. Although increasing evidence is available on its presence and protecting function in various peripheral tissues, little is known about the role of PACAP in formation of skeletal components. To this end, we aimed to map elements of PACAP signalling in developing cartilage under physiological conditions and during oxidative stress. mRNAs of PACAP and its receptors (PAC1,VPAC1, VPAC2 were detectable during differentiation of chicken limb bud-derived chondrogenic cells in micromass cell cultures. Expression of PAC1 protein showed a peak on days of final commitment of chondrogenic cells. Administration of either the PAC1 receptor agonist PACAP 1-38, or PACAP 6-38 that is generally used as a PAC1 antagonist, augmented cartilage formation, stimulated cell proliferation and enhanced PAC1 and Sox9 protein expression. Both variants of PACAP elevated the protein expression and activity of the Ca-calmodulin dependent Ser/Thr protein phosphatase calcineurin. Application of PACAPs failed to rescue cartilage formation when the activity of calcineurin was pharmacologically inhibited with cyclosporine A. Moreover, exogenous PACAPs prevented diminishing of cartilage formation and decrease of calcineurin activity during oxidative stress. As an unexpected phenomenon, PACAP 6-38 elicited similar effects to those of PACAP 1-38, although to a different extent. On the basis of the above results, we propose calcineurin as a downstream target of PACAP signalling in differentiating chondrocytes either in normal or pathophysiological conditions. Our observations imply the therapeutical perspective that PACAP can be applied as a natural agent that may have protecting effect during joint inflammation and/or may promote

  15. 5α-Bile alcohols function as farnesoid X receptor antagonists

    International Nuclear Information System (INIS)

    Nishimaki-Mogami, Tomoko; Kawahara, Yosuke; Tamehiro, Norimasa; Yoshida, Takemi; Inoue, Kazuhide; Ohno, Yasuo; Nagao, Taku; Une, Mizuho

    2006-01-01

    The farnesoid X receptor (FXR) is a bile acid/alcohol-activated nuclear receptor that regulates lipid homeostasis. Unlike other steroid receptors, FXR binds bile acids in an orientation that allows the steroid nucleus A to face helix 12 in the receptor, a crucial domain for coactivator-recruitment. Because most naturally occurring bile acids and alcohols contain a cis-oriented A, which is distinct from that of other steroids and cholesterol metabolites, we investigated the role of this 5β-configuration in FXR activation. The results showed that the 5β-(A/B cis) bile alcohols 5β-cyprinol and bufol are potent FXR agonists, whereas their 5α-(A/B trans) counterparts antagonize FXR transactivation and target gene expression. Both isomers bound to FXR, but their ability to induce coactivator-recruitment and thereby induce transactivation differed. These findings suggest a critical role for the A orientation of bile salts in agonist/antagonist function

  16. MDM2 Antagonists Counteract Drug-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Anna E. Vilgelm

    2017-10-01

    Full Text Available Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.

  17. Gonadotrophin releasing hormone antagonist in IVF/ICSI

    Directory of Open Access Journals (Sweden)

    M S Kamath

    2008-01-01

    Full Text Available Objective : To study the efficacy of gonadotrophin releasing hormone (GnRH antagonist in In-vitro-fertilization/Intracytoplasmic sperm injection (IVF/ICSI cycles. Type of Study : Observational study. Setting: Reproductive Medicine Unit, Christian Medical College Hospital, Vellore, Tamil Nadu. Materials and Methods: GnRH antagonists were introduced into our practice in November 2005. Fifty-two women undergoing the antagonist protocol were studied and information gathered regarding patient profile, treatment parameters (total gonadotrophin dosage, duration of treatment, and oocyte yield, and outcomes in terms of embryological parameters (cleavage rates, implantation rates and clinical pregnancy. These parameters were compared with 121 women undergoing the standard long protocol. The costs between the two groups were also compared. Main Outcome : Clinical pregnancy rate. Results : The clinical pregnancy rate per embryo transfer in the antagonist group was 31.7% which was comparable to the clinical pregnancy rate in women undergoing the standard long protocol (30.63%. The costs between the two groups were comparable. Conclusions : GnRH antagonist protocol was found to be effective and comparable to the standard long protocol regimen. In addition it was simple, convenient, and patient friendly.

  18. Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test.

    Science.gov (United States)

    Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Ostadhadi, Sattar; Amini-Khoei, Hossein; Dehpour, Ahmad Reza

    2016-02-01

    Recent evidence indicates that 5-hydroxytryptamine 3 (5-HT3) antagonists such as ondansetron and tropisetron exert positive behavioral effects in animal models of depression. Due to the ionotropic nature of 5-HT3 and N-methyl-d-aspartate (NMDA) receptors, plus their contribution to the pathophysiology of depression, we investigated the possible role of NMDA receptors in the antidepressant-like effect of 5-HT3 receptor antagonists in male mice. In order to evaluate the animals' behavior in response to different treatments, we performed open-field test (OFT), forced swimming test (FST), and tail-suspension test (TST), which are considered as valid tasks for measuring locomotor activity and depressive-like behaviors in mice. Our data revealed that intraperitoneal (i.p.) administration of tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01, and 0.1μg/kg) significantly decreased the immobility time in FST and TST. Also, co-administration of subeffective doses of tropisetron (1mg/kg, i.p.) or ondansetron (0.001μg/kg, i.p.) with subeffective doses of NMDA receptor antagonists, ketamine (1mg/kg, i.p.), MK-801 (0.05mg/kg, i.p.) and magnesium sulfate (10mg/kg, i.p.) resulted in a reduced immobility time both in FST and TST. The subeffective dose of NMDA (NMDA receptor agonist, 75mg/kg, i.p.) abolished the effects of 5-HT3 antagonists in FST and TST, further supporting the presumed interaction between 5-HT3 and NMDA receptors. These treatments did not affect the locomotor behavior of animals in OFT. Finally, the results of our study suggest that the positive effects of 5-HT3 antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Potent and long-acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists.

    Science.gov (United States)

    Rivier, J; Gulyas, J; Kirby, D; Low, W; Perrin, M H; Kunitake, K; DiGruccio, M; Vaughan, J; Reubi, J C; Waser, B; Koerber, S C; Martinez, V; Wang, L; Taché, Y; Vale, W

    2002-10-10

    We present evidence that members of the corticotropin releasing factor (CRF) family assume distinct structures when interacting with the CRF(1) and CRF(2) receptors. Predictive methods, physicochemical measurements, and structure-activity relationship studies have suggested that CRF, its family members, and competitive antagonists such as astressin [cyclo(30-33)[DPhe(12),Nle(21),Glu(30),Lys(33),Nle(38)]hCRF((12-41))] assume an alpha-helical conformation when interacting with their receptors. We had shown that alpha-helical CRF((9-41)) and sauvagine showed some selectivity for CRF receptors other than that responsible for ACTH secretion(1) and later for CRF2.(2) More recently, we suggested the possibility of a helix-turn-helix motif around a turn encompassing residues 30-33(3) that would confer high affinity for both CRF(1) and CRF(2)(2,4) in agonists and antagonists of all members of the CRF family.(3) On the other hand, the substitutions that conferred ca. 100-fold CRF(2) selectivity to the antagonist antisauvagine-30 [[DPhe(11),His(12)]sauvagine((11-40))] did not confer such property to the corresponding N-terminally extended agonists. We find here that a Glu(32)-Lys(35) side chain to side chain covalent lactam constraint in hCRF and the corresponding Glu(31)-Lys(34) side chain to side chain covalent lactam constraint in sauvagine yield potent ligands that are selective for CRF(2). Additionally, we introduced deletions and substitutions known to increase duration of action to yield antagonists such as cyclo(31-34)[DPhe(11),His(12),C(alpha)MeLeu(13,39),Nle(17),Glu(31),Lys(34)]Ac-sauvagine((8-40)) (astressin(2)-B) with CRF(2) selectivities greater than 100-fold. CRF receptor autoradiography was performed in rat tissue known to express CRF(2) and CRF(1) in order to confirm that astressin(2)-B could indeed bind to established CRF(2) but not CRF(1) receptor-expressing tissues. Extended duration of action of astressin(2)-B vs that of antisauvagine-30 is demonstrated in

  20. Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours

    Energy Technology Data Exchange (ETDEWEB)

    Mansi, Rosalba; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); University of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Wang, Xuejuan [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Forrer, Flavio [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Erasmus Medical Centre, Nuclear Medicine, Rotterdam (Netherlands); Waser, Beatrice; Cescato, Renzo; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, Berne (Switzerland); Graham, Keith; Borkowski, Sandra [Bayer Schering Pharma AG, Global Drug Discovery, Berlin (Germany)

    2011-01-15

    Radiolabelled somatostatin-based antagonists show a higher uptake in tumour-bearing mouse models than agonists of similar or even distinctly higher receptor affinity. Very similar results were obtained with another family of G protein-coupled receptor ligands, the bombesin family. We describe a new conjugate, RM2, with the chelator DOTA coupled to D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH{sub 2} via the cationic spacer 4-amino-1-carboxymethyl-piperidine for labelling with radiometals such as {sup 111}In and {sup 68}Ga. RM2 was synthesized on a solid support and evaluated in vitro in PC-3 cells. IC{sub 50} and K{sub d} values were determined. The antagonist potency was evaluated by immunofluorescence-based internalization and Ca{sup 2+} mobilization assays. Biodistribution studies were performed in PC-3 and LNCaP tumour-bearing mice with {sup 111}In-RM2 and {sup 68}Ga-RM2, respectively. PET/CT studies were performed on PC-3 and LNCaP tumour-bearing nude mice with {sup 68}Ga-RM2. RM2 and {sup 111}In-RM2 are high-affinity and selective ligands for the GRP receptor (7.7{+-}3.3 nmol/l for RM2; 9.3{+-}3.3 nmol/l for {sup nat}In-RM2). The potent antagonistic properties were confirmed by an immunofluorescence-based internalization and Ca{sup 2+} mobilization assays. {sup 68}Ga- and {sup 111}In-RM2 showed high and specific uptake in both the tumour and the pancreas. Uptake in the tumour remained high (15.2{+-}4.8%IA/g at 1 h; 11.7{+-}2.4%IA/g at 4 h), whereas a relatively fast washout from the pancreas and the other abdominal organs was observed. Uptake in the pancreas decreased rapidly from 22.6{+-}4.7%IA/g at 1 h to 1.5{+-}0.5%IA/g at 4 h. RM2 was shown to be a potent GRPr antagonist. Pharmacokinetics and imaging studies indicate that {sup 111}In-RM2 and {sup 68}Ga-RM2 are ideal candidates for clinical SPECT and PET studies. (orig.)

  1. Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours

    International Nuclear Information System (INIS)

    Mansi, Rosalba; Maecke, Helmut R.; Wang, Xuejuan; Forrer, Flavio; Waser, Beatrice; Cescato, Renzo; Reubi, Jean Claude; Graham, Keith; Borkowski, Sandra

    2011-01-01

    Radiolabelled somatostatin-based antagonists show a higher uptake in tumour-bearing mouse models than agonists of similar or even distinctly higher receptor affinity. Very similar results were obtained with another family of G protein-coupled receptor ligands, the bombesin family. We describe a new conjugate, RM2, with the chelator DOTA coupled to D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2 via the cationic spacer 4-amino-1-carboxymethyl-piperidine for labelling with radiometals such as 111 In and 68 Ga. RM2 was synthesized on a solid support and evaluated in vitro in PC-3 cells. IC 50 and K d values were determined. The antagonist potency was evaluated by immunofluorescence-based internalization and Ca 2+ mobilization assays. Biodistribution studies were performed in PC-3 and LNCaP tumour-bearing mice with 111 In-RM2 and 68 Ga-RM2, respectively. PET/CT studies were performed on PC-3 and LNCaP tumour-bearing nude mice with 68 Ga-RM2. RM2 and 111 In-RM2 are high-affinity and selective ligands for the GRP receptor (7.7±3.3 nmol/l for RM2; 9.3±3.3 nmol/l for nat In-RM2). The potent antagonistic properties were confirmed by an immunofluorescence-based internalization and Ca 2+ mobilization assays. 68 Ga- and 111 In-RM2 showed high and specific uptake in both the tumour and the pancreas. Uptake in the tumour remained high (15.2±4.8%IA/g at 1 h; 11.7±2.4%IA/g at 4 h), whereas a relatively fast washout from the pancreas and the other abdominal organs was observed. Uptake in the pancreas decreased rapidly from 22.6±4.7%IA/g at 1 h to 1.5±0.5%IA/g at 4 h. RM2 was shown to be a potent GRPr antagonist. Pharmacokinetics and imaging studies indicate that 111 In-RM2 and 68 Ga-RM2 are ideal candidates for clinical SPECT and PET studies. (orig.)

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

    Science.gov (United States)

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

  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......: 3.1 on a scale of 0 to 10, average WRPE: 3.6 on a scale of 0 to 10) from 18 departments at three participating hospitals. Participants were randomly allocated at the cluster level to 10 weeks of: (1) workplace physical exercise (WORK) performed in groups during working hours for 5×10 minutes per...... exercise may decrease physical exertion during work. This study investigates the effect of workplace-based versus home-based physical exercise on physical exertion during work (WRPE) among healthcare workers. METHODS: 200 female healthcare workers (age: 42.0, body mass index: 24.1, average pain intensity...

  5. First Irish birth following IVF therapy using antagonist protocol.

    LENUS (Irish Health Repository)

    Mocanu, E V

    2012-02-01

    BACKGROUND: During in vitro fertilization (IVF), the prevention of a premature LH surge was traditionally achieved using a gonadotrophin releasing hormone agonist (GnRH-a), and more recently, a GnRH antagonist. AIMS: We report a case of a 37 year old treated using the GnRH antagonist in a second completed cycle of IVF. METHODS: IVF was performed for primary infertility of 5-year duration due to frozen pelvis secondary to endometriosis. RESULTS: Following controlled ovarian hyperstimulation, oocyte recovery and fertilization, cleavage and transfer of two zygotes, a pregnancy established. A twin gestation was diagnosed at 7-weeks scan and pregnancy ended with the delivery of twin girls by emergency caesarean section. CONCLUSION: This is a first report of a delivery following IVF using the antagonist protocol in Ireland. Such therapy is patient friendly and its use should be introduced on a larger scale in clinical practice.

  6. ANTAGONISTIC BACTERIA AGAINST SCHIZOPHYLLUM COMMUNE FR. IN PENINSULAR MALAYSIA

    Directory of Open Access Journals (Sweden)

    ANTARJO DIKIN

    2006-01-01

    Full Text Available Schizophyllum commune Fr., is one of the important fungi, causes brown germ and seed rot of oil palm. Biodiversity of antagonistic bacteria from oil palm plantations in Peninsular Malaysia is expected to support in development of biopesticide. Isolation with liquid assay and screening antagonistic bacteria using dual culture assay were carried out in the bioexploration. A total of 265 bacterial isolates from plant parts of oil palm screened 52 antagonistic bacterial isolates against 5. commune. Bacterial isolates were identified by using Biolog* Identification System i.e. Bacillus macroccanus, B. thermoglucosidasius, Burkholderia cepacia, B. gladioli, B. multivorans, B pyrrocinia, B. spinosa, Corynebacterium agropyri, C. misitidis, Enterobacter aerogenes, Microbacterium testaceum, Pseudomonas aeruginosa, P. citronellolis, Rhodococcus rhodochrous, Serratia ficaria, Serratia sp., S. marcescens, Staphylococcus sciuri, Sternotrophomonas maltophilia.

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

    OpenAIRE

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

    1991-01-01

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

  8. Fungal endophytes isolated from Protium heptaphyllum and Trattinnickia rhoifolia as antagonists of Fusarium oxysporum.

    Science.gov (United States)

    Fierro-Cruz, Juan E; Jiménez, Pedro; Coy-Barrera, Ericsson

    Control of fungal pathogens is mainly addressed by the use of chemically synthesized fungicides which result in environmental pollution, developing resistance after prolonged use. In this context, endophytes have been recognized as potential biocontrollers, and also as a promising source of antifungal metabolites. Therefore, as part of our research on phytopathogen controllers, 355 fungal endophytes were isolated from Protium heptaphyllum and Trattinnickia rhoifolia (Burseraceae), both ethnobotanically important tree species that produce secondary metabolites of agronomic and industrial interest. Endophytes were tested by in vitro dual culture against Fusarium oxysporum, a phytopathogen of agronomic importance. Five endophytes exerted at least 40% inhibition on F. oxysporum growth. Ethyl acetate (EtOAc) extracts were obtained from the most active antagonistic fungi, after growing them in three different liquid media. The extracts were tested against a conidial suspension of F. oxysporum by direct bioautography. Two extracts derived from fungi identified as Chaetomium globosum, F211_UMNG and Meyerozima sp. F281_UMNG showed inhibition of pathogen growth. Isolate C. globosum, F211_UMNG was selected for a chemical analysis by RP-HPLC-DAD-ESI-MS and antifungal molecules such as cladosporin, chaetoatrosin A and chaetoviridin A were annotated and identified based on their MS data. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. JB-9322, a new selective histamine H2-receptor antagonist with potent gastric mucosal protective properties.

    Science.gov (United States)

    Palacios, B; Montero, M J; Sevilla, M A; Román, L S

    1995-05-01

    1. JB-9322 is a selective histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. 2. The affinity of JB-9322 for the guinea-pig atria histamine H2-receptor was approximately 2 times greater than that of ranitidine. 3. In vivo, the ID50 value for the inhibition of gastric acid secretion in pylorus-ligated rats was 5.28 mg kg-1 intraperitoneally. JB-9322 also dose-dependently inhibited gastric juice volume and pepsin secretion. In gastric lumen-perfused rats, intravenous injection of JB-9322 dose-dependently reduced histamine-, pentagastrin- and carbachol-stimulated gastric acid secretion. 4. JB-9322 showed antiulcer activity against aspirin and indomethacin-induced gastric lesions and was more potent than ranitidine. 5. JB-9322 effectively inhibited macroscopic gastric haemorrhagic lesions induced by ethanol. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ID50 value for these lesions was 1.33 mg kg-1. By contrast, ranitidine (50 mg kg-1) failed to reduce these lesions. In addition, the protective effect of JB-9322 was independent of prostaglandin synthesis. 6. These results indicate that JB-9322 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.

  10. Endothelin receptor antagonists influence cardiovascular morphology in uremic rats.

    Science.gov (United States)

    Nabokov, A V; Amann, K; Wessels, S; Münter, K; Wagner, J; Ritz, E

    1999-02-01

    In is generally held that renal failure results in blood pressure (BP)-independent structural changes of the myocardium and the vasculature. The contribution, if any, of endothelin (ET) to these changes has been unknown. We morphometrically studied random samples of the left ventricle myocardium and small intramyocardial arteries in subtotally (5/6) nephrectomized (SNx) male Sprague-Dawley rats treated with either the selective ETA receptor antagonist BMS182874 (30 mg/kg/day) or the nonselective ETA/ETB receptor antagonist Ro46-2005 (30 mg/kg/day) in comparison with either sham-operated rats, untreated SNx, or SNx rats treated with the angiotensin-converting enzyme inhibitor trandolapril (0.1 mg/kg/day). Eight weeks later, systolic BP was lower in trandolapril-treated SNx compared with untreated SNx animals. No decrease in BP was seen following either ET receptor antagonist at the dose used. A significantly increased volume density of the myocardial interstitium was found in untreated SNx rats as compared with sham-operated controls. Such interstitial expansion was prevented by trandolapril and either ET receptor antagonist. SNx caused a substantial increase in the wall thickness of small intramyocardial arteries. The increase was prevented by trandolapril or BMS182874 treatment. The arteriolar wall:lumen ratio was significantly lower in all treated groups when compared with untreated SNx. In contrast, only trandolapril, but not the ET receptor antagonists, attenuated thickening of the aortic media in SNx animals. The ETA-selective and ETA/ETB-nonselective receptor antagonists appear to prevent development of myocardial fibrosis and structural changes of small intramyocardial arteries in experimental chronic renal failure. This effect is independent of systemic BP.

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

    Science.gov (United States)

    2017-03-01

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

  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. Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

    Science.gov (United States)

    Zuercher, William J; Buckholz, Richard G; Campobasso, Nino; Collins, Jon L; Galardi, Cristin M; Gampe, Robert T; Hyatt, Stephen M; Merrihew, Susan L; Moore, John T; Oplinger, Jeffrey A; Reid, Paul R; Spearing, Paul K; Stanley, Thomas B; Stewart, Eugene L; Willson, Timothy M

    2010-04-22

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  14. Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist

    Science.gov (United States)

    Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev

    1982-02-01

    The glucagon analog [l-Nα-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

  15. Exercise order affects the total training volume and the ratings of perceived exertion in response to a super-set resistance training session

    Directory of Open Access Journals (Sweden)

    Balsamo S

    2012-02-01

    Full Text Available Sandor Balsamo1–3, Ramires Alsamir Tibana1,2,4, Dahan da Cunha Nascimento1,2, Gleyverton Landim de Farias1,2, Zeno Petruccelli1,2, Frederico dos Santos de Santana1,2, Otávio Vanni Martins1,2, Fernando de Aguiar1,2, Guilherme Borges Pereira4, Jéssica Cardoso de Souza4, Jonato Prestes41Department of Physical Education, Centro Universitário UNIEURO, Brasília, 2GEPEEFS (Resistance training and Health Research Group, Brasília/DF, 3Graduate Program in Medical Sciences, School of Medicine, Universidade de Brasília (UnB, Brasília, 4Graduation Program in Physical Education, Catholic University of Brasilia (UCB, Brasília/DF, BrazilAbstract: The super-set is a widely used resistance training method consisting of exercises for agonist and antagonist muscles with limited or no rest interval between them – for example, bench press followed by bent-over rows. In this sense, the aim of the present study was to compare the effects of different super-set exercise sequences on the total training volume. A secondary aim was to evaluate the ratings of perceived exertion and fatigue index in response to different exercise order. On separate testing days, twelve resistance-trained men, aged 23.0 ± 4.3 years, height 174.8 ± 6.75 cm, body mass 77.8 ± 13.27 kg, body fat 12.0% ± 4.7%, were submitted to a super-set method by using two different exercise orders: quadriceps (leg extension + hamstrings (leg curl (QH or hamstrings (leg curl + quadriceps (leg extension (HQ. Sessions consisted of three sets with a ten-repetition maximum load with 90 seconds rest between sets. Results revealed that the total training volume was higher for the HQ exercise order (P = 0.02 with lower perceived exertion than the inverse order (P = 0.04. These results suggest that HQ exercise order involving lower limbs may benefit practitioners interested in reaching a higher total training volume with lower ratings of perceived exertion compared with the leg extension plus leg curl

  16. Antagonistic interactions and production of halocin antimicrobial peptides among extremely halophilic prokaryotes isolated from the solar saltern of Sfax, Tunisia.

    Science.gov (United States)

    Ghanmi, Fadoua; Carré-Mlouka, Alyssa; Vandervennet, Manon; Boujelben, Ines; Frikha, Doniez; Ayadi, Habib; Peduzzi, Jean; Rebuffat, Sylvie; Maalej, Sami

    2016-05-01

    Thirty-five extremely halophilic microbial strains isolated from crystallizer (TS18) and non-crystallizer (M1) ponds in the Sfax solar saltern in Tunisia were examined for their ability to exert antimicrobial activity. Antagonistic assays resulted in the selection of eleven strains that displayed such antimicrobial activity and they were further characterized. Three cases of cross-domain inhibition (archaea/bacteria or bacteria/archaea) were observed. Four archaeal strains exerted antimicrobial activity against several other strains. Three strains, for which several lines of evidence suggested the antimicrobial activity was, at least in part, due to peptide/protein agents (Halobacterium salinarum ETD5, Hbt. salinarum ETD8, and Haloterrigena thermotolerans SS1R12), were studied further. Optimal culture conditions for growth and antimicrobial production were determined. Using DNA amplification with specific primers, sequencing and RT-PCR analysis, Hbt. salinarum ETD5 and Hbt. salinarum ETD8 were shown to encode and express halocin S8, a hydrophobic antimicrobial peptide targeting halophilic archaea. Although the gene encoding halocin H4 was amplified from the genome of Htg. thermotolerans SS1R12, no transcript could be detected and the antimicrobial activity was most likely due to multiple antimicrobial compounds. This is also the first report that points to four different strains isolated from different geographical locations with the capacity to produce identical halocin S8 proteins.

  17. 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression.

    Directory of Open Access Journals (Sweden)

    Zaki K Hassan-Smith

    Full Text Available Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia, but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH2D3, but not inactive 25-hydroxyvitamin D3 (25OHD3, correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02, velocity (Vmax, rho = 0.40, p = 0.02 and jump height (rho = 0.36, p = 0.04. Lean mass correlated positively with 1α,25(OH2D3 (rho = 0.47, p = 0.02, in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH2D3 had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively. Serum 25OHD3 and 24,25(OH2D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH2D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH2D3 has limited effects on muscle gene expression, but is associated with increased muscle strength and lean mass in women. These pleiotropic effects of the vitamin D 'metabolome' on muscle function indicate that future supplementation studies should not be restricted to conventional analysis of the major circulating form of vitamin D, 25OHD3.

  18. Deoxycholic acid and selenium metabolite methylselenol exert common and distinct effects on cell cycle, apoptosis, and MAP kinase pathway in HCT116 human colon cancer cells.

    Science.gov (United States)

    Zeng, Huawei; Botnen, James H; Briske-Anderson, Mary

    2010-01-01

    The cell growth inhibition induced by bile acid deoxycholic acid (DCA) may cause compensatory hyperproliferation of colonic epithelial cells and consequently increase colon cancer risk. On the other hand, there is increasing evidence for the efficacy of certain forms of selenium (Se) as anticancer nutrients. Methylselenol has been hypothesized to be a critical Se metabolite for anticancer activity in vivo. In this study, we demonstrated that both DCA (75-300 micromol/l) and submicromolar methylselenol inhibited colon cancer cell proliferation by up to 64% and 63%, respectively. In addition, DCA and methylselenol each increased colon cancer cell apoptosis rate by up to twofold. Cell cycle analyses revealed that DCA induced an increase in only the G1 fraction with a concomitant drop in G2 and S-phase; in contrast, methylselenol led to an increase in the G1 and G2 fractions with a concomitant drop only in the S-phase. Although both DCA and methylselenol significantly promoted apoptosis and inhibited cell growth, examination of mitogen-activated protein kinase (MAPK) pathway activation showed that DCA, but not methylselenol, induced SAPK/JNK1/2, p38 MAPK, ERK1/2 activation. Thus, our data provide, for the first time, the molecular basis for opposite effects of methylselenol and DCA on colon tumorigenesis.

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

    Science.gov (United States)

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

    2014-01-01

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

  20. NMDA receptor antagonists for the treatment of neuropathic pain

    NARCIS (Netherlands)

    Collins, S.; Sigtermans, M.J.; Dahan, A.; Zuurmond, W.W.A.; Perez, R.S.G.M.

    2010-01-01

    Objective. The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis evaluating the effects of (individual) NMDA receptor antagonists on neuropathic pain, and the response

  1. Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists

    Science.gov (United States)

    2016-08-01

    approximately halfway into the solution. All animals were tested at 60, 15 and 0 min before drug injection. For each animal , the first reading was discarded...approval (December 31, 2015), hiring new personnel, conducting baseline testing for procedures not involving animals , testing equipment, developing...treatment; Analgesia; Nociception; Antinociception; Inflammation; Chemokines; Chemokine receptor antagonists; Opioid analgesics; Animal models of pain

  2. Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists

    DEFF Research Database (Denmark)

    Pottegård, Anton; Christensen, Rene dePont; Wang, Shirley V

    2014-01-01

    PurposeWe present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs). We use the putative interaction between VKAs and tramadol as a case study. MethodsWe used...

  3. Komplikationer til langtidsbehandling med vitamin K-antagonister

    DEFF Research Database (Denmark)

    May, O; Garne, E; Mickley, H

    1990-01-01

    Long-term treatment with vitamin K antagonists (vKA) frequently involves complications. The commonest complication is haemorrhage and cases of serious haemorrhage are stated in the literature to occur with a frequency per 1,000 treatment years of 12-108, of which 2-17 are fatal. The majority...

  4. Management of hyperkalaemia consequent to mineralocorticoid-receptor antagonist therapy

    NARCIS (Netherlands)

    Roscioni, Sara S.; de Zeeuw, Dick; Bakker, Stephan J. L.; Lambers Heerspink, Hiddo J.

    2012-01-01

    Mineralocorticoid-receptor antagonists (MRAs) reduce blood pressure and albuminuria in patients treated with angiotensin-converting-enzyme inhibitors or angiotensin-II-receptor blockers. The use of MRAs, however, is limited by the occurrence of hyperkalaemia, which frequently occurs in patients

  5. Effect of Three Calmodulin Antagonists on Subpopulations of CD44 ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical ... cancer stem cells. It is not known, however, whether targeting CD44 can alter the fate of cancer stem cells themselves. In this study, the effect of the calmodulin antagonists (N-(10-.

  6. The Effect of Sympathetic Antagonists on the Antidepressant Action ...

    African Journals Online (AJOL)

    Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor ...

  7. The Effect of Antagonist Muscle Sensory Input on Force Regulation.

    Directory of Open Access Journals (Sweden)

    Tanya Onushko

    Full Text Available The purpose of this study was to understand how stretch-related sensory feedback from an antagonist muscle affects agonist muscle output at different contraction levels in healthy adults. Ten young (25.3 ± 2.4 years, healthy subjects performed constant isometric knee flexion contractions (agonist at 6 torque levels: 5%, 10%, 15%, 20%, 30%, and 40% of their maximal voluntary contraction. For half of the trials, subjects received patellar tendon taps (antagonist sensory feedback during the contraction. We compared error in targeted knee flexion torque and hamstring muscle activity, with and without patellar tendon tapping, across the 6 torque levels. At lower torque levels (5%, 10%, and 15%, subjects produced greater knee torque error following tendon tapping compared with the same torque levels without tendon tapping. In contrast, we did not find any difference in torque output at higher target levels (20%, 30%, and 40% between trials with and without tendon tapping. We also observed a load-dependent increase in the magnitude of agonist muscle activity after tendon taps, with no associated load-dependent increase in agonist and antagonist co-activation, or reflex inhibition from the antagonist tapping. The findings suggest that at relatively low muscle activity there is a deficiency in the ability to correct motor output after sensory disturbances, and cortical centers (versus sub-cortical are likely involved.

  8. Antagonistic bioactivity of an endophytic bacterium isolated from ...

    African Journals Online (AJOL)

    Antagonistic bioactivity of an endophytic bacterium isolated from Epimedium brevicornu Maxim. R He, G Wang, X Liu, C Zhang, F Lin. Abstract. Endophytic bacteria are one of the most potential biological control agents in plant disease protection. The aim of this work was to evaluate the antimicrobial activities of a strain of ...

  9. Multiple sclerosis following treatment with a cannabinoid receptor-1 antagonist

    NARCIS (Netherlands)

    van Oosten, B. W.; Killestein, J.; Mathus-Vliegen, E. M. H.; Polman, C. H.

    2004-01-01

    Laboratory research including animal models of human disease suggests that cannabinoids might have therapeutic potential in multiple sclerosis (MS). We have recently seen a 46-year-old woman who developed MS after starting treatment with a cannabinoid receptor antagonist for obesity. The occurrence

  10. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qun-Yi; Zhang, Meng [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Hallis, Tina M.; DeRosier, Therese A. [Cell Systems Division, Invitrogen, Madison, WI (United States); Yue, Jian-Min; Ye, Yang [State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Mais, Dale E. [The National Center for Drug Screening, Shanghai (China); MPI Research, Mattawan, MI (United States); Wang, Ming-Wei, E-mail: wangmw@mail.shcnc.ac.cn [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China)

    2010-01-15

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  11. Manumycin from a new Streptomyces strain shows antagonistic ...

    African Journals Online (AJOL)

    Manumycin from a new Streptomyces strain shows antagonistic effect against methicillin-resistant Staphylococcus aureus (MRSA)/vancomycin-resistant enterococci (VRE) strains from Korean Hospitals. Yun Hee Choi, Seung Sik Cho, Jaya Ram Simkhada, Chi Nam Seong, Hyo Jeong Lee, Hong Seop Moon, Jin Cheol Yoo ...

  12. Effects of calcium antagonists on hypertension and diastolic function ...

    African Journals Online (AJOL)

    Calcium antagonists are known to decrease blood pressure acutely and chronically in hypertensive patients with hypertensive heart disease, and also to improve their systolic function. However, disorders of diastolic function may occur early in hypertensive heart disease. The improvement of diastolic function by nifedipine ...

  13. Sympatho-inhibitory properties of various AT1 receptor antagonists

    NARCIS (Netherlands)

    Balt, Jippe C.; Mathy, Marie-Jeanne; Pfaffendorf, Martin; van Zwieten, Peter A.

    2002-01-01

    It is well known that angiotensin II (Ang II) can facilitate the effects of sympathetic neurotransmission. In the present study, using various experimental models, we investigated the inhibitory effects of several Ang II subtype 1 receptor (AT1) antagonists on this Ang II-induced facilitation. We

  14. Possible site of action of CGRP antagonists in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Olesen, Jes

    2011-01-01

    The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. Both are effective in migraine but in doses much higher than would be predicted from receptor binding and other in vitro results. This could perhaps suggest an effect of CGRP antagoni...

  15. Christianity and Antagonistic Challenges in Igbo Land of Nigeria: A ...

    African Journals Online (AJOL)

    Christianity and Antagonistic Challenges in Igbo Land of Nigeria: A Reflection. ... The church mission society (CMS) along side the Royal Niger Company was working ... is to win the confidence of the people by establishing agricultural settlements, ... FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use ...

  16. Possible site of action of CGRP antagonists in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Olesen, Jes

    2011-01-01

    The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. Both are effective in migraine but in doses much higher than would be predicted from receptor binding and other in vitro results. This could perhaps suggest an effect of CGRP...

  17. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Kjaergard, L L; Gluud, C

    2001-01-01

    The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...... antagonists for hepatic encephalopathy, but the results are conflicting....

  18. Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Bruce Lyeth

    2013-06-01

    Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability in the United States. Despite more than 30 years of research, no pharmacological agents have been identified that improve neurological function following TBI. However, several lines of research described in this review provide support for further development of voltage gated calcium channel (VGCC antagonists as potential therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and sometimes enduring increase in intracellular calcium ([Ca2+]i. These fluxes in [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to long-term cell dysfunction in surviving cells. In a limited number of in vitro experiments, both L-type and N-type VGCC antagonists successfully reduced calcium loads as well as neuronal and astrocytic cell death following mechanical injury. In rodent models of TBI, administration of VGCC antagonists reduced cell death and improved cognitive function. It is clear that there is a critical need to find effective therapeutics and rational drug delivery strategies for the management and treatment of TBI, and we believe that further investigation of VGCC antagonists should be pursued before ruling out the possibility of successful translation to the clinic.

  19. Antagonistic bioactivity of endophytic strains isolated from Salvia ...

    African Journals Online (AJOL)

    The antibiotic-producing potential of endophytic populations from medical plant of Salvia miltiorrhiza was examined. A total of 63 isolates was screened against five fungal and three bacterial species for the production of antimicrobial compounds. It showed that more isolates was antagonistic to fungi than to bacteria.

  20. Screening and Mechanism of Trapping Ligand Antagonist Peptide ...

    African Journals Online (AJOL)

    Purpose: The aim of the present study was to develop peptide H9 as an efficient antagonist of human cytomegalovirus (HCMV) chemokine receptor US28. Methods: US28 gene was amplified from HCMV, and a stable expression system was constructed using NIH/3T3 cells. Interaction between peptide H9 and receptor ...

  1. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

    NARCIS (Netherlands)

    Parry-Jones, Adrian R.; Di Napoli, Mario; Goldstein, Joshua N.; Schreuder, Floris H B M; Tetri, Sami; Tatlisumak, Turgut; Yan, Bernard; Van Nieuwenhuizen, Koen M.; Dequatre-Ponchelle, Nelly; Lee-Archer, Matthew; Horstmann, Solveig; Wilson, Duncan; Pomero, Fulvio; Masotti, Luca; Lerpiniere, Christine; Godoy, Daniel Agustin; Cohen, Abigail S.; Houben, Rik; Al-Shahi Salman, Rustam; Pennati, Paolo; Fenoglio, Luigi; Werring, David; Veltkamp, Roland; Wood, Edith; Dewey, Helen M.; Cordonnier, Charlotte; Klijn, Catharina J M; Meligeni, Fabrizio; Davis, Stephen M.; Huhtakangas, Juha; Staals, Julie; Rosand, Jonathan; Meretoja, Atte

    2015-01-01

    Objective There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different

  2. Role of muscarinic receptor antagonists in urgency and nocturia

    NARCIS (Netherlands)

    Michel, Martin C.; de La Rosette, Jean J. M. C. H.

    2005-01-01

    The overactive bladder (OAB) syndrome is defined as urgency, with or without urgency incontinence, usually accompanied by frequency and nocturia. Muscarinic receptor antagonists are the most established form of treatment for OAB, but until recently their effectiveness was only confirmed for symptoms

  3. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    International Nuclear Information System (INIS)

    Li, Qun-Yi; Zhang, Meng; Hallis, Tina M.; DeRosier, Therese A.; Yue, Jian-Min; Ye, Yang; Mais, Dale E.; Wang, Ming-Wei

    2010-01-01

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K i = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  4. Efficacy and safety of histamine-2 receptor antagonists

    NARCIS (Netherlands)

    van der Pol, Rachel; Langendam, Miranda; Benninga, Marc; van Wijk, Michiel; Tabbers, Merit

    2014-01-01

    Histamine-2 receptor antagonists (H2RAs) are frequently used in the treatment of gastroesophageal reflux disease (GERD) in children; however, their efficacy and safety is questionable. To systematically review the literature to assess the efficacy and safety of H2RAs in pediatric GERD. PubMed,

  5. NK-1 receptor antagonists as anti-cancer drugs

    Indian Academy of Sciences (India)

    The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, ...

  6. PARTIAL AGONISTS, FULL AGONISTS, ANTAGONISTS - DILEMMAS OF DEFINITION

    NARCIS (Netherlands)

    HOYER, D; BODDEKE, HWGM

    The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or

  7. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children

    DEFF Research Database (Denmark)

    Bisgaard, H; Nielsen, K G

    2000-01-01

    We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5...

  8. Antagonistic interactions between plant competition and insect herbivory.

    Science.gov (United States)

    Schädler, Martin; Brandl, Roland; Haase, Josephine

    2007-06-01

    Interspecific competition between plants and herbivory by specialized insects can have synergistic effects on the growth and performance of the attacked host plant. We tested the hypothesis that competition between plants may also negatively affect the performance of herbivores as well as their top-down effect on the host plant. In such a case, the combined effects of competition and herbivory may be less than expected from a simple multiplicative response. In other words, competition and herbivory may interact antagonistically. In a greenhouse experiment, Poa annua was grown in the presence or absence of a competitor (either Plantago lanceolata or Trifolium repens), as well as with or without a Poa-specialist aphid herbivore. Both competition and herbivory negatively affected Poa growth. Competition also reduced aphid density on Poa. This effect could in part be explained by changes in the biomass and the nitrogen content of Poa shoots. In treatments with competitors, reduced aphid densities alleviated the negative effect of herbivory on above- and belowground Poa biomass. Hence, we were able to demonstrate an antagonistic interaction between plant-plant interspecific competition and herbivory. However, response indices suggested that antagonistic interactions between competition and herbivory were contingent on the identity of the competitor. We found the antagonistic effect only in treatments with T. repens as the competitor. We conclude that both competitor identity and the herbivore's ability to respond with changes in its density or activity to plant competition affect the magnitude and direction (synergistic vs. antagonistic) of the interaction between competition and herbivory on plant growth.

  9. 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.

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

    Science.gov (United States)

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

    2014-09-01

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

  11. Shifting to a non-vitamin K antagonist oral anticoagulation agent from vitamin K antagonist in atrial fibrillation

    DEFF Research Database (Denmark)

    Fosbøl, Emil L; Vinding, Naja Emborg; Lamberts, Morten

    2017-01-01

    Aims: After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran...

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

    Science.gov (United States)

    Gustafsson, Niclas; Salzmann-Erikson, Martin

    2016-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Romain eNardou

    2011-07-01

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

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

    Science.gov (United States)

    Banerjee, Purnajyoti; McLean, Christopher

    2011-06-14

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

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

    Science.gov (United States)

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

    2018-05-01

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

  16. 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.

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

    Science.gov (United States)

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

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

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

    Science.gov (United States)

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

    2011-01-01

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

  19. Antagonistic effect of Lactobacillus strains against gas-producing coliforms isolated from colicky infants

    Directory of Open Access Journals (Sweden)

    Oggero Roberto

    2011-06-01

    Full Text Available Abstract Background Infantile colic is a common disturb within the first 3 months of life, nevertheless the pathogenesis is incompletely understood and treatment remains an open issue. Intestinal gas production is thought to be one of the causes of abdominal discomfort in infants suffering from colic. However, data about the role of the amount of gas produced by infants' colonic microbiota and the correlation with the onset of colic symptoms are scanty. The benefit of supplementation with lactobacilli been recently reported but the mechanisms by which they exert their effects have not yet been fully defined. This study was performed to evaluate the interaction between Lactobacillus spp. strains and gas-forming coliforms isolated from stools of colicky infants. Results Strains of coliforms were isolated from stools of 45 colicky and 42 control breastfed infants in McConkey Agar and identified using PCR with species-specific primers, and the BBL™ Enterotube™ II system for Enterobacteriaceae. Gas-forming capability of coliforms was assessed in liquid cultures containing lactose as sole carbon source. The average count of total coliforms in colicky infants was significantly higher than controls: 5.98 (2.00-8.76 log10 vs 3.90 (2.50-7.10 CFU/g of faeces (p = 0.015. The following strains were identified: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae and Enterococcus faecalis. Then, 27 Lactobacillus strains were tested for their antagonistic effect against coliforms both by halo-forming method and in liquid co-cultures. Lactobacillus delbrueckii subsp.delbrueckii DSM 20074 and L. plantarum MB 456 were able to inhibit all coliforms strains (halo-forming method, also in liquid co-cultures, thus demonstrating an antagonistic activity. Conclusions This study shows that two out of 27 strains of Lactobacillus examined possess an antimicrobial effect against six species of gas-forming coliforms

  20. Antagonistic effect of Lactobacillus strains against gas-producing coliforms isolated from colicky infants.

    Science.gov (United States)

    Savino, Francesco; Cordisco, Lisa; Tarasco, Valentina; Locatelli, Emanuela; Di Gioia, Diana; Oggero, Roberto; Matteuzzi, Diego

    2011-06-30

    Infantile colic is a common disturb within the first 3 months of life, nevertheless the pathogenesis is incompletely understood and treatment remains an open issue. Intestinal gas production is thought to be one of the causes of abdominal discomfort in infants suffering from colic. However, data about the role of the amount of gas produced by infants' colonic microbiota and the correlation with the onset of colic symptoms are scanty. The benefit of supplementation with lactobacilli been recently reported but the mechanisms by which they exert their effects have not yet been fully defined. This study was performed to evaluate the interaction between Lactobacillus spp. strains and gas-forming coliforms isolated from stools of colicky infants. Strains of coliforms were isolated from stools of 45 colicky and 42 control breastfed infants in McConkey Agar and identified using PCR with species-specific primers, and the BBL™ Enterotube™ II system for Enterobacteriaceae. Gas-forming capability of coliforms was assessed in liquid cultures containing lactose as sole carbon source. The average count of total coliforms in colicky infants was significantly higher than controls: 5.98 (2.00-8.76) log10 vs 3.90 (2.50-7.10) CFU/g of faeces (p = 0.015). The following strains were identified: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae and Enterococcus faecalis. Then, 27 Lactobacillus strains were tested for their antagonistic effect against coliforms both by halo-forming method and in liquid co-cultures. Lactobacillus delbrueckii subsp. delbrueckii DSM 20074 and L. plantarum MB 456 were able to inhibit all coliforms strains (halo-forming method), also in liquid co-cultures, thus demonstrating an antagonistic activity. This study shows that two out of 27 strains of Lactobacillus examined possess an antimicrobial effect against six species of gas-forming coliforms isolated from colicky infants. Our findings may stimulate

  1. Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

    Directory of Open Access Journals (Sweden)

    Connie Slocum

    2014-07-01

    Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

  2. Superparamagnetic iron oxide nanoparticles exert different cytotoxic effects on cells grown in monolayer cell culture versus as multicellular spheroids

    Energy Technology Data Exchange (ETDEWEB)

    Theumer, Anja; Gräfe, Christine; Bähring, Franziska [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Bergemann, Christian [Chemicell GmbH, Eresburgstrasse 22–23, 12103 Berlin (Germany); Hochhaus, Andreas [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Clement, Joachim H., E-mail: joachim.clement@med.uni-jena.de [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany)

    2015-04-15

    The aim of this study was to investigate the interaction of superparamagnetic iron oxide nanoparticles (SPION) with human blood–brain barrier-forming endothelial cells (HBMEC) in two-dimensional cell monolayers as well as in three-dimensional multicellular spheroids. The precise nanoparticle localisation and the influence of the NP on the cellular viability and the intracellular Akt signalling were studied in detail. Long-term effects of different polymer-coated nanoparticles (neutral fluidMAG-D, anionic fluidMAG-CMX and cationic fluidMAG-PEI) and the corresponding free polymers on cellular viability of HBMEC were investigated by real time cell analysis studies. Nanoparticles exert distinct effects on HBMEC depending on the nanoparticles' surface charge and concentration, duration of incubation and cellular context. The most severe effects were caused by PEI-coated nanoparticles. Concentrations above 25 µg/ml led to increased amounts of dead cells in monolayer culture as well as in multicellular spheroids. On the level of intracellular signalling, context-dependent differences were observed. Monolayer cultures responded on nanoparticle incubation with an increase in Akt phosphorylation whereas spheroids on the whole show a decreased Akt activity. This might be due to the differential penetration and distribution of PEI-coated nanoparticles.

  3. Opioid antagonists with minimal sedation for opioid withdrawal.

    Science.gov (United States)

    Gowing, Linda; Ali, Robert; White, Jason M

    2017-05-29

    Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications. We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant studies. We included randomised and quasi-randomised controlled clinical trials along with prospective controlled cohort studies comparing opioid antagonists plus minimal sedation versus other approaches or different opioid antagonist regimens for withdrawal in opioid-dependent participants. We used standard methodological procedures expected by Cochrane. Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed.Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha 2 -adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine.Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient

  4. Nonpeptidic urotensin-II receptor antagonists I: in vitro pharmacological characterization of SB-706375

    Science.gov (United States)

    Douglas, Stephen A; Behm, David J; Aiyar, Nambi V; Naselsky, Diane; Disa, Jyoti; Brooks, David P; Ohlstein, Eliot H; Gleason, John G; Sarau, Henry M; Foley, James J; Buckley, Peter T; Schmidt, Dulcie B; Wixted, William E; Widdowson, Katherine; Riley, Graham; Jin, Jian; Gallagher, Timothy F; Schmidt, Stanley J; Ridgers, Lance; Christmann, Lisa T; Keenan, Richard M; Knight, Steven D; Dhanak, Dashyant

    2005-01-01

    SB-706375 potently inhibited [125I]hU-II binding to both mammalian recombinant and ‘native' UT receptors (Ki 4.7±1.5 to 20.7±3.6 nM at rodent, feline and primate recombinant UT receptors and Ki 5.4±0.4 nM at the endogenous UT receptor in SJRH30 cells). Prior exposure to SB-706375 (1 μM, 30 min) did not alter [125I]hU-II binding affinity or density in recombinant cells (KD 3.1±0.4 vs 5.8±0.9 nM and Bmax 3.1±1.0 vs 2.8±0.8 pmol mg−1) consistent with a reversible mode of action. The novel, nonpeptidic radioligand [3H]SB-657510, a close analogue of SB-706375, bound to the monkey UT receptor (KD 2.6±0.4 nM, Bmax 0.86±0.12 pmol mg−1) in a manner that was inhibited by both U-II isopeptides and SB-706375 (Ki 4.6±1.4 to 17.6±5.4 nM) consistent with the sulphonamides and native U-II ligands sharing a common UT receptor binding domain. SB-706375 was a potent, competitive hU-II antagonist across species with pKb 7.29–8.00 in HEK293-UT receptor cells (inhibition of [Ca2+]i-mobilization) and pKb 7.47 in rat isolated aorta (inhibition of contraction). SB-706375 also reversed tone established in the rat aorta by prior exposure to hU-II (Kapp∼20 nM). SB-706375 was a selective U-II antagonist with ⩾100-fold selectivity for the human UT receptor compared to 86 distinct receptors, ion channels, enzymes, transporters and nuclear hormones (Ki/IC50>1 μM). Accordingly, the contractile responses induced in isolated aortae by KCl, phenylephrine, angiotensin II and endothelin-1 were unaltered by SB-706375 (1 μM). In summary, SB-706375 is a high-affinity, surmountable, reversible and selective nonpeptide UT receptor antagonist with cross-species activity that will assist in delineating the pathophysiological actions of U-II in mammals. PMID:15852036

  5. GnRH antagonist versus long agonist protocols in IVF

    DEFF Research Database (Denmark)

    Lambalk, C B; Banga, F R; Huirne, J A

    2017-01-01

    BACKGROUND: Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist...... was not the only variable between the compared study arms. OBJECTIVE AND RATIONALE: The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. SEARCH...... in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF...

  6. Interleukin-1-receptor antagonist in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Larsen, Claus M; Faulenbach, Mirjam; Vaag, Allan

    2007-01-01

    BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell...... proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive...... placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemic-euglycemic clamp study. The primary...

  7. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn

    2011-01-01

    Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia. Areas covered......: Preclinical, clinical and post-mortem studies of the serotonin 5-HT2A system in schizophrenia are reviewed. The implications of a combined D2 and 5-HT2A receptor blockade, which is obtained by several current antipsychotic drugs, are discussed, and the rationale for the development of more selective 5-HT2A...... receptor antagonists is evaluated. Moreover, the investigational pipeline of major pharmaceutical companies is examined and an Internet search conducted to identify other pharmaceutical companies investigating 5-HT2A receptor antagonists for the treatment of schizophrenia. Expert opinion: 5-HT2A receptor...

  8. Cyclic degradation of antagonistic shape memory actuated structures

    International Nuclear Information System (INIS)

    Sofla, A Y N; Elzey, D M; Wadley, H N G

    2008-01-01

    Antagonistic shape memory actuated structures exploit opposing pairs of one-way shape memory alloy (SMA) linear actuators to create devices capable of a fully reversible response. Unlike many conventional reversible SMA devices they do not require bias force components (springs) to return them to their pre-actuated configuration. However, the repeated use of SMA antagonistic devices results in the accumulation of plastic strain in the actuators which can diminish their actuation stroke. We have investigated this phenomenon and the effect of shape memory alloy pre-strain upon it for near equi-atomic NiTi actuators. We find that the degradation eventually stabilizes during cycling. A thermomechanical treatment has been found to significantly reduce degradation in cyclic response of the actuators

  9. In-silico guided discovery of novel CCR9 antagonists

    Science.gov (United States)

    Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

    2018-03-01

    Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

  10. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  11. Potential Clinical Implications of the Urotensin II Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Emilie Kane

    2011-07-01

    Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

  12. Construction, purification, and characterization of a chimeric TH1 antagonist

    Directory of Open Access Journals (Sweden)

    Javier-González Luís

    2006-05-01

    Full Text Available Abstract Background TH1 immune response antagonism is a desirable approach to mitigate some autoimmune and inflammatory reactions during the course of several diseases where IL-2 and IFN-γ are two central players. Therefore, the neutralization of both cytokines could provide beneficial effects in patients suffering from autoimmune or inflammatory illnesses. Results A chimeric antagonist that can antagonize the action of TH1 immunity mediators, IFN-γ and IL-2, was designed, engineered, expressed in E. coli, purified and evaluated for its in vitro biological activities. The TH1 antagonist molecule consists of the extracellular region for the human IFNγ receptor chain 1 fused by a four-aminoacid linker peptide to human 60 N-terminal aminoacid residues of IL-2. The corresponding gene fragments were isolated by RT-PCR and cloned in the pTPV-1 vector. E. coli (W3110 strain was transformed with this vector. The chimeric protein was expressed at high level as inclusion bodies. The protein was partially purified by pelleting and washing. It was then solubilized with strong denaturant and finally refolded by gel filtration. In vitro biological activity of chimera was demonstrated by inhibition of IFN-γ-dependent HLA-DR expression in Colo 205 cells, inhibition of IFN-γ antiproliferative effect on HEp-2 cells, and by a bidirectional effect in assays for IL-2 T-cell dependent proliferation: agonism in the absence versus inhibition in the presence of IL-2. Conclusion TH1 antagonist is a chimeric protein that inhibits the in vitro biological activities of human IFN-γ, and is a partial agonist/antagonist of human IL-2. With these attributes, the chimera has the potential to offer a new opportunity for the treatment of autoimmune and inflammatory diseases.

  13. Suvorexant: The first orexin receptor antagonist to treat insomnia

    OpenAIRE

    Dubey, Ashok K.; Handu, Shailendra S.; Mediratta, Pramod K.

    2015-01-01

    Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, hav...

  14. A prototypical Sigma-1 receptor antagonist protects against brain ischemia

    OpenAIRE

    Schetz, John A.; Perez, Evelyn; Liu, Ran; Chen, Shiuhwei; Lee, Ivan; Simpkins, James W.

    2007-01-01

    Previous studies indicate that the Sigma-1 ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects the brain from ischemia. Less clear is whether protection is mediated by agonism or antagonism of the Sigma-1 receptor, and whether drugs already in use for other indications and that interact with the Sigma-1 receptor might also prevent oxidative damage due to conditions such as cerebral ischemic stroke. The antipsychotic drug haloperidol is an antagonist of Sigma-1 receptors and in this s...

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  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

  19. 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

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

    Science.gov (United States)

    Daikoku, Rie; Saito, Yayoi

    2008-11-01

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

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

    OpenAIRE

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

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  3. 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

  4. [Necrotic leg ulcer revealing vasculitis induced by vitamin K antagonists].

    Science.gov (United States)

    Chabli, H; Hocar, O; Akhdari, N; Amal, S; Hakkou, M; Hamdaoui, A

    2015-12-01

    Vitamin K antagonists are widely used in thromboembolic diseases. Hemorrhagic complications related to drug overdose represent their main side effect. We report a rare side effect, a severe and unexpected type of skin vasculitis - necrotic leg ulcer - induced by vitamin K antagonist. A 63-year-old female with a history of diabetes developed hyperalgesic necrotic ulcerations on the lower limbs one month after starting an acenocoumarol-based treatment for ischemic heart disease. Histological examination revealed lymphocytic vasculitis with fibrinoid necrosis. Etiological explorations searching for vasculitis were negative. In the absence of a precise etiology, drug-induced ulcer was suspected. Low molecular weight heparin was prescribed to replace acenocoumarol. The lesions slowly resolved with topical treatment. The chronological criteria and the negativity of etiological explorations allowed the diagnosis of vitamin K antagonist-induced necrotic skin ulcer. Clinicians should be aware of this rare complication induced by oral anticoagulants because of its practical therapeutic implications. This is the first case of necrotic leg ulcer induced by acenocoumarol corresponding histologically to necrotising lymphocytic vasculitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. Toxicological Differences Between NMDA Receptor Antagonists and Cholinesterase Inhibitors.

    Science.gov (United States)

    Shi, Xiaodong; Lin, Xiaotian; Hu, Rui; Sun, Nan; Hao, Jingru; Gao, Can

    2016-08-01

    Cholinesterase inhibitors (ChEIs), represented by donepezil, rivastigmine, and galantamine, used to be the only approved class of drugs for the treatment of Alzheimer's disease. After the approval of memantine by the Food and Drug Administration (FDA), N-methyl-d-aspartic acid (NMDA) receptor antagonists have been recognized by authorities and broadly used in the treatment of Alzheimer's disease. Along with complementary mechanisms of action, NMDA antagonists and ChEIs differ not only in therapeutic effects but also in adverse reactions, which is an important consideration in clinical drug use. And the number of patients using NMDA antagonists and ChEIs concomitantly has increased, making the matter more complicated. Here we used the FDA Adverse Event Reporting System for statistical analysis , in order to compare the adverse events of memantine and ChEIs. In general, the clinical evidence confirmed the safety advantages of memantine over ChEIs, reiterating the precautions of clinical drug use and the future direction of antidementia drug development. © The Author(s) 2016.

  6. Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.

    Directory of Open Access Journals (Sweden)

    Sachiko Yamada

    Full Text Available Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7 in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1, a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.

  7. Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer

    Science.gov (United States)

    Suzuki, H; Toyota, M; Caraway, H; Gabrielson, E; Ohmura, T; Fujikane, T; Nishikawa, N; Sogabe, Y; Nojima, M; Sonoda, T; Mori, M; Hirata, K; Imai, K; Shinomura, Y; Baylin, S B; Tokino, T

    2008-01-01

    Although mutation of APC or CTNNB1 (β-catenin) is rare in breast cancer, activation of Wnt signalling is nonetheless thought to play an important role in breast tumorigenesis, and epigenetic silencing of Wnt antagonist genes, including the secreted frizzled-related protein (SFRP) and Dickkopf (DKK) families, has been observed in various tumours. In breast cancer, frequent methylation and silencing of SFRP1 was recently documented; however, altered expression of other Wnt antagonist genes is largely unknown. In the present study, we found frequent methylation of SFRP family genes in breast cancer cell lines (SFRP1, 7 out of 11, 64%; SFRP2, 11 out of 11, 100%; SFRP5, 10 out of 11, 91%) and primary breast tumours (SFRP1, 31 out of 78, 40%; SFRP2, 60 out of 78, 77%; SFRP5, 55 out of 78, 71%). We also observed methylation of DKK1, although less frequently, in cell lines (3 out of 11, 27%) and primary tumours (15 out of 78, 19%). Breast cancer cell lines express various Wnt ligands, and overexpression of SFRPs inhibited cancer cell growth. In addition, overexpression of a β-catenin mutant and depletion of SFRP1 using small interfering RNA synergistically upregulated transcriptional activity of T-cell factor/lymphocyte enhancer factor. Our results confirm the frequent methylation and silencing of Wnt antagonist genes in breast cancer, and suggest that their loss of function contributes to activation of Wnt signalling in breast carcinogenesis. PMID:18283316

  8. 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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  11. Gallic Acid Is an Antagonist of Semen Amyloid Fibrils That Enhance HIV-1 Infection*

    Science.gov (United States)

    LoRicco, Josephine G.; Xu, Changmingzi Sherry; Neidleman, Jason; Bergkvist, Magnus; Greene, Warner C.; Roan, Nadia R.; Makhatadze, George I.

    2016-01-01

    Recent in vitro studies have demonstrated that amyloid fibrils found in semen from healthy and HIV-infected men, as well as semen itself, can markedly enhance HIV infection rates. Semen fibrils are made up of multiple naturally occurring peptide fragments derived from semen. The best characterized of these fibrils are SEVI (semen-derived enhancer of viral infection), made up of residues 248–286 of prostatic acidic phosphatase, and the SEM1 fibrils, made up of residues 86–107 of semenogelin 1. A small molecule screen for antagonists of semen fibrils identified four compounds that lowered semen-mediated enhancement of HIV-1 infectivity. One of the four, gallic acid, was previously reported to antagonize other amyloids and to exert anti-inflammatory effects. To better understand the mechanism by which gallic acid modifies the properties of semen amyloids, we performed biophysical measurements (atomic force microscopy, electron microscopy, confocal microscopy, thioflavin T and Congo Red fluorescence assays, zeta potential measurements) and quantitative assays on the effects of gallic acid on semen-mediated enhancement of HIV infection and inflammation. Our results demonstrate that gallic acid binds to both SEVI and SEM1 fibrils and modifies their surface electrostatics to render them less cationic. In addition, gallic acid decreased semen-mediated enhancement of HIV infection but did not decrease the inflammatory response induced by semen. Together, these observations identify gallic acid as a non-polyanionic compound that inhibits semen-mediated enhancement of HIV infection and suggest the potential utility of incorporating gallic acid into a multicomponent microbicide targeting both the HIV virus and host components that promote viral infection. PMID:27226574

  12. Gallic Acid Is an Antagonist of Semen Amyloid Fibrils That Enhance HIV-1 Infection.

    Science.gov (United States)

    LoRicco, Josephine G; Xu, Changmingzi Sherry; Neidleman, Jason; Bergkvist, Magnus; Greene, Warner C; Roan, Nadia R; Makhatadze, George I

    2016-07-01

    Recent in vitro studies have demonstrated that amyloid fibrils found in semen from healthy and HIV-infected men, as well as semen itself, can markedly enhance HIV infection rates. Semen fibrils are made up of multiple naturally occurring peptide fragments derived from semen. The best characterized of these fibrils are SEVI (semen-derived enhancer of viral infection), made up of residues 248-286 of prostatic acidic phosphatase, and the SEM1 fibrils, made up of residues 86-107 of semenogelin 1. A small molecule screen for antagonists of semen fibrils identified four compounds that lowered semen-mediated enhancement of HIV-1 infectivity. One of the four, gallic acid, was previously reported to antagonize other amyloids and to exert anti-inflammatory effects. To better understand the mechanism by which gallic acid modifies the properties of semen amyloids, we performed biophysical measurements (atomic force microscopy, electron microscopy, confocal microscopy, thioflavin T and Congo Red fluorescence assays, zeta potential measurements) and quantitative assays on the effects of gallic acid on semen-mediated enhancement of HIV infection and inflammation. Our results demonstrate that gallic acid binds to both SEVI and SEM1 fibrils and modifies their surface electrostatics to render them less cationic. In addition, gallic acid decreased semen-mediated enhancement of HIV infection but did not decrease the inflammatory response induced by semen. Together, these observations identify gallic acid as a non-polyanionic compound that inhibits semen-mediated enhancement of HIV infection and suggest the potential utility of incorporating gallic acid into a multicomponent microbicide targeting both the HIV virus and host components that promote viral infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Salt Stress and Ethylene Antagonistically Regulate Nucleocytoplasmic Partitioning of COP1 to Control Seed Germination.

    Science.gov (United States)

    Yu, Yanwen; Wang, Juan; Shi, Hui; Gu, Juntao; Dong, Jingao; Deng, Xing Wang; Huang, Rongfeng

    2016-04-01

    Seed germination, a critical stage initiating the life cycle of a plant, is severely affected by salt stress. However, the underlying mechanism of salt inhibition of seed germination (SSG) is unclear. Here, we report that the Arabidopsis (Arabidopsis thaliana) CONSTITUTIVE PHOTOMORPHOGENESIS1 (COP1) counteracts SSG Genetic assays provide evidence that SSG in loss of function of the COP1 mutant was stronger than this in the wild type. A GUS-COP1 fusion was constitutively localized to the nucleus in radicle cells. Salt treatment caused COP1 to be retained in the cytosol, but the addition of ethylene precursor 1-aminocyclopropane-1-carboxylate had the reverse effect on the translocation of COP1 to the nucleus, revealing that ethylene and salt exert opposite regulatory effects on the localization of COP1 in germinating seeds. However, loss of function of the ETHYLENE INSENSITIVE3 (EIN3) mutant impaired the ethylene-mediated rescue of the salt restriction of COP1 to the nucleus. Further research showed that the interaction between COP1 and LONG HYPOCOTYL5 (HY5) had a role in SSG Correspondingly, SSG in loss of function of HY5 was suppressed. Biochemical detection showed that salt promoted the stabilization of HY5, whereas ethylene restricted its accumulation. Furthermore, salt treatment stimulated and ethylene suppressed transcription of ABA INSENSITIVE5 (ABI5), which was directly transcriptionally regulated by HY5. Together, our results reveal that salt stress and ethylene antagonistically regulate nucleocytoplasmic partitioning of COP1, thereby controlling Arabidopsis seed germination via the COP1-mediated down-regulation of HY5 and ABI5. These findings enhance our understanding of the stress response and have great potential for application in agricultural production. © 2016 American Society of Plant Biologists. All Rights Reserved.

  14. Social conformity despite individual preferences for distinctiveness.

    Science.gov (United States)

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

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

    Science.gov (United States)

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

    2009-09-10

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

  16. 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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  19. 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.

  20. Does protein binding modulate the effect of angiotensin II receptor antagonists?

    Directory of Open Access Journals (Sweden)

    Marc P Maillard

    2001-03-01

    Full Text Available IntroductionAngiotensin II AT 1-receptor antagonists are highly bound to plasma proteins (≥ 99%. With some antagonists, such as DuP-532, the protein binding was such that no efficacy of the drug could be demonstrated clinically. Whether protein binding interferes with the efficacy of other antagonists is not known. We have therefore investigated in vitro how plasma proteins may affect the antagonistic effect of different AT1-receptor antagonists.MethodsA radio-receptor binding assay was used to analyse the interaction between proteins and the ability of various angiotensin II (Ang II antagonists to block AT1-receptors. In addition, the Biacore technology, a new technique which enables the real-time monitoring of binding events between two molecules, was used to evaluate the dissociation rate constants of five AT1-receptor antagonists from human serum albumin.ResultsThe in vitro AT 1-antagonistic effects of different Ang II receptor antagonists were differentially affected by the presence of human plasma, with rightward shifts of the IC50 ranging from one to several orders of magnitude. The importance of the shift correlates with the dissociation rate constants of these drugs from albumin. Our experiments also show that the way that AT1-receptor antagonists bind to proteins differs from one compound to another. These results suggest that the interaction with plasma proteins appears to modulate the efficacy of some Ang II antagonists.ConclusionAlthough the high binding level of Ang II receptor antagonist to plasma proteins appears to be a feature common to this class of compounds, the kinetics and characteristics of this binding is of great importance. With some antagonists, protein binding interferes markedly with their efficacy to block AT1-receptors.

  1. Validity of Sensory Systems as Distinct Constructs

    OpenAIRE

    Su, Chia-Ting; Parham, L. Diane

    2014-01-01

    Confirmatory factor analysis testing whether sensory questionnaire items represented distinct sensory system constructs found, using data from two age groups, that such constructs can be measured validly using questionnaire data.

  2. Visual distinctiveness can enhance recency effects.

    Science.gov (United States)

    Bornstein, B H; Neely, C B; LeCompte, D C

    1995-05-01

    Experimental efforts to meliorate the modality effect have included attempts to make the visual stimulus more distinctive. McDowd and Madigan (1991) failed to find an enhanced recency effect in serial recall when the last item was made more distinct in terms of its color. In an attempt to extend this finding, three experiments were conducted in which visual distinctiveness was manipulated in a different manner, by combining the dimensions of physical size and coloration (i.e., whether the stimuli were solid or outlined in relief). Contrary to previous findings, recency was enhanced when the size and coloration of the last item differed from the other items in the list, regardless of whether the "distinctive" item was larger or smaller than the remaining items. The findings are considered in light of other research that has failed to obtain a similar enhanced recency effect, and their implications for current theories of the modality effect are discussed.

  3. Sexually antagonistic "zygotic drive" of the sex chromosomes.

    Directory of Open Access Journals (Sweden)

    William R Rice

    2008-12-01

    Full Text Available Genomic conflict is perplexing because it causes the fitness of a species to decline rather than improve. Many diverse forms of genomic conflict have been identified, but this extant tally may be incomplete. Here, we show that the unusual characteristics of the sex chromosomes can, in principle, lead to a previously unappreciated form of sexual genomic conflict. The phenomenon occurs because there is selection in the heterogametic sex for sex-linked mutations that harm the sex of offspring that does not carry them, whenever there is competition among siblings. This harmful phenotype can be expressed as an antagonistic green-beard effect that is mediated by epigenetic parental effects, parental investment, and/or interactions among siblings. We call this form of genomic conflict sexually antagonistic "zygotic drive", because it is functionally equivalent to meiotic drive, except that it operates during the zygotic and postzygotic stages of the life cycle rather than the meiotic and gametic stages. A combination of mathematical modeling and a survey of empirical studies is used to show that sexually antagonistic zygotic drive is feasible, likely to be widespread in nature, and that it can promote a genetic "arms race" between the homo- and heteromorphic sex chromosomes. This new category of genomic conflict has the potential to strongly influence other fundamental evolutionary processes, such as speciation and the degeneration of the Y and W sex chromosomes. It also fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing traits like the high frequency of spontaneous abortion, sterility, and homosexuality observed in humans.

  4. Central actions of a novel and selective dopamine antagonist

    International Nuclear Information System (INIS)

    Schulz, D.W.

    1985-01-01

    Receptors for the neurotransmitter dopamine traditionally have been divided into two subgroups: the D 1 class, which is linked to the stimulation of adenylate cyclase-activity, and the D 2 class which is not. There is much evidence suggesting that it is the D 2 class which is not. There is much evidence suggesting that it is the D 2 dopamine receptor that mediates the physiological and behavioral actions of dopamine in the intact animal. However, the benzazepine SCH23390 is a dopamine antagonist which has potent behavioral actions while displaying apparent neurochemical selectivity for the D 1 class of dopamine receptors. The purpose of this dissertation was to (1) confirm and characterize this selectivity, and (2) test certain hypothesis related to possible modes of action of SCH233390. The inhibition of adenylate cyclase by SCH23390 occurred via an action at the dopamine receptor only. A radiolabeled analog of SCH23390 displayed the receptor binding properties of a specific high-affinity ligand, and regional receptor densities were highly correlated with dopamine levels. The subcellular distribution of [ 3 H]-SCH23390 binding did not correspond completely with that of dopamine-stimulated adenylate cyclase. The neurochemical potency of SCH23390 as a D 1 receptor antagonist was preserved following parental administration. A variety of dopamine agonists and antagonists displayed a high correlation between their abilities to compete for [ 3 H]-SCH23390 binding in vitro and to act at an adenylate cyclase-linked receptor. Finally, the relative affinities of dopamine and SCH23390 for both D 1 receptors and [ 3 H]-SCH23390 binding sites were comparable. It is concluded that the behavioral effects of SCH23390 are mediated by actions at D 1 dopamine receptors only, and that the physiological importance of this class of receptors should be reevaluated

  5. Modulation of myometrium mitochondrial membrane potential by calmodulin antagonists

    Directory of Open Access Journals (Sweden)

    S. G. Shlykov

    2014-02-01

    Full Text Available Influence of calmodulin antagonists on mitochondrial membrane potential was investigated using­ a flow cytometry method, confocal microscopy and fluorescent potential-sensitive probes TMRM and MTG. Influence of different concentrations of calmodulin antagonists on mitochondrial membrane potential was studied using flow cytometry method and a fraction of myometrium mitochondria of unpregnant rats. It was shown that 1-10 µМ calmidazolium gradually reduced mitochondria membrane potential. At the same time 10-100 µМ trifluope­razine influenced as follows: 10 µМ – increased polarization, while 100 µМ – caused almost complete depolarization of mitochondrial membranes. In experiments which were conducted with the use of confocal microscopy method and myometrium cells it was shown, that MTG addition to the incubation medium­ led to the appearance of fluorescence signal in a green range. Addition of the second probe (ТМRM resulted in the appearance of fluorescent signal in a red range. Mitochondrial membrane depolarization by 1µМ СССР or 10 mМ NaN3 was accompanied by the decline of “red” fluo­rescence intensity, “green” fluorescence was kept. The 10-15 minute incubation of myometrium cells in the presen­ce 10 µМ calmidazolium or 100 µМ trifluoperazine was accompanied by almost complete decrease of the TMRM fluorescent signal. Thus, with the use of potential-sensitive fluorescent probes TMRM and MTG it was shown, that calmodulin antagonists modulate mitochondrial membrane potential of myometrium cells.

  6. Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist.

    Science.gov (United States)

    Shirayama, Yukihiko; Yang, Chun; Zhang, Ji-chun; Ren, Qian; Yao, Wei; Hashimoto, Kenji

    2015-12-01

    Role of brain-derived neurotrophic factor (BDNF)-TrkB signaling in a learned helplessness (LH) model of depression was investigated. LH rats showed a reduction of BDNF in the medial prefrontal cortex (mPFC), CA3, and dentate gyrus (DG) of the hippocampus, whereas LH rats showed an increase in BDNF in the nucleus accumbens (NAc). Furthermore, levels of proBDNF, a BDNF precursor, were higher in the mPFC, but lower in the NAc, of LH rats. A single bilateral infusion of a TrkB agonist 7,8-DHF, but not a TrkB antagonist ANA-12, into the infralimbic (IL) of mPFC, DG, and CA3, but not the prelimbic (PrL) of mPFC, exerted antidepressant effects in LH rats. In contrast, a single bilateral infusion of ANA-12, but not 7,8-DHF, into the core and shell of NAc exerted antidepressant-like effects in LH rats, with more potent effects observed for the NAc core than for NAc shell. Interestingly, a single administration of 7,8-DHF (10mg/kg, i.p.) significantly improved a decreased phosphorylation of TrkB in the mPFC, CA3, and DG of LH rats. Additionally, ANA-12 (0.5mg/kg, i.p.) significantly improved an increased phosphorylation of TrkB in the NAc of LH rats. In conclusion, these results suggest that LH causes depression-like behavior by altering BDNF in the brain regions, and that proBDNF-BDNF processing and transport may be altered in the mPFC-NAc circuit of LH rats. Therefore, TrkB agonists might exert antidepressant effects by stimulating TrkB in the IL, CA3, and DG, while TrkB antagonists might exert antidepressant effects by blocking TrkB in the NAc. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  7. 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).

  8. Salivary Gland Derived BDNF Overexpression in Mice Exerts an Anxiolytic Effect

    OpenAIRE

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

    2017-01-01

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

  9. Effect of Music Tempo on Attentional Focus and Perceived Exertion during Self-selected Paced Walking

    OpenAIRE

    SILVA, ALDO COELHO; DOS SANTOS FERREIRA, SANDRO; ALVES, RAGAMI CHAVES; FOLLADOR, LUCIO; DA SILVA, SERGIO GREGORIO

    2016-01-01

    This study investigated the influence of music on the rating of perceived exertion (RPE) and attentional focus during walking at a self-selected pace. Fifteen overweight and obese women volunteered to participate in the study. They underwent four sessions: the first for incremental maximal test and anthropometric measurement followed by three experimental sessions. After the first session, they were exposed to three 30-minute walking sessions at a self-selected pace in a counterbalanced order...

  10. 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…

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

    Science.gov (United States)

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

    2018-06-01

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

  12. Impact Exerted by Nutritional Risk Screening on Clinical Outcome of Patients with Esophageal Cancer

    OpenAIRE

    Rui Wang; Hongfei Cai; Yang Li; Caiwen Chen; Youbin Cui

    2018-01-01

    Objective. Preoperative nutritional status of patients is closely associated with their recovery after the surgery. This study aims to ascertain the impact exerted by the nutritional risk screening on clinical outcome of patients with esophageal cancer. Methods. 160 patients with esophageal cancer aged over 60, having got therapy at the First Hospital of Jilin University from Jun 2016 to Feb 2017 were evaluated by adopting the NRS2002. 80 cases of patients got active therapy of nutritional su...

  13. Membrane formation in liquids by adding an antagonistic salt

    Science.gov (United States)

    Sadakane, Koichiro; Seto, Hideki

    2018-03-01

    Antagonistic salts are composed of hydrophilic and hydrophobic ions. In a binary mixture, such as water and organic solvent, these ion pairs preferentially dissolve to those phases, respectively, and there is a coupling between the charge density and the composition. The heterogeneous distribution of ions forms a large electric double layer at the interface between these solvents. This reduces the interfacial tension between water and organic solvent, and stabilizes an ordered structure, such as a membrane. These phenomena have been extensively studied from both theoretical and experimental point of view. In addition, the numerical simulations can reproduce such ordered structures.

  14. Effect of a Hypocretin/Orexin Antagonist on Neurocogniive Performance

    Science.gov (United States)

    2014-09-01

    time: Tuesday , Nov 12, 2013, 4:00 PM - 5:00 PM Topic: ++E.08.e Sleep: Systems and behavior Authors: W. LINCOLN1, J. PALMERSTON1, T. NEYLAN2, T...functional impairment results from HcrtR antagonist-induced sleep, we evaluated the performance of rats in the Morris Water Maze in the presence of ALM vs. ZOL... Morris Water Maze. Although the concentrations of ALM and ZOL adminis- tered prior to these tests were equipotent in hypnotic efficacy, the

  15. Membrane Formation in Liquids by Adding an Antagonistic Salt

    Directory of Open Access Journals (Sweden)

    Koichiro Sadakane

    2018-03-01

    Full Text Available Antagonistic salts are composed of hydrophilic and hydrophobic ions. In a binary mixture, such as water and organic solvent, these ion pairs preferentially dissolve to those phases, respectively, and there is a coupling between the charge density and the composition. The heterogeneous distribution of ions forms a large electric double layer at the interface between these solvents. This reduces the interfacial tension between water and organic solvent, and stabilizes an ordered structure, such as a membrane. These phenomena have been extensively studied from both theoretical and experimental point of view. In addition, the numerical simulations can reproduce such ordered structures.

  16. The discovery of tropane-derived CCR5 receptor antagonists.

    Science.gov (United States)

    Armour, Duncan R; de Groot, Marcel J; Price, David A; Stammen, Blanda L C; Wood, Anthony; Perros, Manos; Burt, Catherine

    2006-04-01

    The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

  17. The opiate antagonist, naltrexone, in the treatment of trichotillomania

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N

    2014-01-01

    Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were...... randomized to naltrexone or placebo in an 8-week, double-blind trial. Subjects were assessed with measures of TTM severity and selected cognitive tasks. Naltrexone failed to demonstrate significantly greater reductions in hair pulling compared to placebo. Cognitive flexibility, however, significantly...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

    Science.gov (United States)

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

    2018-01-12

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

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2013-07-01

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

  5. Antagonistic interactions between honey bee bacterial symbionts and implications for disease

    Directory of Open Access Journals (Sweden)

    Armstrong Tamieka-Nicole

    2006-03-01

    Full Text Available Abstract Background Honey bees, Apis mellifera, face many parasites and pathogens and consequently rely on a diverse set of individual and group-level defenses to prevent disease. One route by which honey bees and other insects might combat disease is through the shielding effects of their microbial symbionts. Bees carry a diverse assemblage of bacteria, very few of which appear to be pathogenic. Here we explore the inhibitory effects of these resident bacteria against the primary bacterial pathogen of honey bees, Paenibacillus larvae. Results Here we isolate, culture, and describe by 16S rRNA and protein-coding gene sequences 61 bacterial isolates from honey bee larvae, reflecting a total of 43 distinct bacterial taxa. We culture these bacteria alongside the primary larval pathogen of honey bees, Paenibacillus larvae, and show that many of these isolates severely inhibit the growth of this pathogen. Accordingly, symbiotic bacteria including those described here are plausible natural antagonists toward this widespread pathogen. Conclusion The results suggest a tradeoff in social insect colonies between the maintenance of potentially beneficial bacterial symbionts and deterrence at the individual and colony level of pathogenic species. They also provide a novel mechanism for recently described social components behind disease resistance in insect colonies, and point toward a potential control strategy for an important bee disease.

  6. Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential.

    Directory of Open Access Journals (Sweden)

    Pengpeng Li

    Full Text Available S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens.

  7. Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential.

    Science.gov (United States)

    Li, Pengpeng; Kwok, Amy H Y; Jiang, Jingwei; Ran, Tingting; Xu, Dongqing; Wang, Weiwu; Leung, Frederick C

    2015-01-01

    S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs) in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens.

  8. Comparative Genome Analyses of Serratia marcescens FS14 Reveals Its High Antagonistic Potential

    Science.gov (United States)

    Li, Pengpeng; Kwok, Amy H. Y.; Jiang, Jingwei; Ran, Tingting; Xu, Dongqing; Wang, Weiwu; Leung, Frederick C.

    2015-01-01

    S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs) in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens. PMID:25856195

  9. Antagonistic control of social versus repetitive self-grooming behaviors by separable amygdala neuronal subsets.

    Science.gov (United States)

    Hong, Weizhe; Kim, Dong-Wook; Anderson, David J

    2014-09-11

    Animals display a range of innate social behaviors that play essential roles in survival and reproduction. While the medial amygdala (MeA) has been implicated in prototypic social behaviors such as aggression, the circuit-level mechanisms controlling such behaviors are not well understood. Using cell-type-specific functional manipulations, we find that distinct neuronal populations in the MeA control different social and asocial behaviors. A GABAergic subpopulation promotes aggression and two other social behaviors, while neighboring glutamatergic neurons promote repetitive self-grooming, an asocial behavior. Moreover, this glutamatergic subpopulation inhibits social interactions independently of its effect to promote self-grooming, while the GABAergic subpopulation inhibits self-grooming, even in a nonsocial context. These data suggest that social versus repetitive asocial behaviors are controlled in an antagonistic manner by inhibitory versus excitatory amygdala subpopulations, respectively. These findings provide a framework for understanding circuit-level mechanisms underlying opponency between innate behaviors, with implications for their perturbation in psychiatric disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jessica C. Schoen

    2017-09-01

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

  11. Lu AA21004, a novel multimodal antidepressantwith activity exerted through serotonergic targets

    DEFF Research Database (Denmark)

    Mork, A.; Pehrson, A.; Montezinho, L. C. P.

    2012-01-01

    Background: Lu AA21004 is a multimodal antidepressant that functions as a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter in vitro. Here we investigated preclinical effects of Lu AA21004 1) on target occupancies, 2...... (5-HT), noradrenaline (NA), dopamine (DA), acetylcholine (ACh), histamine (Hist)] were measured by microdialysis. Antidepressant potential was assessed in the forced swim test using Flinders Sensitive Line (FSL) rats. Moreover, effects of Lu AA21004 on acquisition, consolidation and recall...

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

    Science.gov (United States)

    Armed Forces Health Surveillance Branch

    2016-03-01

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

  13. The role of ecology, neutral processes and antagonistic coevolution in an apparent sexual arms race.

    Science.gov (United States)

    Perry, Jennifer C; Garroway, Colin J; Rowe, Locke

    2017-09-01

    Some of the strongest examples of a sexual 'arms race' come from observations of correlated evolution in sexually antagonistic traits among populations. However, it remains unclear whether these cases truly represent sexually antagonistic coevolution; alternatively, ecological or neutral processes might also drive correlated evolution. To investigate these alternatives, we evaluated the contributions of intersex genetic correlations, ecological context, neutral genetic divergence and sexual coevolution in the correlated evolution of antagonistic traits among populations of Gerris incognitus water striders. We could not detect intersex genetic correlations for these sexually antagonistic traits. Ecological variation was related to population variation in the key female antagonistic trait (spine length, a defence against males), as well as body size. Nevertheless, population covariation between sexually antagonistic traits remained substantial and significant even after accounting for all of these processes. Our results therefore provide strong evidence for a contemporary sexual arms race. © 2017 John Wiley & Sons Ltd/CNRS.

  14. Novel quinolinone-phosphonic acid AMPA antagonists devoid of nephrotoxicity.

    Science.gov (United States)

    Cordi, Alex A; Desos, Patrice; Ruano, Elisabeth; Al-Badri, Hashim; Fugier, Claude; Chapman, Astrid G; Meldrum, Brian S; Thomas, Jean-Yves; Roger, Anita; Lestage, Pierre

    2002-10-01

    We reported previously the synthesis and structure-activity relationships (SAR) in a series of 2-(1H)-oxoquinolines bearing different acidic functions in the 3-position. Exploiting these SAR, we were able to identify 6,7-dichloro-2-(1H)-oxoquinoline-3-phosphonic acid compound 3 (S 17625) as a potent, in vivo active AMPA antagonist. Unfortunately, during the course of the development, nephrotoxicity was manifest at therapeutically effective doses. Considering that some similitude exists between S 17625 and probenecid, a compound known to protect against the nephrotoxicity and/or slow the clearance of different drugs, we decided to synthesise some new analogues of S 17625 incorporating some of the salient features of probenecid. Replacement of the chlorine in position 6 by a sulfonylamine led to very potent AMPA antagonists endowed with good in vivo activity and lacking nephrotoxicity potential. Amongst the compounds evaluated, derivatives 7a and 7s appear to be the most promising and are currently evaluated in therapeutically relevant stroke models.

  15. Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

    Science.gov (United States)

    Albertson, T E; Joy, R M; Stark, L G

    1984-03-01

    The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Evodiamine as a novel antagonist of aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Yu, Hui; Tu, Yongjiu; Zhang, Chun; Fan, Xia; Wang, Xi; Wang, Zhanli; Liang, Huaping

    2010-01-01

    Research highlights: → Evodiamine interacted with the AhR. → Evodiamine inhibited the specific binding of [ 3 H]-TCDD to the AhR. → Evodiamine acts as an antagonist of the AhR. -- Abstract: Evodiamine, the major bioactive alkaloid isolated from Wu-Chu-Yu, has been shown to interact with a wide variety of proteins and modify their expression and activities. In this study, we investigated the interaction between evodiamine and the aryl hydrocarbon receptor (AhR). Molecular modeling results revealed that evodiamine directly interacted with the AhR. Cytosolic receptor binding assay also provided the evidence that evodiamine could interact with the AhR with the K i value of 28.4 ± 4.9 nM. In addition, we observed that evodiamine suppressed the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nuclear translocation of the AhR and the expression of CYP1A1 dose-dependently. These results suggested that evodiamine was able to bind to the AhR as ligand and exhibit antagonistic effects.

  17. Rogue sperm indicate sexually antagonistic coevolution in nematodes.

    Directory of Open Access Journals (Sweden)

    Ronald E Ellis

    2014-07-01

    Full Text Available Intense reproductive competition often continues long after animals finish mating. In many species, sperm from one male compete with those from others to find and fertilize oocytes. Since this competition occurs inside the female reproductive tract, she often influences the outcome through physical or chemical factors, leading to cryptic female choice. Finally, traits that help males compete with each other are sometimes harmful to females, and female countermeasures may thwart the interests of males, which can lead to an arms race between the sexes known as sexually antagonistic coevolution. New studies from Caenorhabditis nematodes suggest that males compete with each other by producing sperm that migrate aggressively and that these sperm may be more likely to win access to oocytes. However, one byproduct of this competition appears to be an increased probability that these sperm will go astray, invading the ovary, prematurely activating oocytes, and sometimes crossing basement membranes and leaving the gonad altogether. These harmful effects are sometimes observed in crosses between animals of the same species but are most easily detected in interspecies crosses, leading to dramatically lowered fitness, presumably because the competitiveness of the sperm and the associated female countermeasures are not precisely matched. This mismatch is most obvious in crosses involving individuals from androdioecious species (which have both hermaphrodites and males, as predicted by the lower levels of sperm competition these species experience. These results suggest a striking example of sexually antagonistic coevolution and dramatically expand the value of nematodes as a laboratory system for studying postcopulatory interactions.

  18. Carbobenzoxy amino acids: Structural requirements for cholecystokinin receptor antagonist activity

    International Nuclear Information System (INIS)

    Maton, P.N.; Sutliff, V.E.; Jensen, R.T.; Gardner, J.D.

    1985-01-01

    The authors used dispersed acini prepared from guinea pig pancreas to examine 28 carbobenzoxy (CBZ) amino acids for their abilities to function as cholecystokinin receptor antagonists. All amino acid derivatives tested, except for CBZ-alanine, CBZ-glycine, and N alpha-CBZ- lysine, were able to inhibit the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin. In general, there was a good correlation between the ability of a carbobenzoxy amino acid to inhibit stimulated amylase secretion and the ability of the amino acid derivative to inhibit binding of 125 I-cholecystokinin. The inhibition of cholecystokinin-stimulated amylase secretion was competitive, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor. The potencies with which the various carbobenzoxy amino acids inhibited the action of cholecystokinin varied 100-fold and CBZ-cystine was the most potent cholecystokinin receptor antagonist. This variation in potency was primarily but not exclusively a function of the hydrophobicity of the amino acid side chain

  19. Combination cancer chemotherapy with one compound: pluripotent bradykinin antagonists.

    Science.gov (United States)

    Stewart, John M; Gera, Lajos; Chan, Daniel C; York, Eunice J; Simkeviciene, Vitalija; Bunn, Paul A; Taraseviciene-Stewart, Laimute

    2005-08-01

    Lung and prostate cancers are major health problems worldwide. Treatments with standard chemotherapy agents are relatively ineffective. Combination chemotherapy gives better treatment than a single agent because the drugs can inhibit the cancer in different pathways, but new therapeutic agents are needed for the treatment of both tumor types. Bradykinin (BK) antagonists offer advantages of combination therapy in one compound. These promising multitargeted anti-cancer compounds selectively stimulate apoptosis in cancers and also inhibit both angiogenesis and matrix metalloprotease (MMP) action in treated lung and prostate tumors in nude mice. The highly potent, metabolism-resistant bradykinin antagonist peptide dimer, B-9870 [SUIM-(DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg)2] (SUIM=suberimidyl; Hyp=4-hydroxyproline; Igl=alpha-(2-indanyl)glycine; Oic=octahydroindole-2-carboxylic acid) and its non-peptide mimetic, BKM-570 [2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-L-tyrosine-N-(4-amino-2,2,6,6-tetramethylpiperidyl)amide] are superior to the widely used but toxic chemotherapeutic drugs cisplatin and taxotere. In certain combinations, they act synergistically with standard anti-cancer drugs. Due to its structure and biological activity, BKM-570 is an attractive lead compound for derivatization and evaluation for lung and prostate cancer drugs.

  20. Fires can benefit plants by disrupting antagonistic interactions.

    Science.gov (United States)

    García, Y; Castellanos, M C; Pausas, J G

    2016-12-01

    Fire has a key role in the ecology and evolution of many ecosystems, yet its effects on plant-insect interactions are poorly understood. Because interacting species are likely to respond to fire differently, disruptions of the interactions are expected. We hypothesized that plants that regenerate after fire can benefit through the disruption of their antagonistic interactions. We expected stronger effects on interactions with specialist predators than with generalists. We studied two interactions between two Mediterranean plants (Ulex parviflorus, Asphodelus ramosus) and their specialist seed predators after large wildfires. In A. ramosus we also studied the generalist herbivores. We sampled the interactions in burned and adjacent unburned areas during 2 years by estimating seed predation, number of herbivores and fruit set. To assess the effect of the distance to unburned vegetation we sampled plots at two distance classes from the fire perimeter. Even 3 years after the fires, Ulex plants experienced lower seed damage by specialists in burned sites. The presence of herbivores on Asphodelus decreased in burned locations, and the variability in their presence was significantly related to fruit set. Generalist herbivores were unaffected. We show that plants can benefit from fire through the disruption of their antagonistic interactions with specialist seed predators for at least a few years. In environments with a long fire history, this effect might be one additional mechanism underlying the success of fire-adapted plants.

  1. Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

    Directory of Open Access Journals (Sweden)

    Abbas Aflatoonian

    2017-08-01

    Full Text Available Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30, delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30 treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

  2. Synthesis of 11C-SCH 23390, a dopamine D-1 receptor antagonist, for use in in vivo receptor binding studies with PET

    International Nuclear Information System (INIS)

    Halldin, Christer; Stone-Elander, Sharon; Farde, Lars; Ehrin, Erling; Fasth, Karl-Johan; Langstroem, Bengt; Sedvall, Goeran; Karolinska Hospital, Stockholm; Uppsala Univ.

    1986-01-01

    Central dopamine receptors are generally accepted to exist in at least two distinct subtypes: D-1 and D-2. Recently a benzazepine, SCH 23390, was reported to be a selective D-1 dopaminergic antagonist. PET studies of the radio-brominated 76 Br-SCH 23390 reported by Friedman, et al. indicated that the analog exhibits specific binding in the striatum of the monkey brain. Here we report the synthesis of 11 C-SCH 23390 suitable for the in vivo study of dopamine D-1 receptors in the human brain. (author)

  3. Distinctiveness of Saudi Arabian EFL Learners

    Directory of Open Access Journals (Sweden)

    Manssour Habbash

    2016-04-01

    Full Text Available In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs (Preparatory Year Programs in Saudi Arabia. This study examines the distinctiveness with regard to the learning attitudes of Saudi students that are often cultivated by the culture and academic environment in their homeland. Employing an emic approach for collecting the required data an analysis was carried out in light of the other studies on ‘education’ in Saudi Arabia that have particular reference to the factors that can positively influence student motivation, student success and the academic environment. The findings were used in constructing the rationale behind such distinctiveness. Assuming that the outcome of the discussion on the findings of this exploration can be helpful for teachers in adapting their teaching methodology and improving their teacher efficacy in dealing with students both from the kingdom and in the kingdom, some recommendations are made. Keywords: China Distinctiveness, Saudi Arabian University context, Expatriate teachers’ perspective, Distinctiveness Theory

  4. Orexins control intestinal glucose transport by distinct neuronal, endocrine, and direct epithelial pathways.

    Science.gov (United States)

    Ducroc, Robert; Voisin, Thierry; El Firar, Aadil; Laburthe, Marc

    2007-10-01

    Orexins are neuropeptides involved in energy homeostasis. We investigated the effect of orexin A (OxA) and orexin B (OxB) on intestinal glucose transport in the rat. Injection of orexins led to a decrease in the blood glucose level in oral glucose tolerance tests (OGTTs). Effects of orexins on glucose entry were analyzed in Ussing chambers using the Na(+)-dependent increase in short-circuit current (Isc) to quantify jejunal glucose transport. The rapid and marked increase in Isc induced by luminal glucose was inhibited by 10 nmol/l OxA or OxB (53 and 59%, respectively). Response curves to OxA and OxB were not significantly different with half-maximal inhibitory concentrations at 0.9 and 0.4 nmol/l, respectively. On the one hand, OxA-induced inhibition of Isc was reduced by the neuronal blocker tetrodotoxin (TTX) and by a cholecystokinin (CCK) 2R antagonist, indicating involvement of neuronal and endocrine CCK-releasing cells. The OX(1)R antagonist SB334867 had no effect on OxA-induced inhibition, which is likely to occur via a neuronal and/or endocrine OX(2)R. On the other hand, SB334867 induced a significant right shift of the concentration-effect curve for OxB. This OxB-preferring OX(1)R pathway was not sensitive to TTX or to CCKR antagonists, suggesting that OxB may act directly on enterocytic OX(1)R. These distinct effects of OxA and OxB are consistent with the expression of OX(1)R and OX(2)R mRNA in the epithelial and nonepithelial tissues, respectively. Our data delineate a new function for orexins as inhibitors of intestinal glucose absorption and provide a new basis for orexin-induced short-term control of energy homeostasis.

  5. The Cultivation of Antagonistic Bacteria in Irradiated Sludge for Biological Control of Soft Rot Erwinias : Screening of Antagonistic Bacteria for biological Control of Soft Rot Erwinias

    International Nuclear Information System (INIS)

    Sermkiattipong, Ng.; Sangsuk, L; Rattanapiriyakul, P; Dejsirilert, S.; Thaveechai, N.

    1998-01-01

    Pure cultures of 57 bacterial isolates for antagonistic activity screening were isolated from three areas of soft rot infested vegetable soil and 58 isolates were obtained from commercial seed compost and seed compost product of Division of Soil and Water Conservation, Department of Land Development. A total of 115 bacterial isolates were evaluated for antagonizing activity against Erwinia carotovora subsp. atroceptica in vitro. Out of them, 18 isolates were antagonists by showing zone of inhibition ranging from 1 to 17 mm by diameter. Most of antagonistic bacteria were identified as Bacillus spp. whereas only one isolate was Pseudomonas vesicularis

  6. Effects of felodipine, a newly developed calcium antagonist, on blood pressure, and cerebral and renal blood flow in patients with essential hypertension

    International Nuclear Information System (INIS)

    Ono, Yoshiaki; Konno, Yoshio; Shibuya, Hiroshi; Watanabe, Tsuyoshi; Mizuno, Kenji.

    1997-01-01

    Felodipine, a recently developed calcium channel antagonist, was administered twice daily (10 mg/day) for 1 month to 5 patients with mild to moderate essential hypertension. Its antihypertensive effect, as well as its effect on cerebral and renal blood flow, was investigated. After 1 month of therapy, sitting systolic and diastolic blood pressure were significantly decreased. The antihypertensive effect was well tolerated and sustained during the administration period. Total cerebral blood flow, as assessed by 99m Tc-hexamethyl-propyleneamine oxime, increased to 46.8±6.4 ml/100 g/min from a pretreatment level of 43.6±6.4 ml/100 g/min (P 99m Tc-diethylenetriamine pentaacetic acid, unchanged: 70.2±19.9 ml/ min before and 71.8±13.6 ml/min after. Blood viscosity and the number of blood platelet tended to decrease during treatment. There were essentially no significant changes in biochemical parameters, and no severe side effects were encountered during the administration. These results not only confirmed the safety and usefulness of felodipine as an antihypertensive agent for the treatment of essential hypertension, but also suggested that this new calcium channel antagonist may exert beneficial effects on central as well as renal hemodynamics in essential hypertensives. (author)

  7. Differential effects of Rho-kinase inhibitor and angiotensin II type-1 receptor antagonist on the vascular function in hypertensive rats induced by chronic l-NAME treatment

    Directory of Open Access Journals (Sweden)

    Bainian Chen

    2012-10-01

    Full Text Available Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension. We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficial effect on the vascular dysfunction of the NG-nitro-l-arginine methyl ester (l-NAME treated rat, as well as to compare the differential effects of fasudil and angiotensin II receptor antagonist valsartan on vascular function. In the present study, both valsartan and fasudil exerted antihypertensive action on the l-NAME-treated rats, while only valsartan attenuated the cardiac hypertrophy. Treatment with valsartan showed improvement on vascular reactivity to norepinephrine, KCl and CaCl2, whereas fasudil therapy showed little effect on vasoconstriction. Endothelium-dependent vasodilation to acetylcholine was reduced in the NO-deficient group but was normalized by the fasudil therapy. The increased expression of RhoA and Rho-kinase (ROCK in the vasculature was corrected well to normal level by either valsartan or fasudil administration, which seemed to be at least partially responsible for the beneficial effect of the drug infusion. These findings suggest that the angiotensin II receptor antagonist interferes more with the contractile response than Rho-kinase inhibitor, whereas inhibition of Rho-kinase activity exhibits a better improvement on vasorelaxation than blockade of angiotensin II receptor.

  8. On Hobbes’s distinction of accidents

    Directory of Open Access Journals (Sweden)

    Lupoli Agostino

    2012-06-01

    Full Text Available An interpolation introduced by K. Schuhmann in his critical edition of "De corpore" (chap. VI, § 13 diametrically overturns the meaning of Hobbes’s doctrine of distinction of accidents in comparison with all previous editions. The article focuses on the complexity of this crucial juncture in "De corpore" argument on which depends the interpretation of Hobbes’s whole conception of science. It discusses the reasons pro and contra Schuhmann’s interpolation and concludes against it, because it is not compatible with the rationale underlying the complex architecture of "De corpore", which involves a symmetry between the ‘logical’ distinction of accidents and the ‘metaphysical’ distinction of phantasms.

  9. What makes health promotion research distinct?

    Science.gov (United States)

    Woodall, James; Warwick-Booth, Louise; South, Jane; Cross, Ruth

    2018-02-01

    There have been concerns about the decline of health promotion as a practice and discipline and, alongside this, calls for a clearer articulation of health promotion research and what, if anything, makes it distinct. This discussion paper, based on a review of the literature, the authors' own experiences in the field, and a workshop delivered by two of the authors at the 8th Nordic Health Promotion Conference, seeks to state the reasons why health promotion research is distinctive. While by no means exhaustive, the paper suggests four distinctive features. The paper hopes to be a catalyst to enable health promotion researchers to be explicit in their practice and to begin the process of developing an agreed set of research principles.

  10. Intergroup Leadership Across Distinct Subgroups and Identities.

    Science.gov (United States)

    Rast, David E; Hogg, Michael A; van Knippenberg, Daan

    2018-03-01

    Resolving intergroup conflict is a significant and often arduous leadership challenge, yet existing theory and research rarely, if ever, discuss or examine this situation. Leaders confront a significant challenge when they provide leadership across deep divisions between distinct subgroups defined by self-contained identities-The challenge is to avoid provoking subgroup identity distinctiveness threat. Drawing on intergroup leadership theory, three studies were conducted to test the core hypothesis that, where identity threat exists, leaders promoting an intergroup relational identity will be better evaluated and are more effective than leaders promoting a collective identity; in the absence of threat, leaders promoting a collective identity will prevail. Studies 1 and 2 ( N = 170; N = 120) supported this general proposition. Study 3 ( N = 136) extended these findings, showing that leaders promoting an intergroup relational identity, but not a collective identity, improved intergroup attitudes when participants experienced an identity distinctiveness threat.

  11. Distinctive Dynamic Capabilities for New Business Creation

    DEFF Research Database (Denmark)

    Rosenø, Axel; Enkel, Ellen; Mezger, Florian

    2013-01-01

    This study examines the distinctive dynamic capabilities for new business creation in established companies. We argue that these are very different from those for managing incremental innovation within a company's core business. We also propose that such capabilities are needed in both slow...... and fast-paced industries, and that similarities exist across industries. Hence, the study contributes to dynamic capabilities literature by: 1) identifying the distinctive dynamic capabilities for new business creation; 2) shifting focus away from dynamic capabilities in environments characterised by high...... clock-speed and uncertainty towards considering dynamic capabilities for the purpose of developing new businesses, which also implies a high degree of uncertainty. Based on interviews with 33 companies, we identify distinctive dynamic capabilities for new business creation, find that dynamic...

  12. "Effects of the novel relatively short-acting kappa opioid receptor antagonist LY2444296 in behaviors observed after chronic extended-access cocaine self-administration in rats".

    Science.gov (United States)

    Valenza, Marta; Butelman, Eduardo R; Kreek, Mary Jeanne

    2017-08-01

    The recruitment of the stress circuitry contributes to a shift from positive to negative reinforcement mechanisms sustaining long-term cocaine addiction. The kappa opioid receptor (KOPr) signaling is upregulated by stress and chronic cocaine exposure. While KOPr agonists induce anhedonia and dysphoria, KOPr antagonists display antidepressant and anxiolytic properties. Most of the knowledge on KOPr antagonism is based on drugs with unusual pharmacokinetic and pharmacodynamic properties, complicating interpretation of results. Here we characterized in vivo behavioral and neuroendocrine effects of the novel relatively short-acting KOPr antagonist LY2444296. To date, no study has investigated whether systemic KOPr blockade reduced anxiety-like and depressive-like behaviors in animals previously exposed to chronic extended access cocaine self-administration. We tested the effect of LY2444296 in blocking KOPr-mediated aversive and neuroendocrine effects. Then, we tested acute systemic LY2444296 in reducing anxiety- and depression-like behaviors, as well as releasing the stress hormone corticosterone (CORT), observed after chronic extended access (18 h/day for 14 days) cocaine self-administration. LY2444296 blocked U69,593-induced place aversion and -reduced motor activity as well as U69,593-induced release of serum CORT, confirming its major site of action, without exerting an effect per se. Acute systemic administration of LY2444296 reduced anxiety-like and depressive-like behaviors, as well as CORT release, in rats tested after chronic extended access cocaine self-administration, but not in cocaine-naïve rats. Results suggest that acute blockade of KOPr by a relatively short-acting antagonist produces therapeutic-like effects selectively in rats with a history of chronic extended access cocaine self-administration.

  13. Receptors for luteinizing hormone-releasing hormone (LHRH) in benign prostatic hyperplasia (BPH) as potential molecular targets for therapy with LHRH antagonist cetrorelix.

    Science.gov (United States)

    Rozsa, Bernadett; Nadji, Mehrdad; Schally, Andrew V; Dezso, Balazs; Flasko, Tibor; Toth, Gyorgy; Mile, Melinda; Block, Norman L; Halmos, Gabor

    2011-04-01

    The majority of men will develop symptoms of benign prostatic hyperplasia (BPH) after 70 years of age. Various studies indicate that antagonists of LHRH, such as cetrorelix, exert direct inhibitory effects on BPH mediated by specific LHRH receptors. Our aim was to investigate the mRNA for LHRH and LHRH receptors and the expression of LHRH receptors in specimens of human BPH. The expression of mRNA for LHRH (n=35) and LHRH receptors (n=55) was investigated by RT-PCR in surgical specimens of BPH, using specific primers. The characteristics of binding sites for LHRH on 20 samples were determined by ligand competition assays. The LHRH receptor expression was also examined in 64 BPH specimens by immunohistochemistry. PCR products for LHRH were found in 18 of 35 (51%) BPH tissues and mRNA for LHRH receptors was detected in 39 of 55 (71%) BPH specimens. Eighteen of 20 (90%) samples showed a single class of high affinity binding sites for [D-Trp(6) ]LHRH with a mean K(d) of 4.04 nM and a mean B(max) of 527.6 fmol/mg membrane protein. LHRH antagonist cetrorelix showed high affinity binding to LHRH receptors in BPH. Positive immunohistochemical reaction for LHRH receptors was present in 42 of 64 (67%) BPH specimens. A high incidence of LHRH receptors in BPH supports the use of LHRH antagonists such as cetrorelix, for treatment of patients with lower urinary tract symptoms from BPH. Copyright © 2010 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2017-01-01

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

  15. Fermionic bound states in distinct kinklike backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Bazeia, D. [Universidade Federal da Paraiba, Departamento de Fisica, Joao Pessoa, Paraiba (Brazil); Mohammadi, A. [Universidade Federal de Campina Grande, Departamento de Fisica, Caixa Postal 10071, Campina Grande, Paraiba (Brazil)

    2017-04-15

    This work deals with fermions in the background of distinct localized structures in the two-dimensional spacetime. Although the structures have a similar topological character, which is responsible for the appearance of fractionally charged excitations, we want to investigate how the geometric deformations that appear in the localized structures contribute to the change in the physical properties of the fermionic bound states. We investigate the two-kink and compact kinklike backgrounds, and we consider two distinct boson-fermion interactions, one motivated by supersymmetry and the other described by the standard Yukawa coupling. (orig.)

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Enoch C.Chow; Jennifer L.Etnier

    2017-01-01

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

  18. Acute kidney injury mediated by oxidative stress in Egyptian horses with exertional rhabdomyolysis.

    Science.gov (United States)

    el-Ashker, Maged R

    2011-06-01

    The present study was carried out to evaluate the role of oxidative stress in the pathophysiologic process of acute renal failure associated with exertional rhabdomyolysis (ER) in Egyptian horses. ER was tentatively diagnosed in 31 Baladi horses based on case history, physical examination findings and confirmed by elevation of plasma creatine kinase (CK) and urine myoglobin concentrations. According to severity of the condition, the diseased horses were categorized into two main groups; the first group included 18 horses with minimal clinical signs and plasma CK 100 000 IU/L). It was found that plasma creatol (CTL) was positively correlated (p Baladi horses with severe rhabdomyolysis.

  19. 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.

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

    Science.gov (United States)

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

    2000-06-01

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

  1. Two distinct microbial communities revealed in the sponge Cinachyrella

    Science.gov (United States)

    Cuvelier, Marie L.; Blake, Emily; Mulheron, Rebecca; McCarthy, Peter J.; Blackwelder, Patricia; Thurber, Rebecca L. Vega; Lopez, Jose V.

    2014-01-01

    Marine sponges are vital components of benthic and coral reef ecosystems, providing shelter and nutrition for many organisms. In addition, sponges act as an essential carbon and nutrient link between the pelagic and benthic environment by filtering large quantities of seawater. Many sponge species harbor a diverse microbial community (including Archaea, Bacteria and Eukaryotes), which can constitute up to 50% of the sponge biomass. Sponges of the genus Cinachyrella are common in Caribbean and Floridian reefs and their archaeal and bacterial microbiomes were explored here using 16S rRNA gene tag pyrosequencing. Cinachyrella specimens and seawater samples were collected from the same South Florida reef at two different times of year. In total, 639 OTUs (12 archaeal and 627 bacterial) belonging to 2 archaeal and 21 bacterial phyla were detected in the sponges. Based on their microbiomes, the six sponge samples formed two distinct groups, namely sponge group 1 (SG1) with lower diversity (Shannon-Weiner index: 3.73 ± 0.22) and SG2 with higher diversity (Shannon-Weiner index: 5.95 ± 0.25). Hosts' 28S rRNA gene sequences further confirmed that the sponge specimens were composed of two taxa closely related to Cinachyrella kuekenthalli. Both sponge groups were dominated by Proteobacteria, but Alphaproteobacteria were significantly more abundant in SG1. SG2 harbored many bacterial phyla (>1% of sequences) present in low abundance or below detection limits (<0.07%) in SG1 including: Acidobacteria, Chloroflexi, Gemmatimonadetes, Nitrospirae, PAUC34f, Poribacteria, and Verrucomicrobia. Furthermore, SG1 and SG2 only had 95 OTUs in common, representing 30.5 and 22.4% of SG1 and SG2's total OTUs, respectively. These results suggest that the sponge host may exert a pivotal influence on the nature and structure of the microbial community and may only be marginally affected by external environment parameters. PMID:25408689

  2. Two distinct microbial communities revealed in the sponge Cinachyrella

    Directory of Open Access Journals (Sweden)

    Marie Laure Cuvelier

    2014-11-01

    Full Text Available Marine sponges are vital components of benthic and coral reef ecosystems, providing shelter and nutrition for many organisms. In addition, sponges act as an essential carbon and nutrient link between the pelagic and benthic environment by filtering large quantities of seawater. Many sponge species harbor a diverse microbial community (including Archaea, Bacteria and Eukaryotes, which can constitute up to 50% of the sponge biomass. Sponges of the genus Cinachyrella are common in Caribbean and Floridian reefs and their archaeal and bacterial microbiomes were explored here using 16S rDNA tag pyrosequencing. Cinachyrella specimens and seawater samples were collected from the same South Florida reef at two different times of year. In total, 639 OTUs (12 archaeal and 627 bacterial belonging to 2 archaeal and 21 bacterial phyla were detected in the sponges. Based on their microbiomes, the six sponge samples formed two distinct groups, namely sponge group 1 (SG1 with low diversity (Shannon-Weiner index: 3.73 ± 0.22 and SG2 with higher diversity (Shannon-Weiner index: 5.95 ± 0.25. Hosts’ 28S rDNA sequences further confirmed that the sponge specimens were composed of two taxa closely related to Cinachyrella kuekenthalli. Both sponge groups were dominated by Proteobacteria, but Alphaproteobacteria were significantly more abundant in SG1. SG2 harbored many bacterial phyla (>1% of sequences present in low abundance or below detection limits (<0.07% in SG1 including: Acidobacteria, Chloroflexi, Gemmatimonadetes, Nitrospirae, PAUC34f, Poribacteria and Verrucomicrobia. Furthermore, SG1 and SG2 only had 95 OTUs in common, representing 30.5% and 22.4% of SG1 and SG2’s total OTUs, respectively. These results suggest that the sponge host may exert a pivotal influence on the nature and structure of the microbial community and may only be marginally affected by external environment parameters.

  3. Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

    Science.gov (United States)

    Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

    2013-01-01

    Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

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

    Science.gov (United States)

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

    2018-04-06

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

  5. Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

    Science.gov (United States)

    Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

    2011-04-01

    Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

  6. Research progress of antagonistic interactions among root canal irrigations disease

    Directory of Open Access Journals (Sweden)

    Chen QU

    2013-07-01

    Full Text Available Root canal therapy is the most effective way to treat various pulposis and periapical disease. Simple mechanical apparatus can not clean root canal thoroughly, but may affect tight filling instead. It can achieve a satisfactory cleansing effect only when it is combined with a chemical solution. Irrigation fluid for root canal should possess the properties of tissue dissolution, antimicrobial, lubrication, and removal of smear layer. So far, no solution is able to fulfill all these functions. Therefore, a combined use of multiple irrigation solutions is suggested. It can not only achieve good effect in cleaning and disinfection, also it can lower the concentration of different solutions, thus reducing the side effects. Nevertheless, some experiments proved that antagonism existed among the chemicals used for irrigations. The purpose of present article is to review the antagonistic effect among the chemicals used for irrigation when they are used together for root canal treatment.

  7. Identification of Bexarotene as a PPARγ Antagonist with HDX

    Directory of Open Access Journals (Sweden)

    David P. Marciano

    2015-01-01

    Full Text Available The retinoid x receptors (RXRs are the pharmacological target of Bexarotene, an antineoplastic agent indicated for the treatment of cutaneous T cell lymphoma (CTCL. The RXRs form heterodimers with several nuclear receptors (NRs, including peroxisome proliferator-activated receptor gamma (PPARγ, to regulate target gene expression through cooperative recruitment of transcriptional machinery. Here we have applied hydrogen/deuterium exchange (HDX mass spectrometry to characterize the effects of Bexarotene on the conformational plasticity of the intact RXRα:PPARγ heterodimer. Interestingly, addition of Bexarotene to PPARγ in the absence of RXRα induced protection from solvent exchange, suggesting direct receptor binding. This observation was confirmed using a competitive binding assay. Furthermore, Bexarotene functioned as a PPARγ antagonist able to alter rosiglitazone induced transactivation in a cell based promoter:reporter transactivation assay. Together these results highlight the complex polypharmacology of lipophilic NR targeted small molecules and the utility of HDX for identifying and characterizing these interactions.

  8. Rational use of calcium-channel antagonists in Raynaud's phenomenon.

    Science.gov (United States)

    Sturgill, M G; Seibold, J R

    1998-11-01

    Raynaud's phenomenon (RP) is a peripheral circulatory disorder characterized by sudden episodes of digital artery spasm, often precipitated by cold temperature or emotional stress. Although the cause of RP is not fully known, it appears to involve inappropriate adrenergic response to cold stimuli. Treatment of RP is conservative in most patients, but in patients with severe disease includes the use of agents that promote digital vasodilation. The calcium-channel antagonists, particularly the dihydropyridine derivative nifedipine, are the most thoroughly studied drug class for the treatment of RP. Approximately two thirds of patients respond favorably, with significant reductions in the frequency and severity of vasospastic attacks. Nifedipine use is often limited by the appearance of adverse vasodilatory effects such as headache or peripheral edema. The newer second-generation dihydropyridines such as amlodipine, isradipine, nicardipine, and felodipine also appear to be effective in patients with RP and may be associated with fewer adverse effects.

  9. Antagonistic Bioactivity of Endophytic Actinomycetes Isolated from Medicinal Plants

    Directory of Open Access Journals (Sweden)

    M. Gangwar

    2011-10-01

    Full Text Available Endophytic actinomycetes are promising biocontrol agents for use in agriculture and have been isolated from various plant species. In the present study, 40 endophytic actinomycetes were isolated from roots, stems and leaves of three medicinal plants viz. Aloe vera, Mentha arvensis and Ocimum sanctum. The identification revealed that the majority of the isolates were Streptomyces spp. and the rest were identified as Saccharopolyspora spp., Micromonospora spp. and Actinopolyspora spp. The dual tests revealed that nine endophytic actinomycete isolates displayed a wide spectrum activity against nine fungal phytopathogens. Out of 8 isolates, 90% inhibited the growth of at least one or more phytopathogenic fungi and Saccharopolyspora 0-9 (Out of 8 isolates, 90% inhibited the growth of at least one or more phytopathogenic fungi and Saccharopolyspora 0-9 exhibited antagonistic activity against Aspergillus niger, Aspergillus flavus, Alternaria brassicicola, Botrytis cinerea, Penicillium digitatum, Fusarium oxysporum, Penicillium pinophilum, Phytophthora dresclea and Colletotrichum falcatum.

  10. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.

    Science.gov (United States)

    Morselli, Eugenia; Mariño, Guillermo; Bennetzen, Martin V; Eisenberg, Tobias; Megalou, Evgenia; Schroeder, Sabrina; Cabrera, Sandra; Bénit, Paule; Rustin, Pierre; Criollo, Alfredo; Kepp, Oliver; Galluzzi, Lorenzo; Shen, Shensi; Malik, Shoaib Ahmad; Maiuri, Maria Chiara; Horio, Yoshiyuki; López-Otín, Carlos; Andersen, Jens S; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

    2011-02-21

    Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that the acetylase inhibitor spermidine stimulates autophagy independent of SIRT1 in human and yeast cells as well as in nematodes. Although resveratrol and spermidine ignite autophagy through distinct mechanisms, these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome. Both agents favor convergent deacetylation and acetylation reactions in the cytosol and in the nucleus, respectively. Both resveratrol and spermidine were able to induce autophagy in cytoplasts (enucleated cells). Moreover, a cytoplasm-restricted mutant of SIRT1 could stimulate autophagy, suggesting that cytoplasmic deacetylation reactions dictate the autophagic cascade. At doses at which neither resveratrol nor spermidine stimulated autophagy alone, these agents synergistically induced autophagy. Altogether, these data underscore the importance of an autophagy regulatory network of antagonistic deacetylases and acetylases that can be pharmacologically manipulated.

  11. Identifying Two Groups of Entitled Individuals: Cluster Analysis Reveals Emotional Stability and Self-Esteem Distinction.

    Science.gov (United States)

    Crowe, Michael L; LoPilato, Alexander C; Campbell, W Keith; Miller, Joshua D

    2016-12-01

    The present study hypothesized that there exist two distinct groups of entitled individuals: grandiose-entitled, and vulnerable-entitled. Self-report scores of entitlement were collected for 916 individuals using an online platform. Model-based cluster analyses were conducted on the individuals with scores one standard deviation above mean (n = 159) using the five-factor model dimensions as clustering variables. The results support the existence of two groups of entitled individuals categorized as emotionally stable and emotionally vulnerable. The emotionally stable cluster reported emotional stability, high self-esteem, more positive affect, and antisocial behavior. The emotionally vulnerable cluster reported low self-esteem and high levels of neuroticism, disinhibition, conventionality, psychopathy, negative affect, childhood abuse, intrusive parenting, and attachment difficulties. Compared to the control group, both clusters reported being more antagonistic, extraverted, Machiavellian, and narcissistic. These results suggest important differences are missed when simply examining the linear relationships between entitlement and various aspects of its nomological network.

  12. Common and distinct components in data fusion

    DEFF Research Database (Denmark)

    Smilde, Age Klaas; Mage, Ingrid; Næs, Tormod

    2016-01-01

    and understanding their relative merits. This paper provides a unifying framework for this subfield of data fusion by using rigorous arguments from linear algebra. The most frequently used methods for distinguishing common and distinct components are explained in this framework and some practical examples are given...

  13. Knowledge Affords Distinctive Processing in Memory

    Science.gov (United States)

    Hunt, R. Reed; Rawson, Katherine A.

    2011-01-01

    The effect of knowledge on memory generally is processing. However, both conceptual and empirical reasons exist to suspect that the organizational account is incomplete. Recently a revised version of that account has been proposed under the rubric of distinctiveness theory (Rawson & Van Overschelde, 2008). The goal of the experiments reported…

  14. Distinctiveness of Saudi Arabian EFL Learners

    Science.gov (United States)

    Habbash, Manssour; Idapalapati, Srinivasa Rao

    2016-01-01

    In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs…

  15. High-Throughput Screening of Small Molecules Identifies Hepcidin Antagonists

    Science.gov (United States)

    Fung, Eileen; Sugianto, Priscilla; Hsu, Jason; Damoiseaux, Robert; Ganz, Tomas

    2013-01-01

    Anemia of inflammation (AI) is common in patients with infection, autoimmune diseases, cancer, and chronic kidney disease. Unless the underlying condition can be reversed, treatment options are limited to erythropoiesis-stimulating agents with or without intravenous iron therapy, modalities that are not always effective and can cause serious adverse effects. Hepcidin, the iron regulatory hormone, has been identified as a pathogenic factor in the development of AI. To explore new therapeutic options for AI and other iron-related disorders caused by hepcidin excess, we developed a cell-based screen to identify hepcidin antagonists. Of the 70,000 small molecules in the library, we identified 14 compounds that antagonized the hepcidin effect on ferroportin. One of these was fursultiamine, a Food and Drug Administration (FDA)–approved thiamine derivative. Fursultiamine directly interfered with hepcidin binding to its receptor, ferroportin, by blocking ferroportin C326 thiol residue essential for hepcidin binding. Consequently, fursultiamine prevented hepcidin-induced ferroportin ubiquitination, endocytosis, and degradation in vitro and allowed continuous cellular iron export despite the presence of hepcidin, with IC50 in the submicromolar range. Thiamine, the fursultiamine metabolite, and benfotiamine, another thiamine derivative, did not interfere with the effect of hepcidin on ferroportin. Other FDA-approved thiol-reactive compounds were at least 1000-fold less potent than fursultiamine in antagonizing hepcidin. In vivo, fursultiamine did not reproducibly antagonize the effect of hepcidin on serum iron, likely because of its rapid conversion to inactive metabolites. Fursultiamine is a unique antagonist of hepcidin in vitro that could serve as a template for the development of drug candidates that inhibit the hepcidin-ferroportin interaction. PMID:23292796

  16. Alpha antagonists and intraoperative floppy iris syndrome: A spectrum

    Directory of Open Access Journals (Sweden)

    Sharif A Issa

    2008-07-01

    Full Text Available Sharif A Issa, Omar H Hadid, Oliver Baylis, Margaret DayanDepartment of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, UKBackground: To determine occurrence of features of intraoperative floppy iris syndrome (IFIS during cataract surgery in patients taking systemic alpha-antagonists (AA.Methods: We prospectively studied patients on AA and who underwent phacoemulsification. The following were recorded: pupil diameter preoperatively, iris flaccidity, iris prolapse and peroperative miosis.Results: We studied 40 eyes of 31 subjects. Mean age was 78 years. Overall, 14 eyes (13 patients showed signs of IFIS: 9/13 (69% eyes of patients on tamsulosin, 1/18 (6% eyes in the doxazosin group, 2/2 prazosin patients, 1/4 eyes in the indoramin group, and 1/2 eyes in two patients on a combination of doxazosin and tamsulosin. Most cases (92% had only one or two signs of IFIS. Bilateral cataract surgery was undertaken in 9 patients but only one patient (on tamsulosin had features of IFIS in both eyes, while 4 patients (2 on tamsulosin and 2 on other AA showed signs of IFIS in one eye only, and 4 patients did not show IFIS in either eye.Conclusion: Most AA were associated with IFIS, but it tends to present as a spectrum of signs rather than full triad originally described. Tamsulosin was most likely to be associated with IFIS; however, its intake does not necessarily mean that IFIS will occur. For patients on AA, the behavior of the iris intraoperatively in one eye is a poor predictor of the other eye. Surgeons should anticipate the occurrence of IFIS in any patient on AA.Keywords: alpha blocker, alpha antagonist, cataract surgery, intraoperative floppy iris syndrome, tamsulosin.

  17. 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.

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

    Science.gov (United States)

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

    2015-02-16

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

  19. 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.

  20. Influence of fatigue, stress, muscle soreness and sleep on perceived exertion during submaximal effort.

    Science.gov (United States)

    Haddad, Monoem; Chaouachi, Anis; Wong, Del P; Castagna, Carlo; Hambli, Mourad; Hue, Olivier; Chamari, Karim

    2013-07-02

    The aim of this study was to assess the effects of the Hooper's Index variations (i.e., self-ratings of fatigue, stress, delayed onset muscle soreness (DOMS), and sleep) on rating of perceived exertion during a 10 min submaximal exercise training session (RPE-10 min) and then check the stability and the internal consistency of RPE-10 min. Seventeen junior soccer players took part in this study. The individual Hooper's indices taken before each training session were correlated with RPE-10 min during a constant intensity and duration effort (10 min) using Pearson product moment correlation. Intraclass correlation (ICC) was used to assess the internal consistency of the RPE-10 min. All individual correlations between RPE-10 min and quality of sleep and quantity of fatigue, stress, and DOMS were non-significant (p>0.05). No significant correlations were resulted between RPE-10 min and Hooper's Index in all athletes. The ICC of RPE-10 min was 0.77 thus demonstrating internal consistency. The results of the present study demonstrated the objectivity and utility of RPE as a psychological tool for monitoring training during traditional soccer training. Therefore, the results of the present study suggest that fatigue, stress, DOMS and sleep are not major contributors of perceived exertion during traditional soccer training without excessive training loads. It seems that psychobiological factors other than fatigue, stress, DOMS and sleep may have mediated the 10 min exercise perceptual intensity. © 2013.

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

    Science.gov (United States)

    Fessi, Mohamed Saifeddin; Moalla, Wassim

    2018-01-18

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

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

    Science.gov (United States)

    Rogerson, Mike; Barton, Jo

    2015-06-30

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

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

    Science.gov (United States)

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

    2003-10-15

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

    James, Shaun; Kjerulf Greer, Beau

    2018-06-28

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

  6. Magnetic tweezers optimized to exert high forces over extended distances from the magnet in multicellular systems

    Science.gov (United States)

    Selvaggi, L.; Pasakarnis, L.; Brunner, D.; Aegerter, C. M.

    2018-04-01

    Magnetic tweezers are mainly divided into two classes depending on the ability of applying torque or forces to the magnetic probe. We focused on the second category and designed a device composed by a single electromagnet equipped with a core having a special asymmetric profile to exert forces as large as 230 pN-2.8 μm Dynabeads at distances in excess of 100 μm from the magnetic tip. Compared to existing solutions our magnetic tweezers overcome important limitations, opening new experimental paths for the study of a wide range of materials in a variety of biophysical research settings. We discuss the benefits and drawbacks of different magnet core characteristics, which led us to design the current core profile. To demonstrate the usefulness of our magnetic tweezers, we determined the microrheological properties inside embryos of Drosophila melanogaster during the syncytial stage. Measurements in different locations along the dorsal-ventral axis of the embryos showed little variation, with a slight increase in cytoplasm viscosity at the periphery of the embryos. The mean cytoplasm viscosity we obtain by active force exertion inside the embryos is comparable to that determined passively using high-speed video microrheology.

  7. Estimation of the flow resistances exerted in coronary arteries using a vessel length-based method.

    Science.gov (United States)

    Lee, Kyung Eun; Kwon, Soon-Sung; Ji, Yoon Cheol; Shin, Eun-Seok; Choi, Jin-Ho; Kim, Sung Joon; Shim, Eun Bo

    2016-08-01

    Flow resistances exerted in the coronary arteries are the key parameters for the image-based computer simulation of coronary hemodynamics. The resistances depend on the anatomical characteristics of the coronary system. A simple and reliable estimation of the resistances is a compulsory procedure to compute the fractional flow reserve (FFR) of stenosed coronary arteries, an important clinical index of coronary artery disease. The cardiac muscle volume reconstructed from computed tomography (CT) images has been used to assess the resistance of the feeding coronary artery (muscle volume-based method). In this study, we estimate the flow resistances exerted in coronary arteries by using a novel method. Based on a physiological observation that longer coronary arteries have more daughter branches feeding a larger mass of cardiac muscle, the method measures the vessel lengths from coronary angiogram or CT images (vessel length-based method) and predicts the coronary flow resistances. The underlying equations are derived from the physiological relation among flow rate, resistance, and vessel length. To validate the present estimation method, we calculate the coronary flow division over coronary major arteries for 50 patients using the vessel length-based method as well as the muscle volume-based one. These results are compared with the direct measurements in a clinical study. Further proving the usefulness of the present method, we compute the coronary FFR from the images of optical coherence tomography.

  8. 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.

  9. Double dissociation of spike timing-dependent potentiation and depression by subunit-preferring NMDA receptor antagonists in mouse barrel cortex.

    Science.gov (United States)

    Banerjee, Abhishek; Meredith, Rhiannon M; Rodríguez-Moreno, Antonio; Mierau, Susanna B; Auberson, Yves P; Paulsen, Ole

    2009-12-01

    Spike timing-dependent plasticity (STDP) is a strong candidate for an N-methyl-D-aspartate (NMDA) receptor-dependent form of synaptic plasticity that could underlie the development of receptive field properties in sensory neocortices. Whilst induction of timing-dependent long-term potentiation (t-LTP) requires postsynaptic NMDA receptors, timing-dependent long-term depression (t-LTD) requires the activation of presynaptic NMDA receptors at layer 4-to-layer 2/3 synapses in barrel cortex. Here we investigated the developmental profile of t-LTD at layer 4-to-layer 2/3 synapses of mouse barrel cortex and studied their NMDA receptor subunit dependence. Timing-dependent LTD emerged in the first postnatal week, was present during the second week and disappeared in the adult, whereas t-LTP persisted in adulthood. An antagonist at GluN2C/D subunit-containing NMDA receptors blocked t-LTD but not t-LTP. Conversely, a GluN2A subunit-preferring antagonist blocked t-LTP but not t-LTD. The GluN2C/D subunit requirement for t-LTD appears to be synapse specific, as GluN2C/D antagonists did not block t-LTD at horizontal cross-columnar layer 2/3-to-layer 2/3 synapses, which was blocked by a GluN2B antagonist instead. These data demonstrate an NMDA receptor subunit-dependent double dissociation of t-LTD and t-LTP mechanisms at layer 4-to-layer 2/3 synapses, and suggest that t-LTD is mediated by distinct molecular mechanisms at different synapses on the same postsynaptic neuron.

  10. Purification and reconstitution of the calcium antagonist receptor of the voltage-sensitive calcium channel

    International Nuclear Information System (INIS)

    Curtis, B.M.

    1986-01-01

    Treatment with digitonin solubilized the calcium antagonist receptor as a stable complex with [ 3 H]nitrendipine from rat brain membranes. The solubilized complex retains allosteric coupling to binding sites for diltiazem, verapamil, and inorganic calcium antagonist sites. The calcium antagonist receptor from cardiac sarcolemma and the transverse-tubule membrane of skeletal muscle is also efficiently solubilized with digitonin and the receptor in all three tissues is a large glycoprotein with a sedimentation coefficient of 20 S. The T-tubule calcium antagonist receptor complex was extensively purified by a combination of chromatography on WGA-Sepharose, ion exchange chromatography, and sedimentation on sucrose gradients to yield preparations estimated to be 41% homogeneous by specific activity and 63% homogeneous by SDS gel electrophoresis. Analysis of SDS gels detect three polypeptides termed α(Mr 135,000), β(Mr 50,000), and γ(Mr 32,000) as noncovalently associated subunits of the calcium antagonist receptor. The α and γ subunits are glycosylated polypeptides, and the molecular weight of the core polypeptides are 108,000 and 24,000 respectively. The calcium antagonist receptor was reconstituted into a phospholipid bilayer by adding CHAPS and exogeneous lipid to the purified receptor followed by rapid detergent removal. This procedure resulted in the incorporation of 45% of the calcium antagonist receptor into closed phospholipid vesicles. Data suggests that the α, β, and γ subunits of the T-tubule calcium antagonist receptor are sufficient to form a functional calcium channel

  11. Survivin mRNA antagonists using locked nucleic acid, potential for molecular cancer therapy

    DEFF Research Database (Denmark)

    Fisker, Niels; Westergaard, Majken; Hansen, Henrik Frydenlund

    2007-01-01

    We have investigated the effects of different locked nucleic acid modified antisense mRNA antagonists against Survivin in a prostate cancer model. These mRNA antagonists were found to be potent inhibitors of Survivin expression at low nanomolar concentrations. Additionally there was a pronounced ...

  12. Agar composition affects in vitro screening of biocontrol activity of antagonistic microorganisms

    NARCIS (Netherlands)

    Bosmans, Lien; De Bruijn, I.; de Mot, Rene; Readers, Hans; Lievens, Bart

    2016-01-01

    Agar-based screening assays are the method of choice when evaluating antagonistic potential of bacterial biocontrol-candidates against pathogens.Weshowed thatwhen using the samemedium, but different agar compositions, the activity of a bacterial antagonist against Agrobacteriumwas strongly affected.

  13. Benzimidazoles as benzamide replacements within cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists.

    Science.gov (United States)

    Cherney, Robert J; Mo, Ruowei; Meyer, Dayton T; Pechulis, Anthony D; Guaciaro, Michael A; Lo, Yvonne C; Yang, Gengjie; Miller, Persymphonie B; Scherle, Peggy A; Zhao, Qihong; Cvijic, Mary Ellen; Barrish, Joel C; Decicco, Carl P; Carter, Percy H

    2012-10-01

    We describe the design, synthesis, and evaluation of benzimidazoles as benzamide replacements within a series of trisubstituted cyclohexane CCR2 antagonists. 7-Trifluoromethylbenzimidazoles displayed potent binding and functional antagonism of CCR2 while being selective over CCR3. These benzimidazoles were also incorporated into lactam-containing antagonists, thus completely eliminating the customary bis-amide. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Pablo Pancardo

    2018-01-01

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

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

    OpenAIRE

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

    2018-01-01

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

  16. Refractory versus resistant hypertension: Novel distinctive phenotypes

    Science.gov (United States)

    Dudenbostel, Tanja; Siddiqui, Mohammed; Gharpure, Nitin; Calhoun, David A.

    2017-01-01

    Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed. PMID:29034321

  17. Embarrassment: its distinct form and appeasement functions.

    Science.gov (United States)

    Keltner, D; Buswell, B N

    1997-11-01

    The authors address 2 questions about embarrassment. First, Is embarrassment a distinct emotion? The evidence indicates that the antecedents, experience, and display of embarrassment, and to a limited extent its autonomic physiology, are distinct from shame, guilt, and amusement and share the dynamic, temporal characteristics of emotion. Second, What are the theoretical accounts of embarrassment? Three accounts focus on the causes of embarrassment, positioning that it follows the loss of self-esteem, concern for others' evaluations, or absence of scripts to guide interactions. A fourth account focuses on the effects of the remedial actions of embarrassment, which correct preceding transgressions. A fifth account focuses on the functional parallels between embarrassment and nonhuman appeasement. The discussion focuses on unanswered questions about embarrassment.

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

    Science.gov (United States)

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

    2014-04-15

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

  19. Distinctive skeletal dysplasia in Cockayne syndrome

    International Nuclear Information System (INIS)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-01-01

    Cockayne syndrom is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvment of the spine. (orig.)

  20. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  1. Army nurses in wartime: distinction and pride.

    Science.gov (United States)

    Higgins, L P

    1996-08-01

    Nurses have served with distinction in wartime since Florence Nightingale went to the Crimea. Women often accompanied their husbands to battle during the Revolutionary and Civil Wars, caring for the sick and wounded. Although not officially given officer status until 1920, Army nurses served in the Spanish-American War and World War I. As officers, thousands of nurses served in subsequent wars, distinguishing themselves by their heroism, devotion to duty, and sheer tenacity of spirit.

  2. Human multipotent adult progenitor cells are nonimmunogenic and exert potent immunomodulatory effects on alloreactive T-cell responses.

    Science.gov (United States)

    Jacobs, Sandra A; Pinxteren, Jef; Roobrouck, Valerie D; Luyckx, Ariane; van't Hof, Wouter; Deans, Robert; Verfaillie, Catherine M; Waer, Mark; Billiau, An D; Van Gool, Stefaan W

    2013-01-01

    Multipotent adult progenitor cells (MAPCs) are bone marrow-derived nonhematopoietic stem cells with a broad differentiation potential and extensive expansion capacity. A comparative study between human mesenchymal stem cells (hMSCs) and human MAPCs (hMAPCs) has shown that hMAPCs have clearly distinct phenotypical and functional characteristics from hMSCs. In particular, hMAPCs express lower levels of MHC class I than hMSCs and cannot only differentiate into typical mesenchymal cell types but can also differentiate in vitro and in vivo into functional endothelial cells. The use of hMSCs as cellular immunomodulatory stem cell products gained much interest since their immunomodulatory capacities in vitro became evident over the last decade. Currently, the clinical grade stem cell product of hMAPCs is already used in clinical trials to prevent graft-versus-host disease (GVHD), as well as for the treatment of acute myocardial infarct, ischemic stroke, and Crohn's disease. Therefore, we studied the immune phenotype, immunogenicity, and immunosuppressive effect of hMAPCs in vitro. We demonstrated that hMAPCs are nonimmunogenic for T-cell proliferation and cytokine production. In addition, hMAPCs exert strong immunosuppressive effects on T-cell alloreactivity and on T-cell proliferation induced by mitogens and recall antigens. This immunomodulatory effect was not MHC restricted, which makes off-the-shelf use promising. The immunosuppressive effect of hMAPCs is partially mediated via soluble factors and dependent on indoleamine 2,3-dioxygenase (IDO) activity. At last, we isolated hMAPCs, the clinical grade stem cell product of hMAPCs, named MultiStem, and hMSCs from one single donor and observed that both the immunogenicity and the immunosuppressive capacities of all three stem cell products are comparable in vitro. In conclusion, hMAPCs have potent immunomodulatory properties in vitro and can serve as a valuable cell source for the clinical use of immunomodulatory cellular

  3. Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Sadek B

    2016-11-01

    , in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-ylpropoxyphenylmethanol, and its (S-enantiomer (4 significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R-enantiomer (3 in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and reversed when rats were pretreated with the selective H3R agonist R-(α-methyl-histamine. Comparisons of the observed antagonistic in vitro affinities among the ligands 1–6 revealed profound stereoselectivity at human H3Rs with varying preferences for this receptor subtype. Moreover, the in vivo anticonvulsant effects observed in this study for ligands 1–6 showed stereoselectivity in different convulsion models in male adult rats. Keywords: histamine, H3 receptor, isomeric antagonists, anticonvulsant activity, stereo­selectivity

  4. Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism

    NARCIS (Netherlands)

    van der Heijden, J. F.; Hutten, B. A.; Büller, H. R.; Prins, M. H.

    2002-01-01

    BACKGROUND: People with venous thromboembolism are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin followed by three months of vitamin K antagonists treatment. Treatment with vitamin K antagonists requires regular laboratory

  5. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

    Science.gov (United States)

    Ma, Frank Y; Han, Yingjie; Nikolic-Paterson, David J; Kolkhof, Peter; Tesch, Greg H

    2015-01-01

    Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

  6. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

    Directory of Open Access Journals (Sweden)

    Frank Y Ma

    Full Text Available Steroidal mineralocorticoid receptor antagonists (MRAs are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis.Accelerated anti-glomerular basement membrane (GBM glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid from day 0 until being killed on day 15 of disease. Mice were examined for renal injury.Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ and profibrotic molecules (collagen I, fibronectin. In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction.The non-steroidal MRA (BR-4628 provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

  7. Preclinical development of a novel class of CXCR4 antagonist impairing solid tumors growth and metastases.

    Directory of Open Access Journals (Sweden)

    Luigi Portella

    Full Text Available The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X in CXCL12, also found in the reverse orientation (X-Ar-Ar in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.

  8. Locus Coeruleus and Tuberomammillary Nuclei Ablations Attenuate Hypocretin/Orexin Antagonist-Mediated REM Sleep.

    Science.gov (United States)

    Schwartz, Michael D; Nguyen, Alexander T; Warrier, Deepti R; Palmerston, Jeremiah B; Thomas, Alexia M; Morairty, Stephen R; Neylan, Thomas C; Kilduff, Thomas S

    2016-01-01

    Hypocretin 1 and 2 (Hcrts; also known as orexin A and B), excitatory neuropeptides synthesized in cells located in the tuberal hypothalamus, play a central role in the control of arousal. Hcrt inputs to the locus coeruleus norepinephrine (LC NE) system and the posterior hypothalamic histaminergic tuberomammillary nuclei (TMN HA) are important efferent pathways for Hcrt-induced wakefulness. The LC expresses Hcrt receptor 1 (HcrtR1), whereas HcrtR2 is found in the TMN. Although the dual Hcrt/orexin receptor antagonist almorexant (ALM) decreases wakefulness and increases NREM and REM sleep time, the neural circuitry that mediates these effects is currently unknown. To test the hypothesis that ALM induces sleep by selectively disfacilitating subcortical wake-promoting populations, we ablated LC NE neurons (LCx) or TMN HA neurons (TMNx) in rats using cell-type-specific saporin conjugates and evaluated sleep/wake following treatment with ALM and the GABAA receptor modulator zolpidem (ZOL). Both LCx and TMNx attenuated the promotion of REM sleep by ALM without affecting ALM-mediated increases in NREM sleep. Thus, eliminating either HcrtR1 signaling in the LC or HcrtR2 signaling in the TMN yields similar effects on ALM-induced REM sleep without affecting NREM sleep time. In contrast, neither lesion altered ZOL efficacy on any measure of sleep-wake regulation. These results contrast with those of a previous study in which ablation of basal forebrain cholinergic neurons attenuated ALM-induced increases in NREM sleep time without affecting REM sleep, indicating that Hcrt neurotransmission influences distinct aspects of NREM and REM sleep at different locations in the sleep-wake regulatory network.

  9. Shared epitope-antagonistic ligands: a new therapeutic strategy in mice with erosive arthritis.

    Science.gov (United States)

    Ling, Song; Liu, Ying; Fu, Jiaqi; Colletta, Alessandro; Gilon, Chaim; Holoshitz, Joseph

    2015-05-01

    The mechanisms underlying bone damage in rheumatoid arthritis (RA) are incompletely understood. We recently identified the shared epitope (SE), an HLA-DRB1-coded 5-amino acid sequence motif carried by the majority of RA patients as a signal transduction ligand that interacts with cell surface calreticulin and accelerates osteoclast (OC)-mediated bone damage in collagen-induced arthritis (CIA). Given the role of the SE/calreticulin pathway in arthritis-associated bone damage, we sought to determine the therapeutic targetability of calreticulin. A library of backbone-cyclized peptidomimetic compounds, all carrying an identical core DKCLA sequence, was synthesized. The ability of these compounds to inhibit SE-activated signaling and OC differentiation was tested in vitro. The effect on disease severity and OC-mediated bone damage was studied by weekly intraperitoneal administration of the compounds to DBA/1 mice with CIA. Two members of the peptidomimetics library were found to have SE-antagonistic effects and antiosteoclast differentiation effects at picomolar concentrations in vitro. The lead mimetic compound, designated HS(4-4)c Trp, potently ameliorated arthritis and bone damage in vivo when administered in picogram doses to mice with CIA. Another mimetic analog, designated HS(3-4)c Trp, was found to lack activity, both in vitro and in vivo. The differential activity of the 2 analogs depended on minor differences in their respective ring sizes and correlated with distinctive geometry when computationally docked to the SE binding site on calreticulin. These findings identify calreticulin as a novel therapeutic target in erosive arthritis and provide sound rationale and early structure/activity relationships for future drug design. © 2015, American College of Rheumatology.

  10. Effects of the N-methyl-D-Aspartate receptor antagonist dextromethorphan on vibrotactile adaptation

    Directory of Open Access Journals (Sweden)

    Folger Stephen E

    2008-09-01

    Full Text Available Abstract Background Previous reports have demonstrated that short durations of vibrotactile stimuli (less than or equal to 2 sec effectively and consistently modify both the perceptual response in humans as well as the neurophysiological response in somatosensory cortex. The change in cortical response with adaptation has been well established by a number of studies, and other reports have extended those findings in determining that both GABA- and NMDAR-mediated neurotransmission play a significant role in the dynamic response of somatosensory cortical neurons. In this study, we evaluated the impact that dextromethorphan (DXM, an NMDAR antagonist, had on two distinct vibrotactile adaptation tasks. Results All subjects, both those that ingested 60 mg DXM and those that ingested placebo, were evaluated for their amplitude discriminative capacity between two simultaneously delivered vibrotactile stimuli both with and without 3 conditions of pre-exposure to adapting stimulation. The results demonstrated that the perceptual metrics of subjects who ingested 60 mg DXM were significantly altered from that of controls when the amplitude discrimination task followed one of the conditions of adapting stimulation. Without the condition of pre-exposure to an adapting stimulus (or stimuli, there was little difference between the observations obtained from the subjects that ingested DXM and controls. Peak impact on subject response occurred at 60 min post-ingestion, whereas the scores of controls who ingested placebo were not impacted. Conclusion The results – that DXM blocks vibrotactile adaptation – is consistent with the suggestion that NMDAR-mediated neurotransmission plays a significant role in the perceptual adaptive response. This finding is also consistent with neurophysiological findings that report observations of the effects of NMDAR block on the SI cortical response to repetitive vibrotactile stimulation.

  11. Antagonistic studies and hyphal interactions of the new antagonist Aspergillus piperis against some phytopathogenic fungi in vitro in comparison with Trichoderma harzianum.

    Science.gov (United States)

    El-Debaiky, Samah A

    2017-12-01

    The present study represents, for the first time, the detailed studies about the hyphal interactions of Aspergillus piperis, as a new antagonist, against some isolated plant pathogenic fungi (Alternaria alternata, Alternaria solani, Botrytis cinerea, Sclerotium cepivorum and Sclerotinia sclerotiorum) in vitro. The bio-controlling capability of A. piperis against the tested phytopathogens was tested using the dual culture method. This experiment revealed that A. piperis had antagonistic activity and reduced the growth of the tested phytopathogens and grew over their mycelia in the paired plates. Also, several antagonistic mechanisms were recorded, in this study, between A. piperis and the tested phytopathogens using the microscopic examination. The bio-controlling activity and the antagonistic mechanisms exhibited by the new antagonist, A. piperis were compared with those obtained by the common antagonist, Trichoderma harzianum against the same phytopathogens. The obtained results showed that, A. piperis was more effective than T. harzianum in inhibiting all the tested species in the dual culture plates. The best result was 81.85% inhibition percentage against S. sclerotiorum by A. piperis while, T. harzianum exhibits only 45.18%. Moreover, several antagonistic mechanisms and hyphal interactions were investigated among the hyphae of both A.piperis and T. harzianum and the hyphae of the tested phytopathogens. These mechanisms were summarized as; mycoparasitism (coiling and penetration of the hyphae) and antibiosis in the form of lysis of the hyphal cells and spores, denaturation and breaking of the hyphae. The indirect interaction (antibiosis) and the direct mycoparasitism were observed by A. piperis against all the tested phytopathogens, but it attacked the hyphae and conidiophores of A. alternata by only the antibiosis interaction. The microscopic examination revealed also that T. harzianum attacked the tested phytopathogens by both antibiosis and mycoparasitism

  12. 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.

  13. Influence of plane bed on the force exerted on a cylinder oscillating in still water

    Energy Technology Data Exchange (ETDEWEB)

    Naeeni, S.T.O. [Tehran Univ., Dept. of Civil Engineering, Tehran (Iran); Narayanan, R. [Universiti Teknologi Malaysia, Faculty of Civil Engineering, Johor Bahru (Malaysia)

    2005-12-01

    The wall pressure field on a cylinder oscillating over a plane bed in still water is reported in this paper. Two gaps between the cylinder and the bed were considered. Pressures on the periphery of the cylinder were measured by a transducer and were found to be essentially repeatable from one cycle to the next. The forces determined from the pressure profiles compare well with those measured directly by a force transducer except significantly at Keulegan-Carpenter number of 15.0. The importance of the plane bed when it is stationary or moving with the cylinder is examined. The significance of the roughness of the bed with respect to the oscillatory forces exerted on the cylinder is also assessed. (Author)

  14. Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube.

    Science.gov (United States)

    Crespo-Enriquez, Ivan; Partanen, Juha; Martinez, Salvador; Echevarria, Diego

    2012-01-01

    Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens) detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO) and the anterior neural ridge (anr) but not on zona limitans intrathalamica (zli). Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and positional information during early brain development.

  15. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    Science.gov (United States)

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  17. A 29-Year-Old Man With Nonproductive Cough, Exertional Dyspnea, and Chest Discomfort.

    Science.gov (United States)

    Halpenny, Darragh; Suh, James; Garofano, Suzette; Alpert, Jeffrey

    2015-09-01

    A 29-year-old man presented with a 5-month history of worsening dry cough, exertional dyspnea, chest tightness, and palpitations. He had been treated by his primary care physician with trials of guaifenesin/codeine, azithromycin, albuterol, and omeprazole without improvement. He denied wheezing, fever, sweats, anorexia, joint pain, swelling, or rash. He had no past medical history. He denied a history of tobacco smoking or IV drug use. He kept no pets, worked as a manager in an office environment, and had no history of occupational inhalational exposure. He reported using aerosolized insect spray to eradicate bed bugs in his house shortly before the cough began but did not report any acute symptoms when using the spray.

  18. Locked-in syndrome caused by the pressure exerted by the sound gun

    Directory of Open Access Journals (Sweden)

    Ayse Belin Ozer

    2014-01-01

    Full Text Available A 19-year-old male patient who wounded himself with a gun in the cranial region had a Glasgow coma scale of 3E. At posttraumatic day 7, locked-in syndrome was considered upon detection of vertical eye movements, meaningful winks, and quadriplegia. Apart from the classical view, computed tomography (CT and postmortem examination of the brain showed an infarct area in the cerebellum. However, vertebrobasilar artery system was normal. In this case report, we would like to present that unlike cases with ischemia, specific CT findings may not be evident in posttraumatic cases and ischemia may occur in the cerebellum as a result of the pressure exerted by a sound gun.

  19. Optical force exerted on a Rayleigh particle by a vector arbitrary-order Bessel beam

    International Nuclear Information System (INIS)

    Yang, Ruiping; Li, Renxian

    2016-01-01

    An analytical description of optical force on a Rayleigh particle by a vector Bessel beam is investigated. Linearly, radially, azimuthally, and circularly polarized Bessel beams are considered. The radial, azimuthal, and axial forces by a vector Bessel beam are numerically simulated. The effect of polarization, order of beams, and half-cone angle to the optical force are mainly discussed. For Bessel beams of larger half-cone angle, the non-paraxiality of beams plays an important role in optical forces. Numerical calculations show that optical forces, especially azimuthal forces, are very sensitive to the polarization of beams. - Highlights: • Optical force exerted on a Rayleigh particle by a vector Bessel beam is analytically derived. • Radial, azimuthal, and axial forces are numerically analyzed. • The effect of polarization, order of beam, and non-paraxiality is analyzed.

  20. Dynamic Changes in Amygdala Psychophysiological Connectivity Reveal Distinct Neural Networks for Facial Expressions of Basic Emotions.

    Science.gov (United States)

    Diano, Matteo; Tamietto, Marco; Celeghin, Alessia; Weiskrantz, Lawrence; Tatu, Mona-Karina; Bagnis, Arianna; Duca, Sergio; Geminiani, Giuliano; Cauda, Franco; Costa, Tommaso

    2017-03-27

    The quest to characterize the neural signature distinctive of different basic emotions has recently come under renewed scrutiny. Here we investigated whether facial expressions of different basic emotions modulate the functional connectivity of the amygdala with the rest of the brain. To this end, we presented seventeen healthy participants (8 females) with facial expressions of anger, disgust, fear, happiness, sadness and emotional neutrality and analyzed amygdala's psychophysiological interaction (PPI). In fact, PPI can reveal how inter-regional amygdala communications change dynamically depending on perception of various emotional expressions to recruit different brain networks, compared to the functional interactions it entertains during perception of neutral expressions. We found that for each emotion the amygdala recruited a distinctive and spatially distributed set of structures to interact with. These changes in amygdala connectional patters characterize the dynamic signature prototypical of individual emotion processing, and seemingly represent a neural mechanism that serves to implement the distinctive influence that each emotion exerts on perceptual, cognitive, and motor responses. Besides these differences, all emotions enhanced amygdala functional integration with premotor cortices compared to neutral faces. The present findings thus concur to reconceptualise the structure-function relation between brain-emotion from the traditional one-to-one mapping toward a network-based and dynamic perspective.

  1. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

  3. 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

  4. Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain.

    Science.gov (United States)

    Zhang, Jin; Wu, Dan; Xie, Cheng; 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.

  5. 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

  6. Effect of Bench Press Load Knowledge on Repetitions, Rating of Perceived Exertion, and Attentional Focus.

    Science.gov (United States)

    Beaudoin, Christina M; Cox, Zachary; Dundore, Tyler; Thomas, Tayler; Kim, Johnathon; Pillivant, Daniel

    2018-02-01

    Beaudoin, CM, Cox, Z, Dundore, T, Thomas, T, Kim, J, and Pillivant, D. Effect of bench press load knowledge on repetitions, rating of perceived exertion, and attentional focus. J Strength Cond Res 32(2): 514-519, 2018-Few studies have examined the role of the teleoanticipation during resistance training. The purpose of this study was to examine the effect of bench press (BP) load knowledge on repetitions completed, ratings of perceived exertion (RPEs), and attentional focus (% associative). Thirty-six recreationally active resistance-trained men (n = 25) and women (n = 11) participated in this study (age = 20.97 ± 1.87 years; ht = 174.12 ± 9.41 cm; and mass = 80.14 ± 14.03 kg). All subjects completed 3 testing sessions: (a) 1 repetition maximum (1RM) BP determination; (b) submaximal BP repetitions to fatigue known load (KL); and (c) submaximal BP repetitions to fatigue unknown load (UL). Known load and UL sessions were randomized and counterbalanced and both completed at 70% 1RM. An estimated weight ratio was computed using the subject's estimate of the UL weight relative to the KL weight. An independent samples t-test revealed no significant testing order difference for the estimated weight ratio. Two-way repeated-measures analysis of variances revealed no significant differences in the number of repetitions (p = 0.63), RPE (p = 0.18), or attentional focus (% associative) (p = 0.93) between the KL and UL conditions. Pearson correlations found a moderate positive association between KL repetitions completed and % associative focus when the UL was completed before the KL. Load knowledge did not influence the number of repetitions, RPE, or attentional focus while completing the BP. Further research examining the use of pacing strategies, RPE, and attentional focus during KL and UL conditions are warranted.

  7. Heart rate variability during exertional heat stress: effects of heat production and treatment.

    Science.gov (United States)

    Flouris, Andreas D; Bravi, Andrea; Wright-Beatty, Heather E; Green, Geoffrey; Seely, Andrew J; Kenny, Glen P

    2014-04-01

    We assessed the efficacy of different treatments (i.e., treatment with ice water immersion vs. natural recovery) and the effect of exercise intensities (i.e., low vs. high) for restoring heart rate variability (HRV) indices during recovery from exertional heat stress (EHS). Nine healthy adults (26 ± 3 years, 174.2 ± 3.8 cm, 74.6 ± 4.3 kg, 17.9 ± 2.8 % body fat, 57 ± 2 mL·kg·(-1) min(-1) peak oxygen uptake) completed four EHS sessions incorporating either walking (4.0-4.5 km·h(-1), 2 % incline) or jogging (~7.0 km·h(-1), 2 % incline) on a treadmill in a hot-dry environment (40 °C, 20-30 % relative humidity) while wearing a non-permeable rain poncho for a slow or fast rate of rectal temperature (T re) increase, respectively. Upon reaching a T re of 39.5 °C, participants recovered until T re returned to 38 °C either passively or with whole-body immersion in 2 °C water. A comprehensive panel of 93 HRV measures were computed from the time, frequency, time-frequency, scale-invariant, entropy and non-linear domains. Exertional heat stress significantly affected 60/93 HRV measures analysed. Analyses during recovery demonstrated that there were no significant differences between HRV measures that had been influenced by EHS at the end of passive recovery vs. whole-body cooling treatment (p > 0.05). Nevertheless, the cooling treatment required statistically significantly less time to reduce T re (p whole-body immersion in 2 °C water results in faster cooling, there were no observed differences in restoration of autonomic heart rate modulation as measured by HRV indices with whole-body cold-water immersion compared to passive recovery in thermoneutral conditions.

  8. 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.

  9. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

  11. 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.

  12. Exploitation of microbial antagonists for the control of postharvest diseases of fruits: a review.

    Science.gov (United States)

    Dukare, Ajinath Shridhar; Paul, Sangeeta; Nambi, V Eyarkai; Gupta, Ram Kishore; Singh, Rajbir; Sharma, Kalyani; Vishwakarma, Rajesh Kumar

    2018-01-16

    Fungal diseases result in significant losses of fruits and vegetables during handling, transportation and storage. At present, post-production fungal spoilage is predominantly controlled by using synthetic fungicides. Under the global climate change scenario and with the need for sustainable agriculture, biological control methods of fungal diseases, using antagonistic microorganisms, are emerging as ecofriendly alternatives to the use of fungicides. The potential of microbial antagonists, isolated from a diversity of natural habitats, for postharvest disease suppression has been investigated. Postharvest biocontrol systems involve tripartite interaction between microbial antagonists, the pathogen and the host, affected by environmental conditions. Several modes for fungistatic activities of microbial antagonists have been suggested, including competition for nutrients and space, mycoparasitism, secretion of antifungal antibiotics and volatile metabolites and induction of host resistance. Postharvest application of microbial antagonists is more successful for efficient disease control in comparison to pre-harvest application. Attempts have also been made to improve the overall efficacy of antagonists by combining them with different physical and chemical substances and methods. Globally, many microbe-based biocontrol products have been developed and registered for commercial use. The present review provides a brief overview on the use of microbial antagonists as postharvest biocontrol agents and summarises information on their isolation, mechanisms of action, application methods, efficacy enhancement, product formulation and commercialisation.

  13. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    International Nuclear Information System (INIS)

    Chen, Yi; Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi; Jing, Qian; Yue, Jiaqi; Liu, Yang; Cheng, Zhong; Li, Jingyi; Song, Haixing; Li, Guoyu; Liu, Rui; Wang, Jinhui

    2016-01-01

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  14. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Jing, Qian; Yue, Jiaqi; Liu, Yang [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Cheng, Zhong [Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Li, Jingyi, E-mail: li--jingyi@hotmail.com [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Song, Haixing [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Li, Guoyu, E-mail: liguoyulisa@163.com [School of Pharmacy, Shihezi University, Shihezi 832003 (China); Liu, Rui, E-mail: liurui_scu@hotmail.com [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Wang, Jinhui [School of Pharmacy, Shihezi University, Shihezi 832003 (China)

    2016-05-20

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  15. Novel Abscisic Acid Antagonists Identified with Chemical Array Screening.

    Science.gov (United States)

    Ito, Takuya; Kondoh, Yasumitsu; Yoshida, Kazuko; Umezawa, Taishi; Shimizu, Takeshi; Shinozaki, Kazuo; Osada, Hiroyuki

    2015-11-01

    Abscisic acid (ABA) signaling is involved in multiple processes in plants, such as water stress control and seed dormancy. Major regulators of ABA signaling are the PYR/PYL/RCAR family receptor proteins, group A protein phosphatases 2C (PP2Cs), and subclass III of SNF1-related protein kinase 2 (SnRK2). Novel ABA agonists and antagonists to modulate the functions of these proteins would not only contribute to clarification of the signaling mechanisms but might also be used to improve crop yields. To obtain small molecules that interact with Arabidopsis ABA receptor PYR1, we screened 24 275 compounds from a chemical library at the RIKEN Natural Products Depository by using a chemical array platform. Subsequent SnRK2 and PP2C assays narrowed down the candidates to two molecules. One antagonized ABA in a competitive manner and inhibited the formation of the PYR1-ABA-PP2C ternary complex. These compounds might have potential as bioprobes to analyze ABA signaling. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Streptomycetes and micromycetes as perspective antagonists of fungal phytopathogens.

    Science.gov (United States)

    Postolaky, O; Syrbu, T; Poiras, N; Baltsat, K; Maslobrod, S; Boortseva, S

    2012-01-01

    Among natural factors that permanently influence on the plants, the soil microorganisms play a special role for the growing of plants as habitants of their rhizosphere. Mainly they are the representatives of actinomycetes genus Streptomyces and fungal genus Penicillium and their metabolic products stimulate plant growth and inhibit the growth of pathogenic fungi and bacteria. The aim of our study was to determine the antagonism of actinomycetes and micromycetes isolated from soils of R. Moldova against the fungal pathogens of agricultural plants. The strains were isolated from 5 types of chernozem (black soil) from central zone of R. Moldova, with different concentration of humus. Most of micromycetes and streptomycetes were isolated from soil sample 1 (monoculture of maize) and soil sample 2 (Poltava road border) with similar humus content (2.4-2.6%). The antifungal activity of micromycetes strains was occurring mostly against Fusarium solani and Thelaviopsis basicola, at streptomycetes against Alternaria alternata and Botrytis cinerea. It was revealed the strains completely inhibit the growth of Alt. alternata (streptomycetes strains 23, 33, 37), B. cinerea (Streptomyces sp. 17), and F. solani (Penicillium sp. 104). Our results allow to consider the actinomycetes Streptomyces sp.9, Streptomyces sp. 12, Streptomyces sp. 17, Streptomyces sp. 37 Streptomyces sp. 66 and micromycetes Penicillium sp. 5, Penicillium sp. 65, Penicillium sp. 104 isolated from soils of R. Moldova, as prospective strains-antagonists against the phytopathogenic fungus, the causative agents of agricultural plants deseasis.

  17. Orexin receptor antagonists as therapeutic agents for insomnia

    Directory of Open Access Journals (Sweden)

    Ana Clementina Equihua

    2013-12-01

    Full Text Available Insomnia is a common clinical condition characterized by difficulty initiating or maintaining sleep, or non-restorative sleep with impairment of daytime functioning.Currently, treatment for insomnia involves a combination of cognitive behavioral therapy and pharmacological therapy. Among pharmacological interventions, the most evidence exists for benzodiazepine receptor agonist drugs (GABAA receptor, although concerns persist regarding their safety and their limited efficacy. The use of these hypnotic medications must be carefully monitored for adverse effects.Orexin (hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep by promoting cholinergic/monoaminergic neural pathways. This has led to the development of a new class of pharmacological agents that antagonize the physiological effects of orexin. The development of these agents may lead to novel therapies for insomnia without the side effect profile of hypnotics (e.g. impaired cognition, disturbed arousal, and motor balance difficulties. However, antagonizing a system that regulates the sleep-wake cycle may create an entirely different side effect profile. In this review, we discuss the role of orexin and its receptors on the sleep-wake cycle and that of orexin antagonists in the treatment of insomnia.

  18. Blood flow distribution with adrenergic and histaminergic antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Baker, C.H.; Davis, D.L.; Sutton, E.T.

    1989-03-01

    Superficial fibular nerve stimulation (SFNS) causes increased pre- and post-capillary resistances as well as increased capillary permeability in the dog hind paw. These responses indicate possible adrenergic and histaminergic interactions. The distribution of blood flow between capillaries and arteriovenous anastomoses (AVA) may depend on the relative effects of these neural inputs. Right hind paws of anesthetized heparinized dogs were vascularly and neurally isolated and perfused with controlled pressure. Blood flow distribution was calculated from the venous recovery of 85Sr-labeled microspheres (15 microns). The mean transit times of 131I-albumin and 85Sr-labeled microspheres were calculated. The effects of adrenergic and histaminergic antagonists with and without SFNS were determined. Phentolamine blocked the entire response to SFNS. Prazosin attenuated increases in total and AVA resistance. Yohimbine prevented increased total resistance, attenuated the AVA resistance increase, and revealed a decrease in capillary circuit resistance. Pyrilamine attenuated total resistance increase while SFNS increased capillary and AVA resistances. Metiamide had no effect on blood flow distribution with SFNS. The increase in AVA resistance with SFNS apparently resulted from a combination of alpha 1 and alpha 2 receptor stimulation but not histaminergic effects.

  19. Blood flow distribution with adrenergic and histaminergic antagonists

    International Nuclear Information System (INIS)

    Baker, C.H.; Davis, D.L.; Sutton, E.T.

    1989-01-01

    Superficial fibular nerve stimulation (SFNS) causes increased pre- and post-capillary resistances as well as increased capillary permeability in the dog hind paw. These responses indicate possible adrenergic and histaminergic interactions. The distribution of blood flow between capillaries and arteriovenous anastomoses (AVA) may depend on the relative effects of these neural inputs. Right hind paws of anesthetized heparinized dogs were vascularly and neurally isolated and perfused with controlled pressure. Blood flow distribution was calculated from the venous recovery of 85Sr-labeled microspheres (15 microns). The mean transit times of 131I-albumin and 85Sr-labeled microspheres were calculated. The effects of adrenergic and histaminergic antagonists with and without SFNS were determined. Phentolamine blocked the entire response to SFNS. Prazosin attenuated increases in total and AVA resistance. Yohimbine prevented increased total resistance, attenuated the AVA resistance increase, and revealed a decrease in capillary circuit resistance. Pyrilamine attenuated total resistance increase while SFNS increased capillary and AVA resistances. Metiamide had no effect on blood flow distribution with SFNS. The increase in AVA resistance with SFNS apparently resulted from a combination of alpha 1 and alpha 2 receptor stimulation but not histaminergic effects

  20. Iontophoresis of endothelin receptor antagonists in rats and men.

    Directory of Open Access Journals (Sweden)

    Matthieu Roustit

    Full Text Available The treatment of scleroderma-related digital ulcers is challenging. The oral endothelin receptor antagonist (ERA bosentan has been approved but it may induce liver toxicity. The objective of this study was to test whether ERAs bosentan and sitaxentan could be locally delivered using iontophoresis.Cathodal and anodal iontophoresis of bosentan and sitaxentan were performed on anaesthetized rat hindquarters without and during endothelin-1 infusion. Skin blood flow was quantified using laser-Doppler imaging and cutaneous tolerability was assessed. Iontophoresis of sitaxentan (20 min, 20 or 100 µA was subsequently performed on the forearm skin of healthy men (n = 5.In rats neither bosentan nor sitaxentan increased skin blood flux compared to NaCl. When simultaneously infusing endothelin-1, cathodal iontophoresis of sitaxentan increased skin blood flux compared to NaCl (AUC(0-20 were 44032.2 ± 12277 and 14957.5 ± 23818.8 %BL.s, respectively; P = 0.01. In humans, sitaxentan did not significantly increase skin blood flux as compared to NaCl. Iontophoresis of ERAs was well tolerated both in animals and humans.This study shows that cathodal iontophoresis of sitaxentan but not bosentan partially reverses endothelin-induced skin vasoconstriction in rats, suggesting that sitaxentan diffuses into the dermis. However, sitaxentan does not influence basal skin microvascular tone in rats or in humans.

  1. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton

    Science.gov (United States)

    Kinnaird, Catherine R.; Ferris, Daniel P.

    2013-01-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to “fight” the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations. PMID:23307949

  2. Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

    International Nuclear Information System (INIS)

    Pan, G.Z.; Lu, L.; Qian, J.; Xue, B.G.

    1987-01-01

    In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 μM, respectively, could significantly inhibit amylase secretion stimulated by carbachol, and this inhibition by BPP was dose dependent. 45 Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45 Ca outflux. BPP was also capable of displacing the specific binding of [ 3 H]-quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (K/sub i/35nM) than carbachol (K/sub i/ 1.8 μM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant

  3. NMDA receptor antagonist ketamine impairs feature integration in visual perception.

    Science.gov (United States)

    Meuwese, Julia D I; van Loon, Anouk M; Scholte, H Steven; Lirk, Philipp B; Vulink, Nienke C C; Hollmann, Markus W; Lamme, Victor A F

    2013-01-01

    Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA) receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

  4. NMDA receptor antagonist ketamine impairs feature integration in visual perception.

    Directory of Open Access Journals (Sweden)

    Julia D I Meuwese

    Full Text Available Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

  5. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton.

    Science.gov (United States)

    Gordon, Keith E; Kinnaird, Catherine R; Ferris, Daniel P

    2013-04-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to "fight" the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations.

  6. Discovery and Characterization of an Endogenous CXCR4 Antagonist

    Directory of Open Access Journals (Sweden)

    Onofrio Zirafi

    2015-05-01

    Full Text Available CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.

  7. Antagonistic Activity Of Endophytic Bacteria Isolated From Mentha Rotundifolia L.

    Directory of Open Access Journals (Sweden)

    Elhartiti Abla

    2015-08-01

    Full Text Available Abstract This study is implemented for the isolation purification and identification of endophytic bacteria which produces antifungal substances from the roots of Mentha rotundifolia L. The 59 obtained bacterial isolates were tested for their antagonistic activity by the dual confrontation against the phytopathogenic fungi Fusarium oxysporum Aspergillus Niger and Botrytis cinerea. Eight bacterial strains were selected for their strong antifungal activity. These are strains M21 M23 M3a M4 M14d and M3c which belong to the family Bacillaceae M12 and M3b which belongs to the family of Pseudomonadaceae. Among these three bacterial strains namely M21 M23 and M12 induce 70 of inhibition of mycelial growth of phytopathogenic fungi Fusarium oxysporum and Aspergillus Niger while the five bacterial strains M3a M3c M3b M4 and M14d have proved to be effective in inhibiting more than 60 of mycelial growth of Botrytis cinerea.

  8. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-03-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor.

  9. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    International Nuclear Information System (INIS)

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-01-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor

  10. Return of D4 Dopamine Receptor Antagonists in Drug Discovery.

    Science.gov (United States)

    Lindsley, Craig W; Hopkins, Corey R

    2017-09-14

    The dopamine D 4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D 4 , relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Unfortunately, D 4 antagonists that were developed for schizophrenia failed in the clinic. Thus, D 4 fell out of favor as a therapeutic target, and work in this area was silent for decades. Recently, D 4 ligands with improved selectivity for D 4 against not only D 1-3,5 but also other biogenic amine targets have emerged, and D 4 is once again in the spotlight as a novel target for both addiction and Parkinson's disease (PD), as well as other emerging diseases. This report will review the historical data for D 4 , review the known D 4 ligands, and then highlight new data supporting a role for D 4 inhibition in addiction, PD, and cancer.

  11. Development of specific dopamine D-1 agonists and antagonists

    International Nuclear Information System (INIS)

    Sakolchai, S.

    1987-01-01

    To develop potentially selective dopamine D-1 agonists and to investigate on the structural requirement for D-1 activity, the derivatives of dibenzocycloheptadiene are synthesized and pharmacologically evaluated. The target compounds are 5-aminomethyl-10,11-dihydro-1,2-dihydroxy-5H-dibenzo[a,d]cycloheptene hydrobromide 10 and 9,10-dihydroxy-1,2,3,7,8,12b-hexahydrobenzo[1,2]cyclohepta[3,4,5d,e]isoquinoline hydrobromide 11. In a dopamine-sensitive rat retinal adenylate cyclase assay, a model for D-1 activity, compound 10 is essentially inert for both agonist and antagonist activity. In contrast, compound 11 is approximately equipotent to dopamine in activation of the D-1 receptor. Based on radioligand and binding data, IC 50 of compound 11 for displacement of 3 H-SCH 23390, a D-1 ligand, is about 7 fold less than that for displacement of 3 H-spiperone, a D-2 ligand. These data indicate that compound 11 is a potent selective dopamine D-1 agonist. This study provides a new structural class of dopamine D-1 acting agent: dihydroxy-benzocycloheptadiene analog which can serve as a lead compound for further drug development and as a probe for investigation on the nature of dopamine D-1 receptor

  12. Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

    Science.gov (United States)

    Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

    2015-10-01

    Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

  13. Angiotensin antagonists in the dog with chronic pericardial tamponade

    International Nuclear Information System (INIS)

    Moore, G.J.; Taub, K.J.

    1980-01-01

    Assessing the role played by angiotensin in the pathogenesis and maintenance of the renal function and perfusion abnormalities dogs with chronic pericardial tamponade were used in the experiment as a stable model of chronic low output heart failure. The heptapeptide and octapeptide antagonist were used. The results of the experiments suggest that there is a role for angiotensin in the pathologenesis of congestive heart failure. The renin-angiotensin system was activated in the model. Plasma renin activity was elevated and increased further in response to angiotensin blockade. Under the experiment condition there was no evidence for a role for angiotensin in the maintenance of arterial blood pressure. But there was angiotensin-mediated renal vasoconstriction and a reduction in renal blood flow. Both analogues of angiotensin were able to antagonize this effect in similar fashion. Failure to achieve a natriuresis in response to angiotensin blockade may reflect the redistribution of blood flow that occured and suggests that additional factors are operative in this model. (APR)

  14. A general population genetic framework for antagonistic selection that accounts for demography and recurrent mutation.

    Science.gov (United States)

    Connallon, Tim; Clark, Andrew G

    2012-04-01

    Antagonistic selection--where alleles at a locus have opposing effects on male and female fitness ("sexual antagonism") or between components of fitness ("antagonistic pleiotropy")--might play an important role in maintaining population genetic variation and in driving phylogenetic and genomic patterns of sexual dimorphism and life-history evolution. While prior theory has thoroughly characterized the conditions necessary for antagonistic balancing selection to operate, we currently know little about the evolutionary interactions between antagonistic selection, recurrent mutation, and genetic drift, which should collectively shape empirical patterns of genetic variation. To fill this void, we developed and analyzed a series of population genetic models that simultaneously incorporate these processes. Our models identify two general properties of antagonistically selected loci. First, antagonistic selection inflates heterozygosity and fitness variance across a broad parameter range--a result that applies to alleles maintained by balancing selection and by recurrent mutation. Second, effective population size and genetic drift profoundly affect the statistical frequency distributions of antagonistically selected alleles. The "efficacy" of antagonistic selection (i.e., its tendency to dominate over genetic drift) is extremely weak relative to classical models, such as directional selection and overdominance. Alleles meeting traditional criteria for strong selection (N(e)s > 1, where N(e) is the effective population size, and s is a selection coefficient for a given sex or fitness component) may nevertheless evolve as if neutral. The effects of mutation and demography may generate population differences in overall levels of antagonistic fitness variation, as well as molecular population genetic signatures of balancing selection.

  15. Positive Modulatory Interactions of NMDA Receptor GluN1/2B Ligand Binding Domains Attenuate Antagonists Activity

    Directory of Open Access Journals (Sweden)

    Douglas Bledsoe

    2017-05-01

    Full Text Available N-methyl D-aspartate receptors (NMDAR play crucial role in normal brain function and pathogenesis of neurodegenerative and psychiatric disorders. Functional tetra-heteromeric NMDAR contains two obligatory GluN1 subunits and two identical or different non-GluN1 subunits that include six different gene products; four GluN2 (A–D and two GluN3 (A–B subunits. The heterogeneity of subunit combination facilities the distinct function of NMDARs. All GluN subunits contain an extracellular N-terminal Domain (NTD and ligand binding domain (LBD, transmembrane domain (TMD and an intracellular C-terminal domain (CTD. Interaction between the GluN1 and co-assembling GluN2/3 subunits through the LBD has been proven crucial for defining receptor deactivation mechanisms that are unique for each combination of NMDAR. Modulating the LBD interactions has great therapeutic potential. In the present work, by amino acid point mutations and electrophysiology techniques, we have studied the role of LBD interactions in determining the effect of well-characterized pharmacological agents including agonists, competitive antagonists, and allosteric modulators. The results reveal that agonists (glycine and glutamate potency was altered based on mutant amino acid sidechain chemistry and/or mutation site. Most antagonists inhibited mutant receptors with higher potency; interestingly, clinically used NMDAR channel blocker memantine was about three-fold more potent on mutated receptors (N521A, N521D, and K531A than wild type receptors. These results provide novel insights on the clinical pharmacology of memantine, which is used for the treatment of mild to moderate Alzheimer's disease. In addition, these findings demonstrate the central role of LBD interactions that can be exploited to develop novel NMDAR based therapeutics.

  16. A distinction of two discourses concerning wellbeing

    DEFF Research Database (Denmark)

    Wistoft, Karen; Qvortrup, Lars

    2017-01-01

    and behavioral mental health interventions, while the latter defines wellbeing in positive terms with a focus on wellbeing as the result of learning and with pedagogical interventions that only indirectly can support the individual’s learning activity. The former sees wellbeing as the result of a “wellbeing cure......The article concerns the current discourses concerning well-being with the point that it is important to make a distinction between a healthcare oriented discourse and a learning oriented discourse. The former defines wellbeing in negative terms and looks at causally oriented aspects of wellbeing......”, while the latter sees wellbeing as the result of wellbeing learning processes....

  17. Approaching the Distinction between Intuition and Insight.

    Science.gov (United States)

    Zhang, Zhonglu; Lei, Yi; Li, Hong

    2016-01-01

    Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight.

  18. Chloroquine, quinine, procaine, quinidine, tricyclic antidepressants, and methylxanthines as prostaglandin agonists and antagonists.

    Science.gov (United States)

    Manku, M S; Horrobin, D F

    1976-11-20

    Chloroquine, quanine, procaine, quinidine, clomipramine, theophylline, and caffeine have been shown to be strong prostaglandin antagonists and weak agonists. The antagonist effect is clearly demonstrable at concentrations reached in human plasma when the drugs are used therapeutically. This suggests that prostaglandins are important in several situations in which their role has hitherto been unsuspected. New approaches to the development of prostaglandin antagonists and new uses for established drugs are indicated. In a preliminary study chloroquine has been successfully used to close patent ductus arteriosus in three infants.

  19. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

    DEFF Research Database (Denmark)

    Solovic, I; Sester, M; Gomez-Reino, J J

    2010-01-01

    risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-¿ release assays or, as an alternative in individuals without a history...... of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test...

  20. West syndrome associated with administration of a histamine H1 antagonist, oxatomide.

    Science.gov (United States)

    Yamashita, Yushiro; Isagai, Takeo; Seki, Yoshitaka; Ohya, Takashi; Nagamitsu, Shinichiro; Matsuishi, Toyojiro

    2004-01-01

    We report a 4-month-old female infant who developed West syndrome eleven days after administration of a histamine H1 antagonist, oxatomide, for atopic dermatitis. It has been reported that some histamine H1 antagonists induce seizures in epileptic patients. The age, the interval between oxatomide administration, and the onset of West syndrome and its clinical course were similar to two previously reported 3-month-old infants with West syndrome associated with ketotifen administration. We should be cautious in using the histamine H1 antagonists, oxatomide and ketotifen, in young infants because such agents could potentially disturb the anticonvulsive central histaminergic system.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Oral tremor induced by the muscarinic agonist pilocarpine is suppressed by the adenosine A2A antagonists MSX-3 and SCH58261, but not the adenosine A1 antagonist DPCPX.

    Science.gov (United States)

    Collins, Lyndsey E; Galtieri, Daniel J; Brennum, Lise T; Sager, Thomas N; Hockemeyer, Jörg; Müller, Christa E; Hinman, James R; Chrobak, James J; Salamone, John D

    2010-02-01

    Tremulous jaw movements in rats, which can be induced by dopamine (DA) antagonists, DA depletion, and cholinomimetics, have served as a useful model for studies of tremor. Although adenosine A(2A) antagonists can reduce the tremulous jaw movements induced by DA antagonists and DA depletion, there are conflicting reports about the interaction between adenosine antagonists and cholinomimetic drugs. The present studies investigated the ability of adenosine antagonists to reverse the tremorogenic effect of the muscarinic agonist pilocarpine. While the adenosine A(2A) antagonist MSX-3 was incapable of reversing the tremulous jaw movements induced by the 4.0mg/kg dose of pilocarpine, both MSX-3 and the adenosine A(2A) antagonist SCH58261 reversed the tremulous jaw movements elicited by 0.5mg/kg pilocarpine. Systemic administration of the adenosine A(1) antagonist DPCPX failed to reverse the tremulous jaw movements induced by either an acute 0.5mg/kg dose of the cholinomimetic pilocarpine or the DA D2 antagonist pimozide, indicating that the tremorolytic effects of adenosine antagonists may be receptor subtype specific. Behaviorally active doses of MSX-3 and SCH 58261 showed substantial in vivo occupancy of A(2A) receptors, but DPCPX did not. The results of these studies support the use of adenosine A(2A) antagonists for the treatment of tremor. Copyright 2009 Elsevier Inc. All rights reserved.

  3. The neural signatures of distinct psychopathic traits.

    Science.gov (United States)

    Carré, Justin M; Hyde, Luke W; Neumann, Craig S; Viding, Essi; Hariri, Ahmad R

    2013-01-01

    Recent studies suggest that psychopathy may be associated with dysfunction in the neural circuitry supporting both threat- and reward-related processes. However, these studies have involved small samples and often focused on extreme groups. Thus, it is unclear to what extent current findings may generalize to psychopathic traits in the general population. Furthermore, no studies have systematically and simultaneously assessed associations between distinct psychopathy facets and both threat- and reward-related brain function in the same sample of participants. Here, we examined the relationship between threat-related amygdala reactivity and reward-related ventral striatum (VS) reactivity and variation in four facets of self-reported psychopathy in a sample of 200 young adults. Path models indicated that amygdala reactivity to fearful facial expressions is negatively associated with the interpersonal facet of psychopathy, whereas amygdala reactivity to angry facial expressions is positively associated with the lifestyle facet. Furthermore, these models revealed that differential VS reactivity to positive versus negative feedback is negatively associated with the lifestyle facet. There was suggestive evidence for gender-specific patterns of association between brain function and psychopathy facets. Our findings are the first to document differential associations between both threat- and reward-related neural processes and distinct facets of psychopathy and thus provide a more comprehensive picture of the pattern of neural vulnerabilities that may predispose to maladaptive outcomes associated with psychopathy.

  4. The Distinction Between Curative and Assistive Technology.

    Science.gov (United States)

    Stramondo, Joseph A

    2018-05-01

    Disability activists have sometimes claimed their disability has actually increased their well-being. Some even say they would reject a cure to keep these gains. Yet, these same activists often simultaneously propose improvements to the quality and accessibility of assistive technology. However, for any argument favoring assistive over curative technology (or vice versa) to work, there must be a coherent distinction between the two. This line is already vague and will become even less clear with the emergence of novel technologies. This paper asks and tries to answer the question: what is it about the paradigmatic examples of curative and assistive technologies that make them paradigmatic and how can these defining features help us clarify the hard cases? This analysis will begin with an argument that, while the common views of this distinction adequately explain the paradigmatic cases, they fail to accurately pick out the relevant features of those technologies that make them paradigmatic and to provide adequate guidance for parsing the hard cases. Instead, it will be claimed that these categories of curative or assistive technologies are defined by the role the technologies play in establishing a person's relational narrative identity as a member of one of two social groups: disabled people or non-disabled people.

  5. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

    Science.gov (United States)

    Le Billan, Florian; Amazit, Larbi; Bleakley, Kevin; Xue, Qiong-Yao; Pussard, Eric; Lhadj, Christophe; Kolkhof, Peter; Viengchareun, Say; Fagart, Jérôme; Lombès, Marc

    2018-05-07

    Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbinding of their corresponding ligands, MR being activated by both aldosterone and cortisol and GR essentially activated by cortisol. Their coexpression and ability to bind similar DNA motifs highlight the need to investigate their respective contributions to overall corticosteroid signaling. Here, we decipher the transcriptional regulatory mechanisms that underlie selective effects of MRs and GRs on shared genomic targets in a human renal cellular model. Kinetic, serial, and sequential chromatin immunoprecipitation approaches were performed on the period circadian protein 1 ( PER1) target gene, providing evidence that both receptors dynamically and cyclically interact at the same target promoter in a specific and distinct transcriptional signature. During this process, both receptors regulate PER1 gene by binding as homo- or heterodimers to the same promoter region. Our results suggest a novel level of MR-GR target gene regulation, which should be considered for a better and integrated understanding of corticosteroid-related pathophysiology.-Le Billan, F., Amazit, L., Bleakley, K., Xue, Q.-Y., Pussard, E., Lhadj, C., Kolkhof, P., Viengchareun, S., Fagart, J., Lombès, M. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

  6. Distinct types of eigenvector localization in networks

    Science.gov (United States)

    Pastor-Satorras, Romualdo; Castellano, Claudio

    2016-01-01

    The spectral properties of the adjacency matrix provide a trove of information about the structure and function of complex networks. In particular, the largest eigenvalue and its associated principal eigenvector are crucial in the understanding of nodes’ centrality and the unfolding of dynamical processes. Here we show that two distinct types of localization of the principal eigenvector may occur in heterogeneous networks. For synthetic networks with degree distribution P(q) ~ q-γ, localization occurs on the largest hub if γ > 5/2 for γ < 5/2 a new type of localization arises on a mesoscopic subgraph associated with the shell with the largest index in the K-core decomposition. Similar evidence for the existence of distinct localization modes is found in the analysis of real-world networks. Our results open a new perspective on dynamical processes on networks and on a recently proposed alternative measure of node centrality based on the non-backtracking matrix.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. Ultrasound-Guided Fasciotomy for Chronic Exertional Compartment Syndrome: A Cadaveric Investigation.

    Science.gov (United States)

    Lueders, Daniel R; Sellon, Jacob L; Smith, Jay; Finnoff, Jonathan T

    2017-07-01

    Chronic exertional compartment syndrome (CECS) is a common cause of exertional leg pain. It is commonly treated with a surgical fasciotomy, which has a surgical complication rate of up to 16% and takes approximately 6-12 weeks to return to preprocedure activity levels. Therefore, the development of a less invasive, effective outpatient intervention to treat CECS is desirable. To describe and validate an ultrasound-guided (USG) fasciotomy technique for the anterior and lateral compartments of the lower limb in an unembalmed cadaveric model. Prospective, cadaveric laboratory investigation. Academic institution procedural skills laboratory. Ten unembalmed cadaveric knee-ankle-foot specimens from 1 female (2 specimens) and 7 male donors aged 62-91 years (mean 78.6 years) with body mass indices of 18.9-35.3 kg/m 2 (mean 27.1 kg/m 2 ). Two experienced operators each performed USG anterior and lateral compartment fasciotomies on 5 unembalmed cadaveric legs. A third physician subsequently dissected the legs to assess the continuity of the fasciotomies and to identify any neurovascular damage related to the procedures. Fasciotomy length (in centimeters) and classification by completeness (achieved target length or did not achieve target length) and continuity (continuous or discontinuous) based on predetermined criteria. Muscles, retinaculae, and neurovascular structures were assessed for damage. No neurovascular injuries occurred in any of the 20 USG fasciotomies. The average fasciotomy length was 22.5 cm. All 20 of the fasciotomies achieved the target length. A continuous cephalocaudal fasciotomy was accomplished in 13 of 20 fasciotomies. When a fasciotomy was not continuous, the average length and number of intact fascial bands was 1.52 cm and 2.3, respectively. USG fasciotomy of the anterior and lateral leg compartments can be safely performed in a cadaveric model and can achieve a fasciotomy length comparable to surgical fasciotomy. Most procedures successfully

  11. Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Borst Mathias M

    2009-12-01

    Full Text Available Abstract Background In idiopathic pulmonary arterial hypertension (IPAH, peripheral airway obstruction is frequent. This is partially attributed to the mediator dysbalance, particularly an excess of endothelin-1 (ET-1, to increased pulmonary vascular and airway tonus and to local inflammation. Bosentan (ET-1 receptor antagonist improves pulmonary hemodynamics, exercise limitation, and disease severity in IPAH. We hypothesized that bosentan might affect airway obstruction. Methods In 32 IPAH-patients (19 female, WHO functional class II (n = 10, III (n = 22; (data presented as mean ± standard deviation pulmonary vascular resistance (11 ± 5 Wood units, lung function, 6 minute walk test (6-MWT; 364 ± 363.7 (range 179.0-627.0 m, systolic pulmonary artery pressure, sPAP, 79 ± 19 mmHg, and NT-proBNP serum levels (1427 ± 2162.7 (range 59.3-10342.0 ng/L were measured at baseline, after 3 and 12 months of oral bosentan (125 mg twice per day. Results and Discussion At baseline, maximal expiratory flow at 50 and 25% vital capacity were reduced to 65 ± 25 and 45 ± 24% predicted. Total lung capacity was 95.6 ± 12.5% predicted and residual volume was 109 ± 21.4% predicted. During 3 and 12 months of treatment, 6-MWT increased by 32 ± 19 and 53 ± 69 m, respectively; p Conclusion This study gives first evidence in IPAH, that during long-term bosentan, improvement of hemodynamics, functional parameters or serum biomarker occur independently from persisting peripheral airway obstruction.

  12. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation.

    Science.gov (United States)

    Cappato, Riccardo; Ezekowitz, Michael D; Klein, Allan L; Camm, A John; Ma, Chang-Sheng; Le Heuzey, Jean-Yves; Talajic, Mario; Scanavacca, Maurício; Vardas, Panos E; Kirchhof, Paulus; Hemmrich, Melanie; Lanius, Vivian; Meng, Isabelle Ling; Wildgoose, Peter; van Eickels, Martin; Hohnloser, Stefan H

    2014-12-14

    X-VeRT is the first prospective randomized trial of a novel oral anticoagulant in patients with atrial fibrillation undergoing elective cardioversion. We assigned 1504 patients to rivaroxaban (20 mg once daily, 15 mg if creatinine clearance was between 30 and 49 mL/min) or dose-adjusted vitamin K antagonists (VKAs) in a 2:1 ratio. Investigators selected either an early (target period of 1-5 days after randomization) or delayed (3-8 weeks) cardioversion strategy. The primary efficacy outcome was the composite of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, and cardiovascular death. The primary safety outcome was major bleeding. The primary efficacy outcome occurred in 5 (two strokes) of 978 patients (0.51%) in the rivaroxaban group and in 5 (two strokes) of 492 patients (1.02%) in the VKA group [risk ratio 0.50; 95% confidence interval (CI) 0.15-1.73]. In the rivaroxaban group, four patients experienced primary efficacy events following early cardioversion (0.71%) and one following delayed cardioversion (0.24%). In the VKA group, three patients had primary efficacy events following early cardioversion (1.08%) and two following delayed cardioversion (0.93%). Rivaroxaban was associated with a significantly shorter time to cardioversion compared with VKAs (P four patients (0.8%) in the VKA group (risk ratio 0.76; 95% CI 0.21-2.67). Oral rivaroxaban appears to be an effective and safe alternative to VKAs and may allow prompt cardioversion. Clinicaltrials.gov; NCT01674647. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  13. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

    Science.gov (United States)

    Cicardi, Marco; Banerji, Aleena; Bracho, Francisco; Malbrán, Alejandro; Rosenkranz, Bernd; Riedl, Marc; Bork, Konrad; Lumry, William; Aberer, Werner; Bier, Henning; Bas, Murat; Greve, Jens; Hoffmann, Thomas K; Farkas, Henriette; Reshef, Avner; Ritchie, Bruce; Yang, William; Grabbe, Jürgen; Kivity, Shmuel; Kreuz, Wolfhart; Levy, Robyn J; Luger, Thomas; Obtulowicz, Krystyna; Schmid-Grendelmeier, Peter; Bull, Christian; Sitkauskiene, Brigita; Smith, William B; Toubi, Elias; Werner, Sonja; Anné, Suresh; Björkander, Janne; Bouillet, Laurence; Cillari, Enrico; Hurewitz, David; Jacobson, Kraig W; Katelaris, Constance H; Maurer, Marcus; Merk, Hans; Bernstein, Jonathan A; Feighery, Conleth; Floccard, Bernard; Gleich, Gerald; Hébert, Jacques; Kaatz, Martin; Keith, Paul; Kirkpatrick, Charles H; Langton, David; Martin, Ludovic; Pichler, Christiane; Resnick, David; Wombolt, Duane; Fernández Romero, Diego S; Zanichelli, Andrea; Arcoleo, Francesco; Knolle, Jochen; Kravec, Irina; Dong, Liying; Zimmermann, Jens; Rosen, Kimberly; Fan, Wing-Tze

    2010-08-05

    Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

  14. Statin use decreases coagulation in users of vitamin K antagonists.

    Science.gov (United States)

    van Rein, Nienke; Biedermann, J S; Bonafacio, S M; Kruip, M J H A; van der Meer, F J M; Lijfering, W M

    2016-12-01

    The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs). We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test. Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower. Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.

  15. A novel antagonistic role of natural compound icariin on neurotoxicity of amyloid β peptide

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    2015-01-01

    Interpretation & conclusions: The results indicated a novel antagonistic role of icariin in the neurotoxicity of Aβ1-42 via inhibiting its aggregation, suggesting that icariin might have potential therapeutic benefits to delay or modify the progression of AD.

  16. Efficacité de l'agent antagoniste Trichoderma harzianum sur ...

    African Journals Online (AJOL)

    Efficacité de l'agent antagoniste Trichoderma harzianum sur Fusarium oxysporum f. sp. lycopersiciagent pathogène de la tomate. LS Gnancadja, DHE Tonon, EMO Faton, KO Douro Kpindou, E Dannon, A Akoegninou ...

  17. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomised controlled trial

    NARCIS (Netherlands)

    Jong, C.A.J. de; Laheij, R.J.F.; Krabbe, P.F.M.

    2005-01-01

    Aim  Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without

  18. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment : a randomized controlled trial

    NARCIS (Netherlands)

    De Jong, Cor A J; Laheij, Robert J F; Krabbe, Paul F M

    AIM: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without

  19. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomized controlled trial.

    NARCIS (Netherlands)

    Jong, C.A.J. de; Laheij, R.J.F.; Krabbe, P.F.M.

    2005-01-01

    AIM: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without

  20. Anti-HIV Effect of Liposomes Bearing CXCR4 Receptor Antagonist ...

    African Journals Online (AJOL)

    Keywords: Antagonist, CXCR4, Liposomes, Receptor, Inflammation, HIV. Tropical Journal of ... receptors and inhibits HIV-1 entry mediated through CCR3, CCR5, and ..... circulation, facilitating HIV-targeted drug delivery. By tissue distribution ...

  1. Melanin concentrating hormone receptor 1 (MCHR1) antagonists - Still a viable approach for obesity treatment?

    DEFF Research Database (Denmark)

    Högberg, T.; Frimurer, T.M.; Sasmal, P.K.

    2012-01-01

    Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the melanin concentrating hormone (MCH) and its receptor 1. The development of MCHR1 antagonists are described with a specific perspective on different chemotypes...

  2. In vitro suppression of fungi caused by combinations of apparently non-antagonistic soil bacteria

    NARCIS (Netherlands)

    De Boer, W.; Wagenaar, A.M.; Klein Gunnewiek, P.J.A.; Van Veen, J.A.

    2007-01-01

    We hypothesized that apparently non-antagonistic soil bacteria may contribute to suppression of fungi during competitive interactions with other bacteria. Four soil bacteria (Brevundimonas sp., Luteibacter sp., Pedobacter sp. and Pseudomonas sp.) that exhibited little or no visible antifungal

  3. Sympatholytic properties of several AT(1)-receptor antagonists in the isolated rabbit thoracic aorta

    NARCIS (Netherlands)

    Nap, Alexander; Balt, Jippe C.; Pfaffendorf, Martin; van Zwieten, Pieter A.

    2002-01-01

    Objective To evaluate the facilitating effect of angiotensin II on sympathetic neurotransmission to quantitatively compare the sympatho-inhibitory potencies of the selective AT(1)-receptor antagonists losartan, irbesartan and telmisartan in the isolated rabbit thoracic aorta. Design To investigate

  4. Antagonist muscle moment is increased in ACL deficient subjects during maximal dynamic knee extension

    DEFF Research Database (Denmark)

    Alkjær, Tine; Simonsen, Erik B; Magnusson, S Peter

    2012-01-01

    INTRODUCTION: Coactivation of the hamstring muscles during dynamic knee extension may compensate for increased knee joint laxity in anterior cruciate ligament (ACL) deficient subjects. This study examined if antagonist muscle coactivation during maximal dynamic knee extension was elevated...

  5. Growth Hormone Receptor Antagonist Treatment Reduces Exercise Performance in Young Males

    DEFF Research Database (Denmark)

    Goto, K.; Doessing, S.; Nielsen, R.H.

    2009-01-01

    between the groups in terms of changes in serum free fatty acids, glycerol, (V) over dotO(2), or relative fat oxidation. Conclusion: GH might be an important determinant of exercise capacity during prolonged exercise, but GHR antagonist did not alter fat metabolism during exercise. (J Clin Endocrinol......Context: The effects of GH on exercise performance remain unclear. Objective: The aim of the study was to examine the effects of GH receptor (GHR) antagonist treatment on exercise performance. Design: Subjects were treated with the GHR antagonist pegvisomant or placebo for 16 d. After the treatment...... period, they exercised to determine exercise performance and hormonal and metabolic responses. Participants: Twenty healthy males participated in the study. Intervention: Subjects were treated with the GHR antagonist (n = 10; 10 mg/d) or placebo (n = 10). After the treatment period, they performed...

  6. Muscarinic receptor antagonists for overactive bladder treatment: does one fit all?

    NARCIS (Netherlands)

    Witte, Lambertus P. W.; Mulder, Wilhelmina M. C.; de La Rosette, Jean J. M. C. H.; Michel, Martin C.

    2009-01-01

    Purpose of review To review evidence and regulatory dosing recommendations for muscarinic receptor antagonists used in the treatment of overactive bladder symptom complex (darifenacin, fesoterodine oxybutynin propiverine solifenacin tolterodine trospium) in special patient populations. Recent

  7. Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles

    DEFF Research Database (Denmark)

    Arce, Joan-Carles; La Marca, Antonio; Mirner Klein, Bjarke

    2013-01-01

    To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol....

  8. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

    DEFF Research Database (Denmark)

    Solovic, I.; Sester, M.; Gomez-Reino, J.J.

    2010-01-01

    risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-gamma release assays or, as an alternative in individuals without...... a history of bacille Calmette-Guerin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test...... and an interferon-gamma release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy...

  9. Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant.

    Science.gov (United States)

    Krause, Karoline; Metz, Martin; Zuberbier, Torsten; Maurer, Marcus; Magerl, Markus

    2010-04-01

    The bradykinin B2 receptor antagonist icatibant has recently become available for treating hereditary angioedema. Our observations demonstrate icatibant to be effective and safe for the treatment of both, abdominal and cutaneous attacks in a practice setting beyond clinical studies.

  10. Biological control of fusarium wilt of tomato by antagonist fungi and ...

    African Journals Online (AJOL)

    Yomi

    2012-01-16

    Jan 16, 2012 ... Key words: Biological control, fusarium wilt, tomato, antagonist fungi, cyanobacteria. INTRODUCTION ... severely affected by wilt disease caused by F. oxysporum f. sp. ..... Changing options for the control of deciduous fruit.

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

    Directory of Open Access Journals (Sweden)

    Kwame Yeboah

    2017-01-01

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

  12. 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

  13. 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.

  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. Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death

    Directory of Open Access Journals (Sweden)

    Hiroto Kambara

    2018-03-01

    Full Text Available Summary: Gasdermin D (GSDMD is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in macrophages, in which activated inflammatory caspases cleave GSDMD to produce an N-terminal fragment (GSDMD-cNT to trigger pyroptosis, GSDMD cleavage and activation in neutrophils was caspase independent. It was mediated by a neutrophil-specific serine protease, neutrophil elastase (ELANE, released from cytoplasmic granules into the cytosol in aging neutrophils. ELANE-mediated GSDMD cleavage was upstream of the caspase cleavage site and produced a fully active ELANE-derived NT fragment (GSDMD-eNT that induced lytic cell death as efficiently as GSDMD-cNT. Thus, GSDMD is pleiotropic, exerting both pro- and anti-inflammatory effects that make it a potential target for antibacterial and anti-inflammatory therapies. : Kambara et al. find that GSDMD deficiency augments host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, establishing GSDMD as a negative regulator of innate immunity. GSDMD cleavage and activation in neutrophils is mediated by ELANE, released from cytoplasmic granules into the cytosol in aging neutrophils. Keywords: GSDMD, neutrophil death, neutrophil elastase, innate immunity, host defense

  16. 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.

  17. Effect of Music Tempo on Attentional Focus and Perceived Exertion during Self-selected Paced Walking

    Science.gov (United States)

    SILVA, ALDO COELHO; DOS SANTOS FERREIRA, SANDRO; ALVES, RAGAMI CHAVES; FOLLADOR, LUCIO; DA SILVA, SERGIO GREGORIO

    2016-01-01

    This study investigated the influence of music on the rating of perceived exertion (RPE) and attentional focus during walking at a self-selected pace. Fifteen overweight and obese women volunteered to participate in the study. They underwent four sessions: the first for incremental maximal test and anthropometric measurement followed by three experimental sessions. After the first session, they were exposed to three 30-minute walking sessions at a self-selected pace in a counterbalanced order: fast-tempo music (FT), medium-tempo music (MT) and no-music control (NM). Borg’s RPE Scale and an Attentional Focus Questionnaire were used to measure the perceptual response and attentional focus, respectively. Results showed that the RPE was higher in the no-music control than in the medium-tempo music (12.05 ± 0.6 vs. 10.5 ± 0.5). Furthermore, dissociative attentional focus was greater for both conditions with music in comparison with the no-music control (NM= 39.0 ± 4.1; MT= 48.4 ± 4.1 and FT= 47.9 ± 4.5). The results indicated that the use of music during walking can modulate attentional focus, increasing dissociative thought, and medium-tempo music can reduce the RPE. PMID:27990220

  18. Modified Polymeric Nanoparticles Exert In Vitro Antimicrobial Activity Against Oral Bacteria.

    Science.gov (United States)

    Toledano-Osorio, Manuel; Babu, Jegdish P; Osorio, Raquel; Medina-Castillo, Antonio L; García-Godoy, Franklin; Toledano, Manuel

    2018-06-14

    Polymeric nanoparticles were modified to exert antimicrobial activity against oral bacteria. Nanoparticles were loaded with calcium, zinc and doxycycline. Ions and doxycycline release were measured by inductively coupled plasma optical emission spectrometer and high performance liquid chromatography. Porphyromonas gingivalis , Lactobacillus lactis , Streptoccocus mutans , gordonii and sobrinus were grown and the number of bacteria was determined by optical density. Nanoparticles were suspended in phosphate-buffered saline (PBS) at 10, 1 and 0.1 mg/mL and incubated with 1.0 mL of each bacterial suspension for 3, 12, and 24 h. The bacterial viability was assessed by determining their ability to cleave the tetrazolium salt to a formazan dye. Data were analyzed by ANOVA and Scheffe’s F ( p Nanoparticles (60% to 99% reduction) followed by Ca-Nanoparticles or Zn-Nanoparticles (30% to 70% reduction) and finally the non-doped nanoparticles (7% to 35% reduction). P. gingivalis , S. mutans and L. lactis were the most susceptible bacteria, being S. gordonii and S. sobrinus the most resistant to the tested nanoparticles.

  19. Hydrocortisone infusion exerts dose- and sex-dependent effects on attention to emotional stimuli.

    Science.gov (United States)

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

    2013-03-01

    Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to negative words. Healthy volunteers received placebo and either low-dose (0.15mg/kg) or high-dose (0.45mg/kg) hydrocortisone intravenously during two separate visits in a double-blind, randomized design. Seventy-five minutes post-infusion, the subjects performed tests of attention (Rapid Visual Information Processing [RVIP]), spatial working memory (Spatial Span) and emotional processing (Affective Go/No-go task [AGNG]). On the attention task, performance was impaired under both hydrocortisone doses relative to placebo, though the effect on error rate was not significant after controlling for age; Spatial Span performance was unaffected by hydrocortisone administration. On the AGNG task, relative to the placebo condition the low-dose hydrocortisone infusion decreased response time to emotional words while high-dose hydrocortisone increased response time. In the females specifically, both high and low dose hydrocortisone administration attenuated the normal attentional bias toward positively valenced words. These data suggest that, in healthy women, the modulation of attention by the emotional salience of stimuli is influenced by glucocorticoid hormone concentrations. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Load variation effects on the pressure fluctuations exerted on a Kaplan turbine runner

    International Nuclear Information System (INIS)

    Amiri, K; Cervantes, M J; Mulu, B; Raisee, M

    2014-01-01

    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

  1. 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.

  2. 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.

  3. Status report on the conceivable outside pressure exerted on nuclear power stations by gaseous explosions

    International Nuclear Information System (INIS)

    Geiger, W.

    1977-01-01

    The following incidents to be taken into account in the whole process beginning with gas release and ending with a possible stress exerted on the power plant building are discussed in detail: Conditions leading to the release of large amounts of gas; formation of an explorable gas mixture cloud; ignition and course of explosion; pressure wave propagation in the surrounding air; construction dynamics and damaging effects. Experimental results obtainable so far and analyses of large explosions are discussed with a view to their consequences. Special emphasis is placed on the question as to whether extremely unfavourable conditions may lead to a detonation of the cloud instead of a deflagration. Considering the physical laws of cloud formation and the special initiation conditions governing free gas-air-mixtures as a result of gas dynamics and reaction kinetics it can be concluded that a detonation seems to be very unlikely. It is examined what kind of studies are still to be canied out in order to clarity the question of a possible detonation. On the other hand, it is not yet possible to give a decisive answer to the question of whether and to what extent nuclear power plants are endangered by gas cloud deflagration. Due to the complex wave field resulting from diffraction and reflexion of the incoming pressure wave by the buildings of the nuclear power station, a variety of stress functions are possible that may, under certain circumstances, lead to a selective excitation of single vibration modes of the structure. (orig.) [de

  4. Evaluation of influence on environment exerted by nuclear and non-nuclear energies

    International Nuclear Information System (INIS)

    Okamoto, Kazuto

    1981-10-01

    Mankind must consume some form of energy, therefore, it is meaningless to discuss the danger or safety of atomic energy only, and the discussion should be made in comparison with the safety when other energy resources are used. The upper limit of the use of fossil fuel is not determined by its amount of deposits, but the danger of changing the climate by the greenhouse effect of carbon dioxide is a serious problem. This book is originated from the text for the one-day seminar on the comparison of the influence on environment exerted by atomic energy and other energy resources, held by the Atomic Energy Information Center on August 29, 1980, of which the contents were made more circumstantial by adding many new data and discussions. Almost all influences produced by the use of energy are treated in it. It is the result of discussions with many experts in the world. The logics of introducing atomic energy, radioactivity, ordinary chemical contamination, chemical carcinogen, large accidents, acid rain, the change of climate due to carbon dioxide and other causes, the effect of greenhouse effect on human society, and the actual state of greenhouse effect and the countermeasures are discussed. (Kako, I.)

  5. Effect of temperature change exerted on plastic deformation of SUS 304

    International Nuclear Information System (INIS)

    Niitsu, Yasushi; Ikegami, Kozo

    1985-01-01

    Under the condition of mechanical load, on which the thermal stress due to temperature change is superposed, the deformation behavior of structural materials is affected by not only loading history but also temperature history. Also at the time of working materials, the case that the relation between plastic deformation and temperature change becomes a problem is not few, such as cold working after hot rolling. In this study, the effect of temperature change exerted on the plastic deformation of SUS 304 stainless steel was examined, as this material has been frequently used as a high temperature structural material. That is, the plastic deformation behavior at a certain temperature after prestrain was applied at a different temperature was experimentally determined under various temperature and load conditions. Moreover, the quantitative evaluation of the results obtained was attempted by using the concept of an equal plastic strain curved surface. The test pieces and the experimental method, the behavior in uniaxial loading and the behavior in combined loading are reported. (Kako, I.)

  6. Revised model for the radiation force exerted by standing surface acoustic waves on a rigid cylinder

    Science.gov (United States)

    Liang, Shen; Chaohui, Wang

    2018-03-01

    In this paper, a model for the radiation force exerted by standing surface acoustic waves (SSAWs) on a rigid cylinder in inviscid fluids is extended to account for the dependence on the Rayleigh angle. The conventional model for the radiation force used in the SSAW-based applications is developed in plane standing waves, which fails to predict the movement of the cylinder in the SSAW. Our revised model reveals that, in the direction normal to the piezoelectric substrate on which the SSAW is generated, acoustic radiation force can be large enough to drive the cylinder even in the long-wavelength limit. Furthermore, the force in this direction can not only push the cylinder away, but also pull it back toward the substrate. In the direction parallel to the substrate, the equilibrium positions for particles can be actively tuned by changing Rayleigh angle. As an example considered in the paper, with the reduction of Rayleigh angle the equilibrium positions for steel cylinders in water change from pressure nodes to pressure antinodes. The model can thus be used in the design of SSAWs for particle manipulations.

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

    Science.gov (United States)

    Zhang, Su-Fang; Chen, Zhe

    2017-09-01

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

  8. 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.

  9. Effect that radiation exerts to insulation breakdown of heat resistant polymer materials

    International Nuclear Information System (INIS)

    Fujita, Shigetaka; Baba, Makoto; Noto, Fumitoshi; Ruike, Mitsuo.

    1990-01-01

    Artificial satellites are always exposed to cosmic rays which contain the radiations which do not reach the ground, therefore, the radiation resistance of the polymer insulators for cables and others used in such environment becomes a problem. Also the polymer insulator materials used for nuclear facilities require excellent radiation resistance. It is important to examine the effect that radiation exerts to electric insulation characteristics from the viewpoint of material development. In this paper, the insulation breakdown characteristics of heat resistant polymer films and the mini-cables made for trial of heat resistant polymer materials in the case without irradiation and in the case of gamma ray irradiation, and the results of the structural analysis are reported. The specimens tested, the experimental method and the results are described. The insulation breakdown strength of PFA and FEP films lowered from 0.15-0.2 MGy, but that of PEEK film did not change up to 5 MGy. It was found that fluorine group resins were apt to deteriorate by oxidation as dose increased. (K.I.)

  10. Exertional Dyspnoea in Chronic Respiratory Diseases: From Physiology to Clinical Application.

    Science.gov (United States)

    Dubé, Bruno-Pierre; Vermeulen, François; Laveneziana, Pierantonio

    2017-02-01

    Dyspnoea is a complex, highly personalized and multidimensional sensory experience, and its underlying cause and mechanisms are still being investigated. Exertional dyspnoea is one of the most frequently encountered symptoms of patients with cardiopulmonary diseases, and is a common reason for seeking medical help. As the symptom usually progresses with the underlying disease, it can lead to an avoidance of physical activity, peripheral muscle deconditioning and decreased quality of life. Dyspnoea is closely associated with quality of life, exercise (in)tolerance and prognosis in various conditions, including chronic obstructive pulmonary disease, heart failure, interstitial lung disease and pulmonary hypertension, and is therefore an important therapeutic target. Effective management and treatment of dyspnoea is an important challenge for caregivers, and therapeutic options that attempt to reverse its underlying cause have been only partially successful This "review" will attempt to shed light on the physiological mechanisms underlying dyspnoea during exercise and to translate/apply them to a broad clinical spectrum of cardio-respiratory disorders. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Effect of Music Tempo on Attentional Focus and Perceived Exertion during Self-selected Paced Walking.

    Science.gov (United States)

    Silva, Aldo Coelho; Dos Santos Ferreira, Sandro; Alves, Ragami Chaves; Follador, Lucio; DA Silva, Sergio Gregorio

    2016-01-01

    This study investigated the influence of music on the rating of perceived exertion (RPE) and attentional focus during walking at a self-selected pace. Fifteen overweight and obese women volunteered to participate in the study. They underwent four sessions: the first for incremental maximal test and anthropometric measurement followed by three experimental sessions. After the first session, they were exposed to three 30-minute walking sessions at a self-selected pace in a counterbalanced order: fast-tempo music (FT), medium-tempo music (MT) and no-music control (NM). Borg's RPE Scale and an Attentional Focus Questionnaire were used to measure the perceptual response and attentional focus, respectively. Results showed that the RPE was higher in the no-music control than in the medium-tempo music (12.05 ± 0.6 vs. 10.5 ± 0.5). Furthermore, dissociative attentional focus was greater for both conditions with music in comparison with the no-music control (NM= 39.0 ± 4.1; MT= 48.4 ± 4.1 and FT= 47.9 ± 4.5). The results indicated that the use of music during walking can modulate attentional focus, increasing dissociative thought, and medium-tempo music can reduce the RPE.

  12. The fruit extract of Berberis crataegina DC: exerts potent antioxidant activity and protects DNA integrity.

    Science.gov (United States)

    Charehsaz, Mohammad; Sipahi, Hande; Celep, Engin; Üstündağ, Aylin; Cemiloğlu Ülker, Özge; Duydu, Yalçın; Aydın, Ahmet; Yesilada, Erdem

    2015-04-17

    Dried fruits of Berberis crataegina (Berberidaceae) have been frequently consumed as food garniture in Turkish cuisine, while its fruit paste has been used to increase stamina and in particular to prevent from cardiovascular dysfunctions in Northeastern Black Sea region of Turkey. This study investigated this folkloric information in order to explain the claimed healing effects as well as to evaluate possible risks. Total phenolic, flavonoid and proanthocyanidin contents and antioxidant capacity of the methanolic fruit extract were evaluated through several in vitro assays. The cytotoxic and genotoxic effects of B. crataegina fruit extract were also assessed in both cervical cancer cell line (HeLa) and human peripheral blood lymphocytes. The extract showed protective effects against ferric-induced oxidative stress and had a relatively good antioxidant activity. It also ameliorated the H2O2 mediated DNA damage in lymphocytes, suggesting the protective effect against oxidative DNA damage. The methanolic extract of B. crataegina fruits may be a potential antioxidant nutrient and also may exert a protective role against lipid peroxidation as well as oxidative DNA damage.

  13. The prozone effect exerted by the complement-binding anti-Lea on anti-D.

    Science.gov (United States)

    Joshi, Sanmukh R; Parekh, Kamlesh H

    2017-01-01

    Prozone phenomenon is seen with very high-titer antibodies in an immune serum. The prozone effect on anti-D by a low-titer anti-Le a was investigated associated with neonatal jaundice. Standard methods were used in investigations. The child was born at full-term developed mild jaundice. With weak direct antiglobulin test+, her indirect serum bilirubin was progressed to 27.5 mg/dL in 48 h. Anti-D and anti-Le a were detected in the mother. Both these antibodies were detected in the child's serum though the eluate from red blood cells (RBCs) contained only anti-D. Mother's anti-D was masked by anti-Le a if the RBCs possessed both the antigens together. Anti-D was revealed only with D-positive RBCs lacking Le a or if the serum was modified by mixing with Le a+ saliva or was heated at 56°C or fortified with citrate solution. An anti-D showed prozone effect exerted by the complement-fixing anti-Le a in the test.

  14. Carvacrol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in Middle Cerebral Artery Occlusion Rats.

    Science.gov (United States)

    Li, Zhenlan; Hua, Cong; Pan, Xiaoqiang; Fu, Xijia; Wu, Wei

    2016-08-01

    Increasing evidence demonstrates that inflammation plays an important role in cerebral ischemia. Carvacrol, a monoterpenic phenol, is naturally occurring in various plants belonging to the family Lamiaceae and exerts protective effects in a mice model of focal cerebral ischemia/reperfusion injury by reducing infarct volume and decreasing the expression of cleaved caspase-3. However, the anti-inflammatory mechanisms by which carvacrol protect the brain have yet to be fully elucidated. We investigated the effects of carvacrol on inflammatory reaction and inflammatory mediators in middle cerebral artery occlusion rats. The results of the present study showed that carvacrol inhibited the levels of inflammatory cytokines and myeloperoxidase (MPO) activity, as well as the expression of iNOS and COX-2. It also increased SOD activity and decreased MDA level in ischemic cortical tissues. In addition, carvacrol treatment suppressed the ischemia/reperfusion-induced increase in the protein expression of nuclear NF-kB p65. In conclusion, we have shown that carvacrol inhibits the inflammatory response via inhibition of the NF-kB signaling pathway in a rat model of focal cerebral ischemia. Therefore, carvacrol may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

  15. Quantifying the Attractive Force Exerted on the Pinned Calcium Spiral Waves by Using the Adventive Field

    International Nuclear Information System (INIS)

    Qiu Kang; Tang Jun; Luo Jin-Ming; Ma Jun

    2013-01-01

    The cytosolic calcium system is inhomogenous because of the discrete and random distribution of ion channels on the ER membrane. It is well known that the spiral tip can be pinned by the heterogenous area, and the field can detach the spiral from the heterogeneity. We use the adventive field to counteract the attractive force exerting on the calcium spiral wave by the heterogeneity, then the strength of the adventive field is used to quantify the attractive force indirectly. Two factors determining the attractive force are studied. It is found that: (1) the attractive force sharply increases with size of the heterogeneity for small-size heterogeneity, whereas the force increases to a saturated value for large-size heterogeneity; (2) for large-size heterogeneity, the force almost remains constant unless the level of the heterogeneity vanishes, the force decreases to zero linearly and sharply, and for small-size heterogeneity, the force decreases successively with the level of the heterogeneity. Furthermore, it is found that the forces exist only when the spiral tip is very close to the heterogenous area. Our study may shed some light on the control or suppression of the calcium spiral wave

  16. The Force Exerted by the Membrane Potential During Protein Import into the Mitochondrial Matrix

    Science.gov (United States)

    Shariff, Karim; Ghosal, Sandip; Matouschek, Andreas

    2002-01-01

    The electrostatic force exerted on a targeting sequence by the electrical potential across the inner mitochondrial membrane is calculated and found to vary from 1.4 pN to 2.2 pN (per unit elementary charge) as the radius of the inner membrane pore (assumed aqueous) is varied from 12 to 6.5 Angstroms, its measured range. Since the pore is not very much wider than the distance between water molecules, the full shielding effect of water may not be present; the extreme case of a nonaqueous pore gives a force of 3.1 pN per unit charge, which represents an upper limit. When applied to mitochondrial import experiments on the protein harness, these results imply that a force of 11 plus or minus 4 pN is sufficient to catalyze the unfolding of harness during import. Comparison of these results with unfolding forces measured using atomic force microscopy suggests that the two are not inconsistent.

  17. Exertional muscle injury: evaluation of concentric versus eccentric actions with serial MR imaging.

    Science.gov (United States)

    Shellock, F G; Fukunaga, T; Mink, J H; Edgerton, V R

    1991-06-01

    Eccentric muscular actions involve the forced lengthening or stretching of muscles and tend to produce exertional injuries. This study used magnetic resonance (MR) imaging to serially evaluate muscles in five healthy, untrained subjects who performed exhaustive biceps exercise by doing isolated eccentric and concentric actions with a dumbbell. Symptoms were assessed, and T2-weighted images of the arms were obtained before exercise and 1, 3, 5, 10, 25, 40, 50, 60, and 80 days after exercise. Statistically significant increases in T2 relaxation times indicative of muscle injury occurred on each day of MR imaging evaluation in muscles performing eccentric actions, peaking on day 3 in two subjects; day 5, two subjects; and day 10, one subject. The pattern and extent of the abnormalities on MR images were variable. Pain, soreness, and joint stiffness were present on days 1, 3, and 5 in muscles that performed eccentric actions. MR imaging showed subclinical abnormalities that lasted as long as 75 days after the disappearance of symptoms (two subjects). Muscles that performed concentric actions had no changes in T2 relaxation times and were asymptomatic throughout the study.

  18. 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.

  19. Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats.

    Science.gov (United States)

    Li, Hui-Qin; Li, Yan; Chen, Zi-Xian; Zhang, Xiao-Guang; Zheng, Xia-Wei; Yang, Wen-Ting; Chen, Shuang; Zheng, Guo-Qing

    2016-01-01

    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 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.

  20. 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