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Sample records for agmatine analogue gamma-guanidinooxypropylamine

  1. Novel agmatine analogue, γ-guanidinooxypropylamine (GAPA) efficiently inhibits proliferation of Leishmania donovani by depletion of intracellular polyamine levels

    International Nuclear Information System (INIS)

    Singh, Sushma; Jhingran, Anupam; Sharma, Ankur; Simonian, Alina R.; Soininen, Pasi; Vepsalainen, Jouko; Khomutov, Alex R.; Madhubala, Rentala

    2008-01-01

    The efficacy of γ-guanidinooxypropylamine (GAPA), a novel agmatine analogue against protozoan parasite, Leishmaniadonovani was evaluated. Wild-type and ornithine decarboxylase-overexpressors of L. donovani were used to study the effect and mode of action of this inhibitor. GAPA inhibited the growth of both promastigotes and amastigotes. Ornithine decarboxylase (ODC) activity and polyamine levels were markedly lower in cells treated with GAPA and proliferation was rescued by addition of putrescine or spermidine. GAPA inhibited L. donovani recombinant ODC with K i value of ∼60 μM. The ODC-overexpressors showed significant resistance to GAPA. GAPA has pK a 6.71 and at physiological pH the analogue can mimic protonated state of putrescine and can probably use putrescine transport system. Transport of putrescine in wild-type L. donovani promastigotes was inhibited by GAPA. We for the first time report that GAPA is a potential antileishmanial lead compound and it possibly inhibits L. donovani growth by depletion of intracellular polyamine levels

  2. A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study.

    Science.gov (United States)

    Calderón, Naima; Betancourt, Luis; Hernández, Luis; Rada, Pedro

    2017-03-06

    The ketogenic diet (KD) is acknowledged as an unconventional option in the treatment of epilepsy. Several lines of investigation point to a possible role of glutamate and gamma-aminobutyric acid (GABA) as main contributors in this protective effect. Other biomolecules could also be involved in the beneficial consequence of the KD, for example, the diamine agmatine has been suggested to block imidazole and glutamate NMDA receptor and serves as an endogenous anticonvulsant in different animal models of epilepsy. In the present report, we have used microdialysis coupled to capillary electrophoresis to monitor microdialysate levels of GABA, glutamate and agmatine in the hippocampus of rats submitted to a KD for 15days compared to rats on a normal rat chow diet. A significant increase in GABA and agmatine levels while no change in glutamate levels was observed. These results support the notion that the KD modifies different transmitters favoring inhibitory over excitatory neurotransmitters. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Development of a Pseudomonas aeruginosa Agmatine Biosensor

    Directory of Open Access Journals (Sweden)

    Adam Gilbertsen

    2014-10-01

    Full Text Available Agmatine, decarboxylated arginine, is an important intermediary in polyamine production for many prokaryotes, but serves higher functions in eukaryotes such as nitric oxide inhibition and roles in neurotransmission. Pseudomonas aeruginosa relies on the arginine decarboxylase and agmatine deiminase pathways to convert arginine into putrescine. One of the two known agmatine deiminase operons, aguBA, contains an agmatine sensitive TetR promoter controlled by AguR. We have discovered that this promoter element can produce a titratable induction of its gene products in response to agmatine, and utilized this discovery to make a luminescent agmatine biosensor in P. aeruginosa. The genome of the P. aeruginosa lab strain UCBPP-PA14 was altered to remove both its ability to synthesize or destroy agmatine, and insertion of the luminescent reporter construct allows it to produce light in proportion to the amount of exogenous agmatine applied from ~100 nM to 1mM. Furthermore it does not respond to related compounds including arginine or putrescine. To demonstrate potential applications the biosensor was used to detect agmatine in spent supernatants, to monitor the development of arginine decarboxylase over time, and to detect agmatine in the spinal cords of live mice.

  4. Agmatine modulates melanogenesis via MITF signaling pathway.

    Science.gov (United States)

    Kwon, Eun-Jeong; Kim, Moon-Moo

    2017-01-01

    Agmatine contained in soybean is also found in Manaca, an anti-aging plant, inhabited in Amazon and induces vasodilation by the promotion of NO synthesis in blood vessel. However, the research of agmatine on melanin synthesis related to hair greying is lacking. The aim of this study was to investigate the melanogenic effect of agmatine via regulation of MITF signaling pathway in B16F1 cells. It was determined whether agmatine regulates melanin synthesis at cellular level in addition to the effect of agmatine on mushroom tyrosinase in vitro in the presence of different concentrations of agmatine. Furthermore, the effect of agmatine on the protein expressions of tyrosinase, TRP-1, TRP-2, BMP-4, BMP-6, C-KIT, p-p38, MITF and C-FOS were examined by western blot analysis. In addition, immunofluorescence staining was carried out to visualize the location of MITF expression in cell. Agmatine at 256μM or more increased melanin synthesis as well as tyrosinase activity. Moreover, whereas agmatine increased the expression levels of TRP-1, BMP-6, p-p38 and MITF, it reduced the expression level of BMP-4. It was also found that agmatine enhanced the expression level of MITF in nucleus. These results suggest that agmatine could induce melanin synthesis though the regulation of MITF transcription factor via BMP-6/p38 signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Development of a Pseudomonas aeruginosa Agmatine Biosensor

    OpenAIRE

    Gilbertsen, Adam; Williams, Bryan

    2014-01-01

    Agmatine, decarboxylated arginine, is an important intermediary in polyamine production for many prokaryotes, but serves higher functions in eukaryotes such as nitric oxide inhibition and roles in neurotransmission. Pseudomonas aeruginosa relies on the arginine decarboxylase and agmatine deiminase pathways to convert arginine into putrescine. One of the two known agmatine deiminase operons, aguBA, contains an agmatine sensitive TetR promoter controlled by AguR. We have discovered that this pr...

  6. Agmatine attenuates silica-induced pulmonary fibrosis.

    Science.gov (United States)

    El-Agamy, D S; Sharawy, M H; Ammar, E M

    2014-06-01

    There is a large body of evidence that nitric oxide (NO) formation is implicated in mediating silica-induced pulmonary fibrosis. As a reactive free radical, NO may not only contribute to lung parenchymal tissue injury but also has the ability to combine with superoxide and form a highly reactive toxic species peroxynitrite that can induce extensive cellular toxicity in the lung tissues. This study aimed to explore the effect of agmatine, a known NO synthase inhibitor, on silica-induced pulmonary fibrosis in rats. Male Sprague Dawley rats were treated with agmatine for 60 days following a single intranasal instillation of silica suspension (50 mg in 0.1 ml saline/rat). The results revealed that agmatine attenuated silica-induced lung inflammation as it decreased the lung wet/dry weight ratio, protein concentration, and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid. Agmatine showed antifibrotic activity as it decreased total hydroxyproline content of the lung and reduced silica-mediated lung inflammation and fibrosis in lung histopathological specimen. In addition, agmatine significantly increased superoxide dismutase (p Agmatine also reduced silica-induced overproduction of pulmonary nitrite/nitrate as well as tumor necrosis factor α. Collectively, these results demonstrate the protective effects of agmatine against the silica-induced lung fibrosis that may be attributed to its ability to counteract the NO production, lipid peroxidation, and regulate cytokine effects. © The Author(s) 2014.

  7. Increased plasma agmatine levels in patients with schizophrenia.

    Science.gov (United States)

    Uzbay, Tayfun; Goktalay, Gokhan; Kayir, Hakan; Eker, Salih S; Sarandol, Asli; Oral, Sema; Buyukuysal, Levent; Ulusoy, Gokhan; Kirli, Selcuk

    2013-08-01

    Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p  0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Effects of agmatine sulphate on facial nerve injuries.

    Science.gov (United States)

    Surmelioglu, O; Sencar, L; Ozdemir, S; Tarkan, O; Dagkiran, M; Surmelioglu, N; Tuncer, U; Polat, S

    2017-03-01

    To evaluate the effect of agmatine sulphate on facial nerve regeneration after facial nerve injury using electron and light microscopy. The study was performed on 30 male Wistar albino rats split into: a control group, a sham-treated group, a study control group, an anastomosis group, and an anastomosis plus agmatine sulphate treatment group. The mandibular branch of the facial nerve was dissected, and a piece was removed for histological and electron microscopic examination. Regeneration was better in the anastomosis group than in the study control group. However, the best regeneration findings were seen in the agmatine sulphate treatment group. There was a significant difference between the agmatine group and the others in terms of median axon numbers (p Agmatine sulphate treatment with anastomosis in traumatic facial paralysis may enhance nerve regeneration.

  9. Agmatine attenuates stress- and lipopolysaccharide-induced fever in rats

    Science.gov (United States)

    Aricioglu, Feyza; Regunathan, Soundar

    2010-01-01

    Physiological stress evokes a number of responses, including a rise in body temperature, which has been suggested to be the result of an elevation in the thermoregulatory set point. This response seems to share similar mechanisms with infectious fever. The aim of the present study was to investigate the effect of agmatine on different models of stressors [(restraint and lipopolysaccaride (LPS)] on body temperature. Rats were either restrained for 4 h or injected with LPS, both of these stressors caused an increase in body temperature. While agmatine itself had no effect on body temperature, treatment with agmatine (20, 40, 80 mg/kg intraperitoneally) dose dependently inhibited stress- and LPS-induced hyperthermia. When agmatine (80 mg/kg) was administered 30 min later than LPS (500 μg/kg) it also inhibited LPS-induced hyperthermia although the effect became significant only at later time points and lower maximal response compared to simultaneous administration. To determine if the decrease in body temperature is associated with an anti-inflammatory effect of agmatine, the nitrite/nitrate levels in plasma was measured. Agmatine treatment inhibited LPS-induced production of nitrates dose dependently. As an endogenous molecule, agmatine has the capacity to inhibit stress- and LPS-induced increases in body temperature. PMID:15936786

  10. Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice.

    Science.gov (United States)

    Wiśniewska, Anna; Olszanecki, Rafał; Totoń-Żurańska, Justyna; Kuś, Katarzyna; Stachowicz, Aneta; Suski, Maciej; Gębska, Anna; Gajda, Mariusz; Jawień, Jacek; Korbut, Ryszard

    2017-08-04

    Atherosclerosis is an inflammatory disease in which dysfunction of mitochondria play an important role, and disorders of lipid management intensify this process. Agmatine, an endogenous polyamine formed by decarboxylation of arginine, exerts a protective effect on mitochondria and modulates fatty acid metabolism. We investigated the effect of exogenous agmatine on the development of atherosclerosis and changes in lipid profile in apolipoprotein E knockout (apoE-/-) mice. Agmatine caused an approximate 40% decrease of atherosclerotic lesions, as estimated by en face and cross-section methods with an influence on macrophage but not on smooth muscle content in the plaques. Agmatine treatment did not changed gelatinase activity within the plaque area. What is more, the action of agmatine was associated with an increase in the number of high density lipoproteins (HDL) in blood. Real-Time PCR analysis showed that agmatine modulates liver mRNA levels of many factors involved in oxidation of fatty acid and cholesterol biosynthesis. Two-dimensional electrophoresis coupled with mass spectrometry identified 27 differentially expressed mitochondrial proteins upon agmatine treatment in the liver of apoE-/- mice, mostly proteins related to metabolism and apoptosis. In conclusion, prolonged administration of agmatine inhibits atherosclerosis in apoE-/- mice; however, the exact mechanisms linking observed changes and elevations of HDL plasma require further investigation.

  11. Enzymes of agmatine degradation and the control of their synthesis in Streptococcus faecalis.

    OpenAIRE

    Simon, J P; Stalon, V

    1982-01-01

    Streptococcus faecalis ATCC 11700 uses agmatine as its sole energy source for growth. Agmatine deiminase and putrescine carbamoyltransferase are coinduced by growth on agmatine. Glucose and arginine were found to exert catabolite repression on the agmatine deiminase pathway. Four mutants unable to utilize agmatine as an energy source, isolated from the wild-type strain, exhibited three distinct phenotypes. Two of these strains showed essentially no agmatine deiminase, one mutant showed neglig...

  12. OCT2 and MATE1 Provide Bi-directional Agmatine Transport

    Science.gov (United States)

    Winter, Tate N.; Elmquist, William F.; Fairbanks, Carolyn A.

    2015-01-01

    Agmatine is a biogenic amine (l-arginine metabolite) of potential relevance to several central nervous system (CNS) conditions. The identities of transporters underlying agmatine and polyamine disposition in mammalian systems are not well defined. The SLC-family organic cation transporters (OCT) OCT1 and OCT2 and multidrug and toxin extrusion transporter-1 (MATE1) are transport systems that may be of importance for the cellular disposition of agmatine and putrescine. We investigated the transport of [3H]-agmatine and [3H]-putrescine in human embryonic kidney (HEK293) cells stably-transfected with hOCT1-, hOCT2-, and hMATE1. Agmatine transport by hOCT1 and hOCT2 was concentration-dependent, whereas only hOCT2 demonstrated pH-dependent transport. hOCT2 exhibited a greater affinity for agmatine (Km = 1.84 ± 0.38 mM) than did hOCT1 (Km = 18.73 ± 4.86 mM). Putrescine accumulation was pH- and concentration-dependent in hOCT2-HEK cells (Km = 11.29 ± 4.26 mM) but not hOCT1-HEK cells. Agmatine accumulation, in contrast to putrescine, was significantly enhanced by hMATE1 over-expression, and was saturable (Km = 240 ± 31 μM; Vmax = 192 ± 10 pmol/min/mg protein). Intracellular agmatine was also trans-stimulated (effluxed) from hMATE1-HEK cells in the presence of an inward proton-gradient. The hMATE1-mediated transport of agmatine was inhibited by polyamines, the prototypical substrates MPP+ and paraquat, as well as guanidine and arcaine, but not l-arginine. These results suggest that agmatine disposition may be influenced by hOCT2 and hMATE1, two transporters critical in the renal elimination of xenobiotic compounds. PMID:21128598

  13. Role of agmatine in neurodegenerative diseases and epilepsy.

    Science.gov (United States)

    Moretti, Morgana; Matheus, Filipe C; de Oliveira, Paulo A; Neis, Vivian B; Ben, Juliana; Walz, Roger; Rodrigues, Ana Lucia S; Prediger, Rui Daniel

    2014-06-01

    Agmatine, a cationic polyamine synthesized after decarboxylation of L-arginine by the enzyme arginine decarboxylase, is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, there is increasing number of preclinical studies demonstrating the beneficial effects of exogenous agmatine administration on depression, anxiety, hypoxic ischemia, nociception, morphine tolerance, memory, Parkinson`s disease, Alzheimer`s disease, traumatic brain injury related alterations/disorders and epilepsy. The aim of this review is to summarize the knowledge about the effects of agmatine in CNS and point out its potential as new pharmacological treatment for diverse neurological and neurodegenerative diseases. Moreover, some molecular mechanisms underlying the neuroprotective effects of agmatine will be discussed.

  14. Antidepressant-like effect of agmatine is not mediated by serotonin

    DEFF Research Database (Denmark)

    Krass, Maarja; Wegener, Gregers; Vasar, Eero

    2008-01-01

    The aim of this study was to characterize the behavioral effects of systemically administered agmatine in animal models predictive of antidepressant- and anxiolytic-like activity and clarify whether the effects of agmatine depend on the intact serotonergic system. Only the highest dose of agmatin...

  15. Characterization and inactivation of an agmatine deiminase from Helicobacter pylori

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Justin E.; Causey, Corey P.; Lovelace, Leslie; Knuckley, Bryan; Flick, Heather; Lebioda, Lukasz; Thompson, Paul R. (SC)

    2010-11-12

    Helicobacter pylori encodes a potential virulence factor, agmatine deiminase (HpAgD), which catalyzes the conversion of agmatine to N-carbamoyl putrescine (NCP) and ammonia - agmatine is decarboxylated arginine. Agmatine is an endogenous human cell signaling molecule that triggers the innate immune response in humans. Unlike H. pylori, humans do not encode an AgD; it is hypothesized that inhibition of this enzyme would increase the levels of agmatine, and thereby enhance the innate immune response. Taken together, these facts suggest that HpAgD is a potential drug target. Herein we describe the optimized expression, isolation, and purification of HpAgD (10-30 mg/L media). The initial kinetic characterization of this enzyme has also been performed. Additionally, the crystal structure of wild-type HpAgD has been determined at 2.1 {angstrom} resolution. This structure provides a molecular basis for the preferential deimination of agmatine, and identifies Asp198 as a key residue responsible for agmatine recognition, which has been confirmed experimentally. Information gathered from these studies led to the development and characterization of a novel class of haloacetamidine-based HpAgD inactivators. These compounds are the most potent AgD inhibitors ever described.

  16. Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

    Science.gov (United States)

    Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

    2017-02-05

    The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Agmatine Modulation of Noradrenergic Neurotransmission in Isolated Rat Blood Vessels.

    Science.gov (United States)

    Török, Jozef; Zemančíková, Anna

    2016-06-30

    Agmatine, a vasoactive metabolite of L-arginine, is widely distributed in mammalian tissues including blood vessels. Agmatine binding to imidazoline and α₂-adrenoceptors induces a variety of physiological and pharmacological effects. We investigated the effect of agmatine on contractile responses of the rat pulmonary artery and portal vein induced by electrical stimulation of perivascular nerves and by exogenous adrenergic substances. Experiments were performed on isolated segments of rat main pulmonary artery and its extralobular branches, and portal vein suspended in organ bath containing modified Krebs bicarbonate solution and connected to a force-displacement transducer for isometric tension recording. Electrical field stimulation (EFS) produced tetrodotoxin-sensitive contractile responses of pulmonary artery and portal vein. Besides the well known vasorelaxant actions, we found that agmatine also produced a concentration-dependent inhibition of neurogenic contractions induced by EFS in pulmonary arteries; however, the agmatine treatment did not influence the responses to exogenous noradrenaline. The inhibitory effect on EFS-induced contractions was not abolished by the α₂-adrenoceptor antagonist rauwolscine. In portal vein, in contrast, agmatine increased spontaneous mechanical contractions and enhanced the contractions induced by EFS. The results suggest that agmatine can significantly influence vascular function of pulmonary arteries and portal veins by modulating sympathetically mediated vascular contractions by pre- and postsynaptic mechanisms.

  18. Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

    Science.gov (United States)

    Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

    2009-01-01

    The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

  19. Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice.

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    Kitanaka, Nobue; Kitanaka, Junichi; Hall, F Scott; Uhl, George R; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Takemura, Motohiko

    2014-04-01

    We investigated whether pretreatment with the neurotransmitter/neuromodulator agmatine (decarboxylated L-arginine) affected methamphetamine (METH)-induced hyperlocomotion and stereotypy in male ICR mice. Agmatine pretreatment alone had no effects on locomotion or stereotypy, but it produced a dose-dependent attenuation of locomotion and the total incidence of stereotyped behavior induced by a low dose of METH (5 mg/kg). The stereotypy induced by this dose was predominantly characterized by stereotyped sniffing. By contrast, agmatine did not affect the total incidence of stereotypy induced by a higher dose of METH (10 mg/kg). However, the nature of stereotypy induced by this dose of METH was substantially altered; agmatine pretreatment significantly reduced stereotyped biting but significantly increased stereotyped sniffing and persistent locomotion. Agmatine pretreatment therefore appears to produce a rightward shift in the dose-response curve for METH. Pretreatment of mice with piperazine-1-carboxamidine (a putative agmatinase inhibitor) had no effect on locomotion or stereotypy induced by a low dose of METH, suggesting that endogenous agmatine may not regulate the METH action.

  20. Novel Route for Agmatine Catabolism in Aspergillus niger Involves 4-Guanidinobutyrase.

    Science.gov (United States)

    Kumar, Sunil; Saragadam, Tejaswani; Punekar, Narayan S

    2015-08-15

    Agmatine, a significant polyamine in bacteria and plants, mostly arises from the decarboxylation of arginine. The functional importance of agmatine in fungi is poorly understood. The metabolism of agmatine and related guanidinium group-containing compounds in Aspergillus niger was explored through growth, metabolite, and enzyme studies. The fungus was able to metabolize and grow on l-arginine, agmatine, or 4-guanidinobutyrate as the sole nitrogen source. Whereas arginase defined the only route for arginine catabolism, biochemical and bioinformatics approaches suggested the absence of arginine decarboxylase in A. niger. Efficient utilization by the parent strain and also by its arginase knockout implied an arginase-independent catabolic route for agmatine. Urea and 4-guanidinobutyrate were detected in the spent medium during growth on agmatine. The agmatine-grown A. niger mycelia contained significant levels of amine oxidase, 4-guanidinobutyraldehyde dehydrogenase, 4-guanidinobutyrase (GBase), and succinic semialdehyde dehydrogenase, but no agmatinase activity was detected. Taken together, the results support a novel route for agmatine utilization in A. niger. The catabolism of agmatine by way of 4-guanidinobutyrate to 4-aminobutyrate into the Krebs cycle is the first report of such a pathway in any organism. A. niger GBase peptide fragments were identified by tandem mass spectrometry analysis. The corresponding open reading frame from the A. niger NCIM 565 genome was located and cloned. Subsequent expression of GBase in both Escherichia coli and A. niger along with its disruption in A. niger functionally defined the GBase locus (gbu) in the A. niger genome. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Transcriptome profiling of Lactococcus lactis subsp. cremoris CECT 8666 in response to agmatine

    Directory of Open Access Journals (Sweden)

    Beatriz del Rio

    2016-03-01

    Full Text Available The dairy strain Lactococcus lactis subsp. cremoris CECT 8666 (formerly GE2-14 synthesizes the biogenic amine putrescine from agmatine via the agmatine deiminase (AGDI pathway [1]. The AGDI cluster of L. lactis is composed by five genes aguR, aguB, aguD, aguA and aguC. The last four genes are co-transcribed as a single policistronic mRNA forming the catabolic operon aguBDAC, which encodes the proteins necessary for agmatine uptake and its conversion into putrescine [1,2]. The first gene of the cluster, aguR, encodes a transmembrane protein that functions as a one-component signal transduction system that senses the agmatine concentration of the medium and accordingly regulates the transcription of aguBDAC [2]. The catabolic operon aguBDAC is transcriptionally activated by agmatine [2] and transcriptionally regulated by carbon catabolite repression (CCR via glucose, but not by other sugars such as lactose or galactose [1,3]. On the contrary, the transcription of the aguR regulatory gene is not subject to CCR regulation [1,3] nor is regulated by agmatine [2]. In this study we report the transcriptional profiling of L. lactis subsp. cremoris CECT 8666 grown in M17 medium with galactose (GalM17 as carbon source and supplemented with agmatine, compared to that of the strain grown in the same culture medium without agmatine. The transcriptional profiling data of agmatine-regulated genes were deposited in the Gene Expression Omnibus (GEO database under Accession no. GSE74808. Keywords: Lactococcus lactis, Biogenic amines, Putrescine, Agmatine deiminase, Agmatine

  2. Agmatine, a potential novel therapeutic strategy for depression.

    Science.gov (United States)

    Freitas, Andiara E; Neis, Vivian B; Rodrigues, Ana Lúcia S

    2016-12-01

    Major depressive disorder is the most common psychiatric disorder with lifetime prevalence of up to 20% worldwide. It is responsible for more years lost to disability than any other disorder. Despite the fact that current available antidepressant drugs are safe and effective, they are far from ideal. In addition to the need to administer the drugs for weeks or months to obtain clinical benefit, side effects are still a serious problem. Agmatine is an endogenous polyamine synthesized by the enzyme arginine decarboxylase. It modulates several receptors and is considered as a neuromodulator in the brain. In this review, studies demonstrating the antidepressant effects of agmatine are presented and discussed, as well as, the mechanisms of action related to these effects. Also, the potential beneficial effects of agmatine for the treatment of other neurological disorders are presented. In particular, we provide evidence to encourage future clinical studies investigating agmatine as a novel antidepressant drug. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  3. Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice.

    Science.gov (United States)

    Neis, Vivian Binder; Moretti, Morgana; Manosso, Luana Meller; Lopes, Mark W; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

    2015-03-01

    Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001 mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  5. Influence of ornithine decarboxylase antizymes and antizyme inhibitors on agmatine uptake by mammalian cells.

    Science.gov (United States)

    Ramos-Molina, Bruno; López-Contreras, Andrés J; Lambertos, Ana; Dardonville, Christophe; Cremades, Asunción; Peñafiel, Rafael

    2015-05-01

    Agmatine (4-aminobutylguanidine), a dicationic molecule at physiological pH, exerts relevant modulatory actions at many different molecular target sites in mammalian cells, having been suggested that the administration of this compound may have therapeutic interest. Several plasma membrane transporters have been implicated in agmatine uptake by mammalian cells. Here we report that in kidney-derived COS-7 cell line, at physiological agmatine levels, the general polyamine transporter participates in the plasma membrane translocation of agmatine, with an apparent Km of 44 ± 7 µM and Vmax of 17.3 ± 3.3 nmol h(-1) mg(-1) protein, but that at elevated concentrations, agmatine can be also taken up by other transport systems. In the first case, the physiological polyamines (putrescine, spermidine and spermine), several diguanidines and bis(2-aminoimidazolines) and the polyamine transport inhibitor AMXT-1501 markedly decreased agmatine uptake. In cells transfected with any of the three ornithine decarboxylase antizymes (AZ1, AZ2 and AZ3), agmatine uptake was dramatically reduced. On the contrary, transfection with antizyme inhibitors (AZIN1 and AZIN2) markedly increased the transport of agmatine. Furthermore, whereas putrescine uptake was significantly decreased in cells transfected with ornithine decarboxylase (ODC), the accumulation of agmatine was stimulated, suggesting a trans-activating effect of intracellular putrescine on agmatine uptake. All these results indicate that ODC and its regulatory proteins (antizymes and antizyme inhibitors) may influence agmatine homeostasis in mammalian tissues.

  6. Upgrading of analogue gamma cameras with PC based computer system

    International Nuclear Information System (INIS)

    Fidler, V.; Prepadnik, M.

    2002-01-01

    Full text: Dedicated nuclear medicine computers for acquisition and processing of images from analogue gamma cameras in developing countries are in many cases faulty and technologically obsolete. The aim of the upgrading project of International Atomic Energy Agency (IAEA) was to support the development of the PC based computer system which would cost 5.000 $ in total. Several research institutions from different countries (China, Cuba, India and Slovenia) were financially supported in this development. The basic demands for the system were: one acquisition card an ISA bus, image resolution up to 256x256, SVGA graphics, low count loss at high count rates, standard acquisition and clinical protocols incorporated in PIP (Portable Image Processing), on-line energy and uniformity correction, graphic printing and networking. The most functionally stable acquisition system tested on several international workshops and university clinics was the Slovenian one with a complete set of acquisition and clinical protocols, transfer of scintigraphic data from acquisition card to PC through PORT, count loss less than 1 % at count rate of 120 kc/s, improvement of integral uniformity index by a factor of 3-5 times, reporting, networking and archiving solutions for simple MS network or server oriented network systems (NT server, etc). More than 300 gamma cameras in 52 countries were digitized and put in the routine work. The project of upgrading the analogue gamma cameras yielded a high promotion of nuclear medicine in the developing countries by replacing the old computer systems, improving the technological knowledge of end users on workshops and training courses and lowering the maintenance cost of the departments. (author)

  7. Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine.

    Science.gov (United States)

    Payandemehr, Borna; Rahimian, Reza; Bahremand, Arash; Ebrahimi, Ali; Saadat, Seyedehpariya; Moghaddas, Peiman; Fadakar, Kaveh; Derakhshanian, Hoda; Dehpour, Ahmad Reza

    2013-06-13

    The anticonvulsant effects of agmatine, an endogenous polyamine and a metabolite of l-arginine, have been shown in various experimental seizure models. Agmatine also potentiates the anti-seizure activity of morphine. The present study aimed to investigate a possible involvement of nitric oxide (NO) pathway in the protection by agmatine and morphine co-administration against pentylenetetrazole (PTZ) -induced seizure in male mice. To this end, the thresholds for the clonic seizures induced by the intravenous administration of PTZ, a GABA antagonist, were assessed. Intraperitoneal administration of morphine at lower dose (1mg/kg) increased the seizure threshold. Also intraperitoneal administration of agmatine (5 and 10mg/kg) increased the seizure threshold significantly. Combination of subeffective doses of morphine and agmatine led to potent anticonvulsant effects. Non-effective doses of morphine (0.1 and 0.5mg/kg) were able to induce anticonvulsant effects in mice pretreated with agmatine (3mg/kg). Concomitant administration of either the non-selective nitric oxide synthase (NOS) inhibitor L-NAME (1, 5mg/kg, i.p.) or the selective NOS inhibitor 7-NI (15, 30mg/kg, i.p.), with an ineffective combination of morphine (0.1mg/kg) plus agmatine (1mg/kg) produced significant anticonvulsant impacts. Moreover, the NO precursor, l-arginine (30, 60mg/kg, i.p.), inhibited the anticonvulsant action of agmatine (3mg/kg) plus morphine (0.5mg/kg) co-administration. Our results indicate that pretreatment of animals with agmatine enhances the anticonvulsant effects of morphine via a mechanism which may involve the NO pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

    Science.gov (United States)

    Taksande, Brijesh G; Gawande, Dinesh Y; Chopde, Chandrabhan T; Umekar, Milind J; Kotagale, Nandkishor R

    2017-02-01

    The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis. Day 8 onwards of CFA administration, rats were injected daily with agmatine for next 7days, and arthritis score, body weights and food intake were monitored daily (g). Since cachexia is known to produce severe inflammation, malnutrition and inhibition of albumin gene expression, we have also monitored the total proteins, albumin, TNF-α and IL-6 levels in arthritic rats and its modulation by agmatine. In the present study, CFA treated rats showed a progressive reduction in both food intake and body weight. In addition analysis of blood serum of arthritis animals showed a significant reduction in proteins and albumin and significant elevation in tumor necrosis factor (TNF)-α and Interleukins (IL)-6. Chronic agmatine (20-40mg/kg, ip) treatment not only attenuated the signs of arthritis but also reverses anorexia and body weight loss in CFA treated rats. In addition, agmatine restored total protein and albumin and reduces TNF-α and IL-6 levels in arthritis rats. These results suggest that agmatine administration can prevent the body weights loss and symptoms of arthritis via inhibition of inflammatory cytokines. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Therapeutic potential of agmatine for CNS disorders.

    Science.gov (United States)

    Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S

    2017-09-01

    Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Evidence for the gastric cytoprotective effect of centrally injected agmatine.

    Science.gov (United States)

    Zádori, Zoltán S; Tóth, Viktória E; Fehér, Ágnes; Philipp, Kirsch; Németh, József; Gyires, Klára

    2014-09-01

    Agmatine (decarboxylated arginine) exerts cytoprotective action in several tissues, such as in the brain, heart or kidneys, but there is still controversy over the effects of agmatine on the gastric mucosa. The aim of the present study was to reveal the potential gastroprotective action of agmatine by using an acid-independent ulcer model to clarify which receptors and peripheral factors are involved in it. Gastric mucosal damage was induced by acidified ethanol. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay. For analysis of gastric motor activity the rubber balloon method was used. It was found that agmatine given intracerebroventricularly (i.c.v., 0.044-220 nmol/rat) significantly inhibited the development of ethanol-induced mucosal damage, while in the case of intraperitoneal injection (0.001-50mg/kg i.p.) it had only a minor effect. The central gastroprotective action of agmatine was completely antagonized by mixed alpha2-adrenoceptor and imidazoline I1 receptor antagonists (idazoxan, efaroxan), but only partially by yohimbine (selective alpha2-adrenoceptor antagonist) and AGN 192403 (selective I1 receptor ligand, putative antagonist). It was also inhibited by the non-selective opioid-receptor antagonist naloxone and the selective δ-opioid receptor antagonist naltrindole, but not by β-funaltrexamine and nor-Binaltorphimine (selective μ- and κ-opioid receptor antagonists, respectively). Furthermore, the effect of agmatine was antagonized by bilateral cervical vagotomy and by pretreatment with indomethacin and NG-nitro-l-arginine. Agmatine also reversed the ethanol-induced reduction of gastric mucosal CGRP and somatostatin content, but did not have any significant effect on gastric motor activity. These results indicate that agmatine given centrally induces gastric cytoprotection, which is mediated by central imidazoline I1 receptors, alpha2-adrenoceptors and δ-opioid receptors. Activation of

  11. Participation of hippocampal agmatine in spatial learning: an in vivo microdialysis study.

    Science.gov (United States)

    Rushaidhi, Madihah; Jing, Yu; Zhang, Hu; Liu, Ping

    2013-02-01

    Agmatine, decarboxylated arginine, is widely distributed in mammalian brains and is considered as a novel putative neurotransmitter. Recent research demonstrates spatial learning-induced increases in agmatine in memory-related structures at the tissue and presynaptic terminal levels. By using the in vivo microdialysis technique coupled with highly sensitive liquid chromatography/mass spectrometry assay, we investigated dynamic changes of extracellular agmatine in the rat dorsal hippocampus before, during and after water maze training to find a fixed hidden platform on the first and forth day of testing. It was firstly noted that the basal level of extracellular agmatine was significantly elevated on day 4. While swimming per se had no effect, a rapid rise (2-6 folds) in extracellular agmatine was observed during water maze training regardless of testing day. Such learning-induced rise was found to successively lessen across the multiple blocks of training on day 1. However, this pattern was reversed on day 4 when the platform was removed during the final training trial. The present study, for the first time, demonstrates water maze training-induced increase of extracellular agmatine in the dorsal hippocampus. The results suggest a role of endogenous agmatine in the encoding and retrieval of spatial information. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y

    Science.gov (United States)

    Taksande, BG; Kotagale, NR; Nakhate, KT; Mali, PD; Kokare, DM; Hirani, K; Subhedar, NK; Chopde, CT; Ugale, RR

    2011-01-01

    BACKGROUND AND PURPOSE Agmatine, a multifaceted neurotransmitter, is abundantly expressed in the hypothalamic paraventricular nucleus (PVN). Our aim was to assess (i) the effect of agmatine on feeding behaviour and (ii) its association, if any, with neuropeptide Y (NPY). EXPERIMENTAL APPROACH Satiated rats fitted with intra-PVN cannulae were administered agmatine, alone or jointly with (i) α2-adrenoceptor agonist, clonidine, or antagonist, yohimbine; (ii) NPY, NPY Y1 receptor agonist, [Leu31, Pro34]-NPY, or antagonist, BIBP3226; or (iii) yohimbine and NPY. Cumulative food intake was monitored at different post-injection time points. Furthermore, the expression of hypothalamic NPY following i.p. treatment with agmatine, alone or in combination with yohimbine (i.p.), was evaluated by immunocytochemistry. KEY RESULTS Agmatine robustly increased feeding in a dose-dependent manner. While pretreatment with clonidine augmented, yohimbine attenuated the orexigenic response to agmatine. Similarly, NPY and [Leu31, Pro34]-NPY potentiated the agmatine-induced hyperphagia, whereas BIBP3226 inhibited it. Moreover, yohimbine attenuated the synergistic orexigenic effect induced by the combination of NPY and agmatine. Agmatine increased NPY immunoreactivity in the PVN fibres and in the cells of the hypothalamic arcuate nucleus (ARC) and this effect was prevented by pretreatment with yohimbine. NPY immunoreactivity in the fibres of the ARC, dorsomedial, ventromedial and lateral nuclei of the hypothalamus was not affected by any of the above treatments. CONCLUSIONS AND IMPLICATIONS The orexigenic effect of agmatine is coupled to increased NPY activity mediated by stimulation of α2-adrenoceptors within the PVN. This signifies the importance of agmatine or α2-adrenoceptor modulators in the development of novel therapeutic agents to treat feeding-related disorders. PMID:21564088

  13. Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats.

    Science.gov (United States)

    Kim, Jae Hwan; Kim, Jae Young; Mun, Chin Hee; Suh, Minah; Lee, Jong Eun

    2017-10-01

    Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206 + & ED1 + cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype.

  14. [Determination of endogenous agmatine in rat plasma by isotope dilution-gas chromatography-mass spectrometry].

    Science.gov (United States)

    Qiu, Zhongli; Lin, Ying; Xiong, Zhili; Xie, Jianwei

    2014-07-01

    A method for the determination of endogenous agmatine in rat plasma was developed by isotope dilution-gas chromatography-negative chemical ionization mass spectrometry (GC-NCI/MS). The plasma samples were analyzed after protein precipitation, evaporation, derivatization by hexafluoroacetone (HFAA), and clean-up on a Florisil SPE column. The GC-MS analysis utilized stable isotope d8-agmatine as internal standard. The samples after treatme were tested by negative chemical ionization with selected ion monitoring (SIM) which was set at m/z 492 (molecular ion of agmatine) and m/z 500 (molecular ion of internal standard). The limit of detection (LOD) of agmatine standard solution was 0.005 7 ng/mL. The calibration curve of the agmatine spiked in rat plasma showed a good linear relationship at the range of 1.14-57.0 ng/mL (r = 0.997). The recoveries of agmatine spiked in rat plasma ranged from 92.3% to 109.8%. Inter-day and intra-day precisions were less than 15%. The average concentration level of agmatine in rat plasma was (22 +/- 9) ng/mL, and there was no significant difference between male and female SD rats (p > 0.05). The method is high sensitive and specific, and can be used for the determination of endogenous agmatine in plasma. It provides a strong support for the subsequent research of agmatine.

  15. Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

    Science.gov (United States)

    El-Awady, Mohammed S; Suddek, Ghada M

    2014-06-01

    The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

  16. Regulation of metabolic products and gene expression in Fusarium asiaticum by agmatine addition.

    Science.gov (United States)

    Suzuki, Tadahiro; Kim, Young-Kyung; Yoshioka, Hifumi; Iwahashi, Yumiko

    2013-05-01

    The metabolic products resulting from the cultivation of F. asiaticum in agmatine were identified using capillary electrophoresis-time of flight mass spectrometry. Glyoxylic acid was detected from fungal cultures grown in agmatine, while it was absent in control cells. The abundance of other metabolic products of the glycolytic pathway also increased because of agmatine; however, there was no increase in the amounts of pyruvic acid or metabolites from the tricarboxylic acid cycle. Moreover, gene expression levels within Fusarium asiaticum exposed to agmatine were analyzed by DNA microarray. Changes in gene expression levels directed the changes in metabolic products. Our results suggest that acetyl coenzyme A, which is a starting substrate for the biosynthesis of deoxynivalenol (DON), was simultaneously produced by activated β-oxidation. Furthermore, the content of 4-aminobutyrate (GABA) was increased in the agmatine addition culture medium. GABA can be synthesized from agmatine through putrescine and might influence the regulation of DON-related genes.

  17. Agmatine: clinical applications after 100 years in translation.

    Science.gov (United States)

    Piletz, John E; Aricioglu, Feyza; Cheng, Juei-Tang; Fairbanks, Carolyn A; Gilad, Varda H; Haenisch, Britta; Halaris, Angelos; Hong, Samin; Lee, Jong Eun; Li, Jin; Liu, Ping; Molderings, Gerhard J; Rodrigues, Ana Lúcia S; Satriano, Joseph; Seong, Gong Je; Wilcox, George; Wu, Ning; Gilad, Gad M

    2013-09-01

    Agmatine (decarboxylated arginine) has been known as a natural product for over 100 years, but its biosynthesis in humans was left unexplored owing to long-standing controversy. Only recently has the demonstration of agmatine biosynthesis in mammals revived research, indicating its exceptional modulatory action at multiple molecular targets, including neurotransmitter systems, nitric oxide (NO) synthesis and polyamine metabolism, thus providing bases for broad therapeutic applications. This timely review, a concerted effort by 16 independent research groups, draws attention to the substantial preclinical and initial clinical evidence, and highlights challenges and opportunities, for the use of agmatine in treating a spectrum of complex diseases with unmet therapeutic needs, including diabetes mellitus, neurotrauma and neurodegenerative diseases, opioid addiction, mood disorders, cognitive disorders and cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain

    Science.gov (United States)

    Zhu, Meng-Yang; Wang, Wei-Ping; Cai, Zheng-Wei; Regunathan, Soundar; Ordway, Gregory

    2009-01-01

    Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with β-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress. PMID:18364017

  19. Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats.

    Science.gov (United States)

    Wang, Xiao-Fei; Zhao, Tai-Yun; Su, Rui-Bin; Wu, Ning; Li, Jin

    2016-12-01

    Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hippocampal extracellular glutamate level induced by naloxone (2 mg/kg, i.p.) precipitation. Agmatine (20 mg/kg, s.c.) administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synaptosomes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agmatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors (NMDARs) was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine prevented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including modulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.

  20. Agmatine Modulates the Phenotype of Macrophage Acute Phase after Spinal Cord Injury in Rats

    OpenAIRE

    Kim, Jae Hwan; Kim, Jae Young; Mun, Chin Hee; Suh, Minah; Lee, Jong Eun

    2017-01-01

    Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macropha...

  1. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

    Science.gov (United States)

    Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

    2013-11-15

    Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

  2. Prostatic relaxation induced by agmatine is decreased in spontaneously hypertensive rats.

    Science.gov (United States)

    Lee, Liang-Ming; Tsai, Tsung-Chin; Chung, Hsien-Hui; Tong, Yat-Ching; Cheng, Juei-Tang

    2012-09-01

    What's known on the subject? and What does the study add? Neurotransmitters are known to control prostate contractility. Agmatine is one of them and induces relaxation through imidazoline receptors. The paper shows that the action of agmatine is reduced in hypertensive rats, and that this change is related to the decrease of ATP-sensitive potassium channels in the prostate. The findings can increase our understanding of the possible underlying mechanism for the development of clinical benign prostatic hyperplasia. To compare agmatine-induced prostatic relaxation in hypertensive and control rats. To investigate the responsible mechanism(s) and the role of the ATP-sensitive potassium channel. Prostate strips were isolated from male spontaneously hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of isometric tension. The strips were precontracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by cumulative administration of agmatine, 1 to 100 µmol/L, into the organ bath. Effects of specific antagonists on agmatine-induced relaxation were studied. Western blotting analysis was used to measure the gene expression of the ATP-sensitive potassium channel in the rat prostate. Prostatic relaxation induced by agmatine was markedly reduced in SH rats compared with WKY rats. The relaxation caused by agmatine was abolished by BU224, a selective imidazoline I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a concentration sufficient to activate ATP-sensitive potassium channels was markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir) 6.2 subunits were both decreased in the prostate of SH rats. The decrease of agmatine-induced prostatic relaxation in SH rats is related to the change in

  3. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons

    Science.gov (United States)

    Wang, Wei-Ping; Iyo, Abiye H.; Miguel-Hidalgo, Javier; Regunathan, Soundar; Zhu, Meng-Yang

    2010-01-01

    Agmatine is a polyamine and has been considered as a novel neurotransmitter or neuromodulator in the central nervous system. In the present study, the neuroprotective effect of agmatine against cell damage caused by N-methyl-d-aspartate (NMDA) and glutamate was investigated in cultured rat hippocampal neurons. Lactate dehydrogenase (LDH) activity assay, β-tubulin III immunocytochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay were conducted to detect cell damage. Exposure of 12-day neuronal cultures of rat hippocampus to NMDA or glutamate for 1 h caused a concentration-dependent neurotoxicity, as indicated by the significant increase in released LDH activities. Addition of 100 µM agmatine into media ablated the neurotoxicity induced by NMDA or glutamate, an effect also produced by the specific NMDA receptor antagonist dizocilpine hydrogen maleate (MK801). Arcaine, an analog of agmatine with similar structure as agmatine, fully prevented the NMDA- or glutamate-induced neuronal damage. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidine moiety of agmatine, failed to show this effect, indicating a structural relevance for this neuroprotection. Immunocytochemical staining and TUNEL assay confirmed the findings in the LDH measurement. That is, agmatine and MK801 markedly attenuated NMDA-induced neuronal death and significantly reduced TUNEL-positive cell numbers induced by exposure of cultured hippocampal neurons to NMDA. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property. PMID:16546145

  4. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

    Science.gov (United States)

    Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

    2010-01-01

    Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

  5. Dual interaction of agmatine with the rat α2D-adrenoceptor: competitive antagonism and allosteric activation

    Science.gov (United States)

    Molderings, G J; Menzel, S; Kathmann, M; Schlicker, E; Göthert, M

    2000-01-01

    In segments of rat vena cava preincubated with [3H]-noradrenaline and superfused with physiological salt solution, the influence of agmatine on the electrically evoked [3H]-noradrenaline release, the EP3 prostaglandin receptor-mediated and the α2D-adrenoceptor-mediated inhibition of evoked [3H]-noradrenaline release was investigated. Agmatine (0.1–10 μM) by itself was without effect on evoked [3H]-noradrenaline release. In the presence of 10 μM agmatine, the prostaglandin E2(PGE2)-induced EP3-receptor-mediated inhibition of [3H]-noradrenaline release was not modified, whereas the α2D-adrenoceptor-mediated inhibition of [3H]-noradrenaline release induced by noradrenaline, moxonidine or clonidine was more pronounced than in the absence of agmatine. However, 1 mM agmatine antagonized the moxonidine-induced inhibition of [3H]-noradrenaline release. Agmatine concentration-dependently inhibited the binding of [3H]-clonidine and [3H]-rauwolscine to rat brain cortex membranes (Ki values 6 μM and 12 μM, respectively). In addition, 30 and 100 μM agmatine increased the rate of association and decreased the rate of dissociation of [3H]-clonidine resulting in an increased affinity of the radioligand for the α2D-adrenoceptors. [14C]-agmatine labelled specific binding sites on rat brain cortex membranes. In competition experiments. [14C]-agmatine was inhibited from binding to its specific recognition sites by unlabelled agmatine, but not by rauwolscine and moxonidine. In conclusion, the present data indicate that agmatine both acts as an antagonist at the ligand recognition site of the α2D-adrenoceptor and enhances the effects of α2-adrenoceptor agonists probably by binding to an allosteric binding site of the α2D-adrenoceptor which seems to be labelled by [14C]-agmatine. PMID:10928978

  6. Psychiatric aspects of acute withdrawal from gamma-hydroxybutyrate (GHB) and its analogue gamma-butyrolactone (GBL): implications for psychiatry services in the general hospital.

    Science.gov (United States)

    Choudhuri, Debajeet; Cross, Sean; Dargan, Paul I; Wood, David M; Ranjith, Gopinath

    2013-06-01

    The objective of this study was to describe the psychiatric symptoms, management and outcomes in a consecutive series of patients being managed medically for symptoms of withdrawal from gamma-hydroxybutyrate (GHB) and its analogue gamma-butyrolactone (GBL) in a general hospital setting. A toxicology database was used to identify patients presenting with a history suggestive of withdrawal from GHB and analogues. Electronic and paper medical records were searched for demographic features, neuropsychiatric symptoms, psychiatric management while in hospital and overall outcome. There were 31 presentations with withdrawal from the drugs involving 20 patients. Of these 17 (54%) were referred to and seen by the liaison psychiatry team. Anxiety (61.3%) and agitation (48.4%) were the most common symptoms. Of the 17 cases seen by the liaison psychiatry team, 52.9% required close constant observation by a mental health nurse and 29.4% required to be detained in hospital under mental health legislation. The significant proportion of patients presenting with neuropsychiatric symptoms and requiring intensive input from the liaison psychiatry team during withdrawal from GHB and its analogues points to the importance of close liaison between medical and psychiatric teams in managing these patients in the general hospital.

  7. Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

    Science.gov (United States)

    Rushaidhi, M; Zhang, H; Liu, P

    2013-03-27

    Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Protective effects of agmatine against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.

    Science.gov (United States)

    El-Agamy, Dina S; Makled, Mirhan N; Gamil, Nareman M

    2014-06-01

    Fulminant hepatic failure (FHF) is a life-threatening syndrome characterized by massive hepatic necrosis and high mortality. There is no effective therapy for the disease other than liver transplantation. This study aimed to investigate the effect of agmatine, inducible nitric oxide synthase (iNOS) inhibitor, on D-galactosamine and lipopolysaccharide (GalN/LPS)-induced FHF in mice and explore its possible mechanism(s). Male Swiss albino mice were injected with a single dose agmatine (14 mg/kg, IP) 8 h prior to challenge with a single intraperitoneal injection of both GalN (800 mg/kg) and LPS (50 μg/kg). Agmatine significantly attenuated all GalN/LPS-induced biochemical and pathological changes in liver. It prevented the increase of serum transaminases and alkaline phosphatase (ALP). In addition, agmatine markedly attenuated GalN/LPS-induced necrosis and inflammation. Agmatine significantly reduced oxidative stress and enhanced antioxidant enzymes. Importantly, agmatine decreased total nitric oxide (NO) and pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α). These findings reveal that agmatine has hepatoprotective effects against GalN/LPS-induced FHF in mice that may be related to its ability to suppress oxidative stress, NO synthesis and TNF-α production. Therefore, agmatine may serve as a novel therapeutic strategy for hepatic inflammatory diseases.

  9. Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.

    Science.gov (United States)

    Gilad, Gad M; Gilad, Varda H

    2013-12-01

    Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their drinking water for 95 days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20 days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Protective effect of agmatine in acute chlorpromazine hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Bratislav Dejanovic

    2014-01-01

    Full Text Available The present study focused on potentially beneficial effects of agmatine on oxidative stress development in the liver during chlorpromazine treatment in rats. We wanted to examine the role of reactive oxygen species and efficiency of antioxidant protection through the determination of malondylaldehyde and total glutathione concentrations in rat liver homogenate, as well as plasma concentrations of malonylaldehyde and sulfhydryl groups after the treatment. Also, liver tissue sections were examined to follow histological changes. Chlorpromazine was applied intraperitoneally at a single dose of 38.7 mg/kg b.w. The second group was treated with both chlorpromazine (at a single dose of 38.7 mg/kg b.w. and agmatine (at a single dose of 75 mg/kg b.w.. Agmatine was applied immediately after the chlorpromazine. The control group was treated with 0.9% saline solution in the same manner. Rats were sacrificed by decapitation 24 h after the treatment and biochemical and immunohistochemical examinations were performed. Analysis of data showed that treatment with agmatine significantly attenuated the oxidative stress indicators as evidenced by lowering malonylaldehyde concentrations in the liver and in plasma while not affecting liver concentrations of total glutathione and plasma concentration of sulfhydryl groups. Additionally, histological evaluation revealed the improvement of liver damage in this respect. The presented data indicated that intraperitoneally administered agmatine protects against chlorpromazine-induced liver disease in rats.

  11. Agmatine attenuates the discriminative stimulus and hyperthermic effects of methamphetamine in male rats.

    Science.gov (United States)

    Thorn, David A; Li, Jiuzhou; Qiu, Yanyan; Li, Jun-Xu

    2016-09-01

    Methamphetamine abuse remains an alarming public heath challenge, with no approved pharmacotherapies available. Agmatine is a naturally occurring cationic polyamine that has previously been shown to attenuate the rewarding and psychomotor-sensitizing effects of methamphetamine. This study examined the effects of agmatine on the discriminative stimulus and hyperthermic effects of methamphetamine. Adult male rats were trained to discriminate 0.32 mg/kg methamphetamine from saline. Methamphetamine dose dependently increased drug-associated lever responding. The nonselective dopamine receptor antagonist haloperidol (0.1 mg/kg) significantly attenuated the discriminative stimulus effects of methamphetamine (5.9-fold rightward shift). Agmatine (10-100 mg/kg) did not substitute for methamphetamine, but significantly attenuated the stimulus effects of methamphetamine, leading to a maximum of a 3.5-fold rightward shift. Acute 10 mg/kg methamphetamine increased the rectal temperature by a maximum of 1.96±0.17°C. Agmatine (10-32 mg/kg) pretreatment significantly attenuated the hyperthermic effect of methamphetamine. Agmatine (10 mg/kg) also significantly reversed methamphetamine-induced temperature increase. Together, these results support further exploration of the value that agmatine may have for the treatment of methamphetamine abuse and overdose.

  12. Depressive-like behavior induced by tumor necrosis factor-α is abolished by agmatine administration.

    Science.gov (United States)

    Neis, Vivian Binder; Manosso, Luana Meller; Moretti, Morgana; Freitas, Andiara E; Daufenbach, Juliana; Rodrigues, Ana Lúcia S

    2014-03-15

    Agmatine, an endogenous cationic amine, has been shown to exert antidepressant-like effects. This study investigated the ability of agmatine administered orally to abolish the depressive-like behavior induced by the administration of the pro-inflammatory cytokine, tumor necrosis factor (TNF-α) in mice. In control animals, agmatine (0.001, 0.01, 0.1, and 1 mg/kg) reduced the immobility time in the tail suspension test (TST). Acute administration of TNF-α (0.001 fg/mouse, i.c.v.) increased immobility time in the TST, indicative of a depressive-like behavior, and agmatine (0.0001, 0.1, and 1 mg/kg) prevented this effect. Additionally, we examined the effects of the combined administration of sub-effective doses of agmatine with antidepressants, the NMDA receptor antagonist MK-801 and the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) in mice exposed to either TNF-α or saline. In control mice, administration of a sub-effective dose of agmatine (0.0001 mg/kg) combined with sub-effective doses of either fluoxetine (5 mg/kg, p.o.), imipramine (0.1 mg/kg, p.o.), bupropion (1 mg/kg, p.o.), MK-801 (0.001 mg/kg, p.o.) or 7-NI (25 mg/kg, i.p.) produced a synergistic antidepressant-like effect in the TST. All these administrations prevented the increased immobility time induced by TNF-α. The effect of agmatine in the TNF-α model of depression appears to be associated, at least partially, with an activation of the monoaminergic systems and inhibition of NMDA receptors and nitric oxide synthesis, although converging signal transduction pathways that may underlie the effect of agmatine should be further investigated. This set of results indicates that agmatine may constitute a new therapeutic alternative for the treatment of depression associated with inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

    Science.gov (United States)

    Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

    2015-05-05

    Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Agmatine: multifunctional arginine metabolite and magic bullet in clinical neuroscience?

    Science.gov (United States)

    Laube, Gregor; Bernstein, Hans-Gert

    2017-07-26

    Agmatine, the decarboxylation product of arginine, was largely neglected as an important player in mammalian metabolism until the mid-1990s, when it was re-discovered as an endogenous ligand of imidazoline and α 2 -adrenergic receptors. Since then, a wide variety of agmatine-mediated effects have been observed, and consequently agmatine has moved from a wallflower existence into the limelight of clinical neuroscience research. Despite this quantum jump in scientific interest, the understanding of the anabolism and catabolism of this amine is still vague. The purification and biochemical characterization of natural mammalian arginine decarboxylase and agmatinase still are open issues. Nevertheless, the agmatinergic system is currently one of the most promising candidates in order to pharmacologically interfere with some major diseases of the central nervous system, which are summarized in the present review. Particularly with respect to major depression, agmatine, its derivatives, and metabolizing enzymes show great promise for the development of an improved treatment of this common disease. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  15. Agmatine promotes the migration of murine brain endothelial cells via multiple signaling pathways.

    Science.gov (United States)

    Jung, Hyun-Joo; Jeon, Yong-Heui; Bokara, Kiran Kumar; Koo, Bon-Nyeo; Lee, Won Taek; Park, Kyung Ah; Lee, Jong-Eun

    2013-01-17

    The combination of adhesion and migration of endothelial cells (ECs) is an integral process for evolution, organization, repair and vessel formation in living organisms. Agmatine, a polycationic amine existing in brain, has been investigated to exert neuroprotective effects. Up to date, there are no studies reporting that agmatine modulates murine brain endothelial (bEnd.3) cells migration. In the present study, we intend to investigate the role of agmatine in bEnd.3 cells migration and the molecular mechanism mediating this action. The effect of agmatine on the bEnd.3 cells migration was examined by migration assay, and the mechanism involved for this effect was investigated by western blot analysis and NO contents measurements. Agmatine treatment (50, 100 and 200 μM) significantly accelerated bEnd.3 cells migration in a concentration-dependent manner. Western blotting revealed that agmatine treatment significantly induced vascular endothelial growth factor (VEGF), VEGF receptor 2 (Flk-1/KDR or VEGFR2), phosphatidylinositol 3-kinase (PI3K), Akt/protein kinase B (also known as PKB, PI3K downstream effector protein), endothelial nitric oxide synthase (eNOS) nitric oxide (NO; product by eNOS) and intercellular adhesion molecule 1 (ICAM-1) expressions during bEnd.3 cells migration. The expression of ICAM-1 and migration of bEnd.3 cells, induced by agmatine, were significantly attenuated by treatment of wortmannin, a specific PI3K inhibitor. Taken together, we provide the first evidence that activation of VEGF/VEGFR2 and the consequential PI3K/Akt/eNOS/NO/ICAM-1 signaling pathways are serial events, through which the treatment of agmatine could lead to bEnd.3 cells migration. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Influence of ornithine decarboxylase antizymes and antizyme inhibitors on agmatine uptake by mammalian cells

    DEFF Research Database (Denmark)

    Ramos-Molina, Bruno; López-Contreras, Andrés J; Lambertos, Ana

    2015-01-01

    Agmatine (4-aminobutylguanidine), a dicationic molecule at physiological pH, exerts relevant modulatory actions at many different molecular target sites in mammalian cells, having been suggested that the administration of this compound may have therapeutic interest. Several plasma membrane...... transporters have been implicated in agmatine uptake by mammalian cells. Here we report that in kidney-derived COS-7cell line, at physiological agmatine levels, the general polyamine transporter participates in the plasma membrane translocation of agmatine, with an apparent Km of 44 ± 7 µM and V max of 17.......3 ± 3.3 nmol h(-1) mg(-1) protein, but that at elevated concentrations, agmatine can be also taken up by other transport systems. In the first case, the physiological polyamines (putrescine, spermidine and spermine), several diguanidines and bis(2-aminoimidazolines) and the polyamine transport inhibitor...

  17. Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

    Science.gov (United States)

    Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

    2010-01-01

    Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that reached brain after peripheral injection. After i.p. injection of agmatine (50 mg/kg), increase of agmatine in rat cortex and hippocampus was observed in 15 min with levels returning to baseline in one hour. Rats, naïve and implanted with microdialysis cannula into the cortex, were administered PTZ (60 mg/kg, i.p.) with prior injection of agmatine (100 mg/kg, i.p.) or saline. Seizure grades were recorded and microdialysis samples were collected every 15 min for 75 min. Agmatine pre-treatment significantly reduced the seizure grade and increased the onset time. The levels of extracellular glutamate in frontal cortex rose two- to three-fold after PTZ injection and agmatine significantly inhibited this increase. In conclusion, the present data suggest that the anticonvulsant activity of agmatine, in part, could be related to the inhibition glutamate release. PMID:16125317

  18. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine.

    OpenAIRE

    Galea, E; Regunathan, S; Eliopoulos, V; Feinstein, D L; Reis, D J

    1996-01-01

    Agmatine, decarboxylated arginine, is a metabolic product of mammalian cells. Considering the close structural similarity between L-arginine and agmatine, we investigated the interaction of agmatine and nitric oxide synthases (NOSs), which use L-arginine to generate nitric oxide (NO) and citrulline. Brain, macrophages and endothelial cells were respectively used as sources for NOS isoforms I, II and III. Enzyme activity was measured by the production of nitrites or L-citrulline. Agmatine was ...

  19. Transport of diamines by Enterococcus faecalis is mediated by an agmatine-putrescine antiporter.

    OpenAIRE

    Driessen, A J; Smid, E J; Konings, W N

    1988-01-01

    Enterococcus faecalis ATCC 11700 is able to use arginine and the diamine agmatine as a sole energy source. Via the highly homologous deiminase pathways, arginine and agmatine are converted into CO2, NH3, and the end products ornithine and putrescine, respectively. In the arginine deiminase pathway, uptake of arginine and excretion of ornithine are mediated by an arginine-ornithine antiport system. The translocation of agmatine was studied in whole cells grown in the presence of arginine, agma...

  20. Acute orexigenic effect of agmatine involves interaction between central α2-adrenergic and GABAergic receptors.

    Science.gov (United States)

    Taksande, Brijesh Gulabrao; Sharma, Omi; Aglawe, Manish Manohar; Kale, Mayur Bhimrao; Gawande, Dinesh Yugraj; Umekar, Milind Janraoji; Kotagale, Nandkishor Ramdas

    2017-09-01

    Agmatine and GABA have been abundantly expressed in brain nuclei involved in regulation of energy homeostasis and promoting stimulation of food intake in rodents. However, their mutual interaction, if any, in the elicitation of feeding behavior is largely remains unclear. The current study provides experimental evidence for the possible interaction of agmatine, adrenergic and GABAergic systems in stimulation of feeding in satiated rats. Satiated rats fitted with intracerebroventricular (i.c.v.) cannulae and were administered agmatine, alone or jointly with (a) GABA A receptor agonist, muscimol, diazepam or antagonist bicuculline and flumazenil, GABA A positive modulator, allopregnanolone or negative modulator of GABA A receptor, dehydroepiandrosterone (b) In view of the high affinity of agmatine for α 2 -adrenoceptors and the close association between α 2 -adrenoceptors and GABAergic system, the effect of their modulators on feeding elicited by agmatine/GABAergic agonists were also examined. I.c.v. administration of agmatine (40-80μg/rat) induces the significant orexigenic effect in satiated rats. The orexigenic effect of agmatine was potentiated by muscimol (25ng/rat, i.c.v.); diazepam (0.5mg/kg, i.p.); allopregnanolone (0.5mg/kg, s.c.) and blocked by bicuculline (1mg/kg, i.p.) and dehydroepiandrosterone (4mg/kg,s.c.). However, it remained unaffected in presence of flumazenil (25ng/rat, i.c.v.). The orexigenic effect of agmatine and GABAergic agonists was potentiated by a α 2 -adrenoceptors agonist, clonidine (10ng/rat, i.c.v.) and blocked by its antagonist, yohimbine (5μg/rat, i.c.v.). Yohimbine also blocked the hyperphagic effect elicited by ineffective dose combination of agmatine (5μg/rat, i.c.v.) with muscimol (25ng/rat, i.c.v.) or diazepam (0.5mg/kg, i.p.) or allopregnanolone (0.5mg/kg,s.c.). The results of the present study suggest that agmatine induced α 2 -adrenoceptors activation might facilitate GABAergic activity to stimulate food intake in

  1. Protective effects of agmatine on lipopolysaccharide-injured microglia and inducible nitric oxide synthase activity.

    Science.gov (United States)

    Ahn, Soo Kyung; Hong, Samin; Park, Yu Mi; Choi, Ja Yong; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2012-12-17

    Proinflammatory factors released from activated microglia contribute to maintaining homeostasis against various noxious stimuli in the central nervous system. If excessive, however, they may initiate a pathologic neuroinflammatory process. In this investigation, we evaluated whether agmatine, a primary polyamine known to protect neurons, reduces lipopolysaccharide (LPS)-induced damage to microglia in vitro and in vivo. For in vitro study, BV2-immortalized murine microglia were exposed to LPS with agmatine treatment. After 24hours, cell viability and the amount of nitrite generated were determined. For in vivo study, LPS was microinjected into the corpus callosum of adult male albino mice. Agmatine was intraperitoneally administered at the time of injury. Brains were evaluated 24hours after LPS microinjection to check for immunoreactivity with a microglial marker of ionized calcium binding adaptor molecule 1 (Iba1) and inducible nitric oxide synthase (iNOS). Using western blot analysis, protein expression of iNOS as well as that of the proinflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, was determined. Agmatine significantly reduced the LPS-induced BV2 microglial cytotoxicity from over 80% to less than 60% (pAgmatine also decreased the activities of microglia and iNOS induced by LPS microinjection into corpus callosum. Our findings reveal that agmatine attenuates LPS-induced microglial damage and suggest that agmatine may serve as a novel therapeutic strategy for neuroinflammatory diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Protective mechanism of agmatine pretreatment on RGC-5 cells injured by oxidative stress

    Directory of Open Access Journals (Sweden)

    Y. Iizuka

    2010-04-01

    Full Text Available Agmatine has neuroprotective effects on retinal ganglion cells (RGCs as well as cortical and spinal neurons. It protects RGCs from oxidative stress even when it is not present at the time of injury. As agmatine has high affinity for various cellular receptors, we assessed protective mechanisms of agmatine using transformed RGCs (RGC-5 cell line. Differentiated RGC-5 cells were pretreated with 100 μM agmatine and consecutively exposed to 1.0 mM hydrogen peroxide (H2O2. Cell viability was determined by measuring lactate dehydrogenase (LDH, and the effects of selective alpha 2-adrenergic receptor antagonist yohimbine (0-500 nM and N-methyl-D-aspartic acid (NMDA receptor agonist NMDA (0-100 µM were evaluated. Agmatine’s protective effect was compared to a selective NMDA receptor antagonist MK-801. After a 16-h exposure to H2O2, the LDH assay showed cell loss greater than 50%, which was reduced to about 30% when agmatine was pretreated before injury. Yohimbine almost completely inhibited agmatine’s protective effect, but NMDA did not. In addition, MK-801 (0-100 µM did not significantly attenuate the H2O2-induced cytotoxicity. Our results suggest that neuroprotective effects of agmatine on RGCs under oxidative stress may be mainly attributed to the alpha 2-adrenergic receptor signaling pathway.

  3. Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.

    Science.gov (United States)

    Kim, Jae Young; Lee, Yong Woo; Kim, Jae Hwan; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2015-07-01

    Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

  4. Agmatine Production by Aspergillus oryzae is Elevated by Low pH During Solid-State Cultivation.

    Science.gov (United States)

    Akasaka, Naoki; Kato, Saori; Kato, Saya; Hidese, Ryota; Wagu, Yutaka; Sakoda, Hisao; Fujiwara, Shinsuke

    2018-05-25

    Sake (rice wine) produced by multiple parallel fermentation (MPF) involving Aspergillus oryzae (strain RW) and Saccharomyces cerevisiae under solid-state cultivation conditions contained 3.5 mM agmatine, while that produced from enzymatically saccharified rice syrup by S. cerevisiae contained oryzae under solid-state cultivation (3.1 mM) but not under submerged cultivation, demonstrating that A. oryzae in solid-state culture produces agmatine. The effect of cultivation conditions on agmatine production was examined. Agmatine production was boosted at 30°C and reached the highest level (6.3 mM) at pH 5.3. The addition of l-lactic, succinic, and citric acids reduced the initial culture pH to 3.0, 3.5, and 3.2, respectively, resulting in further increase in agmatine accumulation (8.2, 8.7, and 8.3 mM, respectively). Homogenate from a solid-state culture exhibited a maximum l-arginine decarboxylase (ADC) activity (74 pmol min -1 μg -1 ) at pH 3.0 at 30°C; that from a submerged culture exhibited an extremely low activity (oryzae , even though A. oryzae lacks ADC orthologs and, instead, possesses four ornithine decarboxylases (ODC1-4). Recombinant ODC1 and ODC2 exhibited no ADC activity at acidic pH (pH 4.0>), suggesting that other decarboxylases or an unidentified ADC is involved in agmatine production. IMPORTANCE It has been speculated that, in general, fungi do not synthesize agmatine from l-arginine because they do not possess genes encoding for arginine decarboxylase. Numerous preclinical studies have shown that agmatine exerts pleiotropic effects on various molecular targets, leading to an improved quality of life. In the present study, we first demonstrated that l-arginine was a feasible substrate for agmatine production by the fungus Aspergillus oryzae RW. We observed that the productivity of agmatine by A. oryzae RW was elevated at low pH only during solid-state cultivation. A. oryzae is utilized in the production of various oriental fermented foods. The

  5. Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report.

    Science.gov (United States)

    Gilad, Gad M; Gilad, Varda H

    2014-11-01

    There is presently a great interest in the therapeutic potential of agmatine, decarboxylated arginine, for various diseases. Recent clinical studies have already shown that oral agmatine sulfate given for up to 3 weeks provides a safe and, as compared with current therapeutics, more effective treatment for neuropathic pain. These studies have ushered in the use of dietary agmatine as a nutraceutical. However, in view of information paucity, assessment of long-term safety of oral agmatine treatment is now clearly required. The authors of this report undertook to assess their own health status during ongoing consumption of a high daily dosage of oral agmatine over a period of 4-5 years. A daily dose of 2.67 g agmatine sulfate was encapsulated in gelatin capsules; the regimen consists of six capsules daily, each containing 445 mg, three in the morning and three in the evening after meals. Clinical follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All measurements thus far remain within normal values and good general health status is sustained throughout the study period, up to 5 years. This case study shows for the first time that the recommended high dosage of agmatine may be consumed for at least 5 years without evidence of any adverse effects. These initial findings are highly important as they provide significant evidence for the extended long-term safety of a high daily dosage of dietary agmatine--a cardinal advantage for its utility as a nutraceutical.

  6. Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain.

    Science.gov (United States)

    Jing, Y; Liu, P; Leitch, B

    2016-01-15

    During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; pagmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. An agmatine-inducible system for the expression of recombinant proteins in Enterococcus faecalis.

    Science.gov (United States)

    Linares, Daniel M; Perez, Marta; Ladero, Victor; Del Rio, Beatriz; Redruello, Begoña; Martin, M Cruz; Fernandez, María; Alvarez, Miguel A

    2014-12-04

    Scientific interest in Enterococcus faecalis has increased greatly over recent decades. Some strains are involved in food fermentation and offer health benefits, whereas others are vancomycin-resistant and cause infections that are difficult to treat. The limited availability of vectors able to express cloned genes efficiently in E. faecalis has hindered biotechnological studies on the bacterium's regulatory and pathogenicity-related genes. The agmatine deiminase (AGDI) pathway of E. faecalis, involved in the conversion of agmatine into putrescine, is driven by a response inducer gene aguR. This study describes that the exposure to the induction factor (agmatine) results in the transcription of genes under the control of the aguB promoter, including the aguBDAC operon. A novel E. faecalis expression vector, named pAGEnt, combining the aguR inducer gene and the aguB promoter followed by a cloning site and a stop codon was constructed. pAGEnt was designed for the overexpression and purification of a protein fused to a 10-amino-acid His-tag at the C-terminus. The use of GFP as a reporter of gene expression in E. faecalis revealed that under induction with 60 mM agmatine, fluorescence reached 40 arbitrary units compared to 0 in uninduced cells. pAGEnt vector can be used for the overexpression of recombinant proteins under the induction of agmatine in E. faecalis, with a close correlation between agmatine concentration and fluorescence when GFP was used as reporter.

  8. Agmatine, by Improving Neuroplasticity Markers and Inducing Nrf2, Prevents Corticosterone-Induced Depressive-Like Behavior in Mice.

    Science.gov (United States)

    Freitas, Andiara E; Egea, Javier; Buendia, Izaskun; Gómez-Rangel, Vanessa; Parada, Esther; Navarro, Elisa; Casas, Ana Isabel; Wojnicz, Aneta; Ortiz, José Avendaño; Cuadrado, Antonio; Ruiz-Nuño, Ana; Rodrigues, Ana Lúcia S; Lopez, Manuela G

    2016-07-01

    Agmatine, an endogenous neuromodulator, is a potential candidate to constitute an adjuvant/monotherapy for the management of depression. A recent study by our group demonstrated that agmatine induces Nrf2 and protects against corticosterone effects in a hippocampal neuronal cell line. The present study is an extension of this previous study by assessing the antidepressant-like effect of agmatine in an animal model of depression induced by corticosterone in mice. Swiss mice were treated simultaneously with agmatine or imipramine at a dose of 0.1 mg/kg/day (p.o.) and corticosterone for 21 days and the daily administrations of experimental drugs were given immediately prior to corticosterone (20 mg/kg/day, p.o.) administrations. Wild-type C57BL/6 mice (Nrf2 (+/+)) and Nrf2 KO (Nrf2 (-/-)) were treated during 21 days with agmatine (0.1 mg/kg/day, p.o.) or vehicle. Twenty-four hours after the last treatments, the behavioral tests and biochemical assays were performed. Agmatine treatment for 21 days was able to abolish the corticosterone-induced depressive-like behavior and the alterations in the immunocontent of mature BDNF and synaptotagmin I, and in the serotonin and glutamate levels. Agmatine also abolished the corticosterone-induced changes in the morphology of astrocytes and microglia in CA1 region of hippocampus. In addition, agmatine treatment in control mice increased noradrenaline, serotonin, and dopamine levels, CREB phosphorylation, mature BDNF and synaptotagmin I immunocontents, and reduced pro-BDNF immunocontent in the hippocampus. Agmatine's ability to produce an antidepressant-like effect was abolished in Nrf2 (-/-) mice. The present results reinforce the participation of Nrf2 in the antidepressant-like effect produced by agmatine and expand literature data concerning its mechanisms of action.

  9. Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction

    Science.gov (United States)

    Raasch, Walter; Schäfer, Ulrich; Qadri, Fatimunnisa; Dominiak, Peter

    2002-01-01

    Since agmatine has been identified as a clonidine displacing substance (CDS), the aim of this study was to investigate whether agmatine can mimic CDS-induced cardiovascular reactions in organ bath experiments, pithed spontaneously hypertensive rats (SHR) and anaesthetized SHR.Intravenously-administered agmatine significantly reduced the blood pressure and heart rate of anaesthetized SHR at doses higher than 1 and 3 mg kg−1, respectively. These effects are probably mediated via central mechanisms, since there was an approximate 8 fold rightward shift of the dose-response curve in the pithed SHR (indicating a weakened cardiovascular effect). Moreover, in organ bath experiments, agmatine failed to alter the contractility of intact or endothelium-denuded aortal rings. When agmatine was administered i.c.v. to anaesthetized SHR, blood pressure was increased without any alteration of heart rate, whereas blood pressure was unchanged and heart rate was increased after injection into the 4th brain ventricle. This suggests that haemodynamic reaction patterns after central application are related to distinct influences on central cardiovascular mechanisms.Agmatine reduces noradrenaline release in pithed SHR while α2-adrenoceptors are irreversibly blocked with phenoxybenzamine, but not while I1-binding sites are selectively blocked with AGN192403. This suggests that agmatine may modulate noradrenaline release in the same way that clonidine does, i.e. via imidazoline binding sites; this involves a reduction in sympathetic tone which in turn reduces blood pressure and heart rate.Finally, CDS-like cardiovascular activity appears not to be due to agmatine, since (i) blood pressure in anaesthetized SHR is decreased by agmatine and clonidine, and (ii) agmatine did not antagonize the blood pressure reaction to clonidine in pithed or anaesthetized SHR. PMID:11834614

  10. Agmatine induces Nrf2 and protects against corticosterone effects in hippocampal neuronal cell line.

    Science.gov (United States)

    Freitas, Andiara E; Egea, Javier; Buendía, Izaskun; Navarro, Elisa; Rada, Patricia; Cuadrado, Antonio; Rodrigues, Ana Lúcia S; López, Manuela G

    2015-01-01

    Hyperactivation of the hypothalamic-pituitary-adrenal axis is a common finding in major depression; this may lead to increased levels of cortisol, which are known to cause oxidative stress imbalance and apoptotic neuronal cell death, particularly in the hippocampus, a key region implicated in mood regulation. Agmatine, an endogenous metabolite of L-arginine, has been proposed for the treatment of major depression. Corticosterone induced apoptotic cell death and increased ROS production in cultured hippocampal neuronal cells, effects that were abolished in a concentration- and time-dependent manner by agmatine. Interestingly, the combination of sub-effective concentrations of agmatine with fluoxetine or imipramine afforded synergic protection. The neuroprotective effect of agmatine was abolished by yohimbine (α2-adrenoceptor antagonist), ketanserin (5-HT2A receptor antagonist), LY294002 (PI3K inhibitor), PD98059 (MEK1/2 inhibitor), SnPP (HO-1 inhibitor), and cycloheximide (protein synthesis inhibitor). Agmatine increased Akt and ERK phosphorylation and induced the transcription factor Nrf2 and the proteins HO-1 and GCLc; induction of these proteins was prevented by yohimbine, ketanserin, LY294002, and PD98059. In conclusion, agmatine affords neuroprotection against corticosterone effects by a mechanism that implicates Nrf2 induction via α2-adrenergic and 5-HT2A receptors, Akt and ERK pathways, and HO-1 and GCLc expression.

  11. Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system

    Science.gov (United States)

    Aricioglu, Feyza; Means, Andrea; Regunathan, Soundar

    2010-01-01

    Agmatine is an endogenous amine derived from arginine that potentiates morphine analgesia and blocks symptoms of naloxone-precipitated morphine withdrawal in rats. In this study, we sought to determine whether treatment with agmatine during the development of morphine dependence inhibits the withdrawal symptoms and that the effect is mediated by cAMP system. Exposure of rats to morphine for 7 days resulted in marked naloxone-induced withdrawal symptoms and agmatine treatment along with morphine significantly decreasing the withdrawal symptoms. The levels of cAMP were markedly increased in morphine-treated rat brain slices when incubated with naloxone and this increase was significantly reduced in rats treated with morphine and agmatine. The induction of tyrosine hydroxylase after morphine exposure was also reduced in locus coeruleus when agmatine was administered along with morphine. We conclude that agmatine reduces the development of dependence to morphine and that this effect is probably mediated by the inhibition of cAMP signaling pathway during chronic morphine exposure. PMID:15541421

  12. Agmatine Ameliorates High Glucose-Induced Neuronal Cell Senescence by Regulating the p21 and p53 Signaling.

    Science.gov (United States)

    Song, Juhyun; Lee, Byeori; Kang, Somang; Oh, Yumi; Kim, Eosu; Kim, Chul-Hoon; Song, Ho-Taek; Lee, Jong Eun

    2016-02-01

    Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-β-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia.

  13. Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

    OpenAIRE

    Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

    2005-01-01

    Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that...

  14. Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test.

    Science.gov (United States)

    Kotagale, Nandkishor R; Tripathi, Sunil J; Aglawe, Manish M; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

    2013-06-01

    Although bupropion has been widely used in the treatment of depression, the precise mechanism of its therapeutic actions is not fully understood. The present study investigated the role of agmatine in an antidepressant like effect of bupropion in mouse forced swim test. The antidepressant like effect of bupropion was potentiated by pretreatment with agmatine (10-20mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz., l-arginine (40 μg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-α-difluoromethyl ornithine hydrochloride, DFMO (12.5 μg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 μg/mouse, icv) and agmatinase inhibitor, arcaine (50 μg/mouse, icv) as well as imidazoline I1 receptor agonists, moxonidine (0.25mg/kg, ip) and clonidine (0.015 mg/kg, ip) and imidazoline I2 receptor agonist, 2-(2-benzofuranyl)-2-imidazoline hydrochloride, 2-BFI (5mg/kg, ip). Conversely, prior administration of I1 receptor antagonist, efaroxan (1mg/kg, ip) and I2 receptor antagonist, idazoxan (0.25mg/kg, ip) blocked the antidepressant like effect of bupropion and its synergistic combination with agmatine. These results demonstrate involvement of agmatine in the antidepressant like effect of bupropion and suggest agmatine and imidazoline receptors as a potential therapeutic target for the treatment of depressive disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

    Science.gov (United States)

    Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

    2014-04-01

    The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Distribution, Regulation and Role of the Agmatine Deiminase System in Mutans Streptococci

    OpenAIRE

    Griswold, Ann R.; Nascimento, Marcelle M.; Burne, Robert A.

    2009-01-01

    The agmatine deiminase system was identified in seven strains of mutans streptococci. Genes encoding the AgDS of Streptococcus rattus FA-1 were sequenced and found to share homology with the agu genes of Streptococcus mutans UA159. Agmatine inhibited bacterial growth, suggesting that the AgDS degrades a deleterious substance into useful compounds.

  17. Imidazoline binding sites mediates anticompulsive-like effect of agmatine in marble-burying behavior in mice.

    Science.gov (United States)

    Dixit, Madhura P; Thakre, Prajwal P; Pannase, Akshay S; Aglawe, Manish M; Taksande, Brijesh G; Kotagale, Nandkishor R

    2014-06-05

    Agmatine is a cationic amine formed by decarboxylation of l-arginine by the mitochondrial enzyme arginine decarboxylase and widely distributed in mammalian brain. Although the precise function of endogenous agmatine has been largely remained unclear, its exogenous administration demonstrated beneficial effects in several neurological and psychiatric disorders. This study was planned to examine the role of imidazoline binding sites in the anticompulsive-like effect of agmatine on marble-burying behavior. Agmatine (20 and 40mg/kg, ip), mixed imidazoline I1/α2 agonists clonidine (60µg/kg, ip) and moxonidine (0.25mg/kg, ip), and imidazoline I2 agonist 2- BFI (10mg/kg, ip) showed significant inhibition of marble burying behavior in mice. In combination studies, the anticompulsive-like effect of agmatine (10mg/kg, ip) was significantly potentiated by prior administration of moxonidine (0.25mg/kg, ip) or clonidine (30µg/kg,) or 2-BFI (5mg/kg, ip). Conversely, efaroxan (1mg/kg, ip), an I1 antagonist and idazoxan (0.25mg/kg, ip), an I2 antagonist completely blocked the anticompulsive-like effect of agmatine (10mg/kg, ip). These drugs at doses used here did not influence the basal locomotor activity in experimental animals. These results clearly indicated the involvement of imidazoline binding sites in anti-compulsive-like effect of agmatine. Thus, imidazoline binding sites can be explored further as novel therapeutic target for treatment of anxiety and obsessive compulsive disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line

    Directory of Open Access Journals (Sweden)

    Kim Chan

    2007-10-01

    Full Text Available Abstract Background Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5. RGC-5 cells were cultured in a closed hypoxic chamber (5% O2 with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38 and nuclear factor-kappa B (NF-κB were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF, a well-known protective neurotrophin for retinal ganglion cells. Results After 48 hours of hypoxic culture, the LDH assay showed 52.3% cell loss, which was reduced to 25.6% and 30.1% when agmatine and BDNF were administered, respectively. This observed cell loss was due to apoptotic cell death, as established by annexin V and caspase-3 assays. Although total expression of MAPKs and NF-κB was not influenced by hypoxic injury, phosphorylation of these two proteins was increased. Agmatine reduced phosphorylation of JNK and NF-κB, while BDNF suppressed phosphorylation of ERK and p38. Conclusion Our results show that agmatine has neuroprotective effects against hypoxia-induced retinal ganglion cell damage in RGC-5 cells and that its effects may act through the JNK and NF-κB signaling pathways. Our data suggest that agmatine may lead to a novel therapeutic strategy to reduce retinal ganglion cell injury related to hypoxia.

  19. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line

    Science.gov (United States)

    Hong, Samin; Lee, Jong Eun; Kim, Chan Yun; Seong, Gong Je

    2007-01-01

    Background Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5). RGC-5 cells were cultured in a closed hypoxic chamber (5% O2) with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH) assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38) and nuclear factor-kappa B (NF-κB) were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF), a well-known protective neurotrophin for retinal ganglion cells. Results After 48 hours of hypoxic culture, the LDH assay showed 52.3% cell loss, which was reduced to 25.6% and 30.1% when agmatine and BDNF were administered, respectively. This observed cell loss was due to apoptotic cell death, as established by annexin V and caspase-3 assays. Although total expression of MAPKs and NF-κB was not influenced by hypoxic injury, phosphorylation of these two proteins was increased. Agmatine reduced phosphorylation of JNK and NF-κB, while BDNF suppressed phosphorylation of ERK and p38. Conclusion Our results show that agmatine has neuroprotective effects against hypoxia-induced retinal ganglion cell damage in RGC-5 cells and that its effects may act through the JNK and NF-κB signaling pathways. Our data suggest that agmatine may lead to a novel therapeutic strategy to reduce retinal ganglion cell injury related to hypoxia. PMID:17908330

  20. Neuropeptide Y in the central nucleus of amygdala regulates the anxiolytic effect of agmatine in rats.

    Science.gov (United States)

    Taksande, Brijesh G; Kotagale, Nandkishor R; Gawande, Dinesh Y; Bharne, Ashish P; Chopde, Chandrabhan T; Kokare, Dadasaheb M

    2014-06-01

    In the present study, modulation of anxiolytic action of agmatine by neuropeptide Y (NPY) in the central nucleus of amygdala (CeA) is evaluated employing Vogel's conflict test (VCT) in rats. The intra-CeA administration of agmatine (0.6 and 1.2µmol/rat), NPY (10 and 20pmol/rat) or NPY Y1/Y5 receptors agonist [Leu(31), Pro(34)]-NPY (30 and 60pmol/rat) significantly increased the number of punished drinking licks following 15min of treatment. Combination treatment of subeffective dose of NPY (5pmol/rat) or [Leu(31), Pro(34)]-NPY (15pmol/rat) and agmatine (0.3µmol/rat) produced synergistic anxiolytic-like effect. However, intra-CeA administration of selective NPY Y1 receptor antagonist, BIBP3226 (0.25 and 0.5mmol/rat) produced anxiogenic effect. In separate set of experiment, pretreatment with BIBP3226 (0.12mmol/rat) reversed the anxiolytic effect of agmatine (0.6µmol/rat). Furthermore, we evaluated the effect of intraperitoneal injection of agmatine (40mg/kg) on NPY-immunoreactivity in the nucleus accumbens shell (AcbSh), lateral part of bed nucleus of stria terminalis (BNSTl) and CeA. While agmatine treatment significantly decreased the fibers density in BNSTl, increase was noticed in AcbSh. In addition, agmatine reduced NPY-immunoreactive cells in the AcbSh and CeA. Immunohistochemical data suggest the enhanced transmission of NPY from the AcbSh and CeA. Taken together, this study suggests that agmatine produced anxiolytic effect which might be regulated via modulation of NPYergic system particularly in the CeA. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  1. Transport of Diamines by Enterococcus faecalis Is Mediated by an Agmatine-Putrescine Antiporter

    NARCIS (Netherlands)

    Driessen, Arnold J.M.; Smid, Eddy J.; Konings, Wilhelmus

    1988-01-01

    Enterococcusfaecalis ATCC 11700 is able to use arginine and the diamine agmatine as a sole energy source. Via the highly homologous deiminase pathways, arginine and agmatine are converted into CO2, NH3, and the end products ornithine and putrescine, respectively. In the arginine deiminase pathway,

  2. Sub-chronic agmatine treatment modulates hippocampal neuroplasticity and cell survival signaling pathways in mice.

    Science.gov (United States)

    Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Moretti, Morgana; Ribeiro, Camille M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    2014-11-01

    Agmatine is an endogenous neuromodulator which, based on animal and human studies, is a putative novel antidepressant drug. In this study, we investigated the ability of sub-chronic (21 days) p.o. agmatine administration to produce an antidepressant-like effect in the tail suspension test and examined the hippocampal cell signaling pathways implicated in such an effect. Agmatine at doses of 0.01 and 0.1 mg/kg (p.o.) produced a significant antidepressant-like effect in the tail suspension test and no effect in the open-field test. Additionally, agmatine (0.001-0.1 mg/kg, p.o.) increased the phosphorylation of protein kinase A substrates (237-258% of control), protein kinase B/Akt (Ser(473)) (116-127% of control), glycogen synthase kinase-3β (Ser(9)) (110-113% of control), extracellular signal-regulated kinases 1/2 (119-137% and 121-138% of control, respectively) and cAMP response elements (Ser(133)) (127-152% of control), and brain-derived-neurotrophic factor (137-175% of control) immunocontent in a dose-dependent manner in the hippocampus. Agmatine (0.001-0.1 mg/kg, p.o.) also reduced the c-jun N-terminal kinase 1/2 phosphorylation (77-71% and 65-51% of control, respectively). Neither protein kinase C nor p38(MAPK) phosphorylation was altered under any experimental conditions. Taken together, the present study extends the available data on the mechanisms that underlie the antidepressant action of agmatine by showing an antidepressant-like effect following sub-chronic administration. In addition, our results are the first to demonstrate the ability of agmatine to elicit the activation of cellular signaling pathways associated with neuroplasticity/cell survival and the inhibition of signaling pathways associated with cell death in the hippocampus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Effect of agmatine on locus coeruleus neuron activity: possible involvement of nitric oxide

    Science.gov (United States)

    Ruiz-Durántez, Eduardo; Ruiz-Ortega, José A; Pineda, Joseba; Ugedo, Luisa

    2002-01-01

    To investigate whether agmatine (the proposed endogenous ligand for imidazoline receptors) controls locus coeruleus neuron activity and to elucidate its mechanism of action, we used single-unit extracellular recording techniques in anaesthetized rats. Agmatine (10, 20 and 40 μg, i.c.v.) increased in a dose-related manner the firing rate of locus coeruleus neurons (maximal increase: 95±13% at 40 μg). I1-imidazoline receptor ligands stimulate locus coeruleus neuron activity through an indirect mechanism originated in the paragigantocellularis nucleus via excitatory amino acids. However, neither electrolytic lesions of the paragigantocellularis nucleus nor pretreatment with the excitatory amino acid antagonist kynurenic acid (1 μmol, i.c.v.) modified agmatine effect (10 μg, i.c.v.). After agmatine administration (20 μg, i.c.v.), dose-response curves for the effect of clonidine (0.625 – 10 μg kg−1 i.v.) or morphine (0.3 – 4.8 mg kg−1 i.v.) on locus coeruleus neurons were not different from those obtained in the control groups. Pretreatment with the nitric oxide synthase inhibitors Nω-nitro-L-arginine (10 μg, i.c.v.) or Nω-nitro-L-arginine methyl ester (100 μg, i.c.v.) but not with the less active stereoisomer Nω-nitro-D-arginine methyl ester (100 μg, i.c.v.) completely blocked agmatine effect (10 and 40 μg, i.c.v.). Similarly, when agmatine (20 pmoles) was applied into the locus coeruleus there was an increase that was blocked by Nω-nitro-L-arginine methyl ester (100 μg, i.c.v.) in the firing rate of the locus coeruleus neurons (maximal increase 53±11% and 14±10% before and after nitric oxide synthase inhibition, respectively). This study demonstrates that agmatine stimulates the firing rate of locus coeruleus neurons via a nitric oxide synthase-dependent mechanism located in this nucleus. PMID:11877321

  4. Agmatine protects Müller cells from high-concentration glucose-induced cell damage via N-methyl-D-aspartic acid receptor inhibition.

    Science.gov (United States)

    Han, Ning; Yu, Li; Song, Zhidu; Luo, Lifu; Wu, Yazhen

    2015-07-01

    Neural injury is associated with the development of diabetic retinopathy. Müller cells provide structural and metabolic support for retinal neurons. High glucose concentrations are known to induce Müller cell activity. Agmatine is an endogenous polyamine, which is enzymatically formed in the mammalian brain and has exhibited neuroprotective effects in a number of experimental models. The aims of the present study were to investigate whether agmatine protects Müller cells from glucose-induced damage and to explore the mechanisms underlying this process. Lactate dehydrogenase activity and tumor necrosis factor-α mRNA expression were significantly reduced in Müller cells exposed to a high glucose concentration, following agmatine treatment, compared with cells not treated with agmatine. In addition, agmatine treatment inhibited glucose-induced Müller cell apoptosis, which was associated with the regulation of Bax and Bcl-2 expression. Agmatine treatment suppressed glucose-induced phosphorylation of mitogen-activated protein kinase (MAPK) protein in Müller cells. The present study demonstrated that the protective effects of agmatine on Müller cells were inhibited by N-methyl-D-aspartic acid (NMDA). The results of the present study suggested that agmatine treatment protects Müller cells from high-concentration glucose-induced cell damage. The underlying mechanisms may relate to the anti-inflammatory and antiapoptotic effects of agmatine, as well as to the inhibition of the MAPK pathway, via NMDA receptor suppression. Agmatine may be of use in the development of novel therapeutic approaches for patients with diabetic retinopathy.

  5. Agmatine enhances the antidepressant-like effect of lithium in mouse forced swimming test through NMDA pathway.

    Science.gov (United States)

    Mohseni, Gholmreza; Ostadhadi, Sattar; Imran-Khan, Muhammad; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Haddadi, Nazgol-Sadat; Dehpour, Ahmad-Reza

    2017-04-01

    Depression is one the world leading global burdens leading to various comorbidities. Lithium as a mainstay in the treatment of depression is still considered gold standard treatment. Similar to lithium another agent agmatine has also central protective role against depression. Since, both agmatine and lithium modulate various effects through interaction with NMDA receptor, therefore, in current study we aimed to investigate the synergistic antidepressant-like effect of agmatine with lithium in mouse force swimming test. Also to know whether if such effect is due to interaction with NMDA receptor. In our present study we found that when potent dose of lithium (30mg/kg) was administered, it significantly decreased the immobility time. Also, when subeffective dose of agmatine (0.01mg/kg) was coadministered with subeffective dose of lithium (3mg/kg), it potentiated the antidepressant-like effect of subeffective dose of lithium. For the involvement of NMDA receptor in such effect, we administered NMDA receptor antagonist MK-801 (0.05mg/kg) with a combination of subeffective dose of lithium (3mg/kg) and agmatine (0.001mg/kg). A significant antidepressant-like effect was observed. Furthermore, when subeffective dose (50 and 75mg/kg) of NMDA was given it inhibited the synergistic effect of agmatine (0.01mg/kg) with lithium (3mg/kg). Hence, our finding demonstrate that agmatine have synergistic effect with lithium which is mediated by NMDA receptor pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Interactions of nitric oxide with α2 -adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine.

    Science.gov (United States)

    Shelkar, Gajanan P; Gakare, Sukanya G; Chakraborty, Suwarna; Dravid, Shashank M; Ugale, Rajesh R

    2016-09-01

    Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α-adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra-LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S-nitrosoglutathione, non-specific (L-NAME) and specific NOS inhibitors (L-NIL, 7-NI, L-NIO), the α2 -adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra-LC before agmatine. Intra-hippocampal injections of the NMDA antagonist, MK-801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. Agmatine (intra-LC or i.p.) facilitated memory retrieval in the IA test. S-nitrosoglutathione potentiated, while L-NAME and L-NIO decreased, these effects of agmatine. L-NIL and 7-NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S-nitrosoglutathione and yohimbine were blocked by intra-hippocampal MK-801. Agmatine increased the population of TH- and eNOS-immunoreactive elements in the LC. The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC. © 2016 The British Pharmacological Society.

  7. Effects of Agmatine on Depressive-Like Behavior Induced by Intracerebroventricular Administration of 1-Methyl-4-phenylpyridinium (MPP(+)).

    Science.gov (United States)

    Moretti, Morgana; Neis, Vivian Binder; Matheus, Filipe Carvalho; Cunha, Mauricio Peña; Rosa, Priscila Batista; Ribeiro, Camille Mertins; Rodrigues, Ana Lúcia S; Prediger, Rui Daniel

    2015-10-01

    Considering that depression is a common non-motor comorbidity of Parkinson's disease and that agmatine is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system disorders, this study investigated the antidepressant-like effect of agmatine in mice intracerebroventricularly (i.c.v.) injected with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)). Male C57BL6 mice were treated with agmatine (0.0001, 0.1 or 1 mg/kg) and 60 min later the animals received an i.c.v. injection of MPP(+) (1.8 µg/site). Twenty-four hours after MPP(+) administration, immobility time, anhedonic behavior, and locomotor activity were evaluated in the tail suspension test (TST), splash test, and open field test, respectively. Using Western blot analysis, we investigated the putative modulation of MPP(+) and agmatine on striatal and frontal cortex levels of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF). MPP(+) increased the immobility time of mice in the TST, as well as induced an anhedonic-like behavior in the splash test, effects which were prevented by pre-treatment with agmatine at the three tested doses. Neither drug, alone or in combination, altered the locomotor activity of mice. I.c.v. administration of MPP(+) increased the striatal immunocontent of TH, an effect prevented by the three tested doses of agmatine. MPP(+) and agmatine did not alter the immunocontent of BDNF in striatum and frontal cortex. These results demonstrate for the first time the antidepressant-like effects of agmatine in an animal model of depressive-like behavior induced by the dopaminergic neurotoxin MPP(+).

  8. Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.

    Science.gov (United States)

    Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

    2016-08-26

    Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Agmatine protects against zymosan-induced acute lung injury in mice by inhibiting NF-κB-mediated inflammatory response.

    Science.gov (United States)

    Li, Xuanfei; Liu, Zheng; Jin, He; Fan, Xia; Yang, Xue; Tang, Wanqi; Yan, Jun; Liang, Huaping

    2014-01-01

    Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson's disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM) challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-α, IL-1β, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of IκB and subsequently blocked the activation of nuclear factor (NF)-κB induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-κB signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI.

  10. Structure and stability of complexes of agmatine with some functional receptor residues of proteins

    Science.gov (United States)

    Remko, Milan; Broer, Ria; Remková, Anna; Van Duijnen, Piet Th.

    2017-04-01

    The paper reports the results of a theoretical study of the conformational behavior and basicity of biogenic amine agmatine. The complexes modelling of agmatine - protein interaction are also under scrutiny of our investigation using the Becke3LYP and B97D levels of the density functional theory. The relative stabilities (Gibbs energies) of individual complexes are by both DFT methods described equally. Hydration has a dramatic effect on the hydrogen bonded complexes studied. The pairing acidic carboxylate group with different agmatine species resulted in charged hydrogen bond complexes containing negatively charged acetate species acting as proton acceptors.

  11. Agmatine ameliorates lipopolysaccharide induced depressive-like behaviour in mice by targeting the underlying inflammatory and oxido-nitrosative mediators.

    Science.gov (United States)

    Gawali, Nitin B; Bulani, Vipin D; Chowdhury, Amrita A; Deshpande, Padmini S; Nagmoti, Dnyaneshwar M; Juvekar, Archana R

    2016-10-01

    Experimental and clinical evidence indicates that pro-inflammatory cytokines, oxidative stress and brain-derived neurotrophic factor (BDNF) signalling mechanisms play a role in the pathophysiology of depression. Agmatine is a neurotransmitter and/or neuromodulator that has emerged as a potential agent to manage diverse central nervous system disorders. Agmatine has been shown to exert antidepressant-like effect. The present study investigated ability of agmatine to abolish the depressive-like behaviour induced by the administration of the lipopolysaccharide (LPS) in mice. Agmatine (20 and 40mg/kg) was administered daily for 7days, then the mice were challenged with saline or LPS (0.83mg/kg; i.p.) on the 7th day. After 24h of LPS administration we tested mice for depressive-like behaviour. LPS treated animals presented an increase in immobility time in the forced-swim test (FST), tail suspension test (TST) which was reversed by agmatine pre-treatment (20 and 40mg/kg). Oxidative/nitrosative stress evoked by LPS was ameliorated by both doses of agmatine in hippocampus (HC) and prefrontal cortex (PFC). Administration of LPS caused an increase in interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas BDNF was down regulated in the HC. Agmatine pre-treatment at 40mg/kg ameliorated LPS-induced neuroinflammation by attenuating brain IL-1β and TNF-α level. In addition, agmatine pre-treatment also up-regulated the BDNF level in the HC. The present study shows that pre-treatment of agmatine is able to abolish the behavioural responses in the FST and TST elicited by the LPS-induced model of depression that may depend on the inhibition of pro-inflammatory mediators, reduction of oxidative stress as well as activation neuroplasticity-related signalling in mice, suggesting that agmatine may constitute an monotherapy/adjuvant for the management of depression associated with inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.

    Science.gov (United States)

    Turan, Inci; Ozacmak, Hale Sayan; Ozacmak, V Haktan; Barut, Figen; Araslı, Mehmet

    2017-11-15

    Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Transcriptome profiling of Lactococcus lactis subsp. cremoris CECT 8666 in response to agmatine

    NARCIS (Netherlands)

    Del Rio, Beatriz; Redruello, Begoña; Martin, M Cruz; Fernandez, Maria; de Jong, Anne; Kuipers, Oscar P; Ladero, Victor; Alvarez, Miguel A

    2016-01-01

    The dairy strain Lactococcus lactis subsp. cremoris CECT 8666 (formerly GE2-14) synthesizes the biogenic amine putrescine from agmatine via the agmatine deiminase (AGDI) pathway [1]. The AGDI cluster of L. lactis is composed by five genes aguR, aguB, aguD, aguA and aguC. The last four genes are

  14. Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

    Science.gov (United States)

    Sameer, Shaikh M; Chakraborty, Suwarna S; Ugale, Rajesh R

    2013-04-01

    The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents. Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1.25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively. Agmatine inhibited the acquisition but not the expression of ethanol CPP. Furthermore, both the I₁ receptor antagonist, efaroxan (9 mg/kg) and the I₂ receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition. In contrast, the I₂ receptor agonist, 2-BFI (5 mg/kg) and I₁ receptor agonist, moxonidine (0.4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP. Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity. Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I₁ or I₂) receptors. In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

  15. Interactions of nitric oxide with α2‐adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine

    Science.gov (United States)

    Shelkar, Gajanan P; Gakare, Sukanya G; Chakraborty, Suwarna; Dravid, Shashank M

    2016-01-01

    Background and Purpose Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α‐adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. Experimental Approach The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra‐LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S‐nitrosoglutathione, non‐specific (L‐NAME) and specific NOS inhibitors (L‐NIL, 7‐NI, L‐NIO), the α2‐adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra‐LC before agmatine. Intra‐hippocampal injections of the NMDA antagonist, MK‐801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. Key Results Agmatine (intra‐LC or i.p.) facilitated memory retrieval in the IA test. S‐nitrosoglutathione potentiated, while L‐NAME and L‐NIO decreased, these effects of agmatine. L‐NIL and 7‐NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S‐nitrosoglutathione and yohimbine were blocked by intra‐hippocampal MK‐801. Agmatine increased the population of TH‐ and eNOS‐immunoreactive elements in the LC. Conclusions and Implications The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC. PMID:27273730

  16. Effect of Agmatine Sulfate on Modulation of Matrix Metalloproteinases via PI3K/Akt-1 in HT1080 Cells.

    Science.gov (United States)

    Kim, Hyejeong; Kim, Moon-Moo

    2017-11-01

    The purpose of this study was to investigate the mechanism by which agmatine sulfate induces an anti-metastatic effect in human HT1080 fibrosarcoma cells, by affecting matrix metalloproteinases (MMPs). For the experiments, we used a non-toxic concentration of agmatine, below 512 μM, that was determined using an MTT assay. The effect of agmatine sulfate on metastasis was gelatin zymography, western blot, immunofluorescence staining and cell invasion assay. Agmatine sulfate inhibited MMP-2 activity stimulated by phenazine methosulfate (PMS). Furthermore, the expression level of MMP-2 stimulated by PMS, was decreased, but the expression level of TIMP-1 was increased in the presence of agmatine sulfate. Moreover, it was observed that the expression levels of ERK and p38 were increased, but those of PI3K and Akt-1 associated with the modulation of MMP-2 were decreased in this study. Furthermore, agmatine sulfate decreased the invasion level of human fibrosarcoma cells stimulated by VEGF. These results suggest that agmatine sulfate could inhibit metastasis through inhibition of MMP-2 via the PI3K/Akt-1 signaling pathway. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: modulation by hippocampal sigma receptors.

    Science.gov (United States)

    Kotagale, Nandkishor Ramdas; Shirbhate, Saurabh Haridas; Shukla, Pradeep; Ugale, Rajesh Ramesh

    2013-08-15

    Present study investigated the influence of the sigma (σ₁ and σ₂) receptors within hippocampus on the agmatine induced antinociception in neuropathic rats. Animals were subjected to sciatic nerve ligation for induction of neuropathic pain and observed the paw withdrawal latency in response to thermal hyperalgesia, cold allodynia and the mechanical hyperalgesia. Intrahippocampal (i.h.) as well as intraperitoneal (i.p.) administration of agmatine attenuated neuropathic pain in sciatic nerve ligated rats. Intrahippocampal administration of σ₁ agonist (+)-pentazocine or σ₂ agonist PB28 sensitized whereas, σ₁ antagonist BD1063 or σ₂ antagonist SM21 potentiated antinociceptive effect of agmatine. The behavioral effects correlated with hippocampal tumor necrosis factor-α (TNF-α) levels observed by western blot analysis. These results suggest that both the σ₁ and σ₂ receptor subunits within hippocampus play an important role in antinociceptive action of agmatine against neuropathic pain. © 2013 Elsevier B.V. All rights reserved.

  18. Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway.

    Science.gov (United States)

    Gawali, Nitin B; Bulani, Vipin D; Gursahani, Malvika S; Deshpande, Padmini S; Kothavade, Pankaj S; Juvekar, Archana R

    2017-05-15

    Agmatine, a neurotransmitter/neuromodulator, has shown to exert numerous effects on the CNS. Chronic stress is a risk factor for development of depression, anxiety and deterioration of cognitive performance. Compelling evidences indicate an involvement of nitric oxide (NO) pathway in these disorders. Hence, investigation of the beneficial effects of agmatine on chronic unpredictable mild stress (CUMS)-induced depression, anxiety and cognitive performance with the involvement of nitrergic pathway was undertaken. Mice were subjected to a battery of stressors for 28days. Agmatine (20 and 40mg/kg, i.p.) alone and in combination with NO modulators like L-NAME (15mg/kg, i.p.) and l-arginine (400mg/kg i.p.) were administered daily. The results showed that 4-weeks CUMS produces significant depression and anxiety-like behaviour. Stressed mice have also shown a significant high serum corticosterone (CORT) and low BDNF level. Chronic treatment with agmatine produced significant antidepressant-like behaviour in forced swim test (FST) and sucrose preference test, whereas, anxiolytic-like behaviour in elevated plus maze (EPM) and open field test (OFT) with improved cognitive impairment in Morris water maze (MWM). Furthermore, agmatine administration reduced the levels of acetylcholinesterase and oxidative stress markers. In addition, agmatine treatment significantly increased the BDNF level and inhibited serum CORT level in stressed mice. Treatment with L-NAME (15mg/kg) potentiated the effect of agmatine whereas l-arginine abolished the anxiolytic, antidepressant and neuroprotective effects of agmatine. Agmatine showed marked effect on depression and anxiety-like behaviour in mice through nitrergic pathway, which may be related to modulation of oxidative-nitrergic stress, CORT and BDNF levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Acute agmatine administration, similar to ketamine, reverses depressive-like behavior induced by chronic unpredictable stress in mice.

    Science.gov (United States)

    Neis, Vivian B; Bettio, Luis E B; Moretti, Morgana; Rosa, Priscila B; Ribeiro, Camille M; Freitas, Andiara E; Gonçalves, Filipe M; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants. The ability of agmatine to reverse CUS-induced behavioral and biochemical alterations was evaluated and compared with those elicited by the fast-acting antidepressant (ketamine) and the conventional antidepressant (fluoxetine). After exposed to CUS for 14days, mice received a single oral dose of agmatine (0.1mg/kg), ketamine (1mg/kg) or fluoxetine (10mg/kg), and were submitted to behavioral evaluation after 24h. The exposure to CUS caused an increased immobility time in the tail suspension test (TST) but did not change anhedonic-related parameters in the splash test. Our findings provided evidence that, similarly to ketamine, agmatine is able to reverse CUS-induced depressive-like behavior in the TST. Western blot analyses of prefrontal cortex (PFC) demonstrated that mice exposed to CUS and/or treated with agmatine, fluoxetine or ketamine did not present alterations in the immunocontent of synaptic proteins [i.e. GluA1, postsynaptic density protein 95 (PSD-95) and synapsin]. Altogether, our findings indicate that a single administration of agmatine is able to reverse behavioral alterations induced by CUS in the TST, suggesting that this compound may have fast-acting antidepressant-like properties. However, there was no alteration in the levels of synaptic proteins in the PFC, a result that need to be further investigated in other time points. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Involvement of α₂-adrenoceptors, imidazoline, and endothelin-A receptors in the effect of agmatine on morphine and oxycodone-induced hypothermia in mice.

    Science.gov (United States)

    Bhalla, Shaifali; Andurkar, Shridhar V; Gulati, Anil

    2013-10-01

    Potentiation of opioid analgesia by endothelin-A (ET(A)) receptor antagonist, BMS182874, and imidazoline receptor/α₂-adrenoceptor agonists such as clonidine and agmatine are well known. It is also known that agmatine blocks morphine hyperthermia in rats. However, the effect of agmatine on morphine or oxycodone hypothermia in mice is unknown. The present study was carried out to study the role of α₂-adrenoceptors, imidazoline, and ET(A) receptors in morphine and oxycodone hypothermia in mice. Body temperature was determined over 6 h in male Swiss Webster mice treated with morphine, oxycodone, agmatine, and combination of agmatine with morphine or oxycodone. Yohimbine, idazoxan, and BMS182874 were used to determine involvement of α₂-adrenoceptors, imidazoline, and ET(A) receptors, respectively. Morphine and oxycodone produced significant hypothermia that was not affected by α₂-adrenoceptor antagonist yohimbine, imidazoline receptor/α₂ adrenoceptor antagonist idazoxan, or ET(A) receptor antagonist, BMS182874. Agmatine did not produce hypothermia; however, it blocked oxycodone but not morphine-induced hypothermia. Agmatine-induced blockade of oxycodone hypothermia was inhibited by idazoxan and yohimbine. The blockade by idazoxan was more pronounced compared with yohimbine. Combined administration of BMS182874 and agmatine did not produce changes in body temperature in mice. However, when BMS182874 was administered along with agmatine and oxycodone, it blocked agmatine-induced reversal of oxycodone hypothermia. This is the first report demonstrating that agmatine does not affect morphine hypothermia in mice, but reverses oxycodone hypothermia. Imidazoline receptors and α₂-adrenoceptors are involved in agmatine-induced reversal of oxycodone hypothermia. Our findings also suggest that ET(A) receptors may be involved in blockade of oxycodone hypothermia by agmatine. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de

  1. Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Xuanfei Li

    2014-01-01

    Full Text Available Acute lung injury (ALI is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson’s disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-α, IL-1β, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of IκB and subsequently blocked the activation of nuclear factor (NF-κB induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-κB signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI.

  2. Possible involvement of neuropeptide Y Y1 receptors in antidepressant like effect of agmatine in rats.

    Science.gov (United States)

    Kotagale, Nandkishor R; Paliwal, Nikhilesh P; Aglawe, Manish M; Umekar, Milind J; Taksande, Brijesh G

    2013-09-01

    Agmatine and neuropeptide Y (NPY) are widely distributed in central nervous system and critically involved in modulation of depressive behavior in experimental animals. However their mutual interaction, if any, in regulation of depression remain largely unexplored. In the present study we explored the possible interaction between agmatine and neuropeptide Y in regulation of depression like behavior in forced swim test. We found that acute intracerebroventricular (i.c.v.) administration of agmatine (20-40μg/rat), NPY (5 and 10μg/rat) and NPY Y1 receptor agonist, [Leu(31), Pro(34)]-NPY (0.4 and 0.8ng/rat) dose dependently decreased immobility time in forced swim test indicating their antidepressant like effects. In combination studies, the antidepressant like effect of agmatine (10μg/rat) was significantly potentiated by NPY (1 and 5μg/rat, icv) or [Leu(31), Pro(34)]-NPY (0.2 and 0.4ng/rat, icv) pretreatment. Conversely, pretreatment of animals with NPY Y1 receptor antagonist, BIBP3226 (0.1ng/rat, i.c.v.) completely blocked the antidepressant like effect of agmatine (20-40μg/rat) and its synergistic effect with NPY (1μg/rat, icv) or [Leu(31), Pro(34)]-NPY (0.2ng/rat, icv). The results of the present study showed that, agmatine exerts antidepressant like effects via NPYergic system possibly mediated by the NPY Y1 receptor subtypes and suggest that interaction between agmatine and neuropeptide Y may be relevant to generate the therapeutic strategies for the treatment of depression. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Agmatine Protects Against 6-OHDA-Induced Apoptosis, and ERK and Akt/GSK Disruption in SH-SY5Y Cells.

    Science.gov (United States)

    Amiri, Esmat; Ghasemi, Rasoul; Moosavi, Maryam

    2016-08-01

    6-Hydroxydopamine (6-OHDA), a metabolite of dopamine is known to induce dopaminergic cell toxicity which makes that a suitable agent inducing an experimental model of Parkinson's disease (PD). Agmatine has been shown to protect against some cellular and animal PD models. This study was aimed to assess whether agmatine prevents 6-OHDA-induced SH-SY5Y cell death and if yes, then how it affects Akt/glycogen synthesis kinase-3β (GSK-3β) and extracellular signal-regulated kinases (ERK) signals. The cells were treated with different drugs, and their viability was examined via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay and morphological observation. Western blot studies were done to assess cleaved caspase-3, Akt/GSK-3β, and ERK proteins. 6-OHDA-induced cell death and caspase-3 cleavage, while agmatine prevented those changes. 6-OHDA also decreased the amount of phosphorylated Akt (pAkt)/Akt while increased GSK-3β activity which was prevented by agmatine. Additionally, this toxin increased pERK/ERK ratio which was averted again by agmatine. The PI3/Akt inhibitor, LY294002, impeded the changes induced by agmatine, while ERK inhibitor (PD98059) did not disturb the effects of agmatine, and by itself, it preserved the cells against 6-OHDA toxicity. This study revealed that agmatine is protective in 6-OHDA model of PD and affects Akt/GSK-3β and ERK pathways.

  4. Retinal protective effects of topically administered agmatine on ischemic ocular injury caused by transient occlusion of the ophthalmic artery

    Science.gov (United States)

    Hong, S.; Hara, H.; Shimazawa, M.; Hyakkoku, K.; Kim, C.Y.; Seong, G.J.

    2012-01-01

    Agmatine, an endogenous polyamine and putative neuromodulator, is known to have neuroprotective effects on various neurons in the central nervous system. We determined whether or not topically administered agmatine could reduce ischemic retinal injury. Transient ocular ischemia was achieved by intraluminal occlusion of the middle cerebral artery of ddY mice (30-35 g) for 2 h, which is known to also induce occlusion of the ophthalmic artery. In the agmatine group (N = 6), a 1.0 mM agmatine-containing ophthalmic solution was administered four times daily for 2 weeks before occlusion. In the control group (N = 6), a 0.1% hyaluronic acid ophthalmic solution was instilled at the same times. At 22 h after reperfusion, the eyeballs were enucleated and the retinal sections were stained by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Transient ocular ischemia induced apoptosis of retinal cells in the entire retinal layer, and topically administered agmatine can significantly reduce this ischemic retinal injury. The proportion of apoptotic cells was definitely decreased (P agmatine application effectively decreases retinal damage in an in vivo ocular ischemic injury model. This implies that agmatine is a good candidate as a direct neuroprotective agent for eyes with ocular ischemic diseases. PMID:22331138

  5. Mechanistic studies of the agmatine deiminase from Listeria monocytogenes.

    Science.gov (United States)

    Soares, Charles A; Knuckley, Bryan

    2016-06-01

    Listeria monocytogenes is a Gram-positive food-borne pathogen that is capable of living within extreme environments (i.e. low temperatures and pH). This ability to survive in such conditions may arise, at least in part, from agmatine catabolism via the agmatine deiminase system (AgDS). This catabolic pathway utilizes an agmatine deiminase (AgD) to hydrolyse agmatine into N-carbamoylputrescine (NCP), with concomitant release of ammonia, which increases the pH, thus mitigating the ill effects of the acidic environment. Given the potential significance of this pathway for cell survival, we set out to study the catalytic mechanism of the AgD encoded by L. monocytogenes In the present paper, we describe the catalytic mechanism employed by this enzyme based on pH profiles, pKa measurements of the active site cysteine and solvent isotope effects (SIE). In addition, we report inhibition of this enzyme by two novel AgD inhibitors, i.e. N-(4-aminobutyl)-2-fluoro-ethanimidamide (ABFA) and N-(4-aminobutyl)-2-chloro-ethanimidamide (ABCA). In contrast with other orthologues, L. monocytogenes AgD does not use the reverse protonation or substrate-assisted mechanism, which requires an active site cysteine with a high pKa and has been commonly seen in other members of the guanidinium-modifying enzyme (GME) superfamily. Instead, the L. monocytogenes AgD has a low pKa cysteine in the active site leading to an alternative mechanism of catalysis. This is the first time that this mechanism has been observed in the GME superfamily and is significant because it explains why previously developed mechanism-based inactivators of AgDs are ineffective against this orthologue. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  6. Multiple Two-Component Systems of Streptococcus mutans Regulate Agmatine Deiminase Gene Expression and Stress Tolerance▿

    OpenAIRE

    Liu, Yaling; Burne, Robert A.

    2009-01-01

    Induction of the agmatine deiminase system (AgDS) of Streptococcus mutans requires agmatine and is optimal at low pH. We show here that the VicRK, ComDE, and CiaRH two-component systems influence AgDS gene expression in response to acidic and thermal stresses.

  7. Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa

    Science.gov (United States)

    McCurtain, Jennifer L.; Gilbertsen, Adam J.; Kalstabakken, Kyle A.; Williams, Bryan J.

    2018-01-01

    A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled 13C5,15N4-agmatine (synthesized by decarboxylation of uniformly labeled 13C6,15N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,l,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1 % (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients. PMID:25957842

  8. Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa.

    Science.gov (United States)

    Dalluge, Joseph J; McCurtain, Jennifer L; Gilbertsen, Adam J; Kalstabakken, Kyle A; Williams, Bryan J

    2015-07-01

    A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled (13)C5,(15)N4-agmatine (synthesized by decarboxylation of uniformly labeled (13)C6,(15)N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1% (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients.

  9. Retinal protective effects of topically administered agmatine on ischemic ocular injury caused by transient occlusion of the ophthalmic artery

    Directory of Open Access Journals (Sweden)

    S. Hong

    2012-03-01

    Full Text Available Agmatine, an endogenous polyamine and putative neuromodulator, is known to have neuroprotective effects on various neurons in the central nervous system. We determined whether or not topically administered agmatine could reduce ischemic retinal injury. Transient ocular ischemia was achieved by intraluminal occlusion of the middle cerebral artery of ddY mice (30-35 g for 2 h, which is known to also induce occlusion of the ophthalmic artery. In the agmatine group (N = 6, a 1.0 mM agmatine-containing ophthalmic solution was administered four times daily for 2 weeks before occlusion. In the control group (N = 6, a 0.1% hyaluronic acid ophthalmic solution was instilled at the same times. At 22 h after reperfusion, the eyeballs were enucleated and the retinal sections were stained by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL. Transient ocular ischemia induced apoptosis of retinal cells in the entire retinal layer, and topically administered agmatine can significantly reduce this ischemic retinal injury. The proportion of apoptotic cells was definitely decreased (P < 0.001; Kruskal-Wallis test. Overall, we determined that topical agmatine application effectively decreases retinal damage in an in vivo ocular ischemic injury model. This implies that agmatine is a good candidate as a direct neuroprotective agent for eyes with ocular ischemic diseases.

  10. The Relationship among Tyrosine Decarboxylase and Agmatine Deiminase Pathways in Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Marta Perez

    2017-11-01

    Full Text Available Enterococci are considered mainly responsible for the undesirable accumulation of the biogenic amines tyramine and putrescine in cheeses. The biosynthesis of tyramine and putrescine has been described as a species trait in Enterococcus faecalis. Tyramine is formed by the decarboxylation of the amino acid tyrosine, by the tyrosine decarboxylase (TDC route encoded in the tdc cluster. Putrescine is formed from agmatine by the agmatine deiminase (AGDI pathway encoded in the agdi cluster. These biosynthesis routes have been independently studied, tyrosine and agmatine transcriptionally regulate the tdc and agdi clusters. The objective of the present work is to study the possible co-regulation among TDC and AGDI pathways in E. faecalis. In the presence of agmatine, a positive correlation between putrescine biosynthesis and the tyrosine concentration was found. Transcriptome studies showed that tyrosine induces the transcription of putrescine biosynthesis genes and up-regulates pathways involved in cell growth. The tyrosine modulation over AGDI route was not observed in the mutant Δtdc strain. Fluorescence analyses using gfp as reporter protein revealed PaguB (the promoter of agdi catabolic genes was induced by tyrosine in the wild-type but not in the mutant strain, confirming that tdc cluster was involved in the tyrosine induction of putrescine biosynthesis. This study also suggests that AguR (the transcriptional regulator of agdi was implicated in interaction among the two clusters.

  11. Phospholipase C-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate underlies agmatine-induced suppression of N-type Ca2+ channel in rat celiac ganglion neurons.

    Science.gov (United States)

    Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

    2017-03-04

    Agmatine suppresses peripheral sympathetic tone by modulating Cav2.2 channels in peripheral sympathetic neurons. However, the detailed cellular signaling mechanism underlying the agmatine-induced Cav2.2 inhibition remains unclear. Therefore, in the present study, we investigated the electrophysiological mechanism for the agmatine-induced inhibition of Cav2.2 current (I Cav2.2 ) in rat celiac ganglion (CG) neurons. Consistent with previous reports, agmatine inhibited I Cav2.2 in a VI manner. The agmatine-induced inhibition of the I Cav2.2 current was also almost completely hindered by the blockade of the imidazoline I 2 receptor (IR 2 ), and an IR 2 agonist mimicked the inhibitory effect of agmatine on I Cav2.2 , implying involvement of IR 2 . The agmatine-induced I Cav2.2 inhibition was significantly hampered by the blockade of G protein or phospholipase C (PLC), but not by the pretreatment with pertussis toxin. In addition, diC8-phosphatidylinositol 4,5-bisphosphate (PIP 2 ) dialysis nearly completely hampered agmatine-induced inhibition, which became irreversible when PIP 2 resynthesis was blocked. These results suggest that in rat peripheral sympathetic neurons, agmatine-induced IR 2 activation suppresses Cav2.2 channel voltage-independently, and that the PLC-dependent PIP 2 hydrolysis is responsible for the agmatine-induced suppression of the Cav2.2 channel. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Potentiation of oxycodone antinociception in mice by agmatine and BMS182874 via an imidazoline I2 receptor-mediated mechanism.

    Science.gov (United States)

    Bhalla, Shaifali; Ali, Izna; Lee, Hyaera; Andurkar, Shridhar V; Gulati, Anil

    2013-01-01

    The potentiation of oxycodone antinociception by BMS182874 (endothelin-A (ET(A)) receptor antagonist) and agmatine (imidazoline receptor/α(2)-adrenoceptor agonist) is well-documented. It is also known that imidazoline receptors but not α(2)-adrenoceptors are involved in potentiation of oxycodone antinociception by agmatine and BMS182874 in mice. However, the involvement of specific imidazoline receptor subtypes (I(1), I(2), or both) in this interaction is not clearly understood. The present study was conducted to determine the involvement of imidazoline I(1) and I(2) receptors in agmatine- and BMS182874-induced potentiation of oxycodone antinociception in mice. Antinociceptive (tail flick and hot-plate) latencies were determined in male Swiss Webster mice treated with oxycodone, agmatine, BMS182874, and combined administration of oxycodone with agmatine or BMS182874. Efaroxan (imidazoline I(1) receptor antagonist) and BU224 (imidazoline I(2) receptor antagonist) were used to determine the involvement of I(1) and I(2) imidazoline receptors, respectively. Oxycodone produced significant antinociceptive response in mice which was not affected by efaroxan but was blocked by BU224. Agmatine-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. Similarly, BMS182874-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. This is the first report demonstrating that BMS182874- or agmatine-induced enhancement of oxycodone antinociception is blocked by BU224 but not by efaroxan. We conclude that imidazoline I(2) receptors but not imidazoline I(1) receptors are involved in BMS182874- and agmatine-induced potentiation of oxycodone antinociception in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. The effect of agmatine on trichothecene type B and zearalenone production in Fusarium graminearum, F. culmorum and F. poae

    Directory of Open Access Journals (Sweden)

    Matias Pasquali

    2016-02-01

    Full Text Available Agmatine and other putrescines are known for being strong inducers of deoxynivalenol (DON production in Fusarium graminearum. Other important species produce DON and/or other trichothecene type B toxins (3 acetylated DON, 15 acetylated DON, Fusarenon-X, Nivalenol, such as F. culmorum and F. poae. In order to verify whether the mechanism of the regulation of trichothecene type B induction by agmatine is shared by different species of Fusarium, we tested the hypothesis on 19 strains belonging to 3 Fusarium species (F. graminearum, F. culmorum, F. poae with diverse genetic chemotypes (3ADON, 15ADON, NIV by measuring trichothecene B toxins such as DON, NIV, Fusarenon-X, 3ADON and 15ADON. Moreover, we tested whether other toxins like zearalenone were also boosted by agmatine. The trichothecene type B boosting effect was observed in the majority of strains (13 out of 19 in all the three species. Representative strains from all three genetic chemotypes were able to boost toxin production after agmatine treatment. We identified the non-responding strains to the agmatine stimulus, which may contribute to deciphering the regulatory mechanisms that link toxin production to agmatine (and, more generally, polyamines.

  14. Control of utilization of L-arginine, L-ornithine, agmatine, and putrescine as nitrogen sources in Escherichia coli K-12.

    OpenAIRE

    Shaibe, E; Metzer, E; Halpern, Y S

    1985-01-01

    The regulation of the synthesis of the enzymes involved in the utilization of L-arginine, L-ornithine, agmatine, and putrescine as a sole nitrogen source in Escherichia coli K-12 was examined. The synthesis of agmatine ureohydrolase, putrescine aminotransferase, and pyrroline dehydrogenase is dually controlled by catabolite repression and nitrogen availability. Catabolite repression of agmatine ureohydrolase, but not that of putrescine aminotransferase or pyrroline dehydrogenase, is relieved ...

  15. Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats.

    Science.gov (United States)

    Sahin, Ceren; Albayrak, Ozgur; Akdeniz, Tuğba F; Akbulut, Zeynep; Yanikkaya Demirel, Gulderen; Aricioglu, Feyza

    2016-10-01

    The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1β and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-κB, PYCARD, caspase-1, IL-1β and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. Pharmacological analysis of the cardiac sympatho-inhibitory actions of moxonidine and agmatine in pithed spontaneously hypertensive rats.

    Science.gov (United States)

    Cobos-Puc, Luis E; Sánchez-López, Araceli; Centurión, David

    2016-11-15

    This study shows that in spontaneously hypertensive rats (SHR) of 14-weeks-old, the sympathetically-induced, but not noradrenaline-induced tachycardic response are higher than age-matched Wistar normotensive rats. Furthermore, in SHR the sympathetically-induced tachycardic response was: (1) unaffected by moxonidine (3μg/kgmin); (2) partially inhibited by B-HT 933 (30μg/kgmin), both at the lowest doses; and (3) completely inhibited by the highest doses of B-HT 933 (100μg/kgmin), moxonidine (10μg/kgmin) or agmatine (1000 and 3000μg/kgmin) while the noradrenaline-induced tachycardic responses remained unaffected by the above compounds, except by 3000μg/kgmin agmatine. In SHR, 300μg/kg rauwolscine failed to block the sympatho-inhibition to 100μg/kgmin B-HT 933 or 10μg/kgmin moxonidine, but 1000μg/kg rauwolscine abolished, partially antagonized, and did not modify the sympatho-inhibition to the highest doses of B-HT 933, moxonidine, and agmatine, respectively, 3000μg/kg AGN 192403 or 300μg/kg BU224 given alone had no effect in the moxonidine- or agmatine-induced sympatho-inhibition, and the combination rauwolscine plus AGN 192403 but not plus BU224, abolished the sympatho-inhibition to the highest doses of moxonidine and agmatine. In conclusion, the sympathetically-induced tachycardic responses in SHR are inhibited by moxonidine and agmatine. The inhibition of moxonidine is mainly mediated by prejunctional α 2 -adrenoceptors and to a lesser extent by I 1 -imidazoline receptors, while the inhibition of agmatine is mediated by prejunctional α 2 -adrenoceptors and I 1 -imidazoline receptors at the same extent. Notwithstanding, the inhibitory function of α 2 -adrenoceptors seems to be altered in SHR compared with Wistar normotensive rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension.

    Science.gov (United States)

    Gadkari, Tushar V; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M; Joshi, Mahesh S

    2013-11-30

    l-Arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. l-Arginine initiated relaxations (EC50, 5.8±0.7mM; n=9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3±1.3mM; n=5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7±12.1μM; n=22), which was compromised by l-NAME (l-N(G)-nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9±23.4μM; n=5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC.

    Science.gov (United States)

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Gapsys, Vytautas; Ucurum, Zöhre; de Groot, Bert L; Fotiadis, Dimitrios

    2016-09-13

    Pathogenic enterobacteria need to survive the extreme acidity of the stomach to successfully colonize the human gut. Enteric bacteria circumvent the gastric acid barrier by activating extreme acid-resistance responses, such as the arginine-dependent acid resistance system. In this response, l-arginine is decarboxylated to agmatine, thereby consuming one proton from the cytoplasm. In Escherichia coli, the l-arginine/agmatine antiporter AdiC facilitates the export of agmatine in exchange of l-arginine, thus providing substrates for further removal of protons from the cytoplasm and balancing the intracellular pH. We have solved the crystal structures of wild-type AdiC in the presence and absence of the substrate agmatine at 2.6-Å and 2.2-Å resolution, respectively. The high-resolution structures made possible the identification of crucial water molecules in the substrate-binding sites, unveiling their functional roles for agmatine release and structure stabilization, which was further corroborated by molecular dynamics simulations. Structural analysis combined with site-directed mutagenesis and the scintillation proximity radioligand binding assay improved our understanding of substrate binding and specificity of the wild-type l-arginine/agmatine antiporter AdiC. Finally, we present a potential mechanism for conformational changes of the AdiC transport cycle involved in the release of agmatine into the periplasmic space of E. coli.

  19. Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice.

    Science.gov (United States)

    Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Santos, Danúbia B; Ribeiro, Camille M; Rosa, Priscila B; Farina, Marcelo; Rodrigues, Ana Lúcia S

    2014-04-03

    Agmatine has been recently emerged as a novel candidate to assist the conventional pharmacotherapy of depression. The acute restraint stress (ARS) is an unavoidable stress situation that may cause depressive-like behavior in rodents. In this study, we investigated the potential antidepressant-like effect of agmatine (10mg/kg, administered acutely by oral route) in the forced swimming test (FST) in non-stressed mice, as well as its ability to abolish the depressive-like behavior and hippocampal antioxidant imbalance induced by ARS. Agmatine reduced the immobility time in the mouse FST (1-100mg/kg) in non-stressed mice. ARS caused an increase in the immobility time in the FST, indicative of a depressive-like behavior, as well as hippocampal lipid peroxidation, and an increase in the activity of hippocampal superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, reduced catalase (CAT) activity and increased SOD/CAT ratio, an index of pro-oxidative conditions. Agmatine was effective to abolish the depressive-like behavior induced by ARS and to prevent the ARS-induced lipid peroxidation and changes in SOD, GR and CAT activities and in SOD/CAT activity ratio. Hippocampal levels of reduced glutathione (GSH) were not altered by any experimental condition. In conclusion, the present study shows that agmatine was able to abrogate the ARS-induced depressive-like behavior and the associated redox hippocampal imbalance observed in stressed restraint mice, suggesting that its antidepressant-like effect may be dependent on its ability to maintain the pro-/anti-oxidative homeostasis in the hippocampus. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. The Decay of Bound Isobaric Analogue States in {sup 28}Si and {sup 32}S Using (d, n{gamma}) Reactions

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, L; Nilsson, A; Bergqvist, I

    1970-03-15

    A method has been developed for recording coincidences between neutrons and gamma - rays produced in (d, n{gamma}) reactions. Neutron energies were measured by time-of-flight techniques and a large Nal(Tl) crystal was used to determine gamma - ray energies and intensities. The neutron detector was placed in the forward direction to emphasize the excitation of l{sub P} = 0 levels in the residual nuclei. The method was applied to the {sup 27}Al (d, n{gamma}) {sup 28}Si and {sup 31}P (d, n{gamma}) {sup 32}S reactions at the deuteron energy 4.0 MeV. The gamma - ray decay of a number of levels below 12 MeV in {sup 28}Si and below 9 MeV in {sup 32}S was studied. The isobaric analogue levels are prominently populated by the (d, n) reaction. The method is in particular suitable for studies of the decay of these levels.

  1. The sub-energetic gamma-ray burst GRB 031203 as a cosmic analogue to the nearby GRB 980425.

    Science.gov (United States)

    Soderberg, A M; Kulkarni, S R; Berger, E; Fox, D W; Sako, M; Frail, D A; Gal-Yam, A; Moon, D S; Cenko, S B; Yost, S A; Phillips, M M; Persson, S E; Freedman, W L; Wyatt, P; Jayawardhana, R; Paulson, D

    2004-08-05

    Over the six years since the discovery of the gamma-ray burst GRB 980425, which was associated with the nearby (distance approximately 40 Mpc) supernova 1998bw, astronomers have debated fiercely the nature of this event. Relative to bursts located at cosmological distance (redshift z approximately 1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed that the explosion was sub-energetic by a factor of 10. Here we report observations of the radio and X-ray afterglow of the recent GRB 031203 (refs 5-7), which has a redshift of z = 0.105. We demonstrate that it too is sub-energetic which, when taken together with the low gamma-ray luminosity, suggests that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. We expect intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRB 031203 and 980425) to reveal a large population of such events.

  2. Agmatine attenuates reserpine-induced oral dyskinesia in mice: Role of oxidative stress, nitric oxide and glutamate NMDA receptors.

    Science.gov (United States)

    Cunha, Andréia S; Matheus, Filipe C; Moretti, Morgana; Sampaio, Tuane B; Poli, Anicleto; Santos, Danúbia B; Colle, Dirleise; Cunha, Mauricio P; Blum-Silva, Carlos H; Sandjo, Louis P; Reginatto, Flávio H; Rodrigues, Ana Lúcia S; Farina, Marcelo; Prediger, Rui D

    2016-10-01

    Dyskinesia consists in a series of trunk, limbs and orofacial involuntary movements that can be observed following long-term pharmacological treatment in some psychotic and neurological disorders such as schizophrenia and Parkinson's disease, respectively. Agmatine is an endogenous arginine metabolite that emerges as neuromodulator and a promising agent to manage diverse central nervous system disorders by modulating nitric oxide (NO) pathway, glutamate NMDA receptors and oxidative stress. Herein, we investigated the effects of a single intraperitoneal (i.p.) administration of different agmatine doses (10, 30 or 100mg/kg) against the orofacial dyskinesia induced by reserpine (1mg/kg,s.c.) in mice by measuring the vacuous chewing movements and tongue protusion frequencies, and the duration of facial twitching. The results showed an orofacial antidyskinetic effect of agmatine (30mg/kg, i.p.) or the combined administration of sub-effective doses of agmatine (10mg/kg, i.p.) with the NMDA receptor antagonists amantadine (1mg/kg, i.p.) and MK801 (0.01mg/kg, i.p.) or the neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI; 0.1mg/kg, i.p.). Reserpine-treated mice displayed locomotor activity deficits in the open field and agmatine had no effect on this response. Reserpine increased nitrite and nitrate levels in cerebral cortex, but agmatine did not reverse it. Remarkably, agmatine reversed the decrease of dopamine and non-protein thiols (NPSH) levels caused by reserpine in the striatum. However, no changes were observed in striatal immunocontent of proteins related to the dopaminergic system including tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter type 2, pDARPP-32[Thr75], dopamine D1 and D2 receptors. These results indicate that the blockade of NO pathway, NMDAR and oxidative stress are possible mechanisms associated with the protective effects of agmatine against the orofacial dyskinesia induced by reserpine in mice

  3. Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling.

    Science.gov (United States)

    Neis, Vivian Binder; Moretti, Morgana; Bettio, Luis Eduardo B; Ribeiro, Camille M; Rosa, Priscila Batista; Gonçalves, Filipe Marques; Lopes, Mark William; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

    2016-06-01

    The activation of AMPA receptors and mTOR signaling has been reported as mechanisms underlying the antidepressant effects of fast-acting agents, specially the NMDA receptor antagonist ketamine. In the present study, oral administration of agmatine (0.1mg/kg), a neuromodulator that has been reported to modulate NMDA receptors, caused a significant reduction in the immobility time of mice submitted to the tail suspension test (TST), an effect prevented by the administration of DNQX (AMPA receptor antagonist, 2.5μg/site, i.c.v.), BDNF antibody (1μg/site, i.c.v.), K-252a (TrkB receptor antagonist, 1μg/site, i.c.v.), LY294002 (PI3K inhibitor, 10nmol/site, i.c.v.) or rapamycin (selective mTOR inhibitor, 0.2nmol/site, i.c.v.). Moreover, the administration of lithium chloride (non-selective GSK-3β inhibitor, 10mg/kg, p.o.) or AR-A014418 (selective GSK-3β inhibitor, 0.01μg/site, i.c.v.) in combination with a sub-effective dose of agmatine (0.0001mg/kg, p.o.) reduced the immobility time in the TST when compared with either drug alone. Furthermore, increased immunocontents of BDNF, PSD-95 and GluA1 were found in the prefrontal cortex of mice just 1h after agmatine administration. These results indicate that the antidepressant-like effect of agmatine in the TST may be dependent on the activation of AMPA and TrkB receptors, PI3K and mTOR signaling as well as inhibition of GSK-3β, and increase in synaptic proteins. The results contribute to elucidate the complex signaling pathways involved in the antidepressant effect of agmatine and reinforce the pivotal role of these molecular targets for antidepressant responses. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  4. Agmatine Reduces Lipopolysaccharide-Mediated Oxidant Response via Activating PI3K/Akt Pathway and Up-Regulating Nrf2 and HO-1 Expression in Macrophages.

    Directory of Open Access Journals (Sweden)

    Jianshen Chai

    Full Text Available Macrophages are key responders of inflammation and are closely related with oxidative stress. Activated macrophages can enhance oxygen depletion, which causes an overproduction of reactive oxygen species (ROS and leads to further excessive inflammatory response and tissue damage. Agmatine, an endogenous metabolite of L-arginine, has recently been shown to have neuroprotective effects based on its antioxidant properties. However, the antioxidant effects of agmatine in peripheral tissues and cells, especially macrophages, remain unclear. In this study we explored the role of agmatine in mediating antioxidant effects in RAW 264.7 cells and studied its antioxidant mechanism. Our data demonstrate that agmatine is an activator of Nrf2 signaling that markedly enhances Nrf2 nuclear translocation, increases nuclear Nrf2 protein level, up-regulates the expression of the Nrf2 downstream effector HO-1, and attenuates ROS generation induced by Lipopolysaccharide (LPS. We further demonstrated that the agmatine-induced activation of Nrf2 is likely through the PI3K/Akt pathway. LY294002, a specific PI3K/Akt inhibitor, abolished agmatine-induced HO-1 up-regulation and ROS suppression significantly. Inhibiting HO-1 pathway significantly attenuated the antioxidant effect of agmatine which the products of HO-1 enzymatic activity contributed to. Furthermore, the common membrane receptors of agmatine were evaluated, revealing that α2-adrenoceptor, I1-imidazoline receptor or I2-imidazoline receptor are not required by the antioxidant properties of agmatine. Taken together, our findings revealed that agmatine has antioxidant activity against LPS-induced ROS accumulation in RAW 264.7 cells involving HO-1 expression induced by Nrf2 via PI3K/Akt pathway activation.

  5. The effect of amixin and agmatine on cytochrome c release from isolated mitochondria

    Directory of Open Access Journals (Sweden)

    K. R. Uspenska

    2017-02-01

    Full Text Available Mitochondrial nicotinic acetylcholine receptors (nAChRs control permeability transition pore formation and cytochrome c release in the presence of apoptogenic factors. This study demonstrates that pharmacological agents amixin and agmatine affect mitochondrial nAChR functioning: they slightly suppress cytochrome c release from mouse brain and liver mitochondria stimulated with apoptogenic dose of Са2+ and prevent the effect of α7 nAChR agonist PNU282987. We conclude that mitochondria may be one of therapeutic targets of amixin and agmatine.

  6. Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism.

    Science.gov (United States)

    Kim, Ji-Woon; Seung, Hana; Kim, Ki Chan; Gonzales, Edson Luck T; Oh, Hyun Ah; Yang, Sung Min; Ko, Mee Jung; Han, Seol-Heui; Banerjee, Sourav; Shin, Chan Young

    2017-02-01

    Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Implementation of the agmatine-controlled expression system for inducible gene expression in Lactococcus lactis.

    Science.gov (United States)

    Linares, Daniel M; Alvarez-Sieiro, Patricia; del Rio, Beatriz; Ladero, Victor; Redruello, Begoña; Martin, Ma Cruz; Fernandez, Maria; Alvarez, Miguel A

    2015-12-30

    Lactococcus lactis has been safely consumed in fermented foods for millennia. This Gram-positive bacterium has now become of industrial importance as an expression host for the overproduction of lipopolysaccharide-free recombinant proteins used as food ingredients, therapeutic proteins and biotechnological enzymes. This paper reports an agmatine-controlled expression (ACE) system for L. lactis, comprising the lactococcal agmatine-sensor/transcriptional activator AguR and its target promoter P(aguB). The usefulness and efficiency of this system was checked via the reporter gene gfp and by producing PEP (Myxococcus xanthus prolyl-endopeptidase), an enzyme of biomedical interest able to degrade the immunotoxic peptides produced during the gastrointestinal breakdown of gluten. The ACE system developed in this work was suitable for the efficient expression of the functional recombinant proteins GFP and PEP. The expression system was tightly regulated by the agmatine concentration and allowed high protein production without leakiness.

  8. Effects of agmatine on blood-brain barrier stabilization assessed by permeability MRI in a rat model of transient cerebral ischemia.

    Science.gov (United States)

    Ahn, S S; Kim, S H; Lee, J E; Ahn, K J; Kim, D J; Choi, H S; Kim, J; Shin, N-Y; Lee, S-K

    2015-02-01

    BBB disruption after acute ischemic stroke and subsequent permeability increase may be enhanced by reperfusion. Agmatine has been reported to attenuate BBB disruption. Our aim was to evaluate the effects of agmatine on BBB stabilization in a rat model of transient cerebral ischemia by using permeability dynamic contrast-enhanced MR imaging at early stages and subsequently to demonstrate the feasibility of dynamic contrast-enhanced MR imaging for the investigation of new therapies. Thirty-four male Sprague-Dawley rats were subjected to transient MCA occlusion for 90 minutes. Immediately after reperfusion, agmatine (100 mg/kg) or normal saline was injected intraperitoneally into the agmatine-treated group (n = 17) or the control group, respectively. MR imaging was performed after reperfusion. For quantitative analysis, regions of interest were defined within the infarct area, and values for volume transfer constant, rate transfer coefficient, volume fraction of extravascular extracellular space, and volume fraction of blood plasma were obtained. Infarct volume, infarct growth, quantitative imaging parameters, and numbers of factor VIII-positive cells after immunohistochemical staining were compared between control and agmatine-treated groups. Among the permeability parameters, volume transfer constant and volume fraction of extravascular extracellular space were significantly lower in the agmatine-treated group compared with the control group (0.05 ± 0.02 minutes(-1) versus 0.08 ± 0.03 minute(-1), P = .012, for volume transfer constant and 0.12 ± 0.06 versus 0.22 ± 0.15, P = .02 for volume fraction of extravascular extracellular space). Other permeability parameters were not significantly different between the groups. The number of factor VIII-positive cells was less in the agmatine-treated group than in the control group (3-fold versus 4-fold, P = .037). In ischemic stroke, agmatine protects the BBB, which can be monitored in vivo by quantification of

  9. Biosynthesis of agmatine in isolated mitochondria and perfused rat liver: studies with 15N-labelled arginine

    Science.gov (United States)

    2005-01-01

    An important but unresolved question is whether mammalian mitochondria metabolize arginine to agmatine by the ADC (arginine decarboxylase) reaction. 15N-labelled arginine was used as a precursor to address this question and to determine the flux through the ADC reaction in isolated mitochondria obtained from rat liver. In addition, liver perfusion system was used to examine a possible action of insulin, glucagon or cAMP on a flux through the ADC reaction. In mitochondria and liver perfusion, 15N-labelled agmatine was generated from external 15N-labelled arginine. The production of 15N-labelled agmatine was time- and dose-dependent. The time-course of [U-15N4]agmatine formation from 2 mM [U-15N4]arginine was best fitted to a one-phase exponential curve with a production rate of approx. 29 pmol·min−1·(mg of protein)−1. Experiments with an increasing concentration (0– 40 mM) of [guanidino-15N2]arginine showed a Michaelis constant Km for arginine of 46 mM and a Vmax of 3.7 nmol·min−1·(mg of protein)−1 for flux through the ADC reaction. Experiments with broken mitochondria showed little changes in Vmax or Km values, suggesting that mitochondrial arginine uptake had little effect on the observed Vmax or Km values. Experiments with liver perfusion demonstrated that over 95% of the effluent agmatine was derived from perfusate [guanidino-15N2]arginine regardless of the experimental condition. However, the output of 15N-labelled agmatine (nmol·min−1·g−1) increased by approx. 2-fold (P<0.05) in perfusions with cAMP. The findings of the present study provide compelling evidence that mitochondrial ADC is present in the rat liver, and suggest that cAMP may stimulate flux through this pathway. PMID:15656789

  10. Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation.

    Science.gov (United States)

    Song, Juhyun; Oh, Yumi; Kim, Jong Youl; Cho, Kyoung Joo; Lee, Jong Eun

    2016-11-01

    Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

  11. Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test.

    Science.gov (United States)

    Budni, Josiane; Gadotti, Vinícius M; Kaster, Manuella P; Santos, Adair R S; Rodrigues, Ana Lúcia S

    2007-12-01

    The administration of agmatine elicits an antidepressant-like effect in the mouse forced swimming test by a mechanism dependent on the inhibition of the NMDA receptors and the L-arginine-nitric oxide (NO) pathway. Since it has been reported that the NO can activate different types of potassium (K(+)) channels in several tissues, the present study investigates the possibility of synergistic interactions between different types of K(+) channel inhibitors and agmatine in the forced swimming test. Treatment of mice by i.c.v. route with subeffective doses of tetraethylammonium (a non specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an ATP-sensitive K(+) channels inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site), augmented the effect of agmatine (0.001 mg/kg, i.p.) in the forced swimming test. Furthermore, the administration of agmatine and the K(+) channel inhibitors, alone or in combination, did not affect locomotion in the open-field test. Moreover, the reduction in the immobility time elicited by an active dose of agmatine (10 mg/kg, i.p.) in the forced swimming test was prevented by the pre-treatment of mice with the K(+) channel openers cromakalim (10 microg/site, i.c.v.) and minoxidil (10 microg/site, i.c.v.), without affecting locomotion. Together these data raise the possibility that the antidepressant-like effect of agmatine in the forced swimming test is related to its modulatory effects on neuronal excitability, via inhibition of K(+) channels.

  12. Involvement of nitric oxide in anticompulsive-like effect of agmatine on marble-burying behaviour in mice.

    Science.gov (United States)

    Gawali, Nitin B; Chowdhury, Amrita A; Kothavade, Pankaj S; Bulani, Vipin D; Nagmoti, Dnyaneshwar M; Juvekar, Archana R

    2016-01-05

    In view of the reports that nitric oxide modulates the neurotransmitters implicated in obsessive-compulsive disorder (OCD), patients with OCD exhibit higher plasma nitrate levels, and drugs useful in OCD influence nitric oxide. Agmatine is a polyamine and widely distributed in mammalian brain which interacts with nitrergic systems. Hence, the present study was carried out to understand the involvement of nitrergic systems in the anticompulsive-like effect of agmatine. We used marble-burying behaviour (MBB) of mice as the animal model of OCD, and nitric oxide levels in hippocampus (HC) and cortex homogenate were measured. Results revealed that, agmatine (20 and 40mg/kg, i.p) significantly inhibited the MBB. Intraperitoneal administration of nitric oxide enhancers viz. nitric oxide precursor - l-arginine (l-ARG) (400mg/kg and 800mg/kg) increased MBB as well as brain nitrites levels, whereas treatment with N(G)-nitro-l-arginine methyl ester (l-NAME) neuronal nitric oxide synthase inhibitor (30mg/kg and 50mg/kg, i.p.) and 7-nitroindazole (7-NI) (20mg/kg and 40mg/kg) attenuated MBB and nitrites levels in brain. Further, in combination studies, the anticompulsive-like effect of agmatine (20mg/kg, ip) was exacerbated by prior administration of l-ARG (400mg/kg) and conversely l-NAME (15mg/kg) or 7-NI (10.0mg/kg) attenuated OCD-like behaviour with HC and cortex changes in the levels of NO. None of the above treatment had any significant influence on locomotor activity. In conclusion, Agmatine is effective in ameliorating the compulsive-like behaviour in mice which appears to be related to nitric oxide in brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption.

    Science.gov (United States)

    Moosavi, Maryam; Zarifkar, Amir Hossein; Farbood, Yaghoub; Dianat, Mahin; Sarkaki, Alireza; Ghasemi, Rasoul

    2014-08-05

    Centrally administered streptozotocin (STZ), is known to cause Alzheimer׳s like memory deterioration. It mainly affects insulin signaling pathways such as PI3/Akt and GSK-3β which are involved in cell survival. Previous studies indicate that STZ increases the ratio of Bax/Bcl-2 and thereby induces caspase-3 activation and apoptosis. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study aimed to assess if agmatine reverses STZ-induced memory deficits, hippocampal Akt/GSK-3β signaling disruption and caspase-3 activation. Adult male Sprague-Dawely rats weighing 200-250 g were used. The canules were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3 mg/kg) and agmatine treatment (40 or 80 mg/kg) was started from day 4 and continued in an every other day manner till day 14. The animal׳s learning and memory capability was assessed on days 15-18 using Morris water maze. After complement of behavioral studies the hippocampi was isolated and the amounts of hippocampal cleaved caspase-3 (the landmark of apoptosis), Bax/Bcl-2 ratio, total and phosphorylated forms of GSK-3β and Akt were analyzed by western blot. The results showed that agmatine in 80 but not 40 mg/kg reversed the memory deterioration induced by STZ. Western blot analysis revealed that STZ prompted elevation of caspase-3; Bax/Bcl-2 ratio and disrupted Akt/GSK-3β signaling in the hippocampus. Agmatine treatment prevented apoptosis and Akt/GSK-3β signaling impairment induced by STZ. This study disclosed that agmatine treatment averts not only STZ-induced memory deterioration but also hippocampal apoptosis and Akt/GSK-3β signaling disruption. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Phosphorylation of inositol 1,4,5-trisphosphate analogues by 3-kinase and dephosphorylation of inositol 1,3,4,5-tetrakisphosphate analogues by 5-phosphatase

    NARCIS (Netherlands)

    Dijken, Peter van; Lammers, Aleida A.; Ozaki, Shoichiro; Potter, Barry V.L.; Erneux, Christophe; Haastert, Peter J.M. van

    1994-01-01

    A series of P-32-labeled D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P-4] analogues was enzymically prepared from the corresponding D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] analogues using recombinant rat brain Ins(1,4,5)P-3 3-kinase and [gamma-P-32]ATP. Ins(1,4,5)P-3 analogues

  15. Agmatine for combined treatment of epilepsy, depression and cognitive impairment in chronic epileptic animals.

    Science.gov (United States)

    Singh, Tanveer; Bagga, Neetu; Kaur, Anureet; Kaur, Navjot; Gawande, Dinesh Yugraj; Goel, Rajesh Kumar

    2017-08-01

    Epilepsy is fourth most common neurological disorders associated with depression and cognitive deficits. As per present scenario, none of the antiseizure drugs have been reported successful to have ameliorative effect on epilepsy associated depression and cognitive deficits. Thus, the study was envisioned to assess an ameliorative potential of agmatine on epilepsy and its efficacy and safety for management of associated depression and cognitive deficits. The animals were made epileptic employing pentylenetetrazole (35mg/kg i.p. every 48±2h) kindling model of epilepsy and subsequently were treated with vehicle, valproic acid (300mg/kg/day i.p.) and agmatine (2.5, 5, and 10mg/kg)/day/i.p. for 15days. Except naïve, all the groups were challenged with same pentylenetetrazole dose as employed during kindling on days 5, 10, and 15 to evaluate seizure severity. Two hours after seizure severity test, tail suspension test and passive shock avoidance paradigm was employed to evaluate depression and cognitive behavior respectively. Results suggested that epileptic animals were significantly associated with depression and cognitive impairment. Chronic valproate treatment significantly reduced seizure severity, but was found unable to mitigate depression and cognitive deficits. However, agmatine treatment dose dependently ameliorated seizure severity as well as associated depression and cognitive deficits. On 15th day, animals were euthanized and pertinent neurochemical estimations were carried out in cortical and hippocampal areas of the mice brain. Thus, study concluded that agmatine ameliorated seizure severity, depression and cognitive impairment in epileptic animals, possibly via restoring glutamate-GABA neurotransmission and serotonin synthesis with decreased nitrosative stress. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling.

    Science.gov (United States)

    Kang, Somang; Kim, Chul-Hoon; Jung, Hosung; Kim, Eosu; Song, Ho-Taek; Lee, Jong Eun

    2017-02-01

    The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, p-Akt, and p-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Neuroprotective effects of agmatine in experimental peripheral nerve injury in rats: a prospective randomized and placebo-controlled trial.

    Science.gov (United States)

    Sezer, Aykut; Guclu, Bulent; Kazanci, Burak; Cakir, Murteza; Coban, Mustafa Kemal

    2014-01-01

    The purpose of this study was to demonstrate the activity of agmatine, an inducible nitric oxide synthase (iNOS) inhibitor and selective N-methyl-D-aspartate receptor (NMDAR) antagonist, on reducing tissue damage in distal part of traumatic nerve in an experimental rat peripheral nerve injury model. Sciatic nerves of 30 Sprague Dawley male rats were used. Rats were divided into 5 groups; group 1 (n=6), control group; group 2 (n=6), axonotmesis + placebo group; group 3 (n=6), axonotmesis + 50 mg/kg agmatine treatment group; group 4 (n=6), neurotmesis + placebo group; group 5 (n=6), neurotmesis + 50 mg/kg agmatine treatment group. Axonolysis, axon degeneration, edema, hemorrhage, and inflammation were evaluated in histopathologic examinations of all the groups. When group 2 was compared with group 3 in histopathologic sections, axonolysis was less in group 3 (p=0.007), as was axon degeneration (p=0.022) and edema (p=0.018). When group 4 was compared with group 5, axonolysis was less in group 5 (p=0.009), as was axon degeneration (p=0.006) and edema (p=0.021). This study demonstrated agmatine to have antioxidant and antineurotoxic effects in an experimental rat peripheral nerve injury model.

  18. [Analog gamma camera digitalization computer system].

    Science.gov (United States)

    Rojas, G M; Quintana, J C; Jer, J; Astudillo, S; Arenas, L; Araya, H

    2004-01-01

    Digitalization of analogue gamma cameras systems, using special acquisition boards in microcomputers and appropriate software for acquisition and processing of nuclear medicine images is described in detail. Microcomputer integrated systems interconnected by means of a Local Area Network (LAN) and connected to several gamma cameras have been implemented using specialized acquisition boards. The PIP software (Portable Image Processing) was installed on each microcomputer to acquire and preprocess the nuclear medicine images. A specialized image processing software has been designed and developed for these purposes. This software allows processing of each nuclear medicine exam, in a semiautomatic procedure, and recording of the results on radiological films. . A stable, flexible and inexpensive system which makes it possible to digitize, visualize, process, and print nuclear medicine images obtained from analogue gamma cameras was implemented in the Nuclear Medicine Division. Such a system yields higher quality images than those obtained with analogue cameras while keeping operating costs considerably lower (filming: 24.6%, fixing 48.2% and developing 26%.) Analogue gamma camera systems can be digitalized economically. This system makes it possible to obtain optimal clinical quality nuclear medicine images, to increase the acquisition and processing efficiency, and to reduce the steps involved in each exam.

  19. Sided functions of an arginine-agmatine antiporter oriented in liposomes.

    Science.gov (United States)

    Tsai, Ming-Feng; Fang, Yiling; Miller, Christopher

    2012-02-28

    The arginine-dependent extreme acid resistance system helps enteric bacteria survive the harsh gastric environment. At the center of this multiprotein system is an arginine-agmatine antiporter, AdiC. To maintain cytoplasmic pH, AdiC imports arginine and exports its decarboxylated product, agmatine, resulting in a net extrusion of one "virtual proton" in each turnover. The random orientation of AdiC in reconstituted liposomes throws up an obstacle to quantifying its transport mechanism. To overcome this problem, we introduced a mutation, S26C, near the substrate-binding site. This mutant exhibits substrate recognition and pH-dependent activity similar to those of the wild-type protein but loses function completely upon reaction with thiol reagents. The membrane-impermeant MTSES reagent can then be used as a cleanly sided inhibitor to silence those S26C-AdiC proteins whose extracellular portion projects from the external side of the liposome. Alternatively, the membrane-permeant MTSEA and membrane-impermeant reducing reagent, TCEP, can be used together to inhibit proteins in the opposite orientation. This approach allows steady-state kinetic analysis of AdiC in a sided fashion. Arginine and agmatine have similar Michaelis-Menten parameters for both sides of the protein, while the extracellular side selects arginine over argininamide, a mimic of the carboxylate-protonated form of arginine, more effectively than does the cytoplasmic side. Moreover, the two sides of AdiC have different pH sensitivities. AdiC activity increases to a plateau at pH 4 as the extracellular side is acidified, while the cytoplasmic side shows an optimal pH of 5.5, with further acidification inhibiting transport. This oriented system allows more precise analysis of AdiC-mediated substrate transport than has been previously available and permits comparison to the situation experienced by the bacterial membrane under acid stress.

  20. Augmenting the Genetic Toolbox for Sulfolobus islandicus with a Stringent Positive Selectable Marker for Agmatine Prototrophy

    Science.gov (United States)

    Cooper, Tara E.; Krause, David J.

    2013-01-01

    Sulfolobus species have become the model organisms for studying the unique biology of the crenarchaeal division of the archaeal domain. In particular, Sulfolobus islandicus provides a powerful opportunity to explore natural variation via experimental functional genomics. To support these efforts, we further expanded genetic tools for S. islandicus by developing a stringent positive selection for agmatine prototrophs in strains in which the argD gene, encoding arginine decarboxylase, has been deleted. Strains with deletions in argD were shown to be auxotrophic for agmatine even in nutrient-rich medium, but growth could be restored by either supplementation of exogenous agmatine or reintroduction of a functional copy of the argD gene from S. solfataricus P2 into the ΔargD host. Using this stringent selection, a robust targeted gene knockout system was established via an improved next generation of the MID (marker insertion and unmarked target gene deletion) method. Application of this novel system was validated by targeted knockout of the upsEF genes involved in UV-inducible cell aggregation formation. PMID:23835176

  1. Identification of functional amino acid residues involved in polyamine and agmatine transport by human organic cation transporter 2.

    Science.gov (United States)

    Higashi, Kyohei; Imamura, Masataka; Fudo, Satoshi; Uemura, Takeshi; Saiki, Ryotaro; Hoshino, Tyuji; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2014-01-01

    Polyamine (putrescine, spermidine and spermine) and agmatine uptake by the human organic cation transporter 2 (hOCT2) was studied using HEK293 cells transfected with pCMV6-XL4/hOCT2. The Km values for putrescine and spermidine were 7.50 and 6.76 mM, and the Vmax values were 4.71 and 2.34 nmol/min/mg protein, respectively. Spermine uptake by hOCT2 was not observed at pH 7.4, although it inhibited both putrescine and spermidine uptake. Agmatine was also taken up by hOCT2, with Km value: 3.27 mM and a Vmax value of 3.14 nmol/min/mg protein. Amino acid residues involved in putrescine, agmatine and spermidine uptake by hOCT2 were Asp427, Glu448, Glu456, Asp475, and Glu516. In addition, Glu524 and Glu530 were involved in putrescine and spermidine uptake activity, and Glu528 and Glu540 were weakly involved in putrescine uptake activity. Furthermore, Asp551 was also involved in the recognition of spermidine. These results indicate that the recognition sites for putrescine, agmatine and spermidine on hOCT2 strongly overlap, consistent with the observation that the three amines are transported with similar affinity and velocity. A model of spermidine binding to hOCT2 was constructed based on the functional amino acid residues.

  2. Further analysis of the inhibition by agmatine on the cardiac sympathetic outflow: Role of the α2-adrenoceptor subtypes.

    Science.gov (United States)

    Cobos-Puc, Luis; Aguayo-Morales, Hilda; Ventura-Sobrevilla, Janeth; Luque-Contreras, Diana; Chin-Chan, Miguel

    2017-06-15

    This study has investigated the role of the α 2 -adrenoceptor subtypes involved in the inhibition of the cardiac sympathetic outflow induced by intravenous (i.v) infusions of agmatine. Therefore, we analysed the effect of an i.v. bolus injections of the selective antagonists BRL 44408 (300μg/kg; α 2A ), imiloxan (3000μg/kg; α 2B ), and JP-1302 (300μg/kg; α 2C ) given separately, and their combinations: BRL 44408 plus Imiloxan, JP 1302 plus imiloxan, BRL 44408 plus JP-1302, BRL 44408 plus imiloxan plus JP-1302 on the cardiac sympatho-inhibition of agmatine. Also, the effect of the combination BRL 44408 plus JP-1302 plus AGN 192403 (3000μg/kg; I 1 antagonist) was evaluated. In this way, i.v. infusions of 1000μg/kg min of agmatine, but not 300, inhibited the tachycardic response induced by electrical stimulation. Furthermore, the antagonists used or their combinations had no effect on the electrically-induced tachycardic response. On the other hand, the inhibitory response of agmatine was: (1) partially antagonized by BRL 44408 or JP-1302 given separately, a similar response was observed when we administered their combination with imiloxan, but not by imiloxan alone, (2) antagonized in greater magnitude by the combination BRL 44408 plus JP-1302 or the combination BRL 44408 plus imiloxan plus JP-1302, and (3) abolished by the combination BRL 44408 plus JP-1302 plus AGN 192403. Taken together, these results demonstrate that the α 2A - and α 2C -adrenoceptor subtypes and I 1 -imidazoline receptors are involved in the inhibition of the cardiac sympathetic outflow induced by agmatine. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Identification of functional amino acid residues involved in polyamine and agmatine transport by human organic cation transporter 2.

    Directory of Open Access Journals (Sweden)

    Kyohei Higashi

    Full Text Available Polyamine (putrescine, spermidine and spermine and agmatine uptake by the human organic cation transporter 2 (hOCT2 was studied using HEK293 cells transfected with pCMV6-XL4/hOCT2. The Km values for putrescine and spermidine were 7.50 and 6.76 mM, and the Vmax values were 4.71 and 2.34 nmol/min/mg protein, respectively. Spermine uptake by hOCT2 was not observed at pH 7.4, although it inhibited both putrescine and spermidine uptake. Agmatine was also taken up by hOCT2, with Km value: 3.27 mM and a Vmax value of 3.14 nmol/min/mg protein. Amino acid residues involved in putrescine, agmatine and spermidine uptake by hOCT2 were Asp427, Glu448, Glu456, Asp475, and Glu516. In addition, Glu524 and Glu530 were involved in putrescine and spermidine uptake activity, and Glu528 and Glu540 were weakly involved in putrescine uptake activity. Furthermore, Asp551 was also involved in the recognition of spermidine. These results indicate that the recognition sites for putrescine, agmatine and spermidine on hOCT2 strongly overlap, consistent with the observation that the three amines are transported with similar affinity and velocity. A model of spermidine binding to hOCT2 was constructed based on the functional amino acid residues.

  4. Neuroprotective effects of agmatine in mice infused with a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

    Science.gov (United States)

    Matheus, Filipe C; Aguiar, Aderbal S; Castro, Adalberto A; Villarinho, Jardel G; Ferreira, Juliano; Figueiredo, Cláudia P; Walz, Roger; Santos, Adair R S; Tasca, Carla I; Prediger, Rui D S

    2012-12-01

    We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in olfactory, cognitive, emotional and motor functions associated with time-dependent disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). Agmatine, an endogenous arginine metabolite, has been proposed as a novel neuromodulator that plays protective roles in several models of neuronal cellular damage. In the present study we demonstrated that repeated treatment with agmatine (30 mg/kg, i.p.) during 5 consecutive days increased the survival rate (from 40% to 80%) of 15-month-old C57BL/6 female mice infused with a single intranasal (i.n.) administration of MPTP (1 mg/nostril), improving the general neurological status of the surviving animals. Moreover, pretreatment with agmatine was found to attenuate short-term social memory and locomotor activity impairments observed at different periods after i.n. MPTP administration. These behavioral benefits of exogenous agmatine administration were accompanied by a protection against the MPTP-induced decrease of hippocampal glutamate uptake and loss of dopaminergic neurons in the substantia nigra pars compacta of aging mice, without altering brain monoamine oxidase B (MAO-B) activity. These results provide new insights in experimental models of PD, indicating that agmatine represents a potential therapeutic tool for the management of cognitive and motor symptoms of PD, together with its neuroprotective effects. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Pharmacological analysis of the inhibition produced by moxonidine and agmatine on the vasodepressor sensory CGRPergic outflow in pithed rats.

    Science.gov (United States)

    Rubio-Beltrán, Eloísa; Labastida-Ramírez, Alejandro; Hernández-Abreu, Oswaldo; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

    2017-10-05

    Calcitonin gene-related peptide (CGRP) plays a role in several (patho)physiological functions, and modulation of its release is considered a therapeutic target. In this respect, electrical spinal (T 9 --T 12 ) stimulation of the perivascular sensory outflow in pithed rats produces vasodepressor responses mediated by CGRP release. This study investigated the role of imidazoline I 1 and I 2 receptors in the inhibition by moxonidine and agmatine of these vasodepressor responses. Male Wistar pithed rats (pretreated i.v. with 25mg/kg gallamine and 2mg/kg⋅min hexamethonium) received i.v. continuous infusions of methoxamine (20μg/kg⋅min) followed by physiological saline (0.02ml/min), moxonidine (1, 3, 10 or 30μg/kg⋅min) or agmatine (1000 or 3000μg/kg⋅min). Under these conditions, electrical stimulation (0.56-5.6Hz; 50V; 2ms) of the spinal cord (T 9 -T 12 ) produced frequency-dependent vasodepressor responses which were: (i) unchanged during saline infusion; and (ii) inhibited during the above infusions of moxonidine or agmatine. Moreover, using i.v. administrations, the inhibition by 3μg/kg⋅min moxonidine or 3000μg/kg⋅min agmatine (which failed to inhibit the vasodepressor responses by α-CGRP; 0.1-1µg/kg) was: (i) unaltered after saline (1ml/kg), rauwolscine (300μg/kg; α 2 -adrenoceptor antagonist) or BU224 (300μg/kg; imidazoline I 2 receptor antagonist); and (ii) reversed after AGN 192403 (3000μg/kg; imidazoline I 1 receptor antagonist). This reversion was relatively more pronounced after AGN 192403 plus rauwolscine. These blocking doses of antagonists lacked any effects on the electrically-induced vasodepressor responses. Therefore, the inhibition of the vasodepressor sensory CGRPergic outflow by moxonidine and agmatine is mainly mediated by prejunctional imidazoline I 1 receptors on perivascular sensory nerves. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Protection by imidazol(ine) drugs and agmatine of glutamate-induced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor.

    Science.gov (United States)

    Olmos, G; DeGregorio-Rocasolano, N; Paz Regalado, M; Gasull, T; Assumpció Boronat, M; Trullas, R; Villarroel, A; Lerma, J; García-Sevilla, J A

    1999-07-01

    This study was designed to assess the potential neuroprotective effect of several imidazol(ine) drugs and agmatine on glutamate-induced necrosis and on apoptosis induced by low extracellular K+ in cultured cerebellar granule cells. Exposure (30 min) of energy deprived cells to L-glutamate (1-100 microM) caused a concentration-dependent neurotoxicity, as determined 24 h later by a decrease in the ability of the cells to metabolize 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) into a reduced formazan product. L-glutamate-induced neurotoxicity (EC50=5 microM) was blocked by the specific NMDA receptor antagonist MK-801 (dizocilpine). Imidazol(ine) drugs and agmatine fully prevented neurotoxicity induced by 20 microM (EC100) L-glutamate with the rank order (EC50 in microM): antazoline (13)>cirazoline (44)>LSL 61122 [2-styryl-2-imidazoline] (54)>LSL 60101 [2-(2-benzofuranyl) imidazole] (75)>idazoxan (90)>LSL 60129 [2-(1,4-benzodioxan-6-yl)-4,5-dihydroimidazole](101)>RX82 1002 (2-methoxy idazoxan) (106)>agmatine (196). No neuroprotective effect of these drugs was observed in a model of apoptotic neuronal cell death (reduction of extracellular K+) which does not involve stimulation of NMDA receptors. Imidazol(ine) drugs and agmatine fully inhibited [3H]-(+)-MK-801 binding to the phencyclidine site of NMDA receptors in rat brain. The profile of drug potency protecting against L-glutamate neurotoxicity correlated well (r=0.90) with the potency of the same compounds competing against [3H]-(+)-MK-801 binding. In HEK-293 cells transfected to express the NR1-1a and NR2C subunits of the NMDA receptor, antazoline and agmatine produced a voltage- and concentration-dependent block of glutamate-induced currents. Analysis of the voltage dependence of the block was consistent with the presence of a binding site for antazoline located within the NMDA channel pore with an IC50 of 10-12 microM at 0 mV. It is concluded that imidazol(ine) drugs and agmatine are

  7. Poly(Amido Amine)s containing agmatine and butanol side chains as efficient gene carriers

    NARCIS (Netherlands)

    Won, Young-Wook; Ankone, Martinus J.K.; Engbersen, Johannes F.J.; Feijen, Jan; Kim, S.W.

    2016-01-01

    A new type of bioreducible poly(amido amine) copolymer is synthesized by the Michael addition polymerization of cystamine bisacrylamide (CBA) with 4-aminobutylguanidine (agmatine, AGM) and 4-aminobutanol (ABOL). Since the positively charged guanidinium groups of AGM and the hydroxybutyl groups of

  8. Evaluation of the protective effect of agmatine against cisplatin nephrotoxicity with 99mTc-DMSA renal scintigraphy and cystatin-C.

    Science.gov (United States)

    Salihoglu, Yavuz Sami; Elri, Tarik; Gulle, Kanat; Can, Murat; Aras, Mustafa; Ozacmak, Hale Sayan; Cabuk, Mehmet

    2016-10-01

    The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity. Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5 mg/kg intraperitoneally); (3) Agmatine (AGM; 10 mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP + AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation. In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone. Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy.

  9. Scintigraphy with labelled analogues of the somatostatin

    International Nuclear Information System (INIS)

    Duet, M.; Ajzenberg, C.; Warnet, A.; Mundler, O.

    1998-01-01

    The receptors of the somatostatin have been localized in a big number of tumors, whom a great number are neuro-endocrine tumors. However, some tumors that have not this differentiation (breast cancer, lymphomas, cerebral tumors) possess them as well. Analogues of somatostatin, labelled with isotopes having a gamma emission, allow from now their detection in vivo. (N.C.)

  10. Purification of influenza deoxyribonucleic acid-based vaccine using agmatine monolith.

    Science.gov (United States)

    Bicho, D; Caramelo-Nunes, C; Sousa, A; Sousa, F; Queiroz, J A; Tomaz, C T

    2016-02-15

    Lately, researchers have made several efforts to improve vaccine production to fight highly contagious respiratory diseases like influenza. One of the most promising options for reducing the impact of this virus is DNA vaccination. However, a large quantity of highly pure plasmid DNA (pDNA) is necessary to attain this goal. The present work describes the production and purification of the plasmid NTC7482-41H-VA2HA expressing influenza virus hemagglutinin using an agmatine monolith. This ligand was chosen to purify supercoiled (sc) pDNA from complex lysates because of its versatile multimodal character. Its natural intervention in several biological systems together with its similarity with the highly studied arginine ligand allowed the development of a simpler and more specific purification process. Agmatine works under two strategies: descending ammonium sulfate gradient and ascending sodium chloride gradient. Furthermore, pH manipulation revealed an important role in pDNA isoforms selectivity. Dynamic binding capacity (DBC) experiments were performed varying different parameters and showed an increase with pDNA concentration, while high flow rate and high pH had the opposite effect. Sc pDNA was purified with high yield and was efficient with respect to cell transfection and cell viability. This monolith showed to be appropriate to purify the plasmid NTC7482-41H-VA2HA, providing a valuable tool for pDNA influenza vaccines preparation. Copyright © 2016. Published by Elsevier B.V.

  11. Electron spin resonance of spin-trapped radicals of amines and polyamines. Hydroxyl radical reactions in aqueous solutions and. gamma. radiolysis in the solid state

    Energy Technology Data Exchange (ETDEWEB)

    Mossoba, M.M.; Rosenthal, I.; Riesz, P. (National Cancer Inst., Bethesda, MD (USA))

    1982-06-15

    The reactions of hydroxyl radicals with methylamine, dimethylamine, trimethylamine, diethylamine, sec-butylamine, ethylene-diamine, 1,3-diaminopropane, putrescine, cadaverine, 1,7-diaminoheptane, ornithine, spermidine, spermine, agmatine, and arcaine in aqueous solutions have been investigated by spin-trapping and esr. Hydroxyl radicals were generated by the uv photolysis of H/sub 2/O/sub 2/ and 2-methyl-2-nitrosopropane (MNP) was used as the spin-trap. The effects of ionizing radiation on the same polyamines in the polycrystalline state were also investigated. The free radicals produced by ..gamma..-radiolysis of these solids at room temperature in the absence of air were identified by dissolution in aqueous solutions of MNP. The predominant reaction of OH radicals with amines and polyamines below pH 7 was the abstraction of hydrogen atoms from a carbon that is not adjacent to the protonated amino group. For agmatine and arcaine which contain guanidinium groups abstraction occurred from the ..cap alpha..-CH. Dimethylamine was oxidized to the dimethylnitroxyl radical by H/sub 2/O/sub 2/ in the dark. ..gamma..-Radiolysis of polyamines in the polycrystalline state generated radicals due to H-abstraction from either the ..cap alpha..-Ch or from a carbon atom in the middle of the alkyl chain. The deamination radical was obtained from ornithine.

  12. Liposomes containing alkylated methotrexate analogues for phospholipase A(2) mediated tumor targeted drug delivery

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars; Jensen, Simon Skøde

    2009-01-01

    of alkylated compounds in liposomes, it was demonstrated that the MTX-analogue partitioned into the water phase and thereby became available for cell uptake. It was concluded that liposomes containing alkylated MTX-analogues show promise as a drug delivery system, although the MTX-analogue needs to be more......Two lipophilic methotrexate analogues have been synthesized and evaluated for cytotoxicity against KATO III and HT-29 human colon cancer cells. Both analogues contained a C-16-alkyl chain attached to the gamma-carboxylic acid and one of the analogues had an additional benzyl group attached...... cytotoxicity was incorporated into liposomes that were designed to be particularly Susceptible to a liposome degrading enzyme, secretory phospholipase A(2) (sPLA(2)), which is found in high concentrations in tumors of several different cancer types. Liposome incorporation was investigated by differential...

  13. Binding mechanisms for histamine and agmatine ligands in plasmid deoxyribonucleic acid purifications.

    Science.gov (United States)

    Sousa, Ângela; Pereira, Patrícia; Sousa, Fani; Queiroz, João A

    2014-10-31

    Histamine and agmatine amino acid derivatives were immobilized into monolithic disks, in order to combine the specificity and selectivity of the ligand with the high mass transfer and binding capacity offered by monolithic supports, to purify potential plasmid DNA biopharmaceuticals. Different elution strategies were explored by changing the type and salt concentration, as well as the pH, in order to understand the retention pattern of different plasmids isoforms The pVAX1-LacZ supercoiled isoform was isolated from a mixture of pDNA isoforms by using NaCl increasing stepwise gradient and also by ammonium sulfate decreasing stepwise gradient, in both histamine and agmatine monoliths. Acidic pH in the binding buffer mainly strengthened ionic interactions with both ligands in the presence of sodium chloride. Otherwise, for histamine ligand, pH values higher than 7 intensified hydrophobic interactions in the presence of ammonium sulfate. In addition, circular dichroism spectroscopy studies revealed that the binding and elution chromatographic conditions, such as the combination of high ionic strength with extreme pH values can reversibly influence the structural stability of the target nucleic acid. Therefore, ascending sodium chloride gradients with pH manipulation can be preferable chromatographic conditions to be explored in the purification of plasmid DNA biopharmaceuticals, in order to avoid the environmental impact of ammonium sulfate. Copyright © 2014. Published by Elsevier B.V.

  14. Inhibition of [gamma]-endorphin generating endopeptidase activity of rat brain by peptides: Structure activity relationship

    NARCIS (Netherlands)

    Lebouille, J.L.M.; Visser, W.H.; Hendriks, R.W.; Nispen, J.W. van; Greven, H.M.; Burbach, J.P.H.

    1985-01-01

    Gamma-Endorphin generating endopeptidase (gammaEGE) activity is an enzyme activity which converts beta-endorphin into gamma-endorphin and beta-endorphin-(18–31). The inhibitory potency on gammaEGE activity of neuropeptides and analogues or fragments of neuropeptides was tested. Dynorphin-(1–13)

  15. Comparison of the precision and accuracy of digital versus analogue gamma-ray spectrometric systems used in INAA for evaluation of homogeneity and certification of reference materials of the IAEA

    International Nuclear Information System (INIS)

    Makarewicz, M.; Burns, K.

    2000-01-01

    Performance of three commercial gamma-ray spectrometric systems was evaluated for precision and accuracy prior to use in characterization of reference materials. Two of the systems were based on fast processing of the analogue signal from the amplifier (EGG Ortec model 672) using a loss free counting module (Canberra model LFC 599) interfaced to one of two analog-to-digital converters (Canberra models 8713 or 8715). The third system was based on a digital signal processor (Canberra model DSP 9660). Performance of the systems was tested over a range of count rates up to a maximum of 70,000 counts per second (dead time up to 90%) using 60 Co and 137 Cs sources. Best resolution was achieved with an analogue system with ADC 8713. The analytical results obtained with the digital system show the lowest and well-quantified uncertainty. (author)

  16. AguR, a Transmembrane Transcription Activator of the Putrescine Biosynthesis Operon in Lactococcus lactis, Acts in Response to the Agmatine Concentration.

    Science.gov (United States)

    Linares, Daniel M; Del Rio, Beatriz; Redruello, Begoña; Ladero, Victor; Martin, M Cruz; de Jong, Anne; Kuipers, Oscar P; Fernandez, Maria; Alvarez, Miguel A

    2015-09-01

    Dairy industry fermentative processes mostly use Lactococcus lactis as a starter. However, some dairy L. lactis strains produce putrescine, a biogenic amine that raises food safety and spoilage concerns, via the agmatine deiminase (AGDI) pathway. The enzymatic activities responsible for putrescine biosynthesis in this bacterium are encoded by the AGDI gene cluster. The role of the catabolic genes aguB, aguD, aguA, and aguC has been studied, but knowledge regarding the role of aguR (the first gene in the cluster) remains limited. In the present work, aguR was found to be a very low level constitutively expressed gene that is essential for putrescine biosynthesis and is transcribed independently of the polycistronic mRNA encoding the catabolic genes (aguBDAC). In response to agmatine, AguR acts as a transcriptional activator of the aguB promoter (PaguB), which drives the transcription of the aguBDAC operon. Inverted sequences required for PaguB activity were identified by deletion analysis. Further work indicated that AguR is a transmembrane protein which might function as a one-component signal transduction system that senses the agmatine concentration of the medium and, accordingly, regulates the transcription of the aguBDAC operon through a C-terminal cytoplasmic DNA-binding domain typically found in LuxR-like proteins. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Some completely monotonic properties for the $(p,q )$-gamma function

    OpenAIRE

    Krasniqi, Valmir; Merovci, Faton

    2014-01-01

    It is defined $\\Gamma_{p,q}$ function, a generalize of $\\Gamma$ function. Also, we defined $\\psi_{p,q}$-analogue of the psi function as the log derivative of $\\Gamma_{p,q}$. For the $\\Gamma_{p,q}$ -function, are given some properties related to convexity, log-convexity and completely monotonic function. Also, some properties of $\\psi_{p,q} $ analog of the $\\psi$ function have been established. As an application, when $p\\to \\infty, q\\to 1,$ we obtain all result of \\cite{Valmir1} and \\cite{SHA}.

  18. CERTAIN INEQUALITIES INVOLVING THE Q-DEFORMED GAMMA FUNCTION

    Directory of Open Access Journals (Sweden)

    K. Nantomah

    2014-11-01

    Full Text Available This paper in inspired by the work of J.Sándor in 2006. In paper, the authors establish some double inequalities involving the ratio (Γq(x+1/(Γq(x+1/2, where Γq(x is the q-deformation of the classical Gamma function denoted by Γ(x. The method employed in presenting the results makes use of Jackson׳s q-integral representation of the q-deformed Gamma function. In addition, Hőlder׳s inequality for the q-integral, as well as some basic analytical techniques involving the q-analogue of the psi function are used. As a consequence, q-analogues of the classical Wendel׳s asymptotic relation are obtained. At the end, sharpness of the inequalities established in this paper is investigated.

  19. Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity

    DEFF Research Database (Denmark)

    Bolvig, T; Larsson, O M; Pickering, D S

    1999-01-01

    The inhibitory action of bicyclic isoxazole gamma-aminobutyric acid (GABA) analogues and their 4,4-diphenyl-3-butenyl (DPB) substituted derivatives has been investigated in cortical neurones and astrocytes as well as in human embryonic kidney (HEK 293) cells transiently expressing either mouse GA...... anticonvulsant activity, lack of proconvulsant activity and the ability of THPO to increase extracellular GABA concentration, indicate that these bicyclic isoxazole GABA analogues and their DPB derivatives may be useful lead structures in future search for new antiepileptic drugs....

  20. Effect of agmatine on experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Nader, M A; Gamiel, N M; El-Kashef, H; Zaghloul, M S

    2016-05-01

    This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium. © The Author(s) 2015.

  1. Analogue Gravity

    Directory of Open Access Journals (Sweden)

    Carlos Barceló

    2011-05-01

    Full Text Available Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

  2. AguR is a transmembrane transcription activator of the putrescine biosynthesis operon in Lactococcus lactis, and acts in response to agmatine concentration

    NARCIS (Netherlands)

    Linares, Daniel M; Del Rio, Beatriz; Redruello, Begoña; Ladero, Victor; Martin, Ma Cruz; de Jong, Anne; Kuipers, Oscar P; Fernandez, Maria; Alvarez, Miguel A

    2015-01-01

    Dairy industry fermentative processes mostly use Lactococcus lactis as a starter. However, some dairy L. lactis strains produce putrescine - a biogenic amine that raises food safety and spoilage concerns - via the agmatine deiminase pathway (AGDI). The enzymatic activities responsible for putrescine

  3. Expression of the Agmatine Deiminase Pathway in Enterococcus faecalis Is Activated by the AguR Regulator and Repressed by CcpA and PTSMan Systems

    Science.gov (United States)

    Blancato, Víctor S.; Magni, Christian

    2013-01-01

    Although the agmatine deiminase system (AgDI) has been investigated in Enterococcus faecalis, little information is available with respect to its gene regulation. In this study we demonstrate that the presence of exogenous agmatine induces the expression of agu genes in this bacterium. In contrast to the homologous and extensively characterized AgDI system of S. mutants, the aguBDAC operon in E. faecalis is not induced in response to low pH. In spite of this, agmatine catabolism in this bacterium contributes by neutralizing the external medium while enhancing bacterial growth. Our results indicate that carbon catabolic repression (CCR) operates on the AgDI system via a mechanism that involves interaction of CcpA and P-Ser-HPr with a cre site found in an unusual position considering the aguB promoter (55 nt upstream the +1 position). In addition, we found that components of the mannose phosphotransferase (PTSMan) system also contributed to CCR in E. faecalis since a complete relief of the PTS-sugars repressive effect was observed only in a PTSMan and CcpA double defective strain. Our gene context analysis revealed that aguR is present in oral and gastrointestinal microorganisms. Thus, regulation of the aguBDAC operon in E. faecalis seems to have evolved to obtain energy and resist low pH conditions in order to persist and colonize gastrointestinal niches. PMID:24155893

  4. Expression of the agmatine deiminase pathway in Enterococcus faecalis is activated by the AguR regulator and repressed by CcpA and PTS(Man systems.

    Directory of Open Access Journals (Sweden)

    Cristian Suárez

    Full Text Available Although the agmatine deiminase system (AgDI has been investigated in Enterococcus faecalis, little information is available with respect to its gene regulation. In this study we demonstrate that the presence of exogenous agmatine induces the expression of agu genes in this bacterium. In contrast to the homologous and extensively characterized AgDI system of S. mutants, the aguBDAC operon in E. faecalis is not induced in response to low pH. In spite of this, agmatine catabolism in this bacterium contributes by neutralizing the external medium while enhancing bacterial growth. Our results indicate that carbon catabolic repression (CCR operates on the AgDI system via a mechanism that involves interaction of CcpA and P-Ser-HPr with a cre site found in an unusual position considering the aguB promoter (55 nt upstream the +1 position. In addition, we found that components of the mannose phosphotransferase (PTS(Man system also contributed to CCR in E. faecalis since a complete relief of the PTS-sugars repressive effect was observed only in a PTS(Man and CcpA double defective strain. Our gene context analysis revealed that aguR is present in oral and gastrointestinal microorganisms. Thus, regulation of the aguBDAC operon in E. faecalis seems to have evolved to obtain energy and resist low pH conditions in order to persist and colonize gastrointestinal niches.

  5. Analogue Gravity

    Directory of Open Access Journals (Sweden)

    Barceló Carlos

    2005-12-01

    Full Text Available Analogue models of (and for gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity.

  6. In vivo regulation of gene transcription by alpha- and gamma-Tocopherol in murine T lymphocytes

    Science.gov (United States)

    Of the 8 different analogues (alpha-, beta-, gamma-, delta-tocopherols and tocotrienols) designated as vitamin E, alpha-tocopherol (a-T) has been mostly studied, together with gamma-tocopherol (g-T) which is abundant in the US diet. We compared the effect of dietary supplementation with adequate or ...

  7. Synthesis, Characterization, and Nonlinear Optical Properties of P-Substituted Poly Gamma-Benzyl

    Science.gov (United States)

    Choi, Dong-Hoon

    Poly gamma-benzyl-L-glutamate (PBLG), poly gamma-p-fluorobenzyl -L-glutamate (PGLU(pFB)), poly gamma -p-nitrobenzyl-L-glutamate (PGLU(pNB)), and poly gamma-p-trifluoromethylbenzyl-L-glutamate (PGLU(pTFMB)) have been synthesized. These PBLG polymers show variations in the side chain conformations in the solid state and solution state. In the solid state, the side chain orientation was assigned to a longitudinal or transverse direction by virtue of the polarized infrared spectrum of each PBLG analogue. The characteristics of the lyotropic liquid crystalline behavior could be observed. The optical waveguiding property of these polymers facilitated measurement of the refractive index and the thickness of each polymer film. Poling the polymer films and using the simple reflection technique, the electro -optic coefficients of the PBLG analogues could be determined. The effect of the para substitution on benzyl ester as it effected the electro-optic coefficient and the relation between the dielectric properties and the electro-optic effect of each polymer were investigated. These studies were able to demonstrate which conformation of the side chain in para substituted poly gamma-benzyl -L-glutamates is a more favorable conformation for enhancing the electro-optic behavior of these polymers.

  8. 6-Peroxo-6-zirconium crown and its hafnium analogue embedded in a triangular polyanion: [M6(O2)6(OH)6(gamma-SiW10O36)3]18- (M = Zr, Hf).

    Science.gov (United States)

    Bassil, Bassem S; Mal, Sib Sankar; Dickman, Michael H; Kortz, Ulrich; Oelrich, Holger; Walder, Lorenz

    2008-05-28

    We have synthesized and structurally characterized the unprecedented peroxo-zirconium(IV) containing [Zr6(O2)6(OH)6(gamma-SiW10O36)3]18- (1). Polyanion 1 comprises a cyclic 6-peroxo-6-zirconium core stabilized by three decatungstosilicate units. We have also prepared the isostructural hafnium(IV) analogue [Hf6(O2)6(OH)6(gamma-SiW10O36)3]18- (2). We investigated the acid/base and redox properties of 1 by UV-vis spectroscopy and electrochemistry studies. Polyanion 1 represents the first structurally characterized Zr-peroxo POM with side-on, bridging peroxo units. The simple, one-pot synthesis of 1 and 2 involving dropwise addition of aqueous hydrogen peroxide could represent a general procedure for incorporating peroxo groups into a large variety of transition metal and lanthanide containing POMs.

  9. Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation.

    Science.gov (United States)

    Huang, Y C; Tzeng, W S; Wang, C C; Cheng, B C; Chang, Y K; Chen, H H; Lin, P C; Huang, T Y; Chuang, T J; Lin, J W; Chang, C P

    2013-09-01

    This study aimed to further investigate the effects of agmatine on brain edema in the rats with middle cerebral artery occlusion (MCAO) injury using magnetic resonance imaging (MRI) monitoring and biochemical and histopathologic evaluation. Following surgical induction of MCAO for 90min, agmatine was injected 5min after beginning of reperfusion and again once daily for the next 3 post-operative days. The events during ischemia and reperfusion were investigated by T2-weighted images (T2WI), serial diffusion-weighted images (DWI), calculated apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted images (CE-T1WI) during 3h-72h in a 1.5T Siemens MAGNETON Avanto Scanner. Lesion volumes were analyzed in a blinded and randomized manner. Triphenyltetrazolium chloride (TTC), Nissl, and Evans Blue stainings were performed at the corresponding sections. Increased lesion volumes derived from T2WI, DWI, ADC, CE-T1WI, and TTC all were noted at 3h and peaked at 24h-48h after MCAO injury. TTC-derived infarct volumes were not significantly different from the T2WI, DWI-, and CE-T1WI-derived lesion volumes at the last imaging time (72h) point except for significantly smaller ADC lesions in the MCAO model (Pagmatine-treated rats compared with the control ischemia rats (Pagmatine has neuroprotective effects against brain edema on a reperfusion model after transient cerebral ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Synthesis of analogues of Eunicea gamma-cembranolides containing cyclic ethers via saponification.

    Science.gov (United States)

    Rodríguez, A D; Piña, I C; Acosta, A L; Ramírez, C; Soto, J J

    2001-02-09

    A method for the synthesis of derivatives of the lead structures euniolide (1), 12,13-bisepieupalmerin (2), and eupalmerin acetate (3) containing tetrahydrofuran and tetrahydropyran ring systems was developed on the basis of alkali-induced intramolecular oxacyclizations. Representatives of the new analogues were submitted to the in vitro antitumor cell-line-screening program of the National Cancer Institute (NCI). While it was shown that a variety of structural modifications are possible, these transformations led typically to nontoxic synthetic cembranoids.

  11. Analogue MIMO Detection

    Directory of Open Access Journals (Sweden)

    McNamara Darren

    2006-01-01

    Full Text Available In this contribution we propose an analogue receiver that can perform turbo detection in MIMO systems. We present the case for a receiver that is built from nonlinear analogue devices, which perform detection in a "free-flow" network (no notion of iterations. This contribution can be viewed as an extension of analogue turbo decoder concepts to include MIMO detection. These first analogue implementations report reductions of few orders of magnitude in the number of required transistors and in consumed energy, and the same order of improvement in processing speed. It is anticipated that such analogue MIMO decoder could bring about the same advantages, when compared to traditional digital implementations.

  12. Gamma Anna’: a classroom demonstration for teaching the concepts of gamma imaging

    Science.gov (United States)

    Wolff, Nicola; Griffiths, Jennifer; Yerworth, Rebecca

    2017-01-01

    Gamma imaging is at the interface of medicine and physics and thus its teaching is important in both fields. Pedagogic literature highlights the benefits of interactive demonstrations in teaching: an increase in enjoyment and interest, as well as improvement in academic achievement. However gamma imaging uses radioactive sources, which are potentially dangerous and thus their use is tightly controlled. We have developed a demonstration which uses a localised exothermic reaction within a rag doll as an analogue of radioactivity. This can be safely used in classrooms to demonstrate the principles of gamma imaging. The tool is easy to make, cheap, robust and portable. The supplementary material in this paper gives teacher notes and a description of how to make the rag doll demonstrator. We have tested the tool using six participants, acting as ‘teachers’, who carried out the demonstration and described the doll as easy to use, and the ‘tumour’ clearly identifiable. The teaching tool was separately demonstrated to a group of 12 GCSE physics students and a group of 12 medical students. Feedback showed increased student engagement, enjoyment and understanding of gamma imaging. Previous research has shown that these benefits have an impact on learning and academic outcomes.

  13. Protective Effects of Agmatine against Chlorpromazine- Induced Toxicity in the Liver of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Dejanović Bratislav

    2016-03-01

    Full Text Available The metabolic pathways of chlorpromazine (CPZ toxicity were tracked by assessing oxidative/nitrosative stress markers. The main objective of the study was to test the hypothesis that agmatine (AGM prevents oxidative/nitrosative stress in the liver of Wistar rats 15 days after administration of CPZ. All tested substances were administered intraperitoneally (i.p. for 15 consecutive days. The rats were divided into four groups: the control group (C, 0.9 % saline solution, the CPZ group (CPZ, 38.7 mg/kg b.w., the CPZ+AGM group (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p. and the AGM group (AGM, 75 mg/kg b.w..

  14. Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats.

    Science.gov (United States)

    Dejanovic, Bratislav; Stevanovic, Ivana; Ninkovic, Milica; Stojanovic, Ivana; Lavrnja, Irena; Radicevic, Tatjana; Pavlovic, Milos

    2016-03-01

    This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.

  15. Modulation of interferon-induced genes by lipoxin analogue in anti-glomerular basement membrane nephritis.

    Science.gov (United States)

    Ohse, Takamoto; Ota, Tatsuru; Kieran, Niamh; Godson, Catherine; Yamada, Koei; Tanaka, Tetsuhiro; Fujita, Toshiro; Nangaku, Masaomi

    2004-04-01

    Immune complex deposition is associated with the accumulation of neutrophils, which play an important role in the various immune-mediated diseases. A novel anti-inflammatory agent, the lipoxin A (LXA) analogue (15-epi-16-(FPhO)-LXA-Me)), a stable synthetic analogue of aspirin-triggered 15-epi-lipoxin A4 (ATLa), was used in experimental anti-glomerular basement membrane (GBM) antibody nephritis in mice. ATLa was administered before the induction of the disease, and 2 h later, the animals were killed. ATLa reduced the infiltrating neutrophils and nitrotyrosine staining in glomeruli. Subsequent changes of gene expression in the early phase were evaluated, and 5674 genes were present under the basal conditions in kidneys from normal mice; 54 upregulated genes and 25 downregulated genes were detected in anti-GBM nephritis. Eighteen of these upregulated genes were those induced by IFN-gamma. Real-time quantitative PCR analysis confirmed the results of the microarrays. To investigate a role of IFN-gamma in neutrophil infiltration, anti-GBM nephritis was induced in IFN-gamma knockout mice. The number of infiltrating neutrophils in these mice did not differ from those in wild-type mice. Also examined were CD11b expression on neutrophils from mice treated with ATLa by flow cytometry, but suppression of this adhesion molecule was not observed. Neutrophil infiltration was successfully inhibited by ATLa in the early phase of murine anti-GBM nephritis. Microarray analysis detected the change of mRNA expression in anti-GBM nephritis and demonstrated amelioration of various genes by ATLa, which may provide a clue to the development of novel therapeutic approaches in immune renal injury.

  16. Tensile behaviour and properties of a bone analogue composite (HA, HDPE) crosslinked by gamma radiation

    International Nuclear Information System (INIS)

    Romero, G.; Smolko, Eduardo E.

    2005-01-01

    A natural composite material, hydroxyapatite (HA) and high density polyethylene (HDPE) crosslinked by ionizing radiations is been developed as a bioactive analogue material for bone replacement. Mechanical properties of the composites irradiated up to 300 kGy under tensile tests was studied. Gel content and micrographs of different composite fractures are shown. (author)

  17. Development and evaluation of a Gamma Camera tuning system

    International Nuclear Information System (INIS)

    Arista Romeu, E. J.; Diaz Garcia, A.; Osorio Deliz, J. F.

    2015-01-01

    Correct operation of conventional analogue Gamma Cameras implies a good conformation of the position signals that correspond to a specific photo-peak of the radionuclide of interest. In order to achieve this goal the energy spectrum from each photo multiplier tube (PMT) has to be set within the same energy window. For this reason a reliable tuning system is an important part of all gamma cameras processing systems. In this work is being tested and evaluated a new prototype of tuning card that was developed and setting up for this purpose. The hardware and software of the circuit allow the regulation if each PMT high voltage. By this means a proper gain control for each of them is accomplished. The Tuning Card prototype was simulated in a virtual model and its satisfactory operation was proven in a Siemens Orbiter Gamma Camera. (Author)

  18. Focused Review: Agmatine in fermented foods

    Directory of Open Access Journals (Sweden)

    Fernanda eGalgano

    2012-06-01

    Full Text Available Polyamines (PAs are ubiquitous substances considered as bioregulators of numerous cell functions, being involved in cell growth, division and differentiation. These biogenic amines are also involved in tissue repairing and in intracellular signaling; in fact, because of their polycationic character, they interact strongly with membrane phospholipids and may play an important role in the regulation of membrane-linked enzymes. The intracellular polyamines content derives from the simultaneous regulation of their synthesis, catabolism, uptake and elimination; furthermore, PAs are present in all cell types at variable concentrations, but the highest levels are found in rapid-turnover tissues. In addition to spermidine, spermine and putrescine, also agmatine (AGM, deriving from arginine and identified in mammals in the 1990s, belongs to PAs and several studies have reported its possible positive role in secretagogues, neuronal, vascular, metabolic and therapeutic functions. Because of the low arginine decarboxylase activity (ADC in mammalians, the amounts of AGM found in their tissues can be only minimally ascribed to an endogenous de novo synthesis by the ADC, while a substantial AGM portion can be of dietary origin. Several food products contain only small amounts of polyamines, while higher concentrations can be found in fermented foods. PAs could also be considered as indicators of freshness in fish and meat products, being these moieties produced during food storage, thus confirming the main role of microorganisms in their synthesis. Although many biological functions have been attributed to polyamines, high levels of these compounds in foodstuffs can have toxicological effects; however, the safe level of dietary polyamines intake has not yet been established. In this paper the presence of AGM in different foodstuffs is discussed, taking also into account the various factors affecting its presence and concentration.

  19. Rethinking of the criteria for natural analogue study. A case of Tono natural analogue study

    International Nuclear Information System (INIS)

    Yoshida, Hidekazu

    1996-01-01

    Natural analogue regarding long-term performance of the geological disposal system for radioactive waste isolation is essentially the study of geochemical process which has been evolved in geological environment. All geochemical studies, however, will not be nominated as natural analogue studies. It is, therefore, important to be clear the criteria for natural analogue study with the view of analogy by following three categories, (1) Conceptual model development, (2) Data provision and (3) Model testing, for the concept of geological disposal and safety assessment model. Rethinking of the criteria for natural analogue study through the case of Tono Natural Analogue Study, and the usefulness of natural analogue study for the safety assessment of geological disposal system in Japan have been presented in this paper. (author)

  20. CEC natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1986-01-01

    The second meeting of the CEC Natural Analogue Working Group took place on June 17-19, 1986, hosted by the Swiss NAGRA in Interlaken (CH). A review of recent progress in natural analogue programmes was carried out, and complemented by detailed discussions about geomicrobiology, archaeological analogues, natural colloids, and use of analogues to increase confidence in safety assessments for radioactive waste disposal. A statement drafted by the Group, and the presentations made, are put together in this report

  1. Analogue-digital conversion in order to evaluate long-term changes in uptake of isotopes in bone scintigraphy of secondary hyperparathyroidism

    International Nuclear Information System (INIS)

    Iida, Akihiko

    1994-01-01

    An analogue-digital conversion was developed, thereby allowing the incorporation of whole-body bone scintigrams, obtained by a gamma camera, into digital data via the video camera and then allowing the processing of the incorporated digital data. Using the new method, 18 hemodialysis patients, who were voluntarily selected from those who had undergone bone scintigraphy with 99m Tc-HMDP for secondary hyperparathyroidism, were examined to determine serial changes in tracer uptake. The mean duration of hemodialysis was 6. 3 years (immediately up to 25.2 years). The tracer count ratio of the central part of the skull to the lower part of the sternum correlated most well with C-PTH. The analogue-digital conversion was found to yield a slightly higher value for the above-mentioned ratio than the original data; however, there was a good correlation between the analogue-digital conversion and original data. (N.K.)

  2. Improved method for HPLC analysis of polyamines, agmatine and aromatic monoamines in plant tissue

    Science.gov (United States)

    Slocum, R. D.; Flores, H. E.; Galston, A. W.; Weinstein, L. H.

    1989-01-01

    The high performance liquid chromatographic (HPLC) method of Flores and Galston (1982 Plant Physiol 69: 701) for the separation and quantitation of benzoylated polyamines in plant tissues has been widely adopted by other workers. However, due to previously unrecognized problems associated with the derivatization of agmatine, this important intermediate in plant polyamine metabolism cannot be quantitated using this method. Also, two polyamines, putrescine and diaminopropane, also are not well resolved using this method. A simple modification of the original HPLC procedure greatly improves the separation and quantitation of these amines, and further allows the simulation analysis of phenethylamine and tyramine, which are major monoamine constituents of tobacco and other plant tissues. We have used this modified HPLC method to characterize amine titers in suspension cultured carrot (Daucas carota L.) cells and tobacco (Nicotiana tabacum L.) leaf tissues.

  3. CEC Natural Analogue Working Group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1989-01-01

    The central theme for the third meeting of the CEC analogue working group was ''How can analogue data be used for performance assessments, both in support of the results and for presentation to the public''. This report puts together the most recent achievements in this field, together with a review of on-going natural analogue programmes

  4. Tinnitus intensity dependent gamma oscillations of the contralateral auditory cortex.

    Directory of Open Access Journals (Sweden)

    Elsa van der Loo

    Full Text Available BACKGROUND: Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. METHODS AND FINDINGS: In unilateral tinnitus patients (N = 15; 10 right, 5 left source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05. CONCLUSION: Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.

  5. Quantification of extracorporal platelet deposition in cardiopulmonary bypass: Effects of ZK 36374, a prostacyclin analogue

    Energy Technology Data Exchange (ETDEWEB)

    Martin, W.; Spyt, T.; Wheatley, D.J.; Thomas, I.; Davidson, J.F.

    1989-03-01

    The degree of extracorporal platelet sequestration in 32 patients undergoing cardiopulmonary bypass has been assessed using /sup 111/In labelled platelets and both a shadow shield whole body monitor and a standard gamma camera. The effects of ZK 36374, a prostacyclin analogue, on deposition of platelets in the oxygenator and atrial line filter were also investigated. Total platelet deposition in the placebo group ranged from 2.2% to 31.7%, mean 13.9+-7.8%; n=15, and was significantly higher than the deposition in the treatment group, range 0.7% to 9.4%, mean 3.9+-2.6%; n=16, P < 0.001. There was also a highly significant correlation between the gamma camera and whole body monitor measurements, r=0.99, P < 0.001, with no systematic difference between the techniques. This study demonstrates that accurate quantitative assessment of platelet deposition can be achieved with either the gamma camera or whole body monitor. In addition, significant reduction in platelet sequestration in the extracorporal circuit can be achieved by using ZK 36374 during the bypass operation.

  6. Anchor of Ni2+ on the Agmatine Sulfate-Modified Electrodes for the Determination of H2O2 in Food

    Science.gov (United States)

    Yan, Yuhua; Zhang, Zhonghui; Xiao, Mingshu; Zhou, Hualan

    2017-07-01

    A method was developed to conveniently and rapidly determine hydrogen peroxide (H2O2) in food. The glassy carbon electrode (GCE) modified with agmatine sulfate (AS) easily anchoring nickel ion was attached to AS with polyamine structure. As a result, more Ni2+ was obtained and transformed to Ni(OH)2/NiOOH on the AS-GCE, which caused the electrode to own much better electrocatalytic performance on H2O2. Based on these, the content of H2O2 in thin sheet of bean curd sample was detected with standard addition method, by which good results were obtained.

  7. Analogue alternative the electronic analogue computer in Britain and the USA, 1930-1975

    CERN Document Server

    Small, James S

    2013-01-01

    We are in the midst of a digital revolution - until recently, the majority of appliances used in everyday life have been developed with analogue technology. Now, either at home or out and about, we are surrounded by digital technology such as digital 'film', audio systems, computers and telephones. From the late 1940s until the 1970s, analogue technology was a genuine alternative to digital, and the two competing technologies ran parallel with each other. During this period, a community of engineers, scientists, academics and businessmen continued to develop and promote the analogue computer.

  8. Prevalence of the lmo0036-0043 gene cluster encoding arginine deiminase and agmatine deiminase systems in Listeria monocytogenes.

    Science.gov (United States)

    Chen, Jianshun; Chen, Fan; Cheng, Changyong; Fang, Weihuan

    2013-04-01

    Arginine deiminase and agmatine deiminase systems are involved in acid tolerance, and their encoding genes form the cluster lmo0036-0043 in Listeria monocytogenes. While lmo0042 and lmo0043 were conserved in all L. monocytogenes strains, the lmo0036-0041 region of this cluster was identified in all lineages I and II, and the majority of lineage IV (83.3%) strains, but absent in all lineage III and a small fraction of lineage IV (16.7%) strains, suggesting that the presence of the complete lmo0036-0043 cluster is dependent on lineages. lmo0036-0043-complete and -deficient lineage IV strains exhibit specific ascB-dapE profiles, which might represent two subpopulations with distinct genetic characteristics.

  9. 2-D DIGE proteomic profiles of three strains of Fusarium graminearum grown in agmatine or glutamic acid medium

    Directory of Open Access Journals (Sweden)

    Tommaso Serchi

    2016-03-01

    Full Text Available 2D DIGE proteomics data obtained from three strains belonging to Fusarium graminearum s.s. species growing in a glutamic acid or agmatine containing medium are provided.A total of 381 protein species have been identified which do differ for abundance among the two treatments and among the strains (ANOVA±1.3.Data on the diversity of protein species profiles between the two media for each strain are made available. Shared profiles among strains are discussed in Pasquali et al. [1].Here proteins that with diverse profile can be used to differentiate strains are highlighted. The full dataset allow to obtaining single strain proteomic profiles. Keywords: Comparative strain proteomics, Toxigenic fungi, Polyamines, Trichothecenes, Strain variability

  10. Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor

    DEFF Research Database (Denmark)

    Geisler, C; Pallesen, G; Platz, P

    1989-01-01

    Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor....... Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected...... deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue....

  11. Natural Analogue Synthesis Report

    Energy Technology Data Exchange (ETDEWEB)

    A. M. Simmons

    2002-05-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the ''Yucca Mountain Site Description'' (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport

  12. NATURAL ANALOGUE SYNTHESIS REPORT

    International Nuclear Information System (INIS)

    Simmons, A.M.

    2004-01-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature along with results of quantitative studies conducted specifically for the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement-drift degradation, waste-form degradation, waste-package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated-zone (SZ) transport, impact of radionuclide release on the biosphere

  13. Use of analogues to build technologists' confidence: NAnet

    International Nuclear Information System (INIS)

    Noseck, Ulrich

    2008-01-01

    The relevance of analogues to radioactive waste management stems from the long timescales that have to be considered. Periods up to a million or more years into the future need to be considered and these are beyond experimental investigation and human experience. Within the last years the term 'Natural Analogue' has got a much wider meaning and includes man-made analogues as well. The role of natural analogues in the safety case depends amongst others on the time scale to be covered. Therefore, it is useful to classify them by the time period addressed in the study. Here it is referred to: industrial analogues which started earliest 150 years ago, archaeological analogues, which cover time frames between the past 10 000 and 150 years, and geological analogues, which usually cover time frames of more than 10 000 years and in most cases more than million years. The current interest in analogues in different countries is reflected by several recent review projects with emphasis on the application of natural analogue study results in performance assessment. The most recent international review was performed within the 5. EURATOM Framework of the EC by the NAnet project, a network on the review of natural analogue studies with emphasis on the application of analogues in long-term safety assessment and communication. The overall aim of the NAnet project was to review the past and present use and understanding of natural analogues, and to make recommendations for their future use. The project covered 'traditional' natural analogue studies, such as large-scale investigations of radionuclide transport around uranium ore bodies, and process or mechanistic analogue studies such as those examining natural glass and bentonite clay stability. To complete the picture, a restricted range of other studies of natural systems which employ a similar philosophy to analogues was also included in the scope. These included studies which have examined radionuclide transport and retardation

  14. Natural and archaeological analogues: a review

    International Nuclear Information System (INIS)

    Brookins, D.G.

    1987-01-01

    In this chapter natural analogues in the geomedia for various aspects of radioactive waste disposal are discussed. Particular reference is made to the Okla Natural Reactor in Gabon. Igneous contact zones are discussed and natural analogues of waste-form materials. The importance of archaeological remains and anthropogenic materials left by man, in assessing weathering conditions and serving as radioactive waste analogues, is also emphasised. (UK)

  15. Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Dejanović Bratislav

    2015-01-01

    Full Text Available The present study was directed to potentially beneficial effects of agmatine (AGM on oxidative/nitrosative stress development in selective vulnerable brain regions during chlorpromazine (HPZ treatment in rats. All tested compounds were administered intraperitoneally (i.p. in one single dose. The animals were divided into control (K, 0.9 % saline solution, HPZ (HPZ, 38.7 mg/kg b.w., HPZ+AGM (AGM, 75 mg/kg b.w. immediately after HPZ, 38.7 mg/kg b.w. i.p. and AGM (AGM, 75 mg/kg b.w. groups. Rats were sacrificed by decapitation 24 hours after the treatment. Analysis of data showed that HPZ+AGM injection significantly decreased drug concentration compared with HPZ-animals (p<0.05. HPZ application increased lipid peroxidation (p<0.001 in cortex, striatum and hippocampus, nitrite and nitrate concentration (p<0.001 in all three brain regions and superoxide anion production (p<0.05 in all three brain structures, while completely damaged enzymatic antioxidative defense system (superoxide dismutase in both cortex and striatum p<0.05 and hippocampus p<0.001; glutathion reductase in both cortex and striatum p<0.001 and hippocampus p<0.05; catalase in cortex p<0.001 and both striatum and hippocampus p<0.05. However, treatment with AGM significantly attenuated the oxidative stress parameters compared to HPZ-group (lipid peroxidation in cortex p<0.001, striatum p<0.01 and hippocampus p<0.05; nitrite and nitrate concentration in all three brain structures p<0.001 and restores antioxidant capacity to control values in all examined brain structures. Immunohistochemical staining of GFAP molecules in rats showed an increase in the number of positive cells 24 h after acute HPZ-administration. All these results indicate that AGM may be effective in the protection of HPZ-induced brain injury in rats.

  16. Poly(Amido Amine)s Containing Agmatine and Butanol Side Chains as Efficient Gene Carriers.

    Science.gov (United States)

    Won, Young-Wook; Ankoné, Marc; Engbersen, Johan F J; Feijen, Jan; Kim, Sung Wan

    2016-04-01

    A new type of bioreducible poly(amido amine) copolymer is synthesized by the Michael addition polymerization of cystamine bisacrylamide (CBA) with 4-aminobutylguanidine (agmatine, AGM) and 4-aminobutanol (ABOL). Since the positively charged guanidinium groups of AGM and the hydroxybutyl groups of ABOL in the side chains have shown to improve the overall transfection efficiency of poly(amido amine)s, it is hypothesized that poly(CBA-ABOL/AGM) synthesized at the optimal ratio of both components would result in high transfection efficiency and minimal toxicity. In this study, a series of the poly(CBA-ABOL/AGM) copolymers is synthesized as gene carriers. The polymers are characterized and luciferase transfection efficiencies of the polymers in various cell lines are investigated to select the ideal ratio between AGM and ABOL. The poly(CBA-ABOL/AGM) containing 80% AGM and 20% ABOL has shown the best transfection efficiency with the lowest cytotoxicity, indicating that this polymer is very promising as a potent and nontoxic gene carrier. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A Short Term Analogue Memory

    DEFF Research Database (Denmark)

    Shah, Peter Jivan

    1992-01-01

    A short term analogue memory is described. It is based on a well-known sample-hold topology in which leakage currents have been minimized partly by circuit design and partly by layout techniques. Measurements on a test chip implemented in a standard 2.4 micron analogue CMOS process show a droop...

  18. Analogue to Digital and Digital to Analogue Converters (ADCs and DACs): A Review Update

    CERN Document Server

    Pickering, J.

    2015-06-15

    This is a review paper updated from that presented for CAS 2004. Essentially, since then, commercial components have continued to extend their performance boundaries but the basic building blocks and the techniques for choosing the best device and implementing it in a design have not changed. Analogue to digital and digital to analogue converters are crucial components in the continued drive to replace analogue circuitry with more controllable and less costly digital processing. This paper discusses the technologies available to perform in the likely measurement and control applications that arise within accelerators. It covers much of the terminology and 'specmanship' together with an application-oriented analysis of the realisable performance of the various types. Finally, some hints and warnings on system integration problems are given.

  19. Quantum analogue computing.

    Science.gov (United States)

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  20. Synthesis and evaluation of antimicrobial activity of halogenated furans and analogue compounds to nostoclides; Sintese e avaliacao da atividade antimicrobiana de furanonas halogenadas e de compostos analogos aos nostoclideos

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Luiz C.A.; Maltha, Celia R.A.; Demuner, Antonio J.; Pinheiro, Patricia F.; Varejao, Jodieh O.S.; Montanari, Ricardo M., E-mail: lcab@ufv.b [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Quimica; Andrade, Nelio J. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Ciencia e Tecnologia de Alimentos

    2010-07-01

    Considering the broad spectrum of biological activity of gamma-butyrolactone derivatives, we presented the synthesis of 3,4-dihalo-5-arylidenefuran-2(5H)-ones (17-21) and analogues (24-28) of the natural product nostoclide (7,8). Furanones 17-21 were synthesized from the condensation of aromatic aldehydes with lactones 14 and 15, that were obtained from mucobromic and mucochloric acids. Lactone 15 was converted into the intermediate 23 in 36% overall yield. Compound 23 was then transformed into the nostoclide analogues 24-28. Some of the compounds prepared showed antimicrobial activities against Escherichia coli, Staphylococcus aureus and Bacillus cereus comparable to commercial antibiotics. (author)

  1. BALANOL ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a solid phase methodology for the preparation of a combinatorial library of structural analogues of the natural product balanol (ophiocordin, azepinostatin), which is a protein kinase C (PKC) and protein kinase A (PKA) inhibitor. The method comprises solid...

  2. Cephalostatin analogues--synthesis and biological activity.

    Science.gov (United States)

    Flessner, Timo; Jautelat, Rolf; Scholz, Ulrich; Winterfeldt, Ekkehard

    2004-01-01

    Starting off in the early 90's the field of cephalostatin analogues has continually expanded over the last 10 years. First syntheses prepared symmetric analogues like 14b (119) and 26 (65), which were subsequently desymmetrized to provide analogues like beta-hydroxy ketone 31 (19). Importantly the straightforward approach provided already compounds with mu-molar potency and the same pattern of activity as cephalostatin 1 (1) (see Chapter 2.1). Chemically more demanding, two new methods for the directed synthesis of (bissteroidal) pyrazines were devised and subsequently applied to a wide variety of differently functionalized coupling partners. These new methods allowed for the synthesis of various analogues (Chapter 2.2.; and, last but not least, for the totals synthesis of several cephalostatin natural products; Chapter 1.). Functionalization and derivatization of the 12-position was performed (Chapter 2.1 and 3) and synthetic approaches to establish the D-ring double bond were successfully investigated (Chapter 3). [figure: see text] Dealing synthetically with the spiroketal moiety, novel oxidative opening procedures on monomeric delta 14, 15-steroids were devised as well as intensive studies regarding spiroketal synthesis and spiroketal rearrangements were conducted (Chapter 3.2. and 4.). Last but not least direct chemical modification of ritterazines and cephalostatins were studied, which provided a limited number of ritterazine analogues (Chapter 4.). All these synthetic activities towards analogues are summarized in Fig. 18. During this period of time the growing number of cephalostatins and ritterazines on the one hand and of analogues on the other hand provided several SAR trends, which can guide future analogue synthesis. The combined SAR findings are displayed in Fig. 19. So far it is apparent that: Additional methoxylations or hydroxylations in the steroidal A ring core structure (1-position) are slightly decreasing activity (compare cephalostatin 1 1 to

  3. Analogue to Digital and Digital to Analogue (AD/DA) Conversion Techniques: An Overview

    CERN Multimedia

    CERN. Geneva

    2002-01-01

    The basic ideas behind modern Analogue to Digital and Digital to Analogue (AD/DA) conversion methods will be introduced: a general view of the importance of these devices will be given, along with the digital representation of time-varying, real-world analogue signals. Some CERN applications will be outlined. The variety of conversion methods, their limitations, error sources and measurement methods will form the major part of this presentation. A review of the technological progress in this field over the last 30 years will be presented, concluding with the present 'state of the art' and a quick look at what is just around the corner. This Technical Training Seminar is in the framework of the FEED-2002 Lecture Series, and it is a prerequisite to attending to any of the FEED-2002 Terms. FEED-2002 is a two-term course that will review the techniques dealing with closed loop systems, focussing on time-invariant linear systems. (free attendance, no registration required) More information on the FEED-2002 ...

  4. Effects of agmatine on secretion of interferon tau and catecholamines and expression of genes related to production of polyamines by ovine trophectoderm cells.

    Science.gov (United States)

    Lenis, Yasser Y; Wang, Xiaoqiu; Tang, Wanjin; Wu, Guoyao; Bazer, Fuller W

    2016-10-01

    Embryonic survival requires histotrophic nutrition, including molecules secreted or transported into the uterine lumen by uterine epithelia. L-Arginine (Arg) is a common substrate for synthesis of nitric oxide, ornithine, proline, glutamate, creatinine, urea, polyamines and agmatine. Agmatine (Agm) is a product of arginine decarboxylation and it is a substrate for agmatinase for synthesis of putrescine and other polyamines in the ovine conceptus. Polyamines are essential for conceptus development. Therefore, this study compared effects of Arg and Agm on the behavior of ovine trophectoderm (oTr1) cells cultured in vitro. Arg, but not Agm, increased proliferation and migration of oTr1 cells, but neither Arg nor Agm affected cell adhesion. The total amount of IFNT in culture medium of oTr1 cells was increased by Arg, but Agm increased the IFNT production per oTr1 cell. Arg and Agm plus Arg decreased secretion of dopamine and norepinephrine by oTr1 cells. Agm upregulates expression of mRNAs SLC7A1, agmatinase and OAZ2 while the combination of Arg and Agm decreased expression of mRNAs for ODC1, SLC7A1, OAZ1 and OAZ3 by oTr1 cells. Although Agm does not stimulate proliferation, migration or adhesion of oTr1 cells or their secretion of catecholamines, Agm did increase transcription of SLC7A1, agmatinase and OAZ2 genes which would increase the capacity of oTr1 cells to produce polyamines. Collectively, our findings suggest a role for Arg and Agm in the regulation of transport of basic amino acids (including Arg), polyamine synthesis, and secretion of catecholamines by oTr1 cells.

  5. Depression of DNA synthesis rate following hyperthermia, gamma irradiation, cyclotron neutrons and mixed modalities

    International Nuclear Information System (INIS)

    Weber, H.J.; Muehlensiepen, H.; Porschen, W.; Feinendegen, L.E.; Dietzel, F.

    1978-01-01

    The incorporation of the thymidine analogue I-UdR is proportional to the activity of DNA synthesis. The maximum depression of 125-I-UdR incorporation occurs approximately 4 hours after all kinds of treatment. The increase which follow reflects cell processes like reoxygeneration, recovery, recycling and recruitment (although a direct relation is not yet demonstrable). The degree of depression 4 hours after treatment and the time required needs to reach control level is dependent on dose and radiation quaility but no such dependence could be clearly seen for the times of hyperthermia treatment we used. Neutron irradiation and the combination gamma irradiation + hyperthermia show a higher depression and a slower return to normal than gamma irradiation at the same dose. (orig.) [de

  6. International video project on natural analogues

    International Nuclear Information System (INIS)

    Guentensperger, Marcel

    1993-01-01

    A natural analogue can be defined as a natural process which has occurred in the past and is studied in order to test predictions about the future evolution of similar processes. In recent years, natural analogues have been used increasingly to test the mathematical models required for repository performance assessment. Analogues are, however, also of considerable use in public relations as they allow many of the principles involved in demonstrating repository safety to be illustrated in a clear manner using natural systems with which man is familiar. The international Natural Analogue Working Group (NAWG), organised under the auspices of the CEC, has recognised that such PR applications are of considerable importance and should be supported from a technical level. At the NAWG meeting in Pitlochry, Scotland (June 1990), it was recommended that the possibilities for making a video film on this topic be investigated and Nagra was requested to take the lead role in setting up such a project

  7. Molecular mechanism of pH-dependent substrate transport by an arginine-agmatine antiporter.

    Science.gov (United States)

    Wang, Sheng; Yan, Renhong; Zhang, Xi; Chu, Qi; Shi, Yigong

    2014-09-02

    Enteropathogenic bacteria, exemplified by Escherichia coli, rely on acid-resistance systems (ARs) to survive the acidic environment of the stomach. AR3 consumes intracellular protons through decarboxylation of arginine (Arg) in the cytoplasm and exchange of the reaction product agmatine (Agm) with extracellular Arg. The latter process is mediated by the Arg:Agm antiporter AdiC, which is activated in response to acidic pH and remains fully active at pH 6.0 and below. Despite our knowledge of structural information, the molecular mechanism by which AdiC senses acidic pH remains completely unknown. Relying on alanine-scanning mutagenesis and an in vitro proteoliposome-based transport assay, we have identified Tyr74 as a critical pH sensor in AdiC. The AdiC variant Y74A exhibited robust transport activity at all pH values examined while maintaining stringent substrate specificity for Arg:Agm. Replacement of Tyr74 by Phe, but not by any other amino acid, led to the maintenance of pH-dependent substrate transport. These observations, in conjunction with structural information, identify a working model for pH-induced activation of AdiC in which a closed conformation is disrupted by cation-π interactions between proton and the aromatic side chain of Tyr74.

  8. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters

    Directory of Open Access Journals (Sweden)

    Hüseyin Ilgü

    2018-03-01

    Full Text Available The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg, agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5, an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  9. Analogue Hawking radiation from astrophysical black-hole accretion

    International Nuclear Information System (INIS)

    Das, Tapas K

    2004-01-01

    We show that spherical accretion onto astrophysical black holes can be considered as a natural example of an analogue system. We provide, for the first time, an exact analytical scheme for calculating the analogue Hawking temperature and surface gravity for general relativistic accretion onto astrophysical black holes. Our calculation may bridge the gap between the theory of transonic astrophysical accretion and the theory of analogue Hawking radiation. We show that the domination of the analogue Hawking temperature over the actual Hawking temperature may be a real astrophysical phenomenon, though observational tests of this fact will at best be difficult and at worst might prove to be impossible. We also discuss the possibilities of the emergence of analogue white holes around astrophysical black holes. Our calculation is general enough to accommodate accreting black holes with any mass

  10. The molecular and metabolic influence of long term agmatine consumption.

    Science.gov (United States)

    Nissim, Itzhak; Horyn, Oksana; Daikhin, Yevgeny; Chen, Pan; Li, Changhong; Wehrli, Suzanne L; Nissim, Ilana; Yudkoff, Marc

    2014-04-04

    Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used (13)C or (15)N tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor-α and its coactivator, PGC1α, and (b) increased expression of peroxisomal proliferator-activated receptor-γ and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased β-oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming.

  11. The Molecular and Metabolic Influence of Long Term Agmatine Consumption*

    Science.gov (United States)

    Nissim, Itzhak; Horyn, Oksana; Daikhin, Yevgeny; Chen, Pan; Li, Changhong; Wehrli, Suzanne L.; Nissim, Ilana; Yudkoff, Marc

    2014-01-01

    Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used 13C or 15N tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor-α and its coactivator, PGC1α, and (b) increased expression of peroxisomal proliferator-activated receptor-γ and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased β-oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming. PMID:24523404

  12. Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

    Science.gov (United States)

    Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

    1991-11-01

    To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and

  13. Synthesis and biological evaluation of febrifugine analogues.

    Science.gov (United States)

    Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

    2014-12-01

    A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

  14. Assessment of six dissimilarity metrics for climate analogues

    Science.gov (United States)

    Grenier, Patrick; Parent, Annie-Claude; Huard, David; Anctil, François; Chaumont, Diane

    2013-04-01

    Spatial analogue techniques consist in identifying locations whose recent-past climate is similar in some aspects to the future climate anticipated at a reference location. When identifying analogues, one key step is the quantification of the dissimilarity between two climates separated in time and space, which involves the choice of a metric. In this communication, spatial analogues and their usefulness are briefly discussed. Next, six metrics are presented (the standardized Euclidean distance, the Kolmogorov-Smirnov statistic, the nearest-neighbor distance, the Zech-Aslan energy statistic, the Friedman-Rafsky runs statistic and the Kullback-Leibler divergence), along with a set of criteria used for their assessment. The related case study involves the use of numerical simulations performed with the Canadian Regional Climate Model (CRCM-v4.2.3), from which three annual indicators (total precipitation, heating degree-days and cooling degree-days) are calculated over 30-year periods (1971-2000 and 2041-2070). Results indicate that the six metrics identify comparable analogue regions at a relatively large scale, but best analogues may differ substantially. For best analogues, it is also shown that the uncertainty stemming from the metric choice does generally not exceed that stemming from the simulation or model choice. A synthesis of the advantages and drawbacks of each metric is finally presented, in which the Zech-Aslan energy statistic stands out as the most recommended metric for analogue studies, whereas the Friedman-Rafsky runs statistic is the least recommended, based on this case study.

  15. The effect of heart-and kidney-Benefiting Chinese Herbal Medicine on the function of cholinergic M-and Gamma amino-butyric acid (GABA) receptor in brain tissues of analogue dementia rats

    International Nuclear Information System (INIS)

    Mo Qizhong; Gong Bin; Fang Jun

    1993-01-01

    3 H-QNB and 3 H-GABA were used as radioactive ligand for M-and GABA receptors respectively. M-and GABA receptors were assayed by radioligand binding assay (RBA) in cerebral cortex, hippocampus and cerebellum of analogue dementia rats. It was found that R t of M receptor was decreased in cerebral cortex and hippocampus and R t of GABA receptor was decreased in cerebellum of analogue dementia rats. The dissociation constant (K D ) of M-receptor was decreased significantly in cerebral cortex and K D value of (GABA) receptor was decreased in cerebellum of analogue dementia rats. The decreased R t of M-and GABA receptor in brain tissue of analogue dementia rats was raised by Heart- and Kidney-Benefiting Chinese Herbs as well as hydergin

  16. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem; Sagar, Sunil; Li, Song; Esau, Luke; Kaur, Mandeep; Khashab, Niveen M.

    2016-01-01

    analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell

  17. Insulin analogues in pregnancy and specific congenital anomalies

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa

    2016-01-01

    Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant...... women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we...... samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. Copyright © 2015 John Wiley & Sons, Ltd....

  18. Glucagon-like peptide-1 analogues: An overview

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2013-01-01

    Full Text Available Abnormalities of the incretin axis have been implicated in the pathogenesis of type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 and gastroinhibitory intestinal peptide constitutes >90% of all the incretin function. Augmentation of GLP-1 results in improvement of beta cell health in a glucose-dependant manner (post-prandial hyperglycemia and suppression of glucagon (fasting hyperglycemia, amongst other beneficial pleiotropic effects. Native GLP-1 has a very short plasma half-life and novel methods have been developed to augment its half life, such that its anti-hyperglycemic effects can be exploited. They can be broadly classified as exendin-based therapies (exenatide, exenatide once weekly, DPP-4-resistant analogues (lixisenatide, albiglutide, and analogues of human GLP-1 (liraglutide, taspoglutide. Currently, commercially available analogues are exenatide, exenatide once weekly, and liraglutide. This review aims to provide an overview of most GLP-1 analogues.

  19. Analogue circuits simulation

    Energy Technology Data Exchange (ETDEWEB)

    Mendo, C

    1988-09-01

    Most analogue simulators have evolved from SPICE. The history and description of SPICE-like simulators are given. From a mathematical formulation of the electronic circuit the following analysis are possible: DC, AC, transient, noise, distortion, Worst Case and Statistical.

  20. Uncertainties and credibility building of safety analyses. Natural analogues

    International Nuclear Information System (INIS)

    Laciok, A.

    2001-07-01

    The substance of natural analogues and their studies is defined as a complementary method to laboratory and in-situ experiments and modelling. The role of natural analogues in the processes of development of repositories is defined, mainly in performance assessment of repository system and communication with public. The criteria for identification of natural analogues which should be evaluated in the phase of initiation of new studies are specified. Review part of this report is divided to study of natural analogues and study of anthropogenic and industrial analogues. The main natural analogue studies performed in various countries, in different geological setting, with various aims are characterized. New results acquired in recently finished studies are included: Palmottu (2nd phase of project financed by European Commission), Oklo (results of research financed also by European Commission), Maqarin (3rd phase) and other information obtained from last meetings and workshops of NAWG. In view of the fact that programmes of development of deep repositories in Czech and Slovak Republics are interconnected, the natural analogues studies carried out in the Czech republic are incorporated in separate chapter - study of uranium accumulation in Tertiary clays at Ruprechtov site and study of degradation of natural glasses. In final part the areas of natural analogue studies as an integral part of development of deep geological repository are proposed along with characterization of broader context and aspects of realization of these studies (international cooperation, preparation and evaluation of procedures, communication with public). (author)

  1. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g...

  2. Introduction to electronic analogue computers

    CERN Document Server

    Wass, C A A

    1965-01-01

    Introduction to Electronic Analogue Computers, Second Revised Edition is based on the ideas and experience of a group of workers at the Royal Aircraft Establishment, Farnborough, Hants. This edition is almost entirely the work of Mr. K. C. Garner, of the College of Aeronautics, Cranfield. As various advances have been made in the technology involving electronic analogue computers, this book presents discussions on the said progress, including some acquaintance with the capabilities of electronic circuits and equipment. This text also provides a mathematical background including simple differen

  3. The effect of heart-and kidney-Benefiting Chinese Herbal Medicine on the function of cholinergic M-and Gamma amino-butyric acid (GABA) receptor in brain tissues of analogue dementia rats

    Energy Technology Data Exchange (ETDEWEB)

    Qizhong, Mo; Bin, Gong; Jun, Fang [Shanghai College of TCM, Shanghai (China); and others

    1993-05-01

    [sup 3]H-QNB and [sup 3]H-GABA were used as radioactive ligand for M-and GABA receptors respectively. M-and GABA receptors were assayed by radioligand binding assay (RBA) in cerebral cortex, hippocampus and cerebellum of analogue dementia rats. It was found that R[sub t] of M receptor was decreased in cerebral cortex and hippocampus and R[sub t] of GABA receptor was decreased in cerebellum of analogue dementia rats. The dissociation constant (K[sub D]) of M-receptor was decreased significantly in cerebral cortex and K[sub D] value of (GABA) receptor was decreased in cerebellum of analogue dementia rats. The decreased R[sub t] of M-and GABA receptor in brain tissue of analogue dementia rats was raised by Heart- and Kidney-Benefiting Chinese Herbs as well as hydergin.

  4. In vitro structure-activity relationship of Re-cyclized octreotide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)

    2010-07-15

    Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.

  5. A novel lunar bed rest analogue.

    Science.gov (United States)

    Cavanagh, Peter R; Rice, Andrea J; Licata, Angelo A; Kuklis, Matthew M; Novotny, Sara C; Genc, Kerim O; Englehaupt, Ricki K; Hanson, Andrea M

    2013-11-01

    Humans will eventually return to the Moon and thus there is a need for a ground-based analogue to enable the study of physiological adaptations to lunar gravity. An important unanswered question is whether or not living on the lunar surface will provide adequate loading of the musculoskeletal system to prevent or attenuate the bone loss that is seen in microgravity. Previous simulations have involved tilting subjects to an approximately 9.5 degrees angle to achieve a lunar gravity component parallel to the long-axis of the body. However, subjects in these earlier simulations were not weight-bearing, and thus these protocols did not provide an analogue for load on the musculoskeletal system. We present a novel analogue which includes the capability to simulate standing and sitting in a lunar loading environment. A bed oriented at a 9.5 degrees angle was mounted on six linear bearings and was free to travel with one degree of freedom along rails. This allowed approximately 1/6 body weight loading of the feet during standing. "Lunar" sitting was also successfully simulated. A feasibility study demonstrated that the analogue was tolerated by subjects for 6 d of continuous bed rest and that the reaction forces at the feet during periods of standing were a reasonable simulation of lunar standing. During the 6 d, mean change in the volume of the quadriceps muscles was -1.6% +/- 1.7%. The proposed analogue would appear to be an acceptable simulation of lunar gravity and deserves further exploration in studies of longer duration.

  6. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters.

    Science.gov (United States)

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

    2018-03-20

    The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures ( T m s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting T m s indicated stabilization of AdiC variants upon ligand binding, in which T m s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  7. The Arginine Decarboxylase Pathways of Host and Pathogen Interact to Impact Inflammatory Pathways in the Lung

    Science.gov (United States)

    Dalluge, Joseph J.; Welchlin, Cole W.; Hughes, John; Han, Wei; Blackwell, Timothy S.; Laguna, Theresa A.; Williams, Bryan J.

    2014-01-01

    The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic. PMID:25350753

  8. The arginine decarboxylase pathways of host and pathogen interact to impact inflammatory pathways in the lung.

    Directory of Open Access Journals (Sweden)

    Nick B Paulson

    Full Text Available The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic.

  9. Causal structure of analogue spacetimes

    International Nuclear Information System (INIS)

    Barcelo, Carlos; Liberati, Stefano; Sonego, Sebastiano; Visser, Matt

    2004-01-01

    The so-called 'analogue models of general relativity' provide a number of specific physical systems, well outside the traditional realm of general relativity, that nevertheless are well-described by the differential geometry of curved spacetime. Specifically, the propagation of perturbations in these condensed matter systems is described by 'effective metrics' that carry with them notions of 'causal structure' as determined by an exchange of quasi-particles. These quasi-particle-induced causal structures serve as specific examples of what can be done in the presence of a Lorentzian metric without having recourse to the Einstein equations of general relativity. (After all, the underlying analogue model is governed by its own specific physics, not necessarily by the Einstein equations.) In this paper we take a careful look at what can be said about the causal structure of analogue spacetimes, focusing on those containing quasi-particle horizons, both with a view to seeing what is different from standard general relativity, and what the similarities might be. For definiteness, and because the physics is particularly simple to understand, we will phrase much of the discussion in terms of acoustic disturbances in moving fluids, where the underlying physics is ordinary fluid mechanics, governed by the equations of traditional hydrodynamics, and the relevant quasi-particles are the phonons. It must however be emphasized that this choice of example is only for the sake of pedagogical simplicity and that our considerations apply generically to wide classes of analogue spacetimes

  10. Natural analogues and radionuclide transport model validation

    International Nuclear Information System (INIS)

    Lever, D.A.

    1987-08-01

    In this paper, some possible roles for natural analogues are discussed from the point of view of those involved with the development of mathematical models for radionuclide transport and with the use of these models in repository safety assessments. The characteristic features of a safety assessment are outlined in order to address the questions of where natural analogues can be used to improve our understanding of the processes involved and where they can assist in validating the models that are used. Natural analogues have the potential to provide useful information about some critical processes, especially long-term chemical processes and migration rates. There is likely to be considerable uncertainty and ambiguity associated with the interpretation of natural analogues, and thus it is their general features which should be emphasized, and models with appropriate levels of sophistication should be used. Experience gained in modelling the Koongarra uranium deposit in northern Australia is drawn upon. (author)

  11. The Palmottu analogue project

    International Nuclear Information System (INIS)

    Ahonen, L.; Blomqvist, R.; Suksi, J.

    1993-01-01

    The report gives a summary of the results of investigations carried out in 1992 at the Palmottu natural analogue study site, which is a small U-Th mineralization in Nummi-Pusula, southwestern Finland. Additionally, the report includes several separate articles dealing with various aspects of the Palmottu Analogue Project: (1) deep groundwater flow, (2) interpretation of hydraulic connections, (3) characterization of groundwater colloids, (4) uranium mineral-groundwater equilibrium, (5) water-rock interaction and (6) modelling of in situ matrix diffusion. The Palmottu Analogue Project aims at a more profound understanding of radionuclide transport processes in fractured crystalline bedrock. The essential factors controlling transport are groundwater flow and interaction between water and rock. Accordingly, the study includes (1) structural interpretations partly based on geophysical measurements, (2) hydrological studies including hydraulic drill-hole measurements, (3) flow modelling, (4) hydrogeochemical characterization of groundwater, uranium chemistry and colloid chemistry, (5) mineralogical studies, (6) geochemical interpretation and modelling, (7) studies of radionuclide mobilization and retardation including matrix diffusion, and (8) modelling of uranium series data. Palaeohydrogeological aspects, due to the anticipated future glaciation of the Fennoscandian Shield, are of special interest. Quaternary sediments are studied to gain information on post-glacial migration in the overburden. (orig.)

  12. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

    Directory of Open Access Journals (Sweden)

    Bryan L Roth

    Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

  13. Application of natural analogues in the Yucca Mountain project - overview

    International Nuclear Information System (INIS)

    Simmons, Ardyth M.

    2003-01-01

    The Natural Analogue Synthesis Report (NASR) [1] provides a compilation of information from analogues that test, corroborate, and add confidence to process models and model predictions pertinent to total system performance assessment (TSPA). The report updated previous work [2] with new literature examples and results of quantitative studies conducted by the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate greater understanding of processes expected to occur during postclosure of a proposed Yucca Mountain repository. Natural analogues, as used here, refer to either natural or anthropogenic systems in which processes similar to those expected to occur in a nuclear waste repository are thought to have occurred over long time periods (decades to millenia) and large spatial scales (up to tens of kilometers). In the past, the YMP has used analogues for testing and building confidence in conceptual and numerical process models in a number of ways. Yucca Mountain mineral alteration phases provided a self-analogue for postclosure alteration [3]. Thermodynamic parameters for silica minerals of the Wairakai, New Zealand geothermal field were added to databases used in geochemical modeling [4]. Scoping calculations of radionuclide transport using the Yucca Mountain TSPA numerical model were conducted for the Peqa Blanca site [5]. Eruption parameters from the Cerro Negro volcano, Nicaragua, were used to verify codes that model ash plume dispersion [6]. Analogues have also been used in supplemental science and performance analyses to provide multiple lines of evidence in support of both analyses and model reports (AMRs) [7]; in screening arguments for inclusion or exclusion of features, events, and processes (FEP)s in TSPAs; in the quantification of uncertainties [7]; in expert elicitations of volcanic and seismic hazards [8, 9] and in peer reviews [10]. Natural analogues may be applied

  14. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  15. Conformationally restrained aromatic analogues of fosmidomycin and FR900098.

    Science.gov (United States)

    Kurz, Thomas; Schlüter, Katrin; Pein, Miriam; Behrendt, Christoph; Bergmann, Bärbel; Walter, Rolf D

    2007-07-01

    The synthesis and in-vitro antimalarial activity of conformationally restrained bis(pivaloyloxymethyl) ester analogues of the natural product fosmidomycin is presented. In contrast to alpha-aryl-substituted analogues, conformationally restrained aromatic analogues exhibit only moderate in-vitro antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The most active derivative displays an IC(50) value of 47 microM.

  16. Downscaling of surface moisture flux and precipitation in the Ebro Valley (Spain using analogues and analogues followed by random forests and multiple linear regression

    Directory of Open Access Journals (Sweden)

    G. Ibarra-Berastegi

    2011-06-01

    Full Text Available In this paper, reanalysis fields from the ECMWF have been statistically downscaled to predict from large-scale atmospheric fields, surface moisture flux and daily precipitation at two observatories (Zaragoza and Tortosa, Ebro Valley, Spain during the 1961–2001 period. Three types of downscaling models have been built: (i analogues, (ii analogues followed by random forests and (iii analogues followed by multiple linear regression. The inputs consist of data (predictor fields taken from the ERA-40 reanalysis. The predicted fields are precipitation and surface moisture flux as measured at the two observatories. With the aim to reduce the dimensionality of the problem, the ERA-40 fields have been decomposed using empirical orthogonal functions. Available daily data has been divided into two parts: a training period used to find a group of about 300 analogues to build the downscaling model (1961–1996 and a test period (1997–2001, where models' performance has been assessed using independent data. In the case of surface moisture flux, the models based on analogues followed by random forests do not clearly outperform those built on analogues plus multiple linear regression, while simple averages calculated from the nearest analogues found in the training period, yielded only slightly worse results. In the case of precipitation, the three types of model performed equally. These results suggest that most of the models' downscaling capabilities can be attributed to the analogues-calculation stage.

  17. U.S. Nuclear Regulatory Commission natural analogue research program

    International Nuclear Information System (INIS)

    Kovach, L.A.; Ott, W.R.

    1995-01-01

    This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process

  18. Insulin analogues and cancer: a note of caution

    Directory of Open Access Journals (Sweden)

    Joseph A.M.J.L. eJanssen

    2014-05-01

    Full Text Available Abstract In view of the lifelong exposure and large patient populations involved, insulin analogues with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogues may possibly induce the growth of pre-existing neoplasms. At present, the available data suggest that insulin analogues are safe. In line with these findings, we observed that serum of diabetic patients treated with insulin analogues, compared to that of diabetic patients treated with human insulin, did not induce an increased phosphorylation of tyrosine residues of the insulin-like growth factor-I receptor (IGF-IR. However, the classical model of the IGF-IR signaling may be insufficient to explain (all mitogenic effects of insulin analogues since also non-canonical signaling pathways of the IGF-IR may play a major role in this respect. Although phosphorylation of tyrosine residues of the IGF-IR is generally considered to be the initial activation step within the intracellular IGF-IR signaling pathway, it has been found that cells undergo a signaling switch under hyperglycemic conditions. After this switch, a completely different mechanism is utilized to activate the mitogenic (mitogen-activated protein kinase (MAPK pathways of the IGF-IR that is independent from tyrosine phosphorylation of the IGF-IR. At present it is unknown whether activation of this alternative intracellular pathway of the IGF-IR occurs during hyperglycemia in vivo and whether it is stronger in patients treated with (some insulin analogues than in patients treated with human insulin. In addition, it is unknown whether the insulin receptors (IRs also undergo a signaling switch during hyperglycemia. This should be investigated in future studies. Finally, relative overexpression of IR isoform A (IR-A in (pre cancer tissues may play a key role in the development and progression of human cancers during treatment with insulin (analogues. Further

  19. Development and labeling of EP-00652218 analogues, NK1 receptors antagonist, for PET and SPECT imaging

    International Nuclear Information System (INIS)

    Bagot-Gueret, C.

    2001-12-01

    The aim of this work was the synthesis and radiosynthesis of compounds labelled either with a positron emitter (fluorine-18, t 1/2 = 109 minutes) or with a gamma emitter (iodine-123, t 1/2 = 16.2 hours), for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) studies. EP-00652218 is a novel potent antagonist, with a sub-nano-molar affinity towards the NK 1 receptors. In order to develop ligands that could be used either in PET or SPECT, we undertook the synthesis of poly-halogenated analogues of EP-00652218. Compound 17 was synthesized through two different synthetic pathways. A series of original compounds has been obtained from compound 17 by halogen exchanges on the naphthyridone or the benzene ring. These molecules were tested to determine their in vitro affinity towards NK 1 receptors. Compound 21 was labelled with fluorine-18 in 135 minutes and with a 20% radiochemical yield. Compound 26 was radioiodinated following reaction with Na 125 I (t 1/2 = 60.14 days) in a 18% radiochemical yield. Despite expectation, these analogues of EP-00652218 exhibited an insufficient affinity for NK 1 receptors (IC 50 = 10 -7 M) and thus unlikely usable for in vivo studies with PET and SPECT. (author)

  20. Characterisation of insulin analogues therapeutically available to patients

    KAUST Repository

    Adams, Gary G.

    2018-03-29

    The structure and function of clinical dosage insulin and its analogues were assessed. This included \\'native insulins\\' (human recombinant, bovine, porcine), \\'fast-acting analogues\\' (aspart, glulisine, lispro) and \\'slow-acting analogues\\' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

  1. Fungal growth inhibitory properties of new phytosphingolipid analogues.

    Science.gov (United States)

    Mormeneo, D; Manresa, A; Casas, J; Llebaria, A; Delgado, A

    2008-04-01

    To study the growth inhibitory properties of a series of phytosphingosine (PHS) and phytoceramide (PHC) analogues. A panel of two yeast (Candida albicans and Saccharomyces cerevisiae) and six moulds (Aspergillus repens, Aspergillus niger, Penicillium chrysogenum, Cladosporium cladosporioides, Arthroderma uncinatum and Penicillium funiculosum) has been used in this study. A series of new PHS and PHC analogues differing at the sphingoid backbone and the functional group at C1 position were synthesized. Among PHS analogues, 1-azido derivative 1c, bearing the natural D-ribo stereochemistry, showed a promising growth inhibitory profile. Among PHC analogues, compound 12, with a bulky N-pivaloyl group and a Z double bond at C3 position of the sphingoid chain, was the most active growth inhibitor. Minimal inhibitory concentration values were in the range of 23-48 micromol l(-1) for 1c and 44-87 micromol l(-1) for 12. Only scattered data on the antifungal activity of phytosphingolipids have been reported in the literature. This is the first time that a series of analogues of this kind are tested and compared to discern their structural requirements for antifungal activity.

  2. CO2 Capture with Enzyme Synthetic Analogue

    Energy Technology Data Exchange (ETDEWEB)

    Cordatos, Harry

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  3. Insulin analogues with improved absorption characteristics.

    Science.gov (United States)

    Brange, J; Hansen, J F; Langkjaer, L; Markussen, J; Ribel, U; Sørensen, A R

    1992-01-01

    The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.

  4. Natural analogue working group

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.

    1986-01-01

    A Natural Analogue Working Group was established by the Commission of the European Communities in 1985. The purpose of this group is to bring together modellers with earth scientists and others, so that maximum benefit can be obtained from natural analogue studies with a view to safe geological disposal of radioactive waste. The first meeting of this group was held in Brussels from November 5 to 7, 1985. The discussions mainly concerned the identification of the modellers' needs and of the earth scientists' capacity to provide for them. Following the debates, a written statement was produced by the Group; this document forms the core of the present Report. Notes and outlines of many of the presentations made are grouped in four appendixes. The valuable contribution of all those involved in the meeting is gratefully acknowledged

  5. Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

    Science.gov (United States)

    Segal, Meirav; Fischer, Bilha

    2012-02-28

    Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

  6. Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

    Science.gov (United States)

    El-Sherbeeny, Nagla A; Nader, Manar A; Attia, Ghalia M; Ateyya, Hayam

    2016-12-01

    Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

  7. A Low-cost Multi-channel Analogue Signal Generator

    CERN Document Server

    Müller, F; The ATLAS collaboration; Shen, W; Stamen, R

    2009-01-01

    A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The signal generator was successfully used as independent test bed for the ATLAS Level-1 Trigger Pre-Processor, providing up to 16 analogue signals.

  8. Quality control of analogue to digital conversion circuitry for artefact-free SPECT imaging

    International Nuclear Information System (INIS)

    Gillen, G.J.; Elliott, A.T.

    1992-01-01

    A simple method for the objective, quantitative assessment of analogue to digital conversion (ADC) differential linearity has been developed for SPECT imaging. The analytical approach uses the fact that a differential non-linearity in the ADC will produce a non-uniformity in the digitized image which has a well defined periodicity. This can be most clearly demonstrated in the frequency space domain by determining the Fourier transform of a thick profile which is taken through the centre of a flood field image. The accuracy of the method permits deteriorations in the performance of ADCs to be detected well before significant reductions in SPECT image quality are produced. The availability of a quantitative measure of ADC performance, which can be tested objectively using a simple data acquisition method, is of value in the specification, acceptance testing and general quality control of gamma camera SPECT systems. (author)

  9. $\\gamma$-$\\gamma$ and $\\gamma$-p events at high energies

    CERN Document Server

    Schuler, Gerhard A.; Gerhard A Schuler; Torbjorn Sjostrand

    1994-01-01

    A real photon has a complicated nature, whereby it may remain unresolved or fluctuate into a vector meson or a perturbative q-qbar pair. Based on this picture, we previously presented a model for gamma-p events that is based on the presence of three main event classes: direct, VMD and anomalous. In gamma-gamma events, a natural generalization gives three-by-three combinations of the nature of the two incoming photons, and thus six distinct event classes. The properties of these classes are constrained by the choices already made, in the gamma-p model, of cut-off procedures and other aspects. It is therefore possible to predict the energy-dependence of the cross section for each of the six components separately. The total cross section thus obtained is in good agreement with data, and also gives support to the idea that a simple factorized ansatz with a pomeron and a reggeon term can be a good approximation. Event properties undergo a logical evolution from p-p to gamma-p to gamma-gamma events, with larger cha...

  10. Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-{gamma} ligand, rosiglitazone

    Energy Technology Data Exchange (ETDEWEB)

    Wakui, Yuta; Inoue, Jun [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan); Ueno, Yoshiyuki, E-mail: yueno@mail.tains.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan); Fukushima, Koji; Kondo, Yasuteru; Kakazu, Eiji; Obara, Noriyuki; Kimura, Osamu; Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan)

    2010-05-28

    Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-{alpha}, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPAR{alpha} ligand, bezafibrate, and a PPAR{gamma} ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPAR{gamma}, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-{alpha}-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.

  11. Extractionless GC/MS analysis of gamma-hydroxybutyrate and gamma-butyrolactone with trifluoroacetic anhydride and heptafluoro-1-butanol from aqueous samples.

    Science.gov (United States)

    Sabucedo, Alberto J; Furton, Kenneth G

    2004-06-01

    gamma-Hydroxybutyrate (GHB) is a DEA Schedule I drug of abuse commonly spiked into beverages to incapacitate victims of sexual assault. GHB is a challenging drug for analysis by GC/MS because of its small size, charged nature, low volatility, and intramolecular esterification leading to gamma-butyrolactone (GBL). In this work an extractionless technique has been developed that allows for the use of an aqueous sample for direct derivatization. The technique uses a solution of trifluoroacetic anhydride (TFAA) and 2,2,3,3,4,4,4-heptafluoro-1-butanol (HFB) to derivatize the active hydrogens of GHB. The conversion of GBL into GHB can be forced under alkaline conditions by diluting the sample in 10 mM borate buffer, pH 12. GBL found in beverages intended for human consumption is treated as a Schedule I control substance analogue. Spikes of the two compounds into several beverage matrices gave quantitative recovery of GHB by GC/MS. The derivatization produces higher molecular mass products whose fragmentation pattern provides multiple peaks for confirmation and quantification. The concentration of GBL can also be indirectly determined by the method developed. Therefore, this extractionless technique is rapid, sensitive, and selective for the confirmation of the presence of GHB and GBL in commercial beverages.

  12. Synthesis of an Orthogonal Topological Analogue of Helicene

    DEFF Research Database (Denmark)

    Wixe, Torbjörn; Wallentin, Carl‐Johan; Johnson, Magnus T.

    2013-01-01

    The synthesis of an orthogonal topological pentamer analogue of helicene is presented. This analogue forms a tubular structure with its aromatic systems directed parallel to the axis of propagation, which creates a cavity with the potential to function as a host molecule. The synthetic strategy r...

  13. On the robustness of entanglement in analogue gravity systems

    International Nuclear Information System (INIS)

    Bruschi, D E; Friis, N; Fuentes, I; Weinfurtner, S

    2013-01-01

    We investigate the possibility of generating quantum-correlated quasi-particles utilizing analogue gravity systems. The quantumness of these correlations is a key aspect of analogue gravity effects and their presence allows for a clear separation between classical and quantum analogue gravity effects. However, experiments in analogue systems, such as Bose–Einstein condensates (BECs) and shallow water waves, are always conducted at non-ideal conditions, in particular, one is dealing with dispersive media at non-zero temperatures. We analyse the influence of the initial temperature on the entanglement generation in analogue gravity phenomena. We lay out all the necessary steps to calculate the entanglement generated between quasi-particle modes and we analytically derive an upper bound on the maximal temperature at which given modes can still be entangled. We further investigate a mechanism to enhance the quantum correlations. As a particular example, we analyse the robustness of the entanglement creation against thermal noise in a sudden quench of an ideally homogeneous BEC, taking into account the super-sonic dispersion relations. (paper)

  14. A preliminary feasibility study on natural analogue in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chun Soo; Bae, Dae Seok; Kim, Kyung Su; Koh, Yong Kwon; Park, Byung Yun

    2000-03-01

    Preliminary study on the assessment of natural analogue study in Korea for the deep geological disposal of high-level radioactive waste was carried out. The project on natural analogue study in other countries are introduced. The uranium-bearing deposit in Okcheon belt are summarized, which reported to be uranium-bearing minerals in order to assess to feasibility for natural analogue study in Korea. Among the uranium-bearing deposits, the Deokpyeong area, reported to be the highest reservoir and grade, are selected as the study site, and the elementary investigation, including survey of radioactivity and geochemistry are carried out. According to the investigation of surface environment, the radioactivity and uranium content in the surface water and shallow groundwater does not show any anormal values. However, the radioactivity is expected to be increased in depth and the groundwater reacted with uranium-bearing graphite formation shows high unanium content, indicating the potential possibility for natural analogue study in Korea. In future, if more detail study are performed, the assessment of natural analogue study in Korea are expected.

  15. Analogue Signal Processing: Collected Papers 1994-95

    DEFF Research Database (Denmark)

    1996-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995....

  16. Precise measurement of {gamma}(K{yields}e {nu}({gamma}))/{gamma}(K{yields}{mu} {nu}({gamma})) and study of K{yields}e {nu} {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosino, F.; Massarotti, P.; Meola, S.; Napolitano, M. [Dipartimento di Scienze Fisiche dell' Universita ' ' Federico II' ' , Napoli (Italy); INFN Sezione di Napoli, Napoli (Italy); Antonelli, A.; Antonelli, M.; Bencivenni, G.; Bloise, C.; Bossi, F.; Capon, G.; Capussela, T.; Ciambrone, P.; De Lucia, E.; De Simone, P.; Dreucci, M.; Felici, G.; Gatti, C.; Giovannella, S.; Jacewicz, M.; Lanfranchi, G.; Miscetti, S.; Moulson, M.; Murtas, F.; Palutan, M.; Santangelo, P.; Sciascia, B.; Sibidanov, A.; Spadaro, T.; Venanzoni, G. [Laboratori Nazionali di Frascati dell' INFN, Frascati (Italy); Archilli, F. [Dipartimento di Fisica dell' Universita ' ' Tor Vergata' ' , Rome (Italy); INFN Sezione di Roma Tor Vergata, Rome (Italy); Beltrame, P.; Denig, A.; Mueller, S. [Johannes Gutenberg-Universitaet, Institut fuer Kernphysik, Mainz (Germany); Bini, C.; De Santis, A.; De Zorzi, G.; Di Domenico, A.; Fiore, S.; Franzini, P.; Gauzzi, P. [Dipartimento di Fisica dell' Universita ' ' La Sapienza' ' , Rome (Italy); INFN Sezione di Roma, Rome (Italy); Bocchetta, S.; Ceradini, F.; Di Micco, B.; Nguyen, F. [Dipartimento di Fisica dell' Universita ' ' Roma Tre' ' , Rome (Italy); INFN Sezione di Roma Tre, Rome (Italy); Branchini, P.; Graziani, E.; Passeri, A.; Tortora, L. [INFN Sezione di Roma Tre, Rome (Italy); Capriotti, D. [Dipartimento di Fisica dell' Universita ' ' Roma Tre' ' , Rome (Italy); Di Donato, C. [INFN Sezione di Napoli, Napoli (Italy); Kulikov, V. [Institute for Theoretical and Experimental Physics, Moscow (Russian Federation); Lee-Franzini, J. [Laboratori Nazionali di Frascati dell' INFN, Frascati (Italy); State University of New York, Physics Department, Stony Brook (United States); Martini, M.; Patera, V.; Versaci, R. [Laboratori Nazionali di Frascati dell' INFN, Frascati (Italy); Dipartimento di Energetica dell' Universita ' ' La Sapienza' ' , Rome (Italy); Valente, P. [INFN Sezione di Roma, Rome (Italy)

    2009-12-15

    We present a precise measurement of the ratio R{sub K}={gamma}(K{yields}e{nu}({gamma}))/{gamma}(K{yields}{mu}{nu}({gamma})) and a study of the radiative process K{yields}e{nu}{gamma}, performed with the KLOE detector. The results are based on data collected at the Frascati e{sup +}e{sup -} collider DA {phi}NE for an integrated luminosity of 2.2 fb{sup -1}. We find R{sub K}=(2.493{+-}0.025{sub stat}{+-}0.019{sub syst}) x 10{sup -5}, in agreement with the Standard Model expectation. This result is used to improve constraints on parameters of the Minimal Supersymmetric Standard Model with lepton flavor violation. We also measured the differential decay rate d {gamma}(K{yields}e{nu}{gamma})/dE{sub {gamma}} for photon energies 10gamma}}<250 MeV. Results are compared with predictions from theory. (orig.)

  17. A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

    Directory of Open Access Journals (Sweden)

    Arno Verlee

    2017-02-01

    Full Text Available For the synthesis of m-sulfamoylbenzamide analogues, small molecules which are known for their bioactivity, a chemoselective procedure has been developed starting from m-(chlorosulfonylbenzoyl chloride. Although a chemoselective process in batch was already reported, a continuous-flow process reveals an increased selectivity at higher temperatures and without catalysts. In total, 15 analogues were synthesized, using similar conditions, with yields ranging between 65 and 99%. This is the first automated and chemoselective synthesis of m-sulfamoylbenzamide analogues.

  18. On Using Current Steering Logic in Mixed Analogue-digital Circuits

    DEFF Research Database (Denmark)

    Lehmann, Torsten

    1998-01-01

    The authors investigate power supply noise in mixed analogue-digital circuits, arising from communication between the analogue and digital parts of the circuit. Current steering techniques and proper buffering are used to show which noise currents can be reduced and which cannot. In addition......, a high-swing current steering buffer for driving analogue switches or external digital signals is proposed....

  19. UK Natural Analogue Coordinating Group: fourth annual report

    International Nuclear Information System (INIS)

    Read, D.; Hooker, P.J.

    1992-01-01

    HMIP has a research programme investigating some naturally radioactive sites as geochemical analogues of radionuclide migration. All of the analogue sites under investigation, both in the U.K. and overseas, are located where elevated uranium concentrations occur naturally. Coordination of the programme is achieved through the UK Natural Analogue Co-ordinating Group (NACG) which has met three times in this reporting period. The NACG is steered by the British Geological Survey. Its purpose is to ensure that the different research projects have an integrated function aimed at increasing our understanding of natural geochemical processes. Effort is also being expended in testing research models which may be used in such assessments. (author)

  20. Analogue computer display of accelerator beam optics

    International Nuclear Information System (INIS)

    Brand, K.

    1984-01-01

    Analogue computers have been used years ago by several authors for the design of magnetic beam handling systems. At Bochum a small analogue/hybrid computer was combined with a particular analogue expansion and logic control unit for beam transport work. This apparatus was very successful in the design and setup of the beam handling system of the tandem accelerator. The center of the stripper canal was the object point for the calculations, instead of the high energy acceleration tube a drift length was inserted into the program neglecting the weak focusing action of the tube. In the course of the installation of a second injector for heavy ions it became necessary to do better calculations. A simple method was found to represent accelerating sections on the computer and a particular way to simulate thin lenses was adopted. The analogue computer system proved its usefulness in the design and in studies of the characteristics of different accelerator installations over many years. The results of the calculations are in very good agreement with real accelerator data. The apparatus is the ideal tool to demonstrate beam optics to students and accelerator operators since the effect of a change of any of the parameters is immediately visible on the oscilloscope

  1. Radiative decay of the eta-, eta'-mesons in the nonlocal quark model. [eta(eta'). --> gamma gamma. ; eta. -->. pi. /sup +/. pi. /sup -/. gamma. ; eta. -->. pi. /sup 0/2. gamma. ; eta'. -->. rho/sup 0/. gamma. ; eta'. -->. omega gamma. ;. pi. /sup 0/. -->. gamma. e/sup +/e/sup -/; eta(eta'). -->. gamma mu. /sup +/. mu. /sup -/

    Energy Technology Data Exchange (ETDEWEB)

    Efimov, G V; Ivanov, M A; Nogovitsyn, E A [Joint Inst. for Nuclear Research, Dubna (USSR)

    1981-07-01

    P..--> gamma gamma.. (P=..pi../sup 0/, eta, eta'), eta..--> pi../sup +/..pi../sup -/..gamma.., eta..--> pi../sup 0/..gamma gamma.., eta/sup 1/..-->..V..gamma.. (V=rho/sup 0/, ..omega..), p..--> gamma..l/sup +/l/sup -/ (p=..pi../sup 0/, eta, eta') radiation decays are studied for testing the applicability of the non-local quark model for description of the experimental data. The Feynman diagrams of these decays are presented, values of the widths of the Veta..--> gamma gamma.., eta..--> pi../sup +/..pi../sup -/..gamma.., eta..--> pi../sup 0/..gamma gamma.., eta'..--> gamma gamma.., eta'..-->..rho/sup 0/..gamma.., eta'..--> omega gamma.. decays are calculated and given in the form of a table. Calculations are carried out for two values of the eta eta'-crossing angle: THETA=-11 deg and -18 deg. Values of invariant amplitudes of these decays are determined for ..pi../sup 0/..--> gamma..e/sup +/e/sup -/, eta..--> gamma mu../sup +/..mu../sup -/, eta'..--> gamma mu../sup +/..mu../sup -/ decays at THETA=-11 deg and -18 deg. The best agreement with the experimental data is noted to take place at THETA=-11 deg, the determined width of the eta..--> pi../sup 0/..gamma gamma.. decays is underestimated as compared with the experimental one.

  2. Determining a pre-mining radiological baseline from historic airborne gamma surveys: A case study

    International Nuclear Information System (INIS)

    Bollhöfer, Andreas; Beraldo, Annamarie; Pfitzner, Kirrilly; Esparon, Andrew; Doering, Che

    2014-01-01

    Knowing the baseline level of radioactivity in areas naturally enriched in radionuclides is important in the uranium mining context to assess radiation doses to humans and the environment both during and after mining. This information is particularly useful in rehabilitation planning and developing closure criteria for uranium mines as only radiation doses additional to the natural background are usually considered ‘controllable’ for radiation protection purposes. In this case study we have tested whether the method of contemporary groundtruthing of a historic airborne gamma survey could be used to determine the pre-mining radiological conditions at the Ranger mine in northern Australia. The airborne gamma survey was flown in 1976 before mining started and groundtruthed using ground gamma dose rate measurements made between 2007 and 2009 at an undisturbed area naturally enriched in uranium (Anomaly 2) located nearby the Ranger mine. Measurements of 226 Ra soil activity concentration and 222 Rn exhalation flux density at Anomaly 2 were made concurrent with the ground gamma dose rate measurements. Algorithms were developed to upscale the ground gamma data to the same spatial resolution as the historic airborne gamma survey data using a geographic information system, allowing comparison of the datasets. Linear correlation models were developed to estimate the pre-mining gamma dose rates, 226 Ra soil activity concentrations, and 222 Rn exhalation flux densities at selected areas in the greater Ranger region. The modelled levels agreed with measurements made at the Ranger Orebodies 1 and 3 before mining started, and at environmental sites in the region. The conclusion is that our approach can be used to determine baseline radiation levels, and provide a benchmark for rehabilitation of uranium mines or industrial sites where historical airborne gamma survey data are available and an undisturbed radiological analogue exists to groundtruth the data. - Highlights:

  3. AcEST: DK948281 [AcEST

    Lifescience Database Archive (English)

    Full Text Available r|A9TMK2|A9TMK2_PHYPA Predicted protein OS=Physcomitrella paten... 87 7e-16 tr|A9ZPL1|A9ZPL1_WHEAT Agmatin...e coumaroyltransferase (Fragment) ... 84 6e-15 tr|A9ZPJ9|A9ZPJ9_WHEAT Agmatine coum...aroyltransferase (Fragment) ... 84 6e-15 tr|A9ZPK0|A9ZPK0_WHEAT Agmatine coumaroyltransferase (Fragment) ...... 84 8e-15 tr|A9ZPK8|A9ZPK8_WHEAT Agmatine coumaroyltransferase (Fragment) ... 83 ...2e-14 tr|A9ZPL0|A9ZPL0_WHEAT Agmatine coumaroyltransferase (Fragment) ... 82 2e-14 tr|A9ZPK4|A9ZPK4_WHEAT Agmatine

  4. Analogue Signal Processing: Collected Papers 1996-97

    DEFF Research Database (Denmark)

    1997-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997....

  5. Análogos de insulina Insulin analogues

    Directory of Open Access Journals (Sweden)

    Manuel E. Licea Puig

    2006-12-01

    diabetes mellitus (DM. The recombinant technology of deoxyribonucleic acid (DNA has allowed the development of human insulin; however, this has not totally solved the problems related to immunogenecity, among other problems. Therefore, the new technologies are applied to create insulin analogues. It is our purpose to review relevant pharmacological and clinical aspects related to the insulin analogues, as well as their usefulness in the treatment of DM. The insulin analogues result from biochemical modifications of human insulin. These modifications of the insulin molecule alter not only the absorption, but also the beginning and duration of the action, which offer advantages over the conventional insulins. At present, there are three rapid acting insulin analogues: insulin lispro, insulin aspart and glulisine; and three long acting analogues; glargine, detemir and albulin. Albulin is the latest long acting analogue reported. At present, it is being subjected to various in vitro and in vivo studies. Besides, there have been developed diverse formulations where the rapid acting insulin analogues are premixed with the long acting analogues. The rapid acting insulin analogues have showed a modest global benefit against the conventional insulins in type 1 diabetics. The long acting analogues focus their attention in those persons with DM with nocturnal hypoglycemic episodes. Longer term studies are necessary to confirm the safety and benefits of these preparations, as well as to determine their effect on the micro- and macroangiopathic complications of DM.

  6. Chemopreventive properties of curcumin analogues ...

    African Journals Online (AJOL)

    Chemopreventive properties of curcumin analogues, ... These compounds .... using microscope with 400 × magnification. APC ... Figure 3: Microscopic images of rat colorectal tissue stained with APC rabbit polyclonal antibody with different.

  7. Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

    Science.gov (United States)

    Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

    1992-02-01

    In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

  8. Insulin analogues and severe hypoglycaemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Kristensen, P L; Hansen, L S; Jespersen, M J

    2012-01-01

    The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed...

  9. How stakeholders view the use of analogues in safety cases: PAMINA

    International Nuclear Information System (INIS)

    Atherton, Elizabeth; Bailey, Lucy

    2008-01-01

    The aim of this presentation is to provide an overview of some research that has been undertaken in the UK to investigate stakeholders' views of analogues. There are various reasons for using analogues including: to try and explain difficult concepts; to compare disposal facility features with familiar and/or natural systems; to provide an alternative, non-numerical line of reasoning to support the Safety Case conclusions; to provide evidence of behaviour over very long timescales, that cannot be achieved in the laboratory. There are some dangers when using analogues that people should be aware of: the analogue conditions may not be the same as those found in a disposal facility, so the analogue may have limited application. Some analogues may have negative implications, for example artefacts that have corroded. Analogues can be taken too far and used in inappropriate ways to try and support an assumption. So it is important to find out how stakeholders view the use of analogues in a safety case. NDA is involved in an EC funded project called Pamina (Performance Assessment Methodologies in Application). The project involves 26 partners from 11 European countries, plus other associated members and runs for 3 years from October 2006 to October 2009. The NDA is involved in several parts of the project: Exploring issues of modelling uncertainty; Evaluating effectiveness of approaches for communicating safety cases with stakeholders. NDA ran a workshop in October 2007 in Manchester. The aims of the workshop were to explore how different methods of communicating aspects of a safety case were received by stakeholders. The workshop presented stakeholders with: Examples of different repository concepts; Descriptions of barrier performance; Different ways of presenting numerical results; Use of natural analogues

  10. Defining reference conditions for acidified waters using a modern analogue approach

    International Nuclear Information System (INIS)

    Simpson, Gavin L.; Shilland, Ewan M.; Winterbottom, Julie M.; Keay, Janey

    2005-01-01

    Analogue matching is a palaeolimnological technique that aims to find matches for fossil sediment samples from a set of modern surface sediment samples. Modern analogues were identified that closely matched the pre-disturbance conditions of eight of the UK Acid Waters Monitoring Network (AWMN) lakes using diatom- and cladoceran-based analogue matching. These analogue sites were assessed in terms of hydrochemistry, aquatic macrophytes and macro-invertebrates as to their suitability for defining wider hydrochemical and biological reference conditions for acidified sites within the AWMN. The analogues identified for individual AWMN sites show a close degree of similarity in terms of their hydrochemical characteristics, aquatic macrophytes and, to a lesser extent, macro-invertebrate fauna. The reference conditions of acidified AWMN sites are inferred to be less acidic than today and to support a wider range of acid-sensitive aquatic macrophyte and macro-invertebrate taxa than that recorded in the AWMN lakes over the period of monitoring since 1988. - The use of a palaeolimnological technique to identify modern ecological reference analogues for acidified lakes is demonstrated

  11. Transferred nuclear Overhauser effect analyses of membrane-bound enkephalin analogues by sup 1 H nuclear magnetic resonance: Correlation between activities and membrane-bound conformations

    Energy Technology Data Exchange (ETDEWEB)

    Milon, Alain; Miyazawa, Tatsuo; Higashijima, Tsutomu (Univ. of Tokyo (Japan))

    1990-01-09

    Leu-enkephalin, (D-Ala{sup 2})Leu-enkephalin, and (D-Ala{sup 2})Leu-enkephalinamide (agonists) and (L-Ala{sup 2})Leu-enkephalin (inactive analogue) bind to lipid bilayer consisting of phosphatidylcholine and phosphatidylserine. The conformations that these compounds assume, once bound to perdeuterated phospholipid bilayer, have been shown to be unique, as shown by the transferred nuclear Overhauser effect (TRNOE) of {sup 1}H NMR spectroscopy. In addition, their location in the bilayer was analyzed by TRNOE in the presence of spin-labeled phospholipids. These analyses showed a clear relationship between the activity and the peptide-membrane interaction. The three active peptides, when bound to membranes, adopt the same conformation, characterized by a type II{prime} {beta}-turn around Gly{sup 3}-Phe and a {gamma}-turn around Gly{sup 2} (or D-Ala{sup 2}). The inactive analogue, (L-Ala{sup 2})Leu-enkephalin, displayed a completely different TRNOE pattern corresponding to a different conformation in the membrane-bound state. The tyrosine residue of the active compounds is not inserted into the interior of membrane, but it is inserted into the bilayer for the L-Ala{sup 2} analogue. According to these results, (L-Ala{sup 2})Leu-enkephalin may be explained to be inactive because the mode of binding to the membranes is different from that of active compounds.

  12. Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

    Energy Technology Data Exchange (ETDEWEB)

    Skagius, K [Kemakta Consultants co., Stockholm (Sweden); Wingefors, S [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

    1993-12-31

    The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

  13. Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

    Energy Technology Data Exchange (ETDEWEB)

    Skagius, K. [Kemakta Consultants co., Stockholm (Sweden); Wingefors, S. [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

    1992-12-31

    The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

  14. Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

    International Nuclear Information System (INIS)

    Skagius, K.; Wingefors, S.

    1992-01-01

    The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

  15. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin...

  16. Concise synthesis of new bridged-nicotine analogues

    DEFF Research Database (Denmark)

    Crestey, François; Hooyberghs, Geert; Kristensen, Jesper Langgaard

    2012-01-01

    This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively.......This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively....

  17. Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue

    NARCIS (Netherlands)

    Fiebrich, H. -B.; van den Berg, G.; Kema, I. P.; Links, T. P.; Kleibeuker, J. H.; van Beek, A. P.; Walenkamp, A. M. E.; Sluiter, W. J.; de Vries, E. G. E.

    2010-01-01

    P>Background Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels

  18. Climate Analogues for agricultural impact projection and adaptation – a reliability test

    Directory of Open Access Journals (Sweden)

    Swen P.M. Bos

    2015-10-01

    Full Text Available The climate analogue approach is often considered a valuable tool for climate change impact projection and adaptation planning, especially for complex systems that cannot be modelled reliably. Important examples are smallholder farming systems using agroforestry or other mixed-cropping approaches. For the projected climate at a particular site of interest, the analogue approach identifies locations where the current climate is similar to these projected conditions. By comparing baseline-analogue site pairs, information on climate impacts and opportunities for adaptation can be obtained. However, the climate analogue approach is only meaningful, if climate is a dominant driver of differences between baseline and analogue site pairs. For a smallholder farming setting on Mt. Elgon in Kenya, we tested this requirement by comparing yield potentials of maize and coffee (obtained from the IIASA Global Agro-ecological Zones dataset among 50 close analogue sites for different future climate scenarios and models, and by comparing local ecological knowledge and farm characteristics for one baseline-analogue pair.Yield potentials among the 50 closest analogue locations varied strongly within all climate scenarios, hinting at factors other than climate as major drivers of what the analogue approach might interpret as climate effects. However, on average future climatic conditions seemed more favourable to maize and coffee cultivation than current conditions. The detailed site comparison revealed substantial differences between farms in important characteristics, such as farm size and presence of cash crops, casting doubt on the usefulness of the comparison for climate change analysis. Climatic constraints were similar between sites, so that no apparent lessons for adaptation could be derived. Pests and diseases were also similar, indicating that climate change may not lead to strong changes in biotic constraints at the baseline site in the near future. From

  19. A new approach for improved time and position measurements for TOF-PET: Time-stamping of the photo-electrons using analogue SiPMs

    CERN Document Server

    Doroud, K

    2017-01-01

    Measurement of the Time-of-Flight (TOF) of the 511 keV gammas brings an important reduction of statistical noise in the PET image, with higher precision time measurements producing clearer images. The common method of coupling a photodetector to scintillating crystals is to have two matching matrices, with a one-to-one coupling between the crystal and the photodetector. We propose a new geometry based on analogue strip SiPMs reading out a scintillator cut into slabs. This technique allows the time stamping of individual photo-electrons and extracts the best time resolution using a specific algorithm. Here we present the results from the first ‘slab module’ test.

  20. A new approach for improved time and position measurements for TOF-PET: Time-stamping of the photo-electrons using analogue SiPMs

    Energy Technology Data Exchange (ETDEWEB)

    Doroud, K., E-mail: Katayoun.Doroud@cern.ch [CERN Geneva (Switzerland); Williams, M.C.S. [CERN Geneva (Switzerland); INFN, Bologna (Italy)

    2017-03-21

    Measurement of the Time-of-Flight (TOF) of the 511 keV gammas brings an important reduction of statistical noise in the PET image, with higher precision time measurements producing clearer images. The common method of coupling a photodetector to scintillating crystals is to have two matching matrices, with a one-to-one coupling between the crystal and the photodetector. We propose a new geometry based on analogue strip SiPMs reading out a scintillator cut into slabs. This technique allows the time stamping of individual photo-electrons and extracts the best time resolution using a specific algorithm. Here we present the results from the first ‘slab module’ test.

  1. Analogue Electrical Circuit for Simulation of the Duffing-Holmes Equation

    DEFF Research Database (Denmark)

    Tamaseviciute, E.; Tamasevicius, A.; Mykolaitis, G.

    2008-01-01

    An extremely simple second order analogue electrical circuit for simulating the two-well Duffing-Holmes mathematical oscillator is described. Numerical results and analogue electrical simulations are illustrated with the snapshots of chaotic waveforms, phase portraits (Lissajous figures...

  2. 3-alkyl fentanyl analogues: Structure-activity-relationship study

    OpenAIRE

    Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

    2012-01-01

    Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

  3. Rheological and physical characteristics of crustal-scaled materials for centrifuge analogue modelling

    Science.gov (United States)

    Waffle, Lindsay; Godin, Laurent; Harris, Lyal B.; Kontopoulou, M.

    2016-05-01

    We characterize a set of analogue materials used for centrifuge analogue modelling simulating deformation at different levels in the crust simultaneously. Specifically, we improve the rheological characterization in the linear viscoelastic region of materials for the lower and middle crust, and cohesive synthetic sands without petroleum-binding agents for the upper crust. Viscoelastic materials used in centrifuge analogue modelling demonstrate complex dynamic behaviour, so viscosity alone is insufficient to determine if a material will be an effective analogue. Two series of experiments were conducted using an oscillating bi-conical plate rheometer to measure the storage and loss moduli and complex viscosities of several modelling clays and silicone putties. Tested materials exhibited viscoelastic and shear-thinning behaviour. The silicone putties and some modelling clays demonstrated viscous-dominant behaviour and reached Newtonian plateaus at strain rates clays demonstrated elastic-dominant power-law relationships. Based on these results, the elastic-dominant modelling clay is recommended as an analogue for basement cratons. Inherently cohesive synthetic sands produce fine-detailed fault and fracture patterns, and developed thrust, strike-slip, and extensional faults in simple centrifuge test models. These synthetic sands are recommended as analogues for the brittle upper crust. These new results increase the accuracy of scaling analogue models to prototype. Additionally, with the characterization of three new materials, we propose a complete lithospheric profile of analogue materials for centrifuge modelling, allowing future studies to replicate a broader range of crustal deformation behaviours.

  4. Flower-Like Nanoparticles of Pt-BiIII Assembled on Agmatine Sulfate Modified Glassy Carbon Electrode and Their Electrocatalysis of H2O2

    Science.gov (United States)

    Xiao, Mingshu; Yan, Yuhua; Feng, Kai; Tian, Yanping; Miao, Yuqing

    2015-04-01

    A new electrochemical technique to detect hydrogen peroxide (H2O2) was developed. The Pt nanoparticles and BiIII were subsequently assembled on agmatine sulfate (AS) modified glassy carbon electrode (GCE) and the prepared GCE-AS-Pt-BiIII was characterized by scanning electron microscopy (SEM) with result showing that the flower-like nanostructure of Pt-BiIII was yielded. Compared with Pt nanoparticles, the flower-like nanostructure of Pt-BiIII greatly enhanced the electrocatalysis of GCE-AS-Pt-BiIII towards H2O2, which is ascribed to more Pt-OH obtained on GCE-AS-Pt-BiIII surface for the presence of BiIII. Based on its high electrocatalysis, GCE-AS-Pt-BiIII was used to determine the content of H2O2 in the sample of sheet bean curd with standard addition method. Meantime, its electrocatalytic activity also was studied.

  5. Labelling and evaluation of new stabilised neurotensin (8-13) analogues for SPET

    International Nuclear Information System (INIS)

    Chavatte, K.; Terriere, D.; Jeannin, L.

    1998-01-01

    Neurotensin (8-13) analogues were biologically stabilised by replacement of the peptide bond between amino acids 8 and 9 by the reduced ψ(CH 2 -NH) isostere. DTPA analogues for In-111 labelling and 2-bromo-phenyl-acetyl analogues for radioiodination, showed receptor affinities in the low nanomolar range in combination with a biological half live in human plasma up to 275 minutes. Biodistribution studies in male Wistar rats of metabolically stabilised and non-stabilised 111 In-DTPA-NT(8-13) analogues showed a major clearance from the blood through the kidneys. 125 I-labelled Neurotensin (8-13) analogues showed accumulation up to 2.2% of the injected dose per g tissue in the liver which might be an important disadvantage when diagnosis of tumours in the gut is aimed. It is strongly suggested that stabilised neurotensin (8-13) analogues whether labelled with In-111, I-123 and the near future with Tc-99m, may act as new potential peptidergic radiopharmaceuticals for SPET diagnosis of different NT-receptor positive tumours like non-endocrine pancreas carcinoma, small cell lung carcinoma or colon adeno carcinoma. It is enticing to speculate that metabolically stabilised Neurotensin (8-13) analogues labelled with an appropriate isotope might be useful in therapy of different human cancers. (author)

  6. Thymidine analogues to assess microperfusion in human tumors

    International Nuclear Information System (INIS)

    Janssen, Hilde L.; Ljungkvist, Anna S.; Rijken, Paul F.; Sprong, Debbie; Bussink, Jan; Kogel, Albert J. van der; Haustermans, Karin M.; Begg, Adrian C.

    2005-01-01

    Purpose: To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Methods and Materials: Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. Results: We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r 85, p = 0.0004), despite some mismatches on a per-vessel basis. Conclusions: Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation

  7. Analogues of estradiol as potential breast tumor imaging agents

    International Nuclear Information System (INIS)

    Gibson, R.E.; Rzeszotarski, W.J.; Ferriera, N.L.; Jagoda, E.M.; Reba, R.C.; Eckelman, W.C.

    1984-01-01

    The radioiodinated analogue of estradiol, 11β-methoxy-17α-[/sup 125/I]iodovinylestradiol (MIVE/sub 2/), has been shown to be a good candidate for the imaging of estrogen dependent breast tumors. Although there has been no extensive study on the sensitivity of radiotracers of this type, the authors have not observed localization of the radiotracer in metastatic lesions containing less than 20 fmole estrogen receptor/mg protein or in bone metasteses. In order to improve the sensitivity, they have examined several structural analogues of moxestrol (the parent structure for MIVE/sub 2/) for affinity to the ER isolated from immature rat uterus. The 11β-ethyl analogue (EEE/sub 2/) of ethynyl estradiol (EE/sub 2/) exhibits the highest affinity with the 11β-methyl analogue second best. Although the lipophilicity is also very high this compound should not be much more lipophilic than 16-iodoestradiol or MIVE/sub 2/ since the introduction of iodine increases the log P by greater than 1. The distribution of the tritiated derivative of EEE/sub 2/ is under study

  8. Application of the similitude principle to gamma-gamma density measurements; Application du principe de similitude a la mesure gamma-gamma de densite

    Energy Technology Data Exchange (ETDEWEB)

    Czubek, J A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires. Departement d' Electronique Generale, Service d' Electronique Industrielle; Institut de Recherches Nucleaires, Dep. VI, Cracow (Poland)

    1966-07-01

    The work presented here deals with the problem of the application of the similitude principle to rock density measurements by the gamma-gamma method. A formula is presented which makes it possible to transform results of gamma-gamma measurements carried out on models in order to make them suitable for comparison with results obtained under actual field conditions. Both the space coordinates and the densities are transformed. This transformation makes it possible to obtain a calibration curve as a function of the density for a gamma-gamma probe using only a single model of given density. The influence has also been studied of the chemical composition on the results obtained from gamma-gamma measurements. A method has been developed for estimating the equivalent Z parameter of the medium; the possibility of completely eliminating the influence of the chemical composition of the medium on the measurement results has been studied. (author) [French] L'etude presentee ci-dessous traite le probleme de l'application du principe de similitude aux mesures de densite des roches par la methode gamma-gamma. Nous indiquons une formule qui permet de transformer les resultats des mesures gamma-gamma effectuees sur les modeles pour les comparer aux resultats obtenus dans les conditions reelles sur le terrain. On transforme les coordonnees spatiales ainsi que les densites. Cette transformation donne la possibilite d'obtenir une courbe d'etalonnage (en fonction de la densite) pour une sonde gamma-gamma en utilisant un seul modele de densite donnee. On a etudie aussi l'influence de la composition chimique sur les resultats obtenus des mesures gamma-gamma. On a etabli une methode d'estimation du parametre Z equivalent du milieu, ainsi que la possibilite d'eliminer completement l'influence de la composition chimique du milieu sur les resultats des mesures de densite. (auteur)

  9. Iodination and stability of somatostatin analogues: comparison of iodination techniques. A practical overview.

    Science.gov (United States)

    de Blois, Erik; Chan, Ho Sze; Breeman, Wouter A P

    2012-01-01

    For iodination ((125/127)I) of tyrosine-containing peptides, chloramin-T, Pre-Coated Iodo-Gen(®) tubes and Iodo-Beads(®) (Pierce) are commonly used for in vitro radioligand investigations and there have been reliant vendors hereof for decades. However, commercial availability of these radio-iodinated peptides is decreasing. For continuation of our research in this field we investigated and optimized (radio-)iodination of somatostatin analogues. In literature, radioiodination using here described somatostatin analogues and iodination techniques are described separately. Here we present an overview, including High Performance Liquid Chromatography (HPLC) separation and characterisation by mass spectrometry, to obtain mono- and di-iodinated analogues. Reaction kinetics of (125/127)I iodinated somatostatin analogues were investigated as function of reaction time and concentration of reactants, including somatostatin analogues, iodine and oxidizing agent. To our knowledge, for the here described somatostatin analogues, no (127)I iodination and optimization are described. (Radio-)iodinated somatostatin analogues could be preserved with a >90% radiochemical purity for 1 month after reversed phase HPLC-purification.

  10. From BPA to its analogues: Is it a safe journey?

    Science.gov (United States)

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? Copyright © 2016. Published by Elsevier Ltd.

  11. Design of a saturated analogue and digital current transducer

    International Nuclear Information System (INIS)

    Pross, Alexander

    2002-01-01

    This project describes the development of a new analogue and digital current transducer, providing a range of new theoretical design methods for these novel devices. The main control feature is the limit cycling operation, and the novel use of the embedded sigma-delta modulator sensor structure to derive a low component count digital sensor. The research programme was initiated into the design, development and evaluation of a novel non-Hall sensing analogue and digital current transducer. These transducers are used for measurement of high currents in power systems applications. The investigation is concerned with a new design which uses a magnetic ferrite core without an air gap for current measurement. The motivation for this work was to design a new control circuit which provides a low component count, and utilises the non-linear properties of the magnetic ferrite core to transmit direct current. The use of a limit cycle control circuit was believed to be particularly suitable for the analogue and digital transducers, for two main reasons: the low component count, and the output signal is directly digital. In line with the motivations outlined above, the outcome of the research has witnessed the design, development and evaluation of a practically realisable analogue and digital current transducer. The design procedure, which is documented in this thesis, is considered to be a major contribution to the field of transducers design and development using a control systems approach. Mathematical models for both analogue and digital transducers were developed and the resulting model based predictions were found to be in good agreement with measured results. Simplification of the new model sensing device was achieved by approximating the non-linear ferrite core using FFT analysis. This is also considered to be a significant contribution. The development analogue and digital current censors employed a sampled data control systems design and utilised limit cycling

  12. Natural analogues, paradigm for manmade repositories for radioactive wastes

    International Nuclear Information System (INIS)

    Pavelescu, M.; Pavelescu, A.

    2004-01-01

    Natural analogues are given by nature. They show the results of natural processes which have lasted thousands or millions of years. They provide an excellent example of what could happen in an underground site, offering in the same time the opportunity to test by observation and measurement, many of the geochemical processes that are expected to influence in a realistic and appropriate way, the predicted reliability of the radioactive waste repository over long periods of geological time. The natural analogue studies attempt to understand the multiprocessing complexity of the natural system, which contrasts with the limitations of the laboratory experiments and bring arguments to overcome the difficult time scale issue. By this the natural analogues are a useful paradigm for manmade repository for radioactive wastes. The paper discusses the implicit link in the public mind between natural analogues and manmade waste repository with an accent of the positive impact on public acceptance. It is also discussed the decisive qualities of the natural analogues concerning providing valid long term data and increasing the confidence of the public for manmade repositories. The debate is conducting in terms of sustainable development, having at base high-level principles in order to protect humans and their environment, both now and in the future, from potential hazards arising from such wastes. Safe radwaste management involves the application of technology and resources in a regulated manner so that the public, workers and the environment are protected in accordance with the accepted national and international standards. There are at least seven high-level principles which are mentioned in the paper. It is presented the general concept of the deep geological repository, very important for an acceptable solution for the management of nuclear waste, what is a prerequisite for a renewal of nuclear power. Further are introduced natural and archaeological (manufactured) analogue

  13. Solid-phase synthesis of new saphenamycin analogues with antimicrobial activity

    DEFF Research Database (Denmark)

    Laursen, Jane B.; de Visser, P.C.; Nielsen, H.K.

    2002-01-01

    in parallel with a series of differently substituted benzoic acid derivatives. Treatment with TFA-CH2Cl2 (5:995) released the expected saphenamycin analogues into solution. These new analogues were purified, characterized and screened for antimicrobial activity against Bacillus subtilis and Proteus mirabilis...

  14. Natural analogues for containment-providing barriers for a HLW repository in salt

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, J.; Noseck, U.

    2015-06-15

    In 2005, a German research project was started to develop a novel approach to prove safety for a HLW repository in a salt formation, to refine the safety concept, to identify open scientific issues and to define necessary R&D work. This project aimed at identifying the key information for a HLW repository in salt. One important question is how this information may be best fulfilled by natural analogue studies. This question is answered by starting a review of the required key information needs of the safety case (post-closure phase) in order to assess whether or not these requirements can be supported by natural analogues information. In order to structure the review and to address the key elements of the safety concepts, three types of natural analogues are distinguished: (i) natural analogues for the integrity of the geological barrier, (ii) natural analogues for the integrity of the geotechnical barriers and (iii) natural analogues for release scenarios. For the safety case in salt type (i) and (ii) are of highest importance and are treated in this paper. The assessment documented in this paper on the one hand indicates the high potential benefit of natural analogues for a safety case in salt and on the other hand helps to focus the available human and financial resources for the safety case on the most safety-relevant aspects. (authors)

  15. Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression

    KAUST Repository

    Meylan, E M; Breuillaud, L; Seredenina, T; Magistretti, Pierre J.; Halfon, O; Luthi-Carter, R; Cardinaux, J-R

    2016-01-01

    Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains

  16. GnRH Analogues in the Prevention of Ovarian Hyperstimulation Syndrome

    Science.gov (United States)

    Alama, Pilar; Bellver, Jose; Vidal, Carmen; Giles, Juan

    2013-01-01

    The GnRH analogue (agonist and antagonist GnRH) changed ovarian stimulation. On the one hand, it improved chances of pregnancy to obtain more oocytes and better embryos. This leads to an ovarian hyper-response, which can be complicated by the ovarian hyperstimulation syndrome (OHSS). On the other hand, the GnRH analogue can prevent the incidence of OHSS: GnRH antagonist protocols, GnRH agonist for triggering final oocyte maturation, either together or separately, coasting, and the GnRH analogue may prove useful for avoiding OHSS in high-risk patients. We review these topics in this article. PMID:23825982

  17. Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1980-01-01

    The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

  18. The development of the prompt system of gamma radiation monitoring in FR Yugoslavia

    International Nuclear Information System (INIS)

    Orlic, M.; Pavlovic, R.; Pavlovic, S.

    1996-01-01

    The needs for and characteriztics of the prompt system of gamma radiation monitoring are analyzed. The basic structure of the new system, based on the PC computer is presented. The system consists of the central unit and a number of field stations connected via telephone lines. GM counter is used as a detector. The software is written in visual basic. The system is capable of performing a variety of tasks: dose rate measurement (analogue and digital), graphical presentation of the results in the given period of time, data base formation and management, data transmission and preparing reports. The basic characteriztics of hardware and software of the system, performance specifications and future plans are presented in this paper. (author)

  19. Optoelectronic properties of higher acenes, their BN analogue and substituted derivatives

    International Nuclear Information System (INIS)

    Armaković, Stevan; Armaković, Sanja J.; Holodkov, Vladimir; Pelemiš, Svetlana

    2016-01-01

    We have investigated optoelectronic properties of higher acenes: pentacene, hexacene, heptacene, octacene, nonacene, decacene and their boron-nitride (BN) analogues, within the framework of density functional theory (DFT). We have also investigated the optoelectronic properties of acenes modified by BN substitution. Calculated optoelectronic properties encompasses: oxidation and reduction potentials, electron and hole reorganization energies and energy difference between excited first singlet and triplet states ΔE(S_1−T_1). Oxidation and reduction potentials indicate significantly better stability of BN analogues, comparing with their all-carbon relatives. Although higher acenes possess lower electron and hole reorganization energies, with both best values much lower than 0.1 eV, their BN analogues also have competitive values of reorganization energies, especially for holes for which reorganization energy is also lower than 0.1 eV. On the other hand ΔE(S_1−T_1) is much better for BN analogues, having values that indicate that BN analogues are possible applicable for thermally activated delayed fluorescence. - Highlights: • Optoelectronic properties of structures based on higher acenes have been investigated. • Oxidation and reduction potentials together with reorganization energies are calculated. • TADF is analyzed through calculation of ΔE(S_1−T_1), which is much better for BN analogues. • Reorganization energies of acenes improve with the increase of number of benzene rings.

  20. Cross-reactivity of amphetamine analogues with Roche Abuscreen radioimmunoassay reagents

    International Nuclear Information System (INIS)

    Cody, J.T.

    1990-01-01

    Cross-reactivity of amphetamine analogues with the Abuscreen amphetamine radioimmunoassay reagents was determined for both the standard and high specificity antibody systems. Compounds tested included 2-methoxyamphetamine, 4-hydroxymethamphetamine, 2,5-dimethoxyamphetamine (DMA), 4-bromo-2,5-dimethoxyamphetamine (DOB), 4-bromo-2,5-dimethoxy-beta-phenethylamine (BDMPEA), 3,4,5-trimethoxyamphetamine (TMA), 3,4-methylenedioxyamphetamine (MDA), N,N-dimethyl-3,4-methylenedioxyamphetamine and N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), 2,5-dimethoxy-4-ethylamphetamine, 2,5-dimethoxy-4-methylamphetamine (DOM), and 3,4,5-trimethoxyphenethylamine (mescaline). Blank negative reference material was spiked with 1,000 to 100,000 ng/mL of the amphetamine analogue and used as sample in the assays. MDA was the only analogue that showed cross reactivity equal to or greater than that of amphetamine. None of the other analogue compounds demonstrated a positive result at even the highest concentration; however several showed depressed counts at various concentration levels

  1. Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues.

    Science.gov (United States)

    Bharate, Sandip B; Bhutani, Kamlesh K; Khan, Shabana I; Tekwani, Babu L; Jacob, Melissa R; Khan, Ikhlas A; Singh, Inder Pal

    2006-03-15

    In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.

  2. The Planetary Terrestrial Analogues Library (PTAL)

    Science.gov (United States)

    Werner, S. C.; Dypvik, H.; Poulet, F.; Rull Perez, F.; Bibring, J.-P.; Bultel, B.; Casanova Roque, C.; Carter, J.; Cousin, A.; Guzman, A.; Hamm, V.; Hellevang, H.; Lantz, C.; Lopez-Reyes, G.; Manrique, J. A.; Maurice, S.; Medina Garcia, J.; Navarro, R.; Negro, J. I.; Neumann, E. R.; Pilorget, C.; Riu, L.; Sætre, C.; Sansano Caramazana, A.; Sanz Arranz, A.; Sobron Grañón, F.; Veneranda, M.; Viennet, J.-C.; PTAL Team

    2018-04-01

    The Planetary Terrestrial Analogues Library project aims to build and exploit a spectral data base for the characterisation of the mineralogical and geological evolution of terrestrial planets and small solar system bodies.

  3. Luciferase-Specific Coelenterazine Analogues for Optical Contamination-Free Bioassays

    OpenAIRE

    Ryo Nishihara; Masahiro Abe; Shigeru Nishiyama; Daniel Citterio; Koji Suzuki; Sung Bae Kim

    2017-01-01

    Spectral overlaps among the multiple optical readouts commonly cause optical contamination in fluorescence and bioluminescence. To tackle this issue, we created five-different lineages of coelenterazine (CTZ) analogues designed to selectively illuminate a specific luciferase with unique luciferase selectivity. In the attempt, we found that CTZ analogues with ethynyl or styryl groups display dramatically biased bioluminescence to specific luciferases and pHs by modifying the functional groups ...

  4. Synthesis and antioxidant activity of peptide-based ebselen analogues.

    Science.gov (United States)

    Satheeshkumar, Kandhan; Mugesh, Govindasamy

    2011-04-18

    A series of di- and tripeptide-based ebselen analogues has been synthesized. The compounds were characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2) , tert-butyl hydroperoxide (tBuOOH), and cumene hydroperoxide (Cum-OOH) as substrates, and glutathione (GSH) as a cosubstrate. Although all the peptide-based compounds have a selenazole ring similar to that of ebselen, the GPx activity of these compounds highly depends on the nature of the peptide moiety attached to the nitrogen atom of the selenazole ring. It was observed that the introduction of a phenylalanine (Phe) amino acid residue in the N-terminal reduces the activity in all three peroxide systems. On the other hand, the introduction of aliphatic amino acid residues such as valine (Val) significantly enhances the GPx activity of the ebselen analogues. The difference in the catalytic activity of dipeptide-based ebselen derivatives can be ascribed mainly to the change in the reactivity of these compounds toward GSH and peroxide. Although the presence of the Val-Ala-CO(2) Me moiety facilitates the formation of a catalytically active selenol species, the reaction of ebselen analogues that has a Phe-Ile-CO(2) Me residue with GSH does not generate the corresponding selenol. To understand the antioxidant activity of the peptide-based ebselen analogues in the absence of GSH, these compounds were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. In contrast to the GPx activity, the PN-scavenging activity of the Phe-based peptide analogues was found to be comparable to that of the Val-based compounds. However, the introduction of an additional Phe residue to the ebselen analogue that had a Val-Ala dipeptide significantly reduced the potency of the parent compound in PN-mediated nitration. Copyright

  5. Conjugate dynamical systems: classical analogue of the quantum energy translation

    International Nuclear Information System (INIS)

    Torres-Vega, Gabino

    2012-01-01

    An aspect of quantum mechanics that has not been fully understood is the energy shift generated by the time operator. In this study, we introduce the use of the eigensurfaces of dynamical variables and commutators in classical mechanics to study the classical analogue of the quantum translation of energy. We determine that there is a conjugate dynamical system that is conjugate to Hamilton's equations of motion, and then we generate the analogue of the time operator and use it in the translation of points along the energy direction, i.e. the classical analogue of the Pauli theorem. The theory is illustrated with a nonlinear oscillator model. (paper)

  6. Luciferase-Specific Coelenterazine Analogues for Optical Contamination-Free Bioassays.

    Science.gov (United States)

    Nishihara, Ryo; Abe, Masahiro; Nishiyama, Shigeru; Citterio, Daniel; Suzuki, Koji; Kim, Sung Bae

    2017-04-19

    Spectral overlaps among the multiple optical readouts commonly cause optical contamination in fluorescence and bioluminescence. To tackle this issue, we created five-different lineages of coelenterazine (CTZ) analogues designed to selectively illuminate a specific luciferase with unique luciferase selectivity. In the attempt, we found that CTZ analogues with ethynyl or styryl groups display dramatically biased bioluminescence to specific luciferases and pHs by modifying the functional groups at the C-2 and C-6 positions of the imidazopyradinone backbone of CTZ. The optical contamination-free feature was exemplified with the luciferase-specific CTZ analogues, which illuminated anti-estrogenic and rapamycin activities in a mixture of optical probes. This unique bioluminescence platform has great potential for specific and high throughput imaging of multiple optical readouts in bioassays without optical contamination.

  7. Sensitivity of groundwater recharge using climatic analogues and HYDRUS-1D

    Directory of Open Access Journals (Sweden)

    B. Leterme

    2012-08-01

    Full Text Available The sensitivity of groundwater recharge to different climate conditions was simulated using the approach of climatic analogue stations, i.e. stations presently experiencing climatic conditions corresponding to a possible future climate state. The study was conducted in the context of a safety assessment of a future near-surface disposal facility for low and intermediate level short-lived radioactive waste in Belgium; this includes estimation of groundwater recharge for the next millennia. Groundwater recharge was simulated using the Richards based soil water balance model HYDRUS-1D and meteorological time series from analogue stations. This study used four analogue stations for a warmer subtropical climate with changes of average annual precipitation and potential evapotranspiration from −42% to +5% and from +8% to +82%, respectively, compared to the present-day climate. Resulting water balance calculations yielded a change in groundwater recharge ranging from a decrease of 72% to an increase of 3% for the four different analogue stations. The Gijon analogue station (Northern Spain, considered as the most representative for the near future climate state in the study area, shows an increase of 3% of groundwater recharge for a 5% increase of annual precipitation. Calculations for a colder (tundra climate showed a change in groundwater recharge ranging from a decrease of 97% to an increase of 32% for four different analogue stations, with an annual precipitation change from −69% to −14% compared to the present-day climate.

  8. Optoelectronic properties of higher acenes, their BN analogue and substituted derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Armaković, Stevan, E-mail: stevan.armakovic@df.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Physics, Trg Dositeja Obradovića 4, 21000, Novi Sad (Serbia); Armaković, Sanja J. [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000, Novi Sad (Serbia); Holodkov, Vladimir [Educons University, Faculty of Sport and Tourism - TIMS, Radnička 30a, 21000, Novi Sad (Serbia); Pelemiš, Svetlana [University of East Sarajevo, Faculty of Technology, Karakaj bb, 75400, Zvornik, Republic of Srpska, Bosnia and Herzegovina (Bosnia and Herzegovina)

    2016-02-15

    We have investigated optoelectronic properties of higher acenes: pentacene, hexacene, heptacene, octacene, nonacene, decacene and their boron-nitride (BN) analogues, within the framework of density functional theory (DFT). We have also investigated the optoelectronic properties of acenes modified by BN substitution. Calculated optoelectronic properties encompasses: oxidation and reduction potentials, electron and hole reorganization energies and energy difference between excited first singlet and triplet states ΔE(S{sub 1}−T{sub 1}). Oxidation and reduction potentials indicate significantly better stability of BN analogues, comparing with their all-carbon relatives. Although higher acenes possess lower electron and hole reorganization energies, with both best values much lower than 0.1 eV, their BN analogues also have competitive values of reorganization energies, especially for holes for which reorganization energy is also lower than 0.1 eV. On the other hand ΔE(S{sub 1}−T{sub 1}) is much better for BN analogues, having values that indicate that BN analogues are possible applicable for thermally activated delayed fluorescence. - Highlights: • Optoelectronic properties of structures based on higher acenes have been investigated. • Oxidation and reduction potentials together with reorganization energies are calculated. • TADF is analyzed through calculation of ΔE(S{sub 1}−T{sub 1}), which is much better for BN analogues. • Reorganization energies of acenes improve with the increase of number of benzene rings.

  9. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

  10. Study of the $e^+ e^- \\to Z\\gamma\\gamma \\to q\\overline{q}\\gamma\\gamma$ Process at LEP

    CERN Document Server

    Acciarri, M.; Adriani, O.; Aguilar-Benitez, M.; Alcaraz, J.; Alemanni, G.; Allaby, J.; Aloisio, A.; Alviggi, M.G.; Ambrosi, G.; Anderhub, H.; Andreev, Valery P.; Angelescu, T.; Anselmo, F.; Arefev, A.; Azemoon, T.; Aziz, T.; Bagnaia, P.; Bajo, A.; Baksay, L.; Balandras, A.; Baldew, S.V.; Banerjee, S.; Banerjee, Sw.; Barczyk, A.; Barillere, R.; Bartalini, P.; Basile, M.; Batalova, N.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bellucci, L.; Berbeco, R.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B.L.; Bhattacharya, S.; Biasini, M.; Biglietti, M.; Biland, A.; Blaising, J.J.; Blyth, S.C.; Bobbink, G.J.; Bohm, A.; Boldizsar, L.; Borgia, B.; Bourilkov, D.; Bourquin, M.; Braccini, S.; Branson, J.G.; Brochu, F.; Buffini, A.; Buijs, A.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Capell, M.; Cara Romeo, G.; Carlino, G.; Cartacci, A.M.; Casaus, J.; Castellini, G.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Cesaroni, F.; Chamizo, M.; Chang, Y.H.; Chaturvedi, U.K.; Chemarin, M.; Chen, A.; Chen, G.; Chen, G.M.; Chen, H.F.; Chen, H.S.; Chiefari, G.; Cifarelli, L.; Cindolo, F.; Civinini, C.; Clare, I.; Clare, R.; Coignet, G.; Colino, N.; Costantini, S.; Cotorobai, F.; de la Cruz, B.; Csilling, A.; Cucciarelli, S.; Dai, T.S.; van Dalen, J.A.; D'Alessandro, R.; de Asmundis, R.; Deglon, P.; Degre, A.; Deiters, K.; della Volpe, D.; Delmeire, E.; Denes, P.; DeNotaristefani, F.; De Salvo, A.; Diemoz, M.; Dierckxsens, M.; van Dierendonck, D.; Dionisi, C.; Dittmar, M.; Dominguez, A.; Doria, A.; Dova, M.T.; Duchesneau, D.; Dufournaud, D.; Duinker, P.; El Mamouni, H.; Engler, A.; Eppling, F.J.; Erne, F.C.; Ewers, A.; Extermann, P.; Fabre, M.; Falagan, M.A.; Falciano, S.; Favara, A.; Fay, J.; Fedin, O.; Felcini, M.; Ferguson, T.; Fesefeldt, H.; Fiandrini, E.; Field, J.H.; Filthaut, F.; Fisher, P.H.; Fisk, I.; Forconi, G.; Freudenreich, K.; Furetta, C.; Galaktionov, Iouri; Ganguli, S.N.; Garcia-Abia, Pablo; Gataullin, M.; Gau, S.S.; Gentile, S.; Gheordanescu, N.; Giagu, S.; Gong, Z.F.; Grenier, Gerald Jean; Grimm, O.; Gruenewald, M.W.; Guida, M.; van Gulik, R.; Gupta, V.K.; Gurtu, A.; Gutay, L.J.; Haas, D.; Hasan, A.; Hatzifotiadou, D.; Hebbeker, T.; Herve, Alain; Hidas, P.; Hirschfelder, J.; Hofer, H.; Holzner, G.; Hoorani, H.; Hou, S.R.; Hu, Y.; Iashvili, I.; Jin, B.N.; Jones, Lawrence W.; de Jong, P.; Josa-Mutuberria, I.; Khan, R.A.; Kafer, D.; Kaur, M.; Kienzle-Focacci, M.N.; Kim, D.; Kim, J.K.; Kirkby, Jasper; Kiss, D.; Kittel, W.; Klimentov, A.; Konig, A.C.; Kopal, M.; Kopp, A.; Koutsenko, V.; Kraber, M.; Kraemer, R.W.; Krenz, W.; Kruger, A.; Kunin, A.; Ladron de Guevara, P.; Laktineh, I.; Landi, G.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Lee, H.J.; Le Goff, J.M.; Leiste, R.; Levtchenko, P.; Li, C.; Likhoded, S.; Lin, C.H.; Lin, W.T.; Linde, F.L.; Lista, L.; Liu, Z.A.; Lohmann, W.; Longo, E.; Lu, Y.S.; Lubelsmeyer, K.; Luci, C.; Luckey, David; Lugnier, L.; Luminari, L.; Lustermann, W.; Ma, W.G.; Maity, M.; Malgeri, L.; Malinin, A.; Mana, C.; Mangeol, D.; Mans, J.; Marian, G.; Martin, J.P.; Marzano, F.; Mazumdar, K.; McNeil, R.R.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W.J.; von der Mey, M.; Mihul, A.; Milcent, H.; Mirabelli, G.; Mnich, J.; Mohanty, G.B.; Moulik, T.; Muanza, G.S.; Muijs, A.J.M.; Musicar, B.; Musy, M.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Niessen, T.; Nisati, A.; Kluge, Hannelies; Ofierzynski, R.; Organtini, G.; Oulianov, A.; Palomares, C.; Pandoulas, D.; Paoletti, S.; Paolucci, P.; Paramatti, R.; Park, H.K.; Park, I.H.; Passaleva, G.; Patricelli, S.; Paul, Thomas Cantzon; Pauluzzi, M.; Paus, C.; Pauss, F.; Pedace, M.; Pensotti, S.; Perret-Gallix, D.; Petersen, B.; Piccolo, D.; Pierella, F.; Pieri, M.; Piroue, P.A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pojidaev, V.; Postema, H.; Pothier, J.; Prokofev, D.O.; Prokofiev, D.; Quartieri, J.; Rahal-Callot, G.; Rahaman, M.A.; Raics, P.; Raja, N.; Ramelli, R.; Rancoita, P.G.; Ranieri, R.; Raspereza, A.; Raven, G.; Razis, P.; Ren, D.; Rescigno, M.; Reucroft, S.; Riemann, S.; Riles, Keith; Rodin, J.; Roe, B.P.; Romero, L.; Rosca, A.; Rosier-Lees, S.; Roth, Stefan; Rosenbleck, C.; Roux, B.; Rubio, J.A.; Ruggiero, G.; Rykaczewski, H.; Saremi, S.; Sarkar, S.; Salicio, J.; Sanchez, E.; Sanders, M.P.; Schafer, C.; Schegelsky, V.; Schmidt-Kaerst, S.; Schmitz, D.; Schopper, H.; Schotanus, D.J.; Schwering, G.; Sciacca, C.; Seganti, A.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shumilov, E.; Shvorob, A.; Siedenburg, T.; Son, D.; Smith, B.; Spillantini, P.; Steuer, M.; Stickland, D.P.; Stone, A.; Stoyanov, B.; Straessner, A.; Sudhakar, K.; Sultanov, G.; Sun, L.Z.; Sushkov, S.; Suter, H.; Swain, J.D.; Szillasi, Z.; Sztaricskai, T.; Tang, X.W.; Tauscher, L.; Taylor, L.; Tellili, B.; Teyssier, D.; Timmermans, Charles; Ting, Samuel C.C.; Ting, S.M.; Tonwar, S.C.; Toth, J.; Tully, C.; Tung, K.L.; Uchida, Y.; Ulbricht, J.; Valente, E.; Vesztergombi, G.; Vetlitsky, I.; Vicinanza, D.; Viertel, G.; Villa, S.; Vivargent, M.; Vlachos, S.; Vodopianov, I.; Vogel, H.; Vogt, H.; Vorobev, I.; Vorobov, A.A.; Vorvolakos, A.; Wadhwa, M.; Wallraff, W.; Wang, M.; Wang, X.L.; Wang, Z.M.; Weber, A.; Weber, M.; Wienemann, P.; Wilkens, H.; Wu, S.X.; Wynhoff, S.; Xia, L.; Xu, Z.Z.; Yamamoto, J.; Yang, B.Z.; Yang, C.G.; Yang, H.J.; Yang, M.; Ye, J.B.; Yeh, S.C.; Zalite, A.; Zalite, Yu.; Zhang, Z.P.; Zhu, G.Y.; Zhu, R.Y.; Zichichi, A.; Zilizi, G.; Zimmermann, B.; Zoller, M.

    2001-01-01

    The process e^+e^- -> Z gamma gamma -> q q~ gamma gamma$ is studied in 0.5\\,fb-1$ of data collected with the L3 detector at centre-of-mass energies between 130.1 GeV and 201.7 GeV. Cross sections are measured and found to be consistent with the Standard Model expectations. The study of the least energetic photon constrains the quartic gauge boson couplings to -0.008 GeV-2 < a_0/\\Lambda^2 < 0.005 GeV-2 and -0.007 GeV-2 < a_c/\\Lambda^2 < 0.011 GeV-2, at 95% confidence level.

  11. Synthesis of the 4’-desmethoxy analogue of RU79115

    Directory of Open Access Journals (Sweden)

    MICHEL KLICH

    2004-11-01

    Full Text Available The synthesis, and biological activity in vitro of the 4’-desmethoxy analogue (3 of RU 79115 (2 is described. Comparison of the biological activity of the two analogues clearly indicated the importance of the 4’-methoxy group in conferring good gyrase B inhibitory activity as well as antibacterial activity.

  12. Nucleoside analogues are activated by bacterial deoxyribonucleoside kinases in a species-specific manner

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, Anders; On, Stephen L. W.

    2007-01-01

    To investigate the bactericidal activity of antiviral and anticancer nucleoside analogues against a variety of pathogenic bacteria and characterize the activating enzymes, deoxyribonucleoside kinases (dNKs). Several FDA-approved nucleoside analogue drugs were screened for their potential bacteric......-specific manner. Therefore, nucleoside analogues have a potential to be employed as antibiotics in the fight against emerging multiresistant bacteria....

  13. System for gamma-gamma formation density logging while drilling

    International Nuclear Information System (INIS)

    Paske, W.C.

    1991-01-01

    The patent relates to a system for logging subterranean formations for the determination of formation density by using gamma radiation. Gamma ray source and detection means are disposed within a housing adapted for positioning within a borehole for the emission and detection of gamma rays propagating through earth formations and borehole drilling fluid. The gamma ray detection means comprises first and second gamma radiation sensors geometrically disposed within the housing, the same longitudinal distance from the gamma ray source and diametrically opposed in a common plane. A formation matrix density output signal is produced in proportion to the output signal from each of the gamma ray sensors and in conjunction with certain constants established by the geometrical configuration of the sensors relative to the gamma ray source and the borehole diameter. Formation density is determined without regard to the radial position of the logging probe within the borehole in a measuring while drilling mode. 6 figs

  14. Reasoning by analogy: rational foundation of natural analogue studies

    International Nuclear Information System (INIS)

    Petit, J.-C.

    1992-01-01

    Long-term extrapolations concerning the safety of a nuclear waste repository cannot be satisfactorily made on the sole basis of short-term laboratory investigations. Most nuclear countries have hence developed an approach relying on the following research directions: 1. laboratory experiments; 2. in situ testing; 3. modeling; and 4. natural analogues, which are the only means by which very slow mechanisms can be identified and by which long-term predictions of models can be tested for pertinence (if not truly validated). Although the field of natural analogues has grown very rapidly in recent years, receiving support from varied specialists and institutions involved in radioactive waste disposal, there is not yet a full consensus on their actual usefulness. More problematic is the criticism sometimes made that analogical reasoning is not ''true science'' and that information retrieved from the study of natural analogues will always remain questionable. The present paper gives some clues about the exact status of reasoning by analogy, compared to more ''scientific'' ways of deriving information from investigated systems. It is not a thorough discussion of this very complex, and by far too philosophical issue but we hope, at least, to present to readers of papers devoted to natural analogue studies arguments showing that this approach has some sound foundation. (author)

  15. A Low-cost Multi-channel Analogue Signal Generator

    CERN Document Server

    Muller, F; Shen, W; Stamen, R

    2009-01-01

    A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The implementation of the signal generator is presented as well as an application where it was successfully utilized.

  16. ORF Alignment: NC_004337 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ... agmatinase [Escherichia coli O157:H7 EDL933] ... sp|P60652|SPEB_ECO57 Agmatinase (Agmatine ...ureohydrolase) ... (AUH) sp|P60651|SPEB_ECOLI Agmatinase (Agmatine ... ureohydrolase) (AUH) sp...|P60657|SPEB_SHIFL Agmatinase ... (Agmatine ureohydrolase) (AUH) ...

  17. ORF Alignment: NC_000913 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ... agmatinase [Escherichia coli O157:H7 EDL933] ... sp|P60652|SPEB_ECO57 Agmatinase (Agmatine ...ureohydrolase) ... (AUH) sp|P60651|SPEB_ECOLI Agmatinase (Agmatine ... ureohydrolase) (AUH) sp...|P60657|SPEB_SHIFL Agmatinase ... (Agmatine ureohydrolase) (AUH) ...

  18. ORF Alignment: NC_002655 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ... agmatinase [Escherichia coli O157:H7 EDL933] ... sp|P60652|SPEB_ECO57 Agmatinase (Agmatine ...ureohydrolase) ... (AUH) sp|P60651|SPEB_ECOLI Agmatinase (Agmatine ... ureohydrolase) (AUH) sp...|P60657|SPEB_SHIFL Agmatinase ... (Agmatine ureohydrolase) (AUH) ...

  19. ORF Alignment: NC_004741 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ... agmatinase [Escherichia coli O157:H7 EDL933] ... sp|P60652|SPEB_ECO57 Agmatinase (Agmatine ...ureohydrolase) ... (AUH) sp|P60651|SPEB_ECOLI Agmatinase (Agmatine ... ureohydrolase) (AUH) sp...|P60657|SPEB_SHIFL Agmatinase ... (Agmatine ureohydrolase) (AUH) ...

  20. ORF Alignment: NC_002695 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ... agmatinase [Escherichia coli O157:H7 EDL933] ... sp|P60652|SPEB_ECO57 Agmatinase (Agmatine ...ureohydrolase) ... (AUH) sp|P60651|SPEB_ECOLI Agmatinase (Agmatine ... ureohydrolase) (AUH) sp...|P60657|SPEB_SHIFL Agmatinase ... (Agmatine ureohydrolase) (AUH) ...

  1. A regulator's perspective on the use of analogues for regulatory confidence

    International Nuclear Information System (INIS)

    Ruiz, Carmen

    2008-01-01

    The NAA Study, promoted and coordinated by the CSN, was carried out in collaboration with ENRESA by CIEMAT and three Spanish Universities UZ, UDC and UCM. The 3 year Study, included in the CSN's R and D Programme, started in 1999, is focussed on Deep Geological disposal (DGD). CSN motivation for NA Analogues arose in 1997 as result of the emerging approaches to increase the confidence in the Safety Assessment (SA) considering multiple lines of reasoning show in: some international documents and some national regulation. After a first preliminary (1997-1998) study, the CSN noticed the large amount and dispersion of the information about NNA, and decided to launch a deeper Study with the aims of: Collecting and reviewing the results of all the relevant studies on analogues developed in the last decades in systematic way; Reaching a better understanding of their potential and real application to the SA and for communication purposes. The results of the Analogue Study has been structured in several documents with different levels of detail and technical content addressed to different audiences. Analogue studies are a source of knowledge for the understanding of the long-term behavior of DGD systems. They represent a complementary method to increase Confidence Building within PA. In the majority of the cases, analogues have been used to transmit information on generic aspects of the geological concept an easily understood message. The need to simplify the content to facilitate their understanding may imply different information to different audiences. Analogue studies are: Considered within the multiple lines of reasoning to increase the confidence in the SA; A source of knowledge for the understanding of the long-term behavior of DGD systems. They represent a complementary method to increase Confidence Building within SA. There are few examples of the direct use of data from natural analogue projects in the consulted SA. They are promoted by International organisations

  2. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G.J. Saulnier Jr; W. Statham

    2006-03-10

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory

  3. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    International Nuclear Information System (INIS)

    G.J. Saulnier Jr; W. Statham

    2006-01-01

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO 2 uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 ± 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory analysis

  4. Very high-energy gamma rays from gamma-ray bursts.

    Science.gov (United States)

    Chadwick, Paula M

    2007-05-15

    Very high-energy (VHE) gamma-ray astronomy has undergone a transformation in the last few years, with telescopes of unprecedented sensitivity having greatly expanded the source catalogue. Such progress makes the detection of a gamma-ray burst at the highest energies much more likely than previously. This paper describes the facilities currently operating and their chances for detecting gamma-ray bursts, and reviews predictions for VHE gamma-ray emission from gamma-ray bursts. Results to date are summarized.

  5. ASIC3 Channels Integrate Agmatine and Multiple Inflammatory Signals through the Nonproton Ligand Sensing Domain

    Directory of Open Access Journals (Sweden)

    Cao Hui

    2010-12-01

    Full Text Available Abstract Background Acid-sensing ion channels (ASICs have long been known to sense extracellular protons and contribute to sensory perception. Peripheral ASIC3 channels represent natural sensors of acidic and inflammatory pain. We recently reported the use of a synthetic compound, 2-guanidine-4-methylquinazoline (GMQ, to identify a novel nonproton sensing domain in the ASIC3 channel, and proposed that, based on its structural similarity with GMQ, the arginine metabolite agmatine (AGM may be an endogenous nonproton ligand for ASIC3 channels. Results Here, we present further evidence for the physiological correlation between AGM and ASIC3. Among arginine metabolites, only AGM and its analog arcaine (ARC activated ASIC3 channels at neutral pH in a sustained manner similar to GMQ. In addition to the homomeric ASIC3 channels, AGM also activated heteromeric ASIC3 plus ASIC1b channels, extending its potential physiological relevance. Importantly, the process of activation by AGM was highly sensitive to mild acidosis, hyperosmolarity, arachidonic acid (AA, lactic acid and reduced extracellular Ca2+. AGM-induced ASIC3 channel activation was not through the chelation of extracellular Ca2+ as occurs with increased lactate, but rather through a direct interaction with the newly identified nonproton ligand sensing domain. Finally, AGM cooperated with the multiple inflammatory signals to cause pain-related behaviors in an ASIC3-dependent manner. Conclusions Nonproton ligand sensing domain might represent a novel mechanism for activation or sensitization of ASIC3 channels underlying inflammatory pain-sensing under in vivo conditions.

  6. The agmatine-containing poly(amidoamine) polymer AGMA1 binds cell surface heparan sulfates and prevents attachment of mucosal human papillomaviruses.

    Science.gov (United States)

    Cagno, Valeria; Donalisio, Manuela; Bugatti, Antonella; Civra, Andrea; Cavalli, Roberta; Ranucci, Elisabetta; Ferruti, Paolo; Rusnati, Marco; Lembo, David

    2015-09-01

    The agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of low-risk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 μg/ml and 0.73 μg/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Accumulation of radium in relation to some chemical analogues in Dicranopteris linearis

    International Nuclear Information System (INIS)

    Chao, J.H.; Chuang, C.Y.

    2011-01-01

    This study elucidates the uptake and accumulation of radium in the field-growing fern Dicranopteris linearis by relating the radium concentration to some potential chemical analogues, including alkaline earth metals, rare earth elements, and some important heavy metals. Time-dependent accumulation of radium and these chemical analogues for D. linearis were described by the 228 Th/ 228 Ra activity ratio, an index for inferring plant age. The correlation between radium and these elements was assessed by statistical analysis and used as a reference to elucidate the uptake and accumulation of radium in relation to the chemical analogues. Analytical and statistical results showed that the concentrations of alkaline earth metals (except for Mg) rare earth elements and some heavy metals in D. linearis increased linearly with plant age. These elements, exhibiting a similar accumulation pattern to radium and significant correlation coefficients with radium, were considered as the chemical analogues to radium. Additionally, the plant/soil concentration ratios (CRs) for radium and most of these analogues in D. linearis exceeded 1, consistent with the definition of hyper-accumulator plants.

  8. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

    Directory of Open Access Journals (Sweden)

    Patrick Rabe

    2014-08-01

    Full Text Available Tropodithietic acid (TDA is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure–activity relationship (SAR study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed.

  9. Somatostatin analogues labelled with 99mTc

    International Nuclear Information System (INIS)

    Obenaus, Esteban R.; Crudo, Jose L.; Edreira, Martin M.; Castiglia, Silvia G.

    1999-01-01

    Biological and radiochemical studies have been carried out on two labelled somatostatin analogues, the peptide RC-150 and the Tyr 3 -Octreotide. Both analogues have been labelled with 99m Tc using the direct and the indirect method and MAG-3 and HYNIC as chelating agents. By the direct method RC-150 was labelled using sodium ascorbate and dithionite as reducing agents. The radiochemical purity was 70%. By the indirect method, in the case of RC-160 with MAG-3 a radiochemical purity higher than 70% was attained while a purity of 100% was reached in the case of Tyr 3 -Octreotide with HYNIC. The biological distribution of HYNIC-Tyr 3 -Octreotide has been studied in rats. (author)

  10. Boron hydride analogues of the fullerenes

    International Nuclear Information System (INIS)

    Quong, A.A.; Pederson, M.R.; Broughton, J.Q.

    1994-01-01

    The BH moiety is isoelectronic with C. We have studied the stability of the (BH) 60 analogue of the C 60 fullerene as well as the dual-structure (BH) 32 icosahedron, both of them being putative structures, by performing local-density-functional electronic calculations. To aid in our analysis, we have also studied other homologues of these systems. We find that the latter, i.e., the dual structure, is the more stable although the former is as stable as one of the latter's lower homologues. Boron hydrides, it seems, naturally form the dual structures used in algorithmic optimization of complex fullerene systems. Fully relaxed geometries are reported as well as electron affinities and effective Hubbard U parameters. These systems form very stable anions and we conclude that a search for BH analogues of the C 60 alkali-metal supeconductors might prove very fruitful

  11. Thymidine analogue-sparing highly active antiretroviral therapy (HAART).

    Science.gov (United States)

    Nolan, David; Mallal, Simon

    2003-02-01

    The use of alternative nucleoside reverse transcriptase inhibitors (NRTIs) to the thymidine analogues stavudine (d4T) and zidovudine(ZDV) has been advocated as a means of limiting long-term NRTI-associated toxicity, particularly the development of lipoatrophy or fat wasting. This approach reflects an increasing knowledge of the distinct toxicity profiles of NRTI drugs. However, recent clinical trials have demonstrated that the use of thymidine analogue NRTIs and newer alternative backbone NRTIs, such as tenofovir (TNF) and abacavir (ABC), is associated with comparable short-term efficacy and tolerability. Given the importance of toxicity profile differences in determining clinical management, it is important to recognise that d4T and ZDV cary significantly different risks for long-term NRTI toxicity. Recognising that all NRTIs, including thymidine analogues, have individual toxicity profiles provides a more appropriate basis for selecting optimal antiretroviral therapy. The safety and efficacy of TNF and ABC are also reviewed here, although the available data provide only limited knowledge of the long-term effects of these drugs in terms of toxicity and antiviral durability.

  12. In vitro and in vivo potency of insulin analogues designed for clinical use.

    Science.gov (United States)

    Vølund, A; Brange, J; Drejer, K; Jensen, I; Markussen, J; Ribel, U; Sørensen, A R; Schlichtkrull, J

    1991-11-01

    Analogues of human insulin designed to have improved absorption properties after subcutaneous injection have been prepared by recombinant DNA technology. Five rapidly absorbed analogues, being predominantly in mono- or di-meric states in the pharmaceutical preparation, and a hexameric analogue with very low solubility at neutral pH and slow absorption, were studied. Receptor binding assays with HEP-G2 cells showed overall agreement with mouse free adipocyte assays. Two analogues, B28Asp and A21Gly + B27Arg + B30Thr-NH2, had nearly the same molar in vitro potency as human insulin. Another two showed increased adipocyte potency and receptor binding, B10Asp 194% and 333% and A8His + B4His + B10Glu + B27His 575% and 511%, while B9Asp + B27Glu showed 29% and 18% and the B25Asp analogue only 0.12% and 0.05% potency. Bioassays in mice or rabbits of the analogues except B25Asp showed that they had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation in in vivo potency reflects the differences in receptor binding affinity. Relative to human insulin a low concentration is sufficient for a high affinity analogue to produce a given receptor complex formation and metabolic response. In conclusion, human insulin and analogues with markedly different in vitro potencies were equipotent in terms of hypoglycaemic effect. This is in agreement with the concept that elimination of insulin from blood and its subsequent degradation is mediated by insulin receptors.

  13. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

    Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

    2012-01-01

    Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While

  14. Optimal digital filtering in gamma-ray spectroscopy

    International Nuclear Information System (INIS)

    Messai, A.; Nour, A.; Abdellani, I.

    2009-01-01

    In this paper, we address the subject of the digital nuclear spectroscopy as seen as a counterpart of the classic analogue approach. Consequently, we will present the design as well as the implementation on a DSP (Digital Signal Processor) board, of the various necessary digital pulse processing techniques via digital filtering in order to provide the principal tasks which often take place in a generic 'Gamma' digital spectroscopic setup. The first part will be devoted to the design of the digital IIR filter used for the charge preamplifier's slow-pole compensation. This will be followed by the practical estimation of the power spectral density relating to the electrical noise components present at the spectrometer's input. Thereafter, a very detailed attention will be given to the design of the digital optimal filter to be used for the charge measurements. We follow by another FIR filter that deals with the digital estimation of the reference line of measurements. Finally, we give a hardware implementation of the designed filters on the board: 'TMS320C6713-DSK', a DSP KIT developed by 'DIGITAL Spectrum'. (authors)

  15. Receptor-isoform-selective insulin analogues give tissue-preferential effects

    DEFF Research Database (Denmark)

    Vienberg, Sara Gry; Bouman, Stephan D; Sørensen, Heidi

    2011-01-01

    The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can...... be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI...... (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI...

  16. The Valles natural analogue project

    International Nuclear Information System (INIS)

    Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and 39 Ar/ 4O isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks

  17. Aspartame and Its Analogues

    Science.gov (United States)

    Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

    1981-04-01

    The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

  18. Cross-Section of Hadron Production in $\\gamma\\gamma$ Collisions at LEP

    CERN Document Server

    Acciarri, M; Aguilar-Benítez, M; Ahlen, S P; Alcaraz, J; Alemanni, G; Allaby, James V; Aloisio, A; Alverson, G; Alviggi, M G; Ambrosi, G; Anderhub, H; Andreev, V P; Angelescu, T; Anselmo, F; Arefev, A; Azemoon, T; Aziz, T; Bagnaia, P; Baksay, L; Banerjee, S; Banerjee, Sw; Banicz, K; Barczyk, A; Barillère, R; Barone, L; Bartalini, P; Baschirotto, A; Basile, M; Battiston, R; Bay, A; Becattini, F; Becker, U; Behner, F; Berdugo, J; Berges, P; Bertucci, B; Betev, B L; Bhattacharya, S; Biasini, M; Biland, A; Bilei, G M; Blaising, J J; Blyth, S C; Bobbink, Gerjan J; Böck, R K; Böhm, A; Boldizsar, L; Borgia, B; Bourilkov, D; Bourquin, Maurice; Braccini, S; Branson, J G; Brigljevic, V; Brock, I C; Buffini, A; Buijs, A; Burger, J D; Burger, W J; Busenitz, J K; Button, A M; Cai, X D; Campanelli, M; Capell, M; Cara Romeo, G; Carlino, G; Cartacci, A M; Casaus, J; Castellini, G; Cavallari, F; Cavallo, N; Cecchi, C; Cerrada-Canales, M; Cesaroni, F; Chamizo-Llatas, M; Chang, Y H; Chaturvedi, U K; Chekanov, S V; Chemarin, M; Chen, A; Chen, G; Chen, G M; Chen, H F; Chen, H S; Chéreau, X J; Chiefari, G; Chien, C Y; Cifarelli, Luisa; Cindolo, F; Civinini, C; Clare, I; Clare, R; Cohn, H O; Coignet, G; Colijn, A P; Colino, N; Commichau, V; Costantini, S; Cotorobai, F; de la Cruz, B; Csilling, Akos; Dai, T S; D'Alessandro, R; De Asmundis, R; Degré, A; Deiters, K; Della Volpe, D; Denes, P; De Notaristefani, F; DiBitonto, Daryl; Diemoz, M; Van Dierendonck, D N; Di Lodovico, F; Dionisi, C; Dittmar, Michael; Dominguez, A; Doria, A; Dova, M T; Duchesneau, D; Duinker, P; Durán, I; Dutta, S; Easo, S; Efremenko, Yu V; El-Mamouni, H; Engler, A; Eppling, F J; Erné, F C; Ernenwein, J P; Extermann, Pierre; Fabre, M; Faccini, R; Falciano, S; Favara, A; Fay, J; Fedin, O; Felcini, Marta; Fenyi, B; Ferguson, T; Ferroni, F; Fesefeldt, H S; Fiandrini, E; Field, J H; Filthaut, Frank; Fisher, P H; Fisk, I; Forconi, G; Fredj, L; Freudenreich, Klaus; Furetta, C; Galaktionov, Yu; Ganguli, S N; García-Abia, P; Gau, S S; Gentile, S; Gheordanescu, N; Giagu, S; Goldfarb, S; Goldstein, J; Gong, Z F; Gougas, Andreas; Gratta, Giorgio; Grünewald, M W; Gupta, V K; Gurtu, A; Gutay, L J; Hartmann, B; Hasan, A; Hatzifotiadou, D; Hebbeker, T; Hervé, A; Van Hoek, W C; Hofer, H; Hong, S J; Hoorani, H; Hou, S R; Hu, G; Innocente, Vincenzo; Jenkes, K; Jin, B N; Jones, L W; de Jong, P; Josa-Mutuberria, I; Kasser, A; Khan, R A; Kamrad, D; Kamyshkov, Yu A; Kapustinsky, J S; Karyotakis, Yu; Kaur, M; Kienzle-Focacci, M N; Kim, D; Kim, D H; Kim, J K; Kim, S C; Kim, Y G; Kinnison, W W; Kirkby, A; Kirkby, D; Kirkby, Jasper; Kiss, D; Kittel, E W; Klimentov, A; König, A C; Kopp, A; Korolko, I; Koutsenko, V F; Krämer, R W; Krenz, W; Kunin, A; Ladrón de Guevara, P; Laktineh, I; Landi, G; Lapoint, C; Lassila-Perini, K M; Laurikainen, P; Lebeau, M; Lebedev, A; Lebrun, P; Lecomte, P; Lecoq, P; Le Coultre, P; Le Goff, J M; Leiste, R; Leonardi, E; Levchenko, P M; Li Chuan; Lin, C H; Lin, W T; Linde, Frank L; Lista, L; Liu, Z A; Lohmann, W; Longo, E; Lu, W; Lü, Y S; Lübelsmeyer, K; Luci, C; Luckey, D; Luminari, L; Lustermann, W; Ma Wen Gan; Maity, M; Majumder, G; Malgeri, L; Malinin, A; Maña, C; Mangeol, D J J; Mangla, S; Marchesini, P A; Marin, A; Martin, J P; Marzano, F; Massaro, G G G; McNally, D; McNeil, R R; Mele, S; Merola, L; Meschini, M; Metzger, W J; Von der Mey, M; Mi, Y; Mihul, A; Van Mil, A J W; Mirabelli, G; Mnich, J; Molnár, P; Monteleoni, B; Moore, R; Morganti, S; Moulik, T; Mount, R; Müller, S; Muheim, F; Muijs, A J M; Nahn, S; Napolitano, M; Nessi-Tedaldi, F; Newman, H; Niessen, T; Nippe, A; Nisati, A; Nowak, H; Oh, Yu D; Opitz, H; Organtini, G; Ostonen, R; Palomares, C; Pandoulas, D; Paoletti, S; Paolucci, P; Park, H K; Park, I H; Pascale, G; Passaleva, G; Patricelli, S; Paul, T; Pauluzzi, M; Paus, C; Pauss, Felicitas; Peach, D; Pei, Y J; Pensotti, S; Perret-Gallix, D; Petersen, B; Petrak, S; Pevsner, A; Piccolo, D; Pieri, M; Pinto, J C; Piroué, P A; Pistolesi, E; Plyaskin, V; Pohl, M; Pozhidaev, V; Postema, H; Produit, N; Prokofev, D; Prokofiev, D O; Rahal-Callot, G; Raja, N; Rancoita, P G; Rattaggi, M; Raven, G; Razis, P A; Read, K; Ren, D; Rescigno, M; Reucroft, S; Van Rhee, T; Riemann, S; Riles, K; Robohm, A; Rodin, J; Roe, B P; Romero, L; Rosier-Lees, S; Rosselet, P; Van Rossum, W; Roth, S; Rubio, Juan Antonio; Ruschmeier, D; Rykaczewski, H; Salicio, J; Sánchez, E; Sanders, M P; Sarakinos, M E; Sarkar, S; Sassowsky, M; Schäfer, C; Shchegelskii, V; Schmidt-Kärst, S; Schmitz, D; Schmitz, P; Scholz, N; Schopper, Herwig Franz; Schotanus, D J; Schwenke, J; Schwering, G; Sciacca, C; Sciarrino, D; Servoli, L; Shevchenko, S; Shivarov, N; Shoutko, V; Shukla, J; Shumilov, E; Shvorob, A V; Siedenburg, T; Son, D; Sopczak, André; Smith, B; Spillantini, P; Steuer, M; Stickland, D P; Stone, A; Stone, H; Stoyanov, B; Strässner, A; Strauch, K; Sudhakar, K; Sultanov, G G; Sun, L Z; Susinno, G F; Suter, H; Swain, J D; Tang, X W; Tauscher, Ludwig; Taylor, L; Ting, Samuel C C; Ting, S M; Tonutti, M; Tonwar, S C; Tóth, J; Tully, C; Tuchscherer, H; Tung, K L; Uchida, Y; Ulbricht, J; Uwer, U; Valente, E; Van de Walle, R T; Vesztergombi, G; Vetlitskii, I; Viertel, Gert M; Vivargent, M; Völkert, R; Vogel, H; Vogt, H; Vorobev, I; Vorobyov, A A; Vorvolakos, A; Wadhwa, M; Wallraff, W; Wang, J C; Wang, X L; Wang, Z M; Weber, A; Wittgenstein, F; Wu, S X; Wynhoff, S; Xu, J; Xu, Z Z; Yang, B Z; Yang, C G; Yao, X Y; Ye, J B; Yeh, S C; You, J M; Zalite, A; Zalite, Yu; Zemp, P; Zeng, Y; Zhang, Z; Zhang, Z P; Zhou, B; Zhu, G Y; Zhu, R Y; Zichichi, Antonino; Ziegler, F

    1997-01-01

    The reaction $\\mathrm{e}^{+} \\mathrm{e}^{-} \\rightarrow \\mathrm{e}^{+} \\mathrm{e}^{-} \\gamma ^{*} \\gamma ^{*} \\rightarrow \\mathrm{e}^{+} \\mathrm{e}^{-} $ {\\sl hadrons} is analysed using data collected by the L3 detector during the LEP runs at $\\sqrt {s}$ = 130-140 GeV and $\\sqrt {s}$ = 161 GeV. The cross sections $\\sigma(\\mathrm{e}^{+} \\mathrm{e}^{-} \\rightarrow \\mathrm{e}^{+} \\mathrm{e}^{-} $ {\\sl hadrons}) and $\\sigma (\\gamma\\gamma \\rightarrow $ {\\sl hadrons}) are measured in the interval 5 $\\leq W_{\\gamma\\gamma} \\leq$ 75 GeV. The energy dependence of the $\\sigma (\\gamma\\gamma \\rightarrow $ {\\sl hadrons}) cross section is consistent with the universal Regge behaviour of total hadronic cross sections. %\\end{abstract}

  19. Analogue studies at the french atomic commission (CEA)

    International Nuclear Information System (INIS)

    Petit, J.C.

    1986-06-01

    The different research activities of the French Atomic Energy Commission in the analogue study field are presented. Most of them are conducted in collaboration with major research organisations, both french and international. In fact, the scientific community has been associated to these programmes at different steps of their realisation. The brief description presented illustrates the great diversity and complementarity of actions conducted by CEA for better understanding, through the study of natural analogues, the basic processes that will rule the long term behaviour of high level radwaste materials in a repository and hence contributing to hopefully guaranty disposal safety

  20. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    Directory of Open Access Journals (Sweden)

    Maarten Walmagh

    2015-06-01

    Full Text Available Trehalose (α-d-glucopyranosyl α-d-glucopyranoside is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals, medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside, offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis.

  1. Superconductive analogue of spin glasses

    International Nuclear Information System (INIS)

    Feigel'man, M.; Ioffe, L.; Vinokur, V.; Larkin, A.

    1987-07-01

    The properties of granular superconductors in magnetic fields, namely the existence of a new superconductive state analogue of the low-temperature superconductive state in spin glasses are discussed in the frame of the infinite-range model and the finite-range models. Experiments for elucidation of spin-glass superconductive state in real systems are suggested. 30 refs

  2. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    Science.gov (United States)

    Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

  3. An Overview of Generalized Gamma Mittag–Leffler Model and Its Applications

    Directory of Open Access Journals (Sweden)

    Seema S. Nair

    2015-08-01

    Full Text Available Recently, probability models with thicker or thinner tails have gained more importance among statisticians and physicists because of their vast applications in random walks, Lévi flights, financial modeling, etc. In this connection, we introduce here a new family of generalized probability distributions associated with the Mittag–Leffler function. This family gives an extension to the generalized gamma family, opens up a vast area of potential applications and establishes connections to the topics of fractional calculus, nonextensive statistical mechanics, Tsallis statistics, superstatistics, the Mittag–Leffler stochastic process, the Lévi process and time series. Apart from examining the properties, the matrix-variate analogue and the connection to fractional calculus are also explained. By using the pathway model of Mathai, the model is further generalized. Connections to Mittag–Leffler distributions and corresponding autoregressive processes are also discussed.

  4. The Algebra of a q-Analogue of Multiple Harmonic Series

    Directory of Open Access Journals (Sweden)

    Yoshihiro Takeyama

    2013-10-01

    Full Text Available We introduce an algebra which describes the multiplication structure of a family of q-series containing a q-analogue of multiple zeta values. The double shuffle relations are formulated in our framework. They contain a q-analogue of Hoffman's identity for multiple zeta values. We also discuss the dimension of the space spanned by the linear relations realized in our algebra.

  5. Naturally occurring crystalline phases: analogues for radioactive waste forms

    International Nuclear Information System (INIS)

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included

  6. Naturally occurring crystalline phases: analogues for radioactive waste forms

    Energy Technology Data Exchange (ETDEWEB)

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  7. Gamma Knife

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Gamma Knife Gamma Knife® is a radiation therapy that uses computerized ... If you're scheduled for radiation therapy using Gamma Knife®, a treatment team consisting of a radiation ...

  8. Formulation of the relationship between indices of neutron-gamma and gamma-gamma method and the percentrage of iron

    International Nuclear Information System (INIS)

    Majorowicz, J.

    1973-01-01

    In this article, the author presents the possibility of a complex utilization of radiometric logging methods, neutron-gamma profiling and gamma-gamma density logging for determining percentage of iron and establishing geophysical possibilities of identifying zones of economically profitable ores in borehole profiles. Figures present the correlations between indices of neutron-gamma and gamma-gamma logging methods and the percentage of iron, as well as the correlation of neutron-gamma and gamma-gamma indices for zones minerallized with iron ores. The article presents the correlational analyses of the results: the correlational coefficients are given as well as total error in determining iron content on the basis of each of the methods described. Next, a multidimensional statistical analysis is carried out on the results obtained. On the basis of the two-dimensional correlational coefficients calculated and the average standard deviation, an equation of linear regression was formulated, simultaneously involving three parameters - the indices of neutron-gamma and gamma-gamma logging and the percentage of iron. The multiple correlational coefficient obtained markedly exceeds the two-dimentional correlation coefficient (r=0.974>rsub(xz)>rsub(yz)>rsub(xy)). The given method of utilizing multidimensional statistics in borehole geophysics for identifying iron ores is an efficient one. On the basis of several relationships among independent variables which are less obvious (smaller values of correlational coefficient), it is possible to obtain a single distinct relationship involving all variables simultaneously. (author)

  9. Design, Synthesis and Cytotoxic Evaluation of o-Carboxamido Stilbene Analogues

    Directory of Open Access Journals (Sweden)

    Mohamad Nurul Azmi

    2013-11-01

    Full Text Available Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50 = 16.68 µM, colon cancer HT-29 (IC50 = 7.51 µM and breast cancer MCF-7 (IC50 = 21.24 µM, respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.

  10. The high intensity {gamma}-ray source (HI{gamma}S) and recent results

    Energy Technology Data Exchange (ETDEWEB)

    Tonchev, A.P. [Duke University and TUNL, Triangle University Nuclear Laboratory, P.O. Box 90308, Durham, NC 27708 0308 (United States)]. E-mail: tonchev@tunl.duke.edu; Boswell, M. [University of North Carolina at Chapel Hill and TUNL, Chapel Hill, NC 27599 (United States); Howell, C.R. [Duke University and TUNL, Triangle University Nuclear Laboratory, P.O. Box 90308, Durham, NC 27708 0308 (United States); Karwowski, H.J. [University of North Carolina at Chapel Hill and TUNL, Chapel Hill, NC 27599 (United States); Kelley, J.H. [North Carolina State University and TUNL, Raleigh, NC 27695 (United States); Tornow, W. [Duke University and TUNL, Triangle University Nuclear Laboratory, P.O. Box 90308, Durham, NC 27708 0308 (United States); Wu, Y.K. [Duke University and Duke Free Electron Laser Laboratory, Durham, NC 27708-0319 (United States)

    2005-12-15

    The high intensity {gamma}-ray source (HI{gamma}S) utilizes intra-cavity backscattering of free electron laser photons from the Duke electron storage ring to produce a unique monoenergetic beam of high-flux {gamma}-rays with high polarization and selectable energy resolution. At present, {gamma}-ray beams with energies from 2 to 58 MeV are available with intensities as high as 10{sup 5}-5 x 10{sup 6} {gamma}/s, energy spreads of 3% or better, and nearly 100% linear polarization. The quality and intensity of the {gamma}-ray beams at HI{gamma}S are responsible for the unprecedented performance of this facility in a broad range of research programs in nuclear structure, nuclear astrophysics and nuclear applications. Recent results from excitation of isomeric states in ({gamma}, n) reactions and parity assignments of dipole states determined via the ({gamma}, {gamma}') reaction are presented.

  11. Evaluation of different physical parameters that affect the clinical image quality for gamma camera by using different radionuclides

    International Nuclear Information System (INIS)

    Salah, F.A.; Ziada, G.; Hejazy, M.A.; Khalil, W.A.

    2008-01-01

    Some scintillation camera manufactures adhere to standard code of performance specification established by National Electric Manufactures Association (NEMA). Items such as differential and integral uniformity, spatial resolution energy resolution, etc. are all calculated with reproducible methodology that allows the user reliable technique for creation of these standards to avoid any lack of clinical service that may violate the ethics of patient care. Because 99m Tc is the most frequently used radionuclide in nuclear medicine, many clinics perform the daily uniformity and weekly resolution checks using this radionuclide. But when other commonly used radionuclide such as Tl-201,Ga-67 and I-131 are used, no standardized quality control is performed. So in these study we perform to evaluate the response of ADAC(digital) gamma camera and SELO(analogue) gamma camera to four radionuclide (Tl-201,Ga-67, I-131, and 99m Tc) flood image acquired using different non-uniformity correction tables. In the planer study uniformity and resolution images were obtained using ADAC and SELO cameras, linearity was obtained only by ADAC camera, while in the SPECT study uniformity and contrast images were obtained using ADAC camera only. The response for using different non-uniformity correction tables acquired using different isotopes was different from gamma camera model to another. We can conclude that the most of the gamma camera quality control parameters (uniformity, resolution and contrast) are influenced by variation in the correction tables, while other parameters not affected by this variation like linearity. (author)

  12. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G. Saulnier and W. Statham

    2006-04-16

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table.

  13. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    International Nuclear Information System (INIS)

    G. Saulnier; W. Statham

    2006-01-01

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO 2 uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table

  14. Transdermal delivery of a melanotropic peptide hormone analogue

    International Nuclear Information System (INIS)

    Dawson, B.V.; Hadley, M.E.; Kreutzfeld, K.; Dorr, R.T.; Hruby, V.J.; Al-Obeidi, F.; Don, S.

    1988-01-01

    We previously reported that topical application of [Nl3 4 ,D-Phe 7 ]alpha-MSH, a superpotent analogue of alpha-melanocyte stimulating hormone, to mice induces a darkening of follicular melanocytes throughout the skin. We now report that the melanotropin analogue can be delivered across mouse but not rat skin in an in vitro model system. Passage of the analogue from the topically applied vehicle (polyethylene glycol) across the skin into a subcutaneous receiving vessel was demonstrated by both bioassay as well as by radioimmunoassay. The bioassay data demonstrate that percutaneous absorption of the melanotropin did not result in loss of biological activity of the peptide. The differential penetration of the peptide across rodent skin reveals that one cannot predict percutaneous absorption of a substance across the stratum corneum from studies on a single species. The present results are the first to demonstrate, by direct quantitative measurements, that a bioactive peptide can be delivered across the vertebrate integument in vitro. These studies point out the potential of a topically applied melanotropin for tanning of the skin and possibly for treatment of certain hypopigmentary disorders

  15. Manipulating lightcone fluctuations in an analogue cosmic string

    Directory of Open Access Journals (Sweden)

    Jiawei Hu

    2018-02-01

    Full Text Available We study the flight time fluctuations in an anisotropic medium inspired by a cosmic string with an effective fluctuating refractive index caused by fluctuating vacuum electric fields, which are analogous to the lightcone fluctuations due to fluctuating spacetime metric when gravity is quantized. The medium can be realized as a metamaterial that mimics a cosmic string in the sense of transformation optics. For a probe light close to the analogue string, the flight time variance is ν times that in a normal homogeneous and isotropic medium, where ν is a parameter characterizing the deficit angle of the spacetime of a cosmic string. The parameter ν, which is always greater than unity for a real cosmic string, is determined by the dielectric properties of the metamaterial for an analogue string. Therefore, the flight time fluctuations of a probe light can be manipulated by changing the electric permittivity and magnetic permeability of the analogue medium. We argue that it seems possible to fabricate a metamaterial that mimics a cosmic string with a large ν in laboratory so that a currently observable flight time variance might be achieved.

  16. Natural analogue studies as supplements to biomineralization research

    International Nuclear Information System (INIS)

    McNeil, M.B.

    1995-01-01

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu 4 SO 4 (OH) 6· H 2 O] and mineral morphologies unusual in corrosion [malachite, Cu 2 CO 3 (OH) 2 , rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena

  17. Manipulating lightcone fluctuations in an analogue cosmic string

    Science.gov (United States)

    Hu, Jiawei; Yu, Hongwei

    2018-02-01

    We study the flight time fluctuations in an anisotropic medium inspired by a cosmic string with an effective fluctuating refractive index caused by fluctuating vacuum electric fields, which are analogous to the lightcone fluctuations due to fluctuating spacetime metric when gravity is quantized. The medium can be realized as a metamaterial that mimics a cosmic string in the sense of transformation optics. For a probe light close to the analogue string, the flight time variance is ν times that in a normal homogeneous and isotropic medium, where ν is a parameter characterizing the deficit angle of the spacetime of a cosmic string. The parameter ν, which is always greater than unity for a real cosmic string, is determined by the dielectric properties of the metamaterial for an analogue string. Therefore, the flight time fluctuations of a probe light can be manipulated by changing the electric permittivity and magnetic permeability of the analogue medium. We argue that it seems possible to fabricate a metamaterial that mimics a cosmic string with a large ν in laboratory so that a currently observable flight time variance might be achieved.

  18. Optimization of gefitinib analogues with potent anticancer activity.

    Science.gov (United States)

    Yin, Kai-Hao; Hsieh, Yi-Han; Sulake, Rohidas S; Wang, Su-Pei; Chao, Jui-I; Chen, Chinpiao

    2014-11-15

    The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Study of {gamma}'s in Naiade; Etude des gamma de Naiade

    Energy Technology Data Exchange (ETDEWEB)

    Millot, J P; Rastoin, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1958-07-01

    Following a study of the gamma sources, the flux of gamma of different energies in the swimming pool is investigated. The biological dose can thus be obtained by calculation, and compared with the results given by photographic plates. The influence of photoneutrons is estimated by calculation, and research is being carried out on their influence on the thermal neutron flux curve on the axis of the uranium plate, with the plate emitting neutrons and with the plate protected by boral. (author) [French] Apres l'etude des sources de gamma, l'on etudie le flux de gamma de differentes energies dans la piscine. La dose biologique peut etre obtenue ainsi par le calcul et comparee avec les resultats donnes par les plaques photographiques. L'influence des photoneutrons est estimee par le calcul et l'on recherche leur influence sur la courbe de flux de neutrons thermiques sur l'axe de la plaque d'uranium, la plaque emettant des neutrons et la plaque protegee par du boral. (auteur)

  20. Measurement of K{sup {+-}}{yields}{pi}{sup {+-}}{gamma}{gamma} decays

    Energy Technology Data Exchange (ETDEWEB)

    Morales Morales, Cristina

    2009-07-21

    The goal of this thesis was an experimental test of an effective theory of strong interactions at low energy, called Chiral Perturbation Theory (ChPT). Weak decays of kaon mesons provide such a test. In particular, K{sup {+-}} {yields} {pi}{sup {+-}}{gamma}{gamma} decays are interesting because there is no tree-level O(p{sup 2}) contribution in ChPT, and the leading contributions start at O(p{sup 4}). At this order, these decays include one undetermined coupling constant, c. Both the branching ratio and the spectrum shape of K{sup {+-}} {yields} {pi}{sup {+-}}{gamma}{gamma} decays are sensitive to this parameter. O(p{sup 6}) contributions to K{sup {+-}} {yields} {pi}{sup {+-}}{gamma}{gamma} ChPT predict a 30-40% increase in the branching ratio. From the measurement of the branching ratio and spectrum shape of K{sup {+-}} {yields} {pi}{sup {+-}}{gamma}{gamma} decays, it is possible to determine a model dependent value of c and also to examine whether the O(p{sup 6}) corrections are necessary and enough to explain the rate. About 40% of the data collected in the year 2003 by the NA48/2 experiment have been analyzed and 908 K{sup {+-}} {yields} {pi}{sup {+-}}{gamma}{gamma} candidates with about 8% background contamination have been selected in the region with z=m{sup 2}{sub {gamma}}{sub {gamma}}/m{sub K}{sup 2}{>=}0.2. Using 5,750,121 selected K{sup {+-}} {yields} {pi}{sup {+-}}{pi}{sup 0} decays as normalization channel, a model independent differential branching ratio of K{sup {+-}} {yields} {pi}{sup {+-}}{gamma}{gamma} has been measured to be: BR(K{sup {+-}} {yields} {pi}{sup {+-}}{gamma}{gamma}, z{>=}0.2)=(1.018{+-}0.038{sub stat}{+-}0.039{sub syst}{+-}0.004{sub ext}).10{sup -6}. From the fit to the O(p{sup 6}) ChPT prediction of the measured branching ratio and the shape of the z-spectrum, a value of c=1.54{+-}0.15{sub stat}{+-}0.18{sub syst} has been extracted. Using the measured c value and the O(p{sup 6}) ChPT prediction, the branching ratio for z=m{sup 2}{sub

  1. Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.

    Directory of Open Access Journals (Sweden)

    Michelle Visagie

    Full Text Available 2-Methoxyestradiol (2ME2 is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25 μM was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.

  2. Difference in brain activations during appreciating paintings and photographic analogues

    Directory of Open Access Journals (Sweden)

    Yoshinori eMizokami

    2014-07-01

    Full Text Available Several studies have investigated neural correlates of aesthetic appreciation for paintings but to date the findings have been heterogeneous. This heterogeneity may be attributed to previous studies’ measurement of aesthetic appreciation of not only the beauty of paintings but also the beauty of motifs of the paintings. In order to better elucidate the beauty of paintings, it seems necessary to compare aesthetic appreciation of paintings and photographic analogues which included corresponding real images. We prepared for famous painters’ pictures and their photographic analogues which were set up to resemble each painting in order to investigate the hypothesis that there exist specific neural correlates associated with the aesthetic appreciation for paintings. Forty-four subjects participated in functional magnetic resonance study which required comparisons of aesthetic appreciation of paintings of still life and landscape versus photographic analogues including corresponding real images of still life and landscape. Bilateral cuneus and the left lingual gyrus were activated in the comparison of aesthetic appreciation of paintings versus photographic analogues. In conclusion, the present findings suggest a possibility of the existence of specific neural correlates associated with the aesthetic appreciation for paintings and that bilateral cuneus and the left lingual gyrus may be involved.

  3. Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model

    Science.gov (United States)

    Song, Juhyun; Hur, Bo Eun; Bokara, Kiran Kumar; Yang, Wonsuk; Cho, Hyun Jin; Park, Kyung Ah; Lee, Won Taek; Lee, Kyoung Min

    2014-01-01

    Purpose Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. Materials and Methods We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 µL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. Results Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and γ-glutamyl cysteine synthetase, in the STZ-Agm group. Conclusion Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD. PMID:24719136

  4. Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model

    Directory of Open Access Journals (Sweden)

    Doaa M. Samy

    2016-09-01

    Full Text Available Secondary damage after acute spinal cord compression injury (SCCI exacerbates initial insult. Nuclear factor kappa-B (NF-κB-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm showed neuroprotection against various CNS injuries. However, Agm impact on NF-κB signaling in acute SCCI remains to be investigated. The present study compared the effectiveness of Agm therapy and decompression laminectomy (DL in functional recovery, oxidative stress, inflammatory and apoptotic responses, and modulation of NF-κB activation in acute SCCI rat model. Rats were either sham-operated or subjected to SCCI at T8–9, using 2-Fr. catheter. SCCI rats were randomly treated with DL at T8–9, intraperitoneal Agm (100 mg/kg/day, combined (DL/Agm treatment or saline (n = 16/group. After 28-days of neurological follow-up, spinal cords were either subjected to biochemical measurement of oxidative stress and inflammatory markers or histopathology and immuno-histochemistry for NF-κB-p65 and caspase-3 expression (n = 8/group. Agm was comparable to DL in facilitating neurological functions recovery, reducing inflammation (TNF-α/interleukin-6, and apoptosis. Agm was distinctive in combating oxidative stress. Agm neuroprotective effects were paralleled with inhibition of NF-κB-p65 nuclear translocation. Combined pharmacological and surgical interventions were proved superior in functional recovery. In conclusion, present research suggested a new mechanism for Agm neuroprotection in rats SCCI through inhibition of NF-κB activation.

  5. Introducing New Antimalarial Analogues of Chloroquine and Amodiaquine: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Arezoo Rafiee Parhizgar

    2017-03-01

    Full Text Available Antimalarial drugs with the 4-aminoquinoline scaffold such as the important drugs, chloroquine (CQ and amodiaquine (AQ, have been used to prevent and treat malaria for many years. The importance of these drugs is related to their simple usage, high efficacy, affordability, and cost-effectiveness of their synthesis. In recent years, with the spread of parasite resistance to CQ and cross-resistance to its other analogues have decreased their consumption in many geographical areas. On the other hand, AQ is an effective antimalarial drug which its usage has been restricted due to hepatic and hematological toxicities. The significance of the quinoline ring at quinoline-based antimalarial drugs has prompted research centers and pharmaceutical companies to focus on the design and synthesis of new analogues of these drugs, especially CQ and AQ analogues. Accordingly, various derivatives have been synthesized and evaluated in vitro and in vivo against the resistant strains of the malaria parasite to solve the problem of drug resistance. Also, the pharmacokinetic properties of these compounds have been evaluated to augment their efficacy and diminish their toxicity. Some of these analogues are currently in clinical and preclinical development. Consequently, the recent researches showed yet 4-aminoquinoline scaffold is active moiety in new compounds with antiplasmodial activity. Hence, the aim of this review article is to introduce of the novel synthetic analogues of CQ and AQ, which may constitute the next generation of antimalarial drugs with the 4-aminoquinoline scaffold.

  6. Introducing New Antimalarial Analogues of Chloroquine and Amodiaquine: A Narrative Review.

    Science.gov (United States)

    Parhizgar, Arezoo Rafiee; Tahghighi, Azar

    2017-03-01

    Antimalarial drugs with the 4-aminoquinoline scaffold such as the important drugs, chloroquine (CQ) and amodiaquine (AQ), have been used to prevent and treat malaria for many years. The importance of these drugs is related to their simple usage, high efficacy, affordability, and cost-effectiveness of their synthesis. In recent years, with the spread of parasite resistance to CQ and cross-resistance to its other analogues have decreased their consumption in many geographical areas. On the other hand, AQ is an effective antimalarial drug which its usage has been restricted due to hepatic and hematological toxicities. The significance of the quinoline ring at quinoline-based antimalarial drugs has prompted research centers and pharmaceutical companies to focus on the design and synthesis of new analogues of these drugs, especially CQ and AQ analogues. Accordingly, various derivatives have been synthesized and evaluated in vitro and in vivo against the resistant strains of the malaria parasite to solve the problem of drug resistance. Also, the pharmacokinetic properties of these compounds have been evaluated to augment their efficacy and diminish their toxicity. Some of these analogues are currently in clinical and preclinical development. Consequently, the recent researches showed yet 4-aminoquinoline scaffold is active moiety in new compounds with antiplasmodial activity. Hence, the aim of this review article is to introduce of the novel synthetic analogues of CQ and AQ, which may constitute the next generation of antimalarial drugs with the 4-aminoquinoline scaffold.

  7. Synthesis of tritium labelled phosphonate analogues of sphinganine-1-phosphate

    International Nuclear Information System (INIS)

    Schick, Andreas; Schwarzmann, Guenter; Kolter, Thomas; Sandhoff, Konrad

    1997-01-01

    Tritiated phosphonate analogues 9 and 10 are prepared as analogues of sphinganine-1-phosphate 4. The key step in this synthesis is the catalytic tritiation of the triple bond in reduction of the protected diethyl-3-(S)-tert.-butoxycarbonylamino -4-hydroxy-5-tridecinyl-1-phosphonate by means of sodium boro[ 3 H]hydride as tritium source. These compounds are synthesized to study their metabolic stability and to evaluate their biological properties. (author)

  8. Gamma ray generator

    Science.gov (United States)

    Firestone, Richard B; Reijonen, Jani

    2014-05-27

    An embodiment of a gamma ray generator includes a neutron generator and a moderator. The moderator is coupled to the neutron generator. The moderator includes a neutron capture material. In operation, the neutron generator produces neutrons and the neutron capture material captures at least some of the neutrons to produces gamma rays. An application of the gamma ray generator is as a source of gamma rays for calibration of gamma ray detectors.

  9. A silyl andrographolide analogue suppresses Wnt/β-catenin signaling pathway in colon cancer.

    Science.gov (United States)

    Reabroi, Somrudee; Chairoungdua, Arthit; Saeeng, Rungnapha; Kasemsuk, Teerapich; Saengsawang, Witchuda; Zhu, Weiming; Piyachaturawat, Pawinee

    2018-05-01

    Hyperactivation of Wnt/β-catenin signaling implicated in oncogenesis of colorectal cancer (CRC) is a potential molecular target for chemotherapy. An andrographolide analogue, 3A.1 (19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide) has previously been reported to be potently cytotoxic toward cancer cells by unknown molecular mechanisms. The present study explored the anti-cancer activity of analogue 3A.1 on Wnt/β-catenin signaling in colon cancer cells (HT29 cells) which were more sensitive to the others (HCT116 and SW480 cells). Analogue 3A.1 inhibited viability of HT29 cells with IC 50 value of 11.1 ± 1.4 μM at 24 h, which was more potent than that of the parent andrographolide. Analogue 3A.1 also suppressed the proliferation of HT29 cells and induced cell apoptosis in a dose-dependent manner. Its apoptotic activity was accompanied with increased expressions of proteins related to DNA damages; PARP-1 and γ-H2AX. In addition, analogue 3A.1 significantly inhibited T-cell factor and lymphoid enhancer factor (TCF/LEF) promoter activity of Wnt/β-catenin signaling. Accordingly, the expressions of Wnt target genes and β-catenin protein were suppressed. Moreover, analogue 3A.1 increased the activity of GSK-3β kinase, which is a negative regulator responsible for degradation of intracellular β-catenin. This mode of action was further supported by the absence of the effects after treatment with a GSK-3β inhibitor, and over-expression of a mutant β-catenin (S33Y). Our findings reveal, for the first time, an insight into the molecular mechanism of the anti-cancer activity of analogue 3A.1 through the inhibition of Wnt/β-catenin/GSK-3β pathway and provide a therapeutic potential of the andrographolide analogue 3A.1 in CRC treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  10. Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability

    DEFF Research Database (Denmark)

    Petersen, Asger Bjørn; Andersen, Nikolaj Sten; Konotop, Gleb

    2017-01-01

    Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer...... potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve...... studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral...

  11. Natural analogue synthesis report, TDR-NBS-GS-000027 REV00 ICN02

    International Nuclear Information System (INIS)

    Simmons, A.; Nieder-Westermann, G.; Stuckless, J.; Dobson, P.; Unger, A.J.A.; Kwicklis, E.; Lichtner, P.; Carey, B.; Wolde, G.; Murrel, M.; Kneafsey, T.J.; Meijer, A.; Faybishenko, B.

    2002-01-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide

  12. Natural analogue synthesis report, TDR-NBS-GS-000027 rev00 icn02

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, A.; Nieder-Westermann, G.; Stuckless, J.; Dobson, P.; Unger, A.J.A.; Kwicklis, E.; Lichtner, P.; Carey, B.; Wolde, G.; Murrel,M.; Kneafsey, T.J.; Meijer, A.; Faybishenko, B.

    2002-04-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M&O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide release

  13. The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century

    Directory of Open Access Journals (Sweden)

    Christian Montag

    2015-12-01

    Full Text Available Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution – particularly since the advent of the smartphone – mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based applications. Of N = 3084 participants, 45% reported wearing a wristwatch and 67% used an analogue alarm clock. We observed that participants who reported using analogue zeitgebers used their mobile-/smartphone significantly less. Use of analogue zeitgebers may prove a practical tool for therapeutic and preventative interventions for problematic Internet use in an increasingly digital age.

  14. PENGEMBANGAN BERAS ANALOG DENGAN MEMANFAATKAN JAGUNG PUTIH [Development of White Corn-Based Rice Analogues

    Directory of Open Access Journals (Sweden)

    Santi Noviasari*

    2013-12-01

    Full Text Available White corn can be utilized as a source of non-rice carbohydrate in the manufacture of rice analogues. The rice analogues with rice-like characteristics were produced by an extrusion technique. The aim of this research was to develop rice analogues from white corn and to evaluate their physicochemical and sensory properties. The study was conducted in several stages, i.e. preparation, formulation, and physicochemical and sensory properties evaluation. The physicochemical properties of rice analogues evaluated included proximate nutritional composition, dietary fiber concentration, cooking time, water loss rate, color, and whiteness percentage, while their sensory preferences were evaluated using hedonic scale test. The rice analogues made of Pulut Harapan and Lokal Purbalingga corns (4.34:65.66% added with 30% sago starch, was found to be the most preferred. The moisture, ash, protein, fat, carbohydrate, and dietary fiber composition of this rice analog was 9.32, 0.38, 6.86, 1.22, 91.54, and 5.35%, respectively.

  15. Synthesis and preliminary pharmacological evaluation of asymmetric chloroquine analogues.

    Science.gov (United States)

    Witiak, D T; Grattan, D A; Heaslip, R J; Rahwan, R G

    1981-06-01

    Asymmetric chloroquine analogues (1-4) were prepared of known absolute configuration in order to assess stereochemical influences on selected biological activities. Since chloroquine has been shown to possess spasmolytic properties, analogues 1-4 were tested for similar pharmacological effects on smooth-muscle contraction. The (S)- and (R)-chlorochloroquine enantiomers (1 and 2, respectively) were more potent antispasmodics than the less lipophilic (S)- and (R)-hydroxychloroquines (3 and 4, respectively) when tested against KCl- or acetylcholine-induced contractions of the isolated mouse ileum. A membrane stabilizing mechanism of action for the chloroquine analogues is proposed since neither cellular toxicity nor calcium antagonism plays a role in the spasmolytic action of these compounds. Although compounds 1-4 also inhibited PGF2 alpha-induced contractions of the ileum, 1 was significantly more potent than 2; the latter in turn was equipotent to 3 and 4. It is tentatively proposed that 1 may possess stereoselective affinity for the PGF2 alpha receptor in the ileum. This observation may be further exploited to obtain more selective profiles of biological activity through molecular manipulation.

  16. Do film soundtracks contain nonlinear analogues to influence emotion?

    Science.gov (United States)

    Blumstein, Daniel T; Davitian, Richard; Kaye, Peter D

    2010-12-23

    A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly regarded films to generate a set of highly ranked action/adventure, dramatic, horror and war films. We then scored the presence of a variety of nonlinear analogues in these film soundtracks. Dramatic films suppressed noise of all types, contained more abrupt frequency transitions and musical sidebands, and fewer noisy screams than expected. Horror films suppressed abrupt frequency transitions and musical sidebands, but had more non-musical sidebands, and noisy screams than expected. Adventure films had more male screams than expected. Together, our results suggest that film-makers manipulate sounds to create nonlinear analogues in order to manipulate our emotional responses.

  17. Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

    KAUST Repository

    Zhang, Xiaomei; Bocca, Silvina Maria; Franchi, Anahí ; Anderson, Sandra; Kaur, Mandeep; Bajic, Vladimir B.; Oehninger, Sergio Carlos

    2010-01-01

    were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues

  18. q-bosons and the q-analogue quantized field

    International Nuclear Information System (INIS)

    Nelson, C.A.

    1994-01-01

    The q-analogue coherent states |z > q are used to identify physical signatures for the presence of a q-analogue quantized radiation field in the | > q classical limit where |z| is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/|z|) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, H N = ℎω(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that (ΔN) 2 / → 0 as |z| → ∞. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, φ q , still exhibits normal classical behavior. The standard number-phase uncertainty-relation, ΔN Δφ q = 1/2, and the approximate commutation relation, [N,φ q ] = i, still hold for the single-mode q-analogue quantized field. So, N and φ q are almost canonically conjugate operators in the |z > q classical limit. The |z > q CS's minimize this uncertainty relation for moderate |z| 2

  19. Higher-dimensional analogues of Donaldson-Witten theory

    International Nuclear Information System (INIS)

    Acharya, B.S.; Spence, B.

    1997-01-01

    We present a Donaldson-Witten-type field theory in eight dimensions on manifolds with Spin(7) holonomy. We prove that the stress tensor is BRST exact for metric variations preserving the holonomy and we give the invariants for this class of variations. In six and seven dimensions we propose similar theories on Calabi-Yau threefolds and manifolds of G 2 holonomy, respectively. We point out that these theories arise by considering supersymmetric Yang-Mills theory defined on such manifolds. The theories are invariant under metric variations preserving the holonomy structure without the need for twisting. This statement is a higher-dimensional analogue of the fact that Donaldson-Witten field theory on hyper-Kaehler 4-manifolds is topological without twisting. Higher-dimensional analogues of Floer cohomology are briefly outlined. All of these theories arise naturally within the context of string theory. (orig.)

  20. Making Connections in Math: Activating a Prior Knowledge Analogue Matters for Learning

    Science.gov (United States)

    Sidney, Pooja G.; Alibali, Martha W.

    2015-01-01

    This study investigated analogical transfer of conceptual structure from a prior-knowledge domain to support learning in a new domain of mathematics: division by fractions. Before a procedural lesson on division by fractions, fifth and sixth graders practiced with a surface analogue (other operations on fractions) or a structural analogue (whole…

  1. The anti-inflammatory activity of dillapiole and some semisynthetic analogues.

    Science.gov (United States)

    Parise-Filho, Roberto; Pastrello, Michelli; Pereira Camerlingo, Carla Emygdio; Silva, Gisele Juni; Agostinho, Leonardo Aguiar; de Souza, Thaís; Motter Magri, Fátima Maria; Ribeiro, Roberto Rodrigues; Brandt, Carlos Alberto; Polli, Michelle Carneiro

    2011-11-01

    Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity. This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy. Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model. Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin. These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.

  2. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    Michael A Weiss

    2013-01-01

    Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

  3. Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

    Science.gov (United States)

    Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

    1988-11-12

    To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and

  4. Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile.

    Science.gov (United States)

    Coney, Leigh D; Maier, Larissa J; Ferris, Jason A; Winstock, Adam R; Barratt, Monica J

    2017-05-01

    This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them. An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues. Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD. LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Isolation and structural identification of a novel minoxidil analogue in an illegal dietary supplement: triaminodil.

    Science.gov (United States)

    Lee, Ji Hyun; Park, Han Na; Park, Hyoung Joon; Kim, Nam Sook; Park, Sung-Kwan; Lee, Jongkook; Baek, Sun Young

    2018-01-01

    A new minoxidil analogue was detected in an illegal dietary supplement advertised as a hair-growth treatment. The analogue was identified using ultra-performance liquid chromatography (UPLC), high-resolution mass spectrometry (LC-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The compound was structurally elucidated as a minoxidil analogue in which the piperidinyl group of minoxidil was replaced with a pyrrolidinyl group corresponding to a molecular formula of C 8 H 13 N 5 O. The new analogue has been named triaminodil. As this is the first report of the compound, there are no chemical, toxicology or pharmacological data available.

  6. Benzoheterocyclic amodiaquine analogues with potent antiplasmodial activity: synthesis and pharmacological evaluation.

    Science.gov (United States)

    Ongarora, Dennis S B; Gut, Jiri; Rosenthal, Philip J; Masimirembwa, Collen M; Chibale, Kelly

    2012-08-01

    The synthesis and evaluation of antiplasmodial activity of benzothiazole, benzimidazole, benzoxazole and pyridine analogues of amodiaquine is hereby reported. Benzothiazole and benzoxazole analogues with a protonatable tertiary nitrogen atom possessed excellent activity against the W2 and K1 chloroquine resistant strains of Plasmodium falciparum, with IC(50)s ranging from 7 to 22 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. New analogues of Cucurbita maxima trypsin inhibitor III (CMTI III) with simplified structure.

    Science.gov (United States)

    Rolka, K; Kupryszewski, G; Rózycki, J; Ragnarsson, U; Zbyryt, T; Otlewski, J

    1992-10-01

    Seven new analogues of trypsin inhibitor CMTI III were obtained by solid-phase peptide synthesis. Three analogues contained only two, instead of three, disulfide bridges, whereas the molecules of the next four analogues were shortened at the N- and/or C-terminus. The elimination of one disulfide bridge in CMTI III induces a decrease in the association equilibrium constants by 6-7 orders of magnitude, whereas the removal of one, two or three amino-acid residues at the N- and/or C-terminus does not significantly affect the activity.

  8. 0+ analogue state in 118Sb from 117Sn(p,nγ) reaction

    International Nuclear Information System (INIS)

    Pal, J.; Dey, C.C.; Bose, S.; Sinha, B.K.; Chatterjee, M.B.; Mahapatra, D.P.

    1996-01-01

    The analogue of the 0 + ground state in 118 Sn has been observed in the compound nucleus 118 Sb through 117 Sn(p,nγ) 117 Sb reaction. The neutron decays of this analogue resonance have been studied from the deexciting γ-rays of the residual nucleus 117 Sb. From off resonance excitation functions, spin assignments have been made to states in 117 Sb, on the basis of Hauser-Feshbach formalism. The resonance parameters of the isobaric analogue resonance have been determined, including the total, proton and neutron decay widths. (orig.)

  9. Differential Top10 promoter regulation by six tetracycline analogues in plant cells

    Science.gov (United States)

    Love, John; Allen, George C.; Gatz, Christiane; Thompson, William F.; Brown, C. S. (Principal Investigator)

    2002-01-01

    The effects of five tetracycline analogues, anhydrotetracycline, doxycycline, minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1 tobacco tissue culture cells have been analysed. The concentration that repressed Top10 promoter activity, the level of transgene repression and the kinetics of transgene de-repression were determined for each analogue, and could not be predicted from in vitro binding affinity to the tetracycline repressor or from comparison with animal cells. Doxycycline had the most potent effect on the Top10 promoter and completely inhibited transgene expression at 4 nmol l(-1). Tetracycline was the most versatile of the analogues tested; tetracycline inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to restore Top10-driven expression in 12-24 h. A study was also made of the suitability for plant research of a novel tetracycline analogue, GR33076X. In animal cells, GR33076X de-repressed Top10 promoter activity in the presence of inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR 33076X can antagonize repression of the Top10 promoter in the presence of tetracycline, but not of anhydrotetracycline or of doxycycline. Different tetracycline analogues can therefore be used to regulate the Top10 promoter in plant cells and this property may be exploited in planning an optimum course of transgene regulation.

  10. Kahalalide F analogues from the mucous secretion of Indian sacoglossan mollusc Elysia ornata

    Digital Repository Service at National Institute of Oceanography (India)

    Ciavatta, M.L.; PrabhaDevi; Carbone, M.; Mathieu, V.; Kiss, R.; Casapullo, A.; Gavagnin, M.

    , better delivery, or longer half-life. More than 150 analogues were obtained by solid phase peptide synthesis8,9 and more recently a semi-synthetic approach to produce KF analogues starting from natural KF has been also performed.10In parallel...

  11. Systematic Review of the Cost Effectiveness of Insulin Analogues in Type 1 and Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Shafie, Asrul Akmal; Ng, Chin Hui; Tan, Yui Ping; Chaiyakunapruk, Nathorn

    2017-02-01

    Insulin analogues have a pharmacokinetic advantage over human insulin and are increasingly used to treat diabetes mellitus. A summary of their cost effectiveness versus other available treatments was required. Our objective was to systematically review the published cost-effectiveness studies of insulin analogues for the treatment of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). We searched major databases and health technology assessment agency reports for economic evaluation studies published up until 30 September 2015. Two reviewers performed data extraction and assessed the quality of the data using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. Seven of the included studies assessed short-acting insulin analogues, 12 assessed biphasic insulin analogues, 30 assessed long-acting insulin analogues and one assessed a combination of short- and long-acting insulin analogues. Only 17 studies involved patients with T1DM, all were modelling studies and 12 were conducted in Canada. The incremental cost-effectiveness ratios (ICERs) for short-acting insulin analogues ranged from dominant to $US435,913 per quality-adjusted life-year (QALY) gained, the ICERs for biphasic insulin analogues ranged from dominant to $US57,636 per QALY gained and the ICERs for long-acting insulin analogues ranged from dominant to $US599,863 per QALY gained. A total of 15 studies met all the CHEERS guidelines reporting quality criteria. Only 26 % of the studies assessed heterogeneity in their analyses. Current evidence indicates that insulin analogues are cost effective for T1DM; however, evidence for their use in T2DM is not convincing. Additional evidence regarding compliance and efficacy is required to support the broader use of long-acting and biphasic insulin analogues in T2DM. The value of insulin analogues depends strongly on reductions in hypoglycaemia event rates and its efficacy in lowering glycated haemoglobin

  12. From boron analogues of amino acids to boronated DNA: potential new pharmaceuticals and neutron capture agents

    International Nuclear Information System (INIS)

    Spielvogel, B.F.; Sood, Anup; Duke Univ., Durham, NC; Shaw, B.R.; Hall, I.H.

    1991-01-01

    Isoelectronic and isostructural boron analogues of the α-amino acids ranging from simple glycine analogues such as H 3 NBH 2 COOH and Me 2 NHBH 2 COOH to alanine analogues have been synthesised. A diverse variety of analogues, including precursors and derivatives (such as peptides) have potent pharmacological activity, including anticancer, antiinflammatory, analgesic, and hypolipidemic activity in animal model studies and in vitro cell cultures. Boronated nucleosides and (oligo)nucleotides, synthetic oligonucleotide analogues of ''antisense'' agents interact with a complementary nucleic acid sequence blocking the biological effect of the target sequence. Nucleosides boronated on the pyrimidine and purine bases have been prepared. It has been established that an entirely new class of nucleic acid derivatives is feasible in which one of the non-bridging oxygens in the internucleotide phosphodiester linkage can be replaced by an isoelectronic analogue, the borane group, (BH 3 ). The boronated oligonucleotides can be viewed as hybrids of the normal oxygen oligonucleotides and the methylphosphonate oligonucleotides. (author)

  13. Insulin biosimilars: the impact on rapid-acting analogue-based therapy.

    Science.gov (United States)

    Franzè, S; Cilurzo, F; Minghetti, P

    2015-04-01

    The impending expiration of patent protection for recombinant insulins provides the opportunity to introduce cost-saving copies, named biosimilars, onto the market. Although there is broad experience in the production and characterisation of insulins, the development of copies is still a challenge. In this paper, the main features of insulins and the EU regulatory framework for their biosimilar products are reviewed. The main focus is on rapid-acting insulin analogues (Humalog(®); Novolog(®)/NovoRapid(®); Apidra(®)). Since they differ by one or two amino acids in chain B, production of one biosimilar for all three drug products is not feasible. However, from post-marketing-collected clinical data, rapid-acting insulin analogues seem to have similar therapeutic efficacy. It is reasonable to suppose that, for prescription to treatment-naïve patients, the cheaper biosimilar would be the preferred choice of physicians, either spontaneously or induced by health insurance. Therefore, its introduction will affect the market share of all the other rapid-acting insulin analogues.

  14. GammaWorkshops Proceedings

    International Nuclear Information System (INIS)

    Ramebaeck, H.; Straelberg, E.; Klemola, S.; Nielsen, Sven P.; Palsson, S.E.

    2012-01-01

    Due to a sparse interaction during the last years between practioners in gamma ray spectrometry in the Nordic countries, a NKS activity was started in 2009. This GammaSem was focused on seminars relevant to gamma spectrometry. A follow up seminar was held in 2010. As an outcome of these activities it was suggested that the 2011 meeting should be focused on practical issues, e.g. different corrections needed in gamma spectrometric measurements. This three day's meeting, GammaWorkshops, was held in September at Risoe-DTU. Experts on different topics relevant for gamma spectrometric measurements were invited to the GammaWorkshops. The topics included efficiency transfer, true coincidence summing corrections, self-attenuation corrections, measurement of natural radionuclides (natural decay series), combined measurement uncertainty calculations, and detection limits. These topics covered both lectures and practical sessions. The practical sessions included demonstrations of tools for e.g. corrections and calculations of the above meantioned topics. (Author)

  15. GammaWorkshops Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Ramebaeck, H. (ed.) (Swedish Defence Research Agency (Sweden)); Straalberg, E. (Institute for Energy Technology, Kjeller (Norway)); Klemola, S. (Radiation and Nuclear Safety Authority, STUK (Finland)); Nielsen, Sven P. (Technical Univ. of Denmark. Risoe National Lab. for Sustainable Energy, Roskilde (Denmark)); Palsson, S.E. (Icelandic Radiation Safety Authority (Iceland))

    2012-01-15

    Due to a sparse interaction during the last years between practioners in gamma ray spectrometry in the Nordic countries, a NKS activity was started in 2009. This GammaSem was focused on seminars relevant to gamma spectrometry. A follow up seminar was held in 2010. As an outcome of these activities it was suggested that the 2011 meeting should be focused on practical issues, e.g. different corrections needed in gamma spectrometric measurements. This three day's meeting, GammaWorkshops, was held in September at Risoe-DTU. Experts on different topics relevant for gamma spectrometric measurements were invited to the GammaWorkshops. The topics included efficiency transfer, true coincidence summing corrections, self-attenuation corrections, measurement of natural radionuclides (natural decay series), combined measurement uncertainty calculations, and detection limits. These topics covered both lectures and practical sessions. The practical sessions included demonstrations of tools for e.g. corrections and calculations of the above meantioned topics. (Author)

  16. ATLAS searches for VH, HH, VV, V+$\\gamma$/$\\gamma\\gamma$ resonances

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00441490; The ATLAS collaboration

    2017-01-01

    The discovery of a Higgs boson at the Large Hadron Collider motivates searches for physics beyond the Standard Model in channels involving coupling to the Higgs boson. A search for massive resonances decaying into couples of bosons is described. The considered final states are: $HH$, $VH$, $VV$, $V\\gamma$ and $\\gamma\\gamma$ with $V$ indicating either the $W$ or the $Z$ boson. Final states with different number of leptons or photons and where, in many cases, at least one Higgs decays into a b-quark pair are studied using different jet reconstruction techniques which allow to optimize the signal acceptance for low or high Higgs boson transverse momentum. The most recent diboson resonance searches using LHC Run 2 data are described.

  17. Method of incident low-energy gamma-ray direction reconstruction in the GAMMA-400 gamma-ray space telescope

    International Nuclear Information System (INIS)

    Kheymits, M D; Leonov, A A; Zverev, V G; Galper, A M; Arkhangelskaya, I V; Arkhangelskiy, A I; Yurkin, Yu T; Bakaldin, A V; Suchkov, S I; Topchiev, N P; Dalkarov, O D

    2016-01-01

    The GAMMA-400 gamma-ray space-based telescope has as its main goals to measure cosmic γ-ray fluxes and the electron-positron cosmic-ray component produced, theoretically, in dark-matter-particles decay or annihilation processes, to search for discrete γ-ray sources and study them in detail, to examine the energy spectra of diffuse γ-rays — both galactic and extragalactic — and to study gamma-ray bursts (GRBs) and γ-rays from the active Sun. Scientific goals of GAMMA-400 telescope require fine angular resolution. The telescope is of a pair-production type. In the converter-tracker, the incident gamma-ray photon converts into electron-positron pair in the tungsten layer and then the tracks are detected by silicon- strip position-sensitive detectors. Multiple scattering processes become a significant obstacle in the incident-gamma direction reconstruction for energies below several gigaelectronvolts. The method of utilising this process to improve the resolution is proposed in the presented work. (paper)

  18. Andrographolide and analogues in cancer prevention.

    Science.gov (United States)

    Mishra, Siddhartha Kumar; Tripathi, Swati; Shukla, Archana; Oh, Seung Hyun; Kim, Hwan Mook

    2015-01-01

    Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents.

  19. The monoamine oxidase inhibition properties of selected structural analogues of methylene blue

    International Nuclear Information System (INIS)

    Delport, Anzelle; Harvey, Brian H.; Petzer, Anél; Petzer, Jacobus P.

    2017-01-01

    The thionine dye, methylene blue (MB), is a potent inhibitor of monoamine oxidase (MAO) A, a property that may, at least in part, mediate its antidepressant effects in humans and animals. The central inhibition of MAO-A by MB has also been linked to serotonin toxicity (ST) which may arise when MB is used in combination with serotonergic drugs. Structural analogues and the principal metabolite of MB, azure B, have also been reported to inhibit the MAO enzymes, with all compounds exhibiting specificity for the MAO-A isoform. To expand on the structure-activity relationships (SARs) of MAO inhibition by MB analogues, the present study investigates the human MAO inhibition properties of five MB analogues: neutral red, Nile blue, new methylene blue, cresyl violet and 1,9-dimethyl methylene blue. Similar to MB, these analogues also are specific MAO-A inhibitors with cresyl violet (IC 50 = 0.0037 μM), Nile blue (IC 50 = 0.0077 μM) and 1,9-dimethyl methylene blue (IC 50 = 0.018 μM) exhibiting higher potency inhibition compared to MB (IC 50 = 0.07 μM). Nile blue also represents a potent MAO-B inhibitor with an IC 50 value of 0.012 μM. From the results it may be concluded that non-thionine MB analogues (e.g. cresyl violet and Nile blue) also may exhibit potent MAO inhibition, a property which should be considered when using these compounds in pharmacological studies. Benzophenoxazines such as cresyl violet and Nile blue are, similar to phenothiazines (e.g. MB), representative of high potency MAO-A inhibitors with a potential risk of ST. - Highlights: • MB analogues, cresyl violet and Nile blue, are high potency MAO-A inhibitors. • Nile blue also represents a potent MAO-B inhibitor. • Potent MAO-A inhibition should alert to potential serotonin toxicity.

  20. The monoamine oxidase inhibition properties of selected structural analogues of methylene blue

    Energy Technology Data Exchange (ETDEWEB)

    Delport, Anzelle [Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Harvey, Brian H. [Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Pharmacology, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Petzer, Anél [Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Petzer, Jacobus P., E-mail: jacques.petzer@nwu.ac.za [Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa); Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520 (South Africa)

    2017-06-15

    The thionine dye, methylene blue (MB), is a potent inhibitor of monoamine oxidase (MAO) A, a property that may, at least in part, mediate its antidepressant effects in humans and animals. The central inhibition of MAO-A by MB has also been linked to serotonin toxicity (ST) which may arise when MB is used in combination with serotonergic drugs. Structural analogues and the principal metabolite of MB, azure B, have also been reported to inhibit the MAO enzymes, with all compounds exhibiting specificity for the MAO-A isoform. To expand on the structure-activity relationships (SARs) of MAO inhibition by MB analogues, the present study investigates the human MAO inhibition properties of five MB analogues: neutral red, Nile blue, new methylene blue, cresyl violet and 1,9-dimethyl methylene blue. Similar to MB, these analogues also are specific MAO-A inhibitors with cresyl violet (IC{sub 50} = 0.0037 μM), Nile blue (IC{sub 50} = 0.0077 μM) and 1,9-dimethyl methylene blue (IC{sub 50} = 0.018 μM) exhibiting higher potency inhibition compared to MB (IC{sub 50} = 0.07 μM). Nile blue also represents a potent MAO-B inhibitor with an IC{sub 50} value of 0.012 μM. From the results it may be concluded that non-thionine MB analogues (e.g. cresyl violet and Nile blue) also may exhibit potent MAO inhibition, a property which should be considered when using these compounds in pharmacological studies. Benzophenoxazines such as cresyl violet and Nile blue are, similar to phenothiazines (e.g. MB), representative of high potency MAO-A inhibitors with a potential risk of ST. - Highlights: • MB analogues, cresyl violet and Nile blue, are high potency MAO-A inhibitors. • Nile blue also represents a potent MAO-B inhibitor. • Potent MAO-A inhibition should alert to potential serotonin toxicity.

  1. Observations of the highest energy gamma-rays from gamma-ray bursts

    International Nuclear Information System (INIS)

    Dingus, Brenda L.

    2001-01-01

    EGRET has extended the highest energy observations of gamma-ray bursts to GeV gamma rays. Such high energies imply the fireball that is radiating the gamma-rays has a bulk Lorentz factor of several hundred. However, EGRET only detected a few gamma-ray bursts. GLAST will likely detect several hundred bursts and may extend the maximum energy to a few 100 GeV. Meanwhile new ground based detectors with sensitivity to gamma-ray bursts are beginning operation, and one recently reported evidence for TeV emission from a burst

  2. The IAEA report on the role of natural analogues in performance assessment

    International Nuclear Information System (INIS)

    Vovk, I.F.

    1989-01-01

    A working draft of the report was prepared with the assistance of a group of consultants who met in Vienna from 29 June to 3 July 1987. The draft was revised by an Advisory Group meeting in Vienna from 2 to 6 November 1987 and examined by the Technical Review Committee on Underground Disposal of Radioactive Waste (TRCUD) convened in Vienna from 15 to 19 February 1988. TRCUD recommended it for publication as a Technical Reports Series. The document appraises the use of natural analogues in improving confidence in the soundness of performance assessments for deep underground disposal of long-lived wastes. For this purpose it reviews several available performance assessments and identifies on this basis factors, processes or parameters which are important to their results, assesses the requirements for validation in each area and identifies those areas where analogues are appropriate. A special section is devoted to discussion of the quantitative and qualitative roles of the analogues. A number of conclusions reflect the state-of-the-art and may guide further natural analogue studies

  3. Bentonite analogue research related to geological disposal of radioactive waste: current status and future outlook

    International Nuclear Information System (INIS)

    Reijonen, H.M.; Russel, A.W.

    2015-01-01

    The practice of utilising natural analogues in assessing the long-term behaviour of various components of geological repositories for radioactive waste is already well established in most disposal programmes. Numerous studies on bentonites, focussing on bentonite interaction with other components of the engineered barrier system and a range of host rock environments, are present in the literature. In this article, recent bentonite natural analogue studies are briefly reviewed, and gaps in the current literature identified, with the aim of (1) suggesting where relevant new information could be obtained by data mining published bentonite natural analogue studies with a new focus on current safety case requirements, (2) collecting relevant information by revisiting known bentonite analogue sites and conducting investigations with more appropriate analytical techniques, and (3) identifying novel study sites where, for example, bentonite longevity in very dilute to highly saline groundwater conditions can be studied. It must be noted that the use of natural analogues in safety case development is likely to be site and repository design-specific in nature and thus emphasis is placed on the appropriate use of relevant natural analogue data on bentonite longevity. (authors)

  4. Bentonite analogue research related to geological disposal of radioactive waste: current status and future outlook

    Energy Technology Data Exchange (ETDEWEB)

    Reijonen, H.M. [Saanio and Rickkola Oy, Helsinki (Finland); Russel, A.W. [Bedrock Geosciences, Auenstein (Switzerland)

    2015-06-15

    The practice of utilising natural analogues in assessing the long-term behaviour of various components of geological repositories for radioactive waste is already well established in most disposal programmes. Numerous studies on bentonites, focussing on bentonite interaction with other components of the engineered barrier system and a range of host rock environments, are present in the literature. In this article, recent bentonite natural analogue studies are briefly reviewed, and gaps in the current literature identified, with the aim of (1) suggesting where relevant new information could be obtained by data mining published bentonite natural analogue studies with a new focus on current safety case requirements, (2) collecting relevant information by revisiting known bentonite analogue sites and conducting investigations with more appropriate analytical techniques, and (3) identifying novel study sites where, for example, bentonite longevity in very dilute to highly saline groundwater conditions can be studied. It must be noted that the use of natural analogues in safety case development is likely to be site and repository design-specific in nature and thus emphasis is placed on the appropriate use of relevant natural analogue data on bentonite longevity. (authors)

  5. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

    The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...

  6. DOTA-derivatives of octreotide dicarba-analogues with high affinity for somatostatin sst2,5 receptors

    Science.gov (United States)

    Pratesi, Alessandro; Ginanneschi, Mauro; Lumini, Marco; Papini, Anna M.; Novellino, Ettore; Brancaccio, Diego; Carotenuto, Alfonso

    2017-02-01

    In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumours and their metastases. In fact, peptide ligands of somatostatin receptors (sst’s) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogues, which show interesting binding profiles at sst’s. In this context, it was mandatory to explore the possibility that our analogues could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogues of octreotide. Interestingly, two conjugated analogues exhibited nanomolar affinities on sst2 and sst5 somatostatin receptor subtypes.

  7. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    OpenAIRE

    Shimshoni, JA; Winkler, I; Golan, E; Nutt, D

    2016-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-...

  8. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

    Science.gov (United States)

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-08-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

  9. Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

    International Nuclear Information System (INIS)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

    1989-01-01

    The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel 6 ]LH-RH (SB-05) and [Ac-D-Nal(2) 1 ,D-Phe(pCl) 2 ,D-Pal(3) 3 ,Arg 5 ,D-Mel 6 ,D-Ala 10 ]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel 6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells

  10. The synthesis and biochemical evaluation of thymidine analogues substituted with nido carborane at the N-3 position

    International Nuclear Information System (INIS)

    Byun, Youngjoo; Yan Junhua; Al-Madhoun, A.S.; Johnsamuel, Jayaseharan; Yang Weilian; Barth, R.F.; Eriksson, Staffan; Tjarks, Werner

    2004-01-01

    Several thymidine analogues substituted with closo- and nido-carborane at the N-3 position were synthesized. The nido-carboranyl thymidine analogues were designed to be effective substrates for human thymidine kinase 1 in combination with an increased water solubility sufficient for clinical application in boron neutron capture therapy. This was done because N-3 substituted closo-carboranyl thymidine analogues previously synthesized in our laboratories were good TK1 substrates but were poorly water-soluble. Newly synthesized zwitterionic amino nido- and the corresponding neutral closo-m-carboranyl thymidine analogues exhibited excellent TK1 phosphorylation rates up to 75% relative to thymidine, indicating that these compounds were good substrates for thymidine kinase 1. Thin layer chromatographic studies were indicative of increased hydrophilicity of the synthesized nido-carboranyl thymidine analogues compared with their closo-carboranyl counterparts and previously reported closo-carboranyl thymidine analogues

  11. Status of natural analogue studies

    International Nuclear Information System (INIS)

    Sekine, Keiichi

    1994-03-01

    This report is based on the materials for the meeting at the Nuclear Safety Commission of Japan held on September 1993. Details are as follows: Alteration of glass as the study of alteration of natural minerals; alteration of uranium minerals, migration of uranium and thorium series radionuclides, alteration of chlorite, fixation of uranium alteration of minerals and migration of uranium as the study of alligator rivers analogue project held at Koongarra uranium deposit, Australia. (author)

  12. Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

    KAUST Repository

    Hasan, Mohammed Nihal

    2018-02-09

    Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

  13. Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

    KAUST Repository

    Hasan, Mohammed Nihal; Choudhry, Hani; Razvi, Syed Shoeb; Moselhy, Said Salama; Kumosani, Taha Abduallah; Zamzami, Mazin A.; Omran, Ziad; Halwani, Majed A.; Al-Babili, Salim; Abualnaja, Khalid Omer; Al-Malki, Abdulrahman Labeed; Alhosin, Mahmoud; Asami, Tadao

    2018-01-01

    Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

  14. Design and Performance of the GAMMA-400 Gamma-Ray Telescope for Dark Matter Searches

    Science.gov (United States)

    Galper, A. M.; Adriani, O.; Aptekar, R. L.; Arkhangelskaja, I. V.; Arkhangelskiy, A. I.; Boezio, M.; Bonvicini, V.; Boyarchuk, K. A.; Fradkin, M. I.; Gusakov, Yu V.; hide

    2012-01-01

    The GAMMA-400 gamma-ray telescope is designed to measure the fluxes of gamma-rays and cosmic-ray electrons (+) positrons, which can be produced by annihilation or decay of the dark matter particles, as well as to survey the celestial sphere in order to study point and extended sources of gamma-rays, measure energy spectra of Galactic and extragalactic diffuse gamma-ray emission, gamma-ray bursts, and gamma-ray emission from the Sun. GAMMA-400 covers the energy range from 100 MeV to 3000 GeV. Its angular resolution is approximately 0.01deg (E(sub gamma) greater than 100 GeV), the energy resolution approximately 1% (E(sub gamma) greater than 10 GeV), and the proton rejection factor approximately 10(exp 6). GAMMA-400 will be installed on the Russian space platform Navigator. The beginning of observations is planned for 2018.

  15. Occurrence and profiles of bisphenol analogues in municipal sewage sludge in China

    International Nuclear Information System (INIS)

    Song, Shanjun; Song, Maoyong; Zeng, Luzhe; Wang, Thanh; Liu, Runzeng; Ruan, Ting; Jiang, Guibin

    2014-01-01

    Extensive use of bisphenol A and its analogues has caused increasing concern over the potential adverse health impacts of these chemicals. In this study, the presence and profiles of 13 bisphenols (BPs) were investigated in 52 municipal sewage sludge samples collected from 30 cities in China. Tetrabromobisphenol A was the most frequently observed analogue (geometric mean: 20.5 ng/g dw). Bisphenol A (4.69 ng/g dw), bisphenol S (3.02 ng/g dw), and bisphenol F (3.84 ng/g dw) were found with similar frequency. Other BP analogues such as tetrachlorobisphenol A, bisphenol AF, bisphenol E, and dihydroxybiphenyl were identified for the first time in sewage sludge in China. Significant correlations were found among BP concentrations, but no relationships were found with wastewater treatment plant characteristics. Profiles of the relative estradiol equivalents suggested that the estrogenic potential of BP mixtures may be associated with the occurrence and contributions of specific analogues. -- Highlights: • The profiles of various bisphenols were studied initially in sludge in China. • Analogous abundances were found for BPA, BPS and BPF. • Halo-substituted BPs have similar portions with BPA and its ascendant alternatives. • BPAF, TCBPA, BPE and DHBP were identified for the first time in sludge in China. -- We analyzed the profiles of bisphenol analogues in 52 sewage sludge samples with several bisphenols identified for the first time in wastewater treatment plants in China

  16. Bivalent metal-based MIL-53 analogues: Synthesis, properties and application

    International Nuclear Information System (INIS)

    Liu, Yongxin; Liu, Dan; Wang, Cheng

    2015-01-01

    Trivalent metal-based MIL-53 (Al 3+ , Cr 3+ , Fe 3+ , In 3+ ) compounds are interesting metal–organic frameworks (MOFs) with breathing effect and are promising gas sorption materials. Replacing bridging μ 2 -OH group by neutral ligands such as pyridine N-oxide and its derivatives (PNOs), the trivalent metal-based MIL-53 analogous structures could be extended to bivalent metal systems. The introduction of PNOs and bivalent metal elements endows the frameworks with new structural features and physical and chemical properties. This minireview summarizes the recent development of bivalent metal-based MIL-53 analogues (Mn 2+ , Co 2+ , Ni 2+ ), typically, focusing on the synthetic strategies and potential applications based on our own works and literatures. We present the synthetic strategy to achieve structures evolution from single-ligand-walled to double-ligand-walled channel. Properties and application of these new materials in a wide range of potential areas are discussed including thermal stability, gas adsorption, magnetism and liquid-phase separation. Promising directions of this research field are also highlighted. - Graphical abstract: The recent development of bivalent metal-based MIL-53 analogues (Mn 2+ , Co 2+ , Ni 2+ ) on their synthetic strategies, properties and potential applications was reviewed. - Highlights: • Structure features of bivalent metal-based MIL-53 analogues are illustrated. • Important properties and application are presented. • Host–guest interactions are main impetus for liquid-phase separation. • Promising directions of bivalent metal-based MIL-53 analogues are highlighted

  17. Ultrasound exfoliation of inorganic analogues of graphene

    Czech Academy of Sciences Publication Activity Database

    Štengl, Václav; Henych, Jiří; Slušná, Michaela; Ecorchard, Petra

    2014-01-01

    Roč. 9, APR (2014), s. 1-14 ISSN 1556-276X R&D Projects: GA ČR(CZ) GA14-05146S Institutional support: RVO:61388980 Keywords : Ultrasound * Exfoliation * Graphene inorganic analogues Subject RIV: CA - Inorganic Chemistry Impact factor: 2.779, year: 2014

  18. Synthesis and Insecticidal Activities of Novel Analogues of Chlorantraniliprole Containing Nitro Group

    Institute of Scientific and Technical Information of China (English)

    FENG Qi; WANG Ming-zhong; XIONG Li-xia; LIU Zhi-li; LI Zheng-ming

    2011-01-01

    Twelve novel analogues of chlorantraniliprole containing nitro group were synthesized,and their structures were characterized by 1H NMR and high-resolution mass spectrometry(HRMS).Their evaluated insecticidal activities against oriental armyworm(Mythimna separata) indicate that the nitro-containing analogues showed favorable insecticidal activities,while the activity of compounds 5g at 0.25 mg/L was 40%,but still lower than chlorantraniliprole.

  19. New analogues of ACPD with selective activity for group II metabotropic glutamate receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Madsen, U; Mikiciuk-Olasik, E

    1997-01-01

    In this study we have determined the pharmacology of a series of 1-aminocyclopentane-1,3-dicarboxylic acid (1,3-ACPD) analogues at cloned metabotropic glutamic acid (mGlu) receptors. The new analogues comprise the four possible stereoisomers of 1-amino-1-carboxycyclopentane-3-acetic acid (1,3-hom...

  20. Total Cross Section in $\\gamma\\gamma$ Collisions at LEP

    CERN Document Server

    Acciarri, M.; Adriani, O.; Aguilar-Benitez, M.; Alcaraz, J.; Alemanni, G.; Allaby, J.; Aloisio, A.; Alviggi, M.G.; Ambrosi, G.; Anderhub, H.; Andreev, Valery P.; Angelescu, T.; Anselmo, F.; Arefev, A.; Azemoon, T.; Aziz, T.; Bagnaia, P.; Bajo, A.; Baksay, L.; Balandras, A.; Baldew, S.V.; Banerjee, S.; Banerjee, Sw.; Barczyk, A.; Barillere, R.; Bartalini, P.; Basile, M.; Batalova, N.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bellucci, L.; Berbeco, R.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B.L.; Bhattacharya, S.; Biasini, M.; Biland, A.; Blaising, J.J.; Blyth, S.C.; Bobbink, G.J.; Bohm, A.; Boldizsar, L.; Borgia, B.; Bourilkov, D.; Bourquin, M.; Braccini, S.; Branson, J.G.; Brochu, F.; Buffini, A.; Buijs, A.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Capell, M.; Cara Romeo, G.; Carlino, G.; Cartacci, A.M.; Casaus, J.; Castellini, G.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Cesaroni, F.; Chamizo, M.; Chang, Y.H.; Chaturvedi, U.K.; Chemarin, M.; Chen, A.; Chen, G.; Chen, G.M.; Chen, H.F.; Chen, H.S.; Chiefari, G.; Cifarelli, L.; Cindolo, F.; Civinini, C.; Clare, I.; Clare, R.; Coignet, G.; Colino, N.; Costantini, S.; Cotorobai, F.; de la Cruz, B.; Csilling, A.; Cucciarelli, S.; Dai, T.S.; van Dalen, J.A.; D'Alessandro, R.; de Asmundis, R.; Deglon, P.; Degre, A.; Deiters, K.; della Volpe, D.; Delmeire, E.; Denes, P.; DeNotaristefani, F.; De Salvo, A.; Diemoz, M.; Dierckxsens, M.; van Dierendonck, D.; Dionisi, C.; Dittmar, M.; Dominguez, A.; Doria, A.; Dova, M.T.; Duchesneau, D.; Dufournaud, D.; Duinker, P.; El Mamouni, H.; Engler, A.; Eppling, F.J.; Erne, F.C.; Ewers, A.; Extermann, P.; Fabre, M.; Falagan, M.A.; Falciano, S.; Favara, A.; Fay, J.; Fedin, O.; Felcini, M.; Ferguson, T.; Fesefeldt, H.; Fiandrini, E.; Field, J.H.; Filthaut, F.; Fisher, P.H.; Fisk, I.; Forconi, G.; Freudenreich, K.; Furetta, C.; Galaktionov, Iouri; Ganguli, S.N.; Garcia-Abia, Pablo; Gataullin, M.; Gau, S.S.; Gentile, S.; Gheordanescu, N.; Giagu, S.; Gong, Z.F.; Grenier, Gerald Jean; Grimm, O.; Gruenewald, M.W.; Guida, M.; van Gulik, R.; Gupta, V.K.; Gurtu, A.; Gutay, L.J.; Haas, D.; Hasan, A.; Hatzifotiadou, D.; Hebbeker, T.; Herve, Alain; Hidas, P.; Hirschfelder, J.; Hofer, H.; Holzner, G.; Hoorani, H.; Hou, S.R.; Hu, Y.; Iashvili, I.; Jin, B.N.; Jones, Lawrence W.; de Jong, P.; Josa-Mutuberria, I.; Khan, R.A.; Kafer, D.; Kaur, M.; Kienzle-Focacci, M.N.; Kim, D.; Kim, J.K.; Kirkby, Jasper; Kiss, D.; Kittel, W.; Klimentov, A.; Konig, A.C.; Kopal, M.; Kopp, A.; Koutsenko, V.; Kraber, M.; Kraemer, R.W.; Krenz, W.; Kruger, A.; Kunin, A.; Ladron de Guevara, P.; Laktineh, I.; Landi, G.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Lee, H.J.; Le Goff, J.M.; Leiste, R.; Levtchenko, P.; Li, C.; Likhoded, S.; Lin, C.H.; Lin, W.T.; Linde, F.L.; Lista, L.; Liu, Z.A.; Lohmann, W.; Longo, E.; Lu, Y.S.; Lubelsmeyer, K.; Luci, C.; Luckey, David; Lugnier, L.; Luminari, L.; Lustermann, W.; Ma, W.G.; Maity, M.; Malgeri, L.; Malinin, A.; Mana, C.; Mangeol, D.; Mans, J.; Marian, G.; Martin, J.P.; Marzano, F.; Mazumdar, K.; McNeil, R.R.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W.J.; von der Mey, M.; Mihul, A.; Milcent, H.; Mirabelli, G.; Mnich, J.; Mohanty, G.B.; Moulik, T.; Muanza, G.S.; Muijs, A.J.M.; Musicar, B.; Musy, M.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Niessen, T.; Nisati, A.; Kluge, Hannelies; Ofierzynski, R.; Organtini, G.; Oulianov, A.; Palomares, C.; Pandoulas, D.; Paoletti, S.; Paolucci, P.; Paramatti, R.; Park, H.K.; Park, I.H.; Passaleva, G.; Patricelli, S.; Paul, Thomas Cantzon; Pauluzzi, M.; Paus, C.; Pauss, F.; Pedace, M.; Pensotti, S.; Perret-Gallix, D.; Petersen, B.; Piccolo, D.; Pierella, F.; Pieri, M.; Piroue, P.A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pojidaev, V.; Postema, H.; Pothier, J.; Prokofev, D.O.; Prokofiev, D.; Quartieri, J.; Rahal-Callot, G.; Rahaman, M.A.; Raics, P.; Raja, N.; Ramelli, R.; Rancoita, P.G.; Ranieri, R.; Raspereza, A.; Raven, G.; Razis, P.; Ren, D.; Rescigno, M.; Reucroft, S.; Riemann, S.; Riles, Keith; Rodin, J.; Roe, B.P.; Romero, L.; Rosca, A.; Rosier-Lees, S.; Roth, Stefan; Rosenbleck, C.; Roux, B.; Rubio, J.A.; Ruggiero, G.; Rykaczewski, H.; Saremi, S.; Sarkar, S.; Salicio, J.; Sanchez, E.; Sanders, M.P.; Schafer, C.; Schegelsky, V.; Schmidt-Kaerst, S.; Schmitz, D.; Schopper, H.; Schotanus, D.J.; Schwering, G.; Sciacca, C.; Seganti, A.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shumilov, E.; Shvorob, A.; Siedenburg, T.; Son, D.; Smith, B.; Spillantini, P.; Steuer, M.; Stickland, D.P.; Stone, A.; Stoyanov, B.; Straessner, A.; Sudhakar, K.; Sultanov, G.; Sun, L.Z.; Sushkov, S.; Suter, H.; Swain, J.D.; Szillasi, Z.; Sztaricskai, T.; Tang, X.W.; Tauscher, L.; Taylor, L.; Tellili, B.; Teyssier, D.; Timmermans, Charles; Ting, Samuel C.C.; Ting, S.M.; Tonwar, S.C.; Toth, J.; Tully, C.; Tung, K.L.; Uchida, Y.; Ulbricht, J.; Valente, E.; Vesztergombi, G.; Vetlitsky, I.; Vicinanza, D.; Viertel, G.; Villa, S.; Vivargent, M.; Vlachos, S.; Vodopianov, I.; Vogel, H.; Vogt, H.; Vorobev, I.; Vorobov, A.A.; Vorvolakos, A.; Wadhwa, M.; Wallraff, W.; Wang, M.; Wang, X.L.; Wang, Z.M.; Weber, A.; Weber, M.; Wienemann, P.; Wilkens, H.; Wu, S.X.; Wynhoff, S.; Xia, L.; Xu, Z.Z.; Yamamoto, J.; Yang, B.Z.; Yang, C.G.; Yang, H.J.; Yang, M.; Ye, J.B.; Yeh, S.C.; Zalite, A.; Zalite, Yu.; Zhang, Z.P.; Zhu, G.Y.; Zhu, R.Y.; Zichichi, A.; Zilizi, G.; Zimmermann, B.; Zoller, M.

    2001-01-01

    The reaction e+e- -> e+e- gamma* gamma* -> e+e- hadrons for quasi-real photons is studied using data from root(s) = 183 GeV up to 202 GeV. Results on the total cross sections sigma(e+e- -> e+e- hadrons) and sigma(+e- gamma* gamma* -> e+e- hadrons) are given for the two-photon centre-of-mass energies 5 GeV < Wgammagamma < 185 GeV. The total cross section of two real photons is described by a Regge parametrisation. We observe a steeper rise with the two-photon centre-of-mass energy as compared to the hadron-hadron and the photon-proton cross sections. The data are also compared to the expectations of different theoretical models.

  1. Gamma ray astronomy

    International Nuclear Information System (INIS)

    Broomhead, Laurent.

    1980-01-01

    The nuclear gamma astronomy is presented, in particular the Gamma Ray Observatory, an enormous eight tonnes machine fitted with gamma telescopes, scheduled for launching around 1985. It is thereby hoped to study the natural nuclear reactions which occur when stars explode [fr

  2. Somatostatin analogue scintigraphy and tuberculosis: case report

    International Nuclear Information System (INIS)

    Biancheri, I.; Rudenko, B.; Vautrin, P.; Raddoul, J.; Lamfichek, N.; Kantelip, B.; Mantion, G.

    2005-01-01

    Scintigraphy using a radiolabelled somatostatin analogue (111 In-pentetreotide) is useful in the detection of neuroendocrine tumors. But this radiopharmaceutical accumulates also in solid tumours or in inflammatory diseases such as granulomatosis. We present a case of 111 In-pentetreotide uptake in a tuberculous adenopathy. (author)

  3. MARSI: metabolite analogues for rational strain improvement

    DEFF Research Database (Denmark)

    Cardoso, João G. R.; Zeidan, Ahmad A; Jensen, Kristian

    2018-01-01

    reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions...

  4. Aminopropyl carbazole analogues as potent enhancers of neurogenesis.

    Science.gov (United States)

    Yoon, Hye Jin; Kong, Sun-Young; Park, Min-Hye; Cho, Yongsung; Kim, Sung-Eun; Shin, Jae-Yeon; Jung, Sunghye; Lee, Jiyoun; Farhanullah; Kim, Hyun-Jung; Lee, Jeewoo

    2013-11-15

    Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. The Brookhaven electron analogue, 1953--1957

    Energy Technology Data Exchange (ETDEWEB)

    Plotkin, M.

    1991-12-18

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

  6. The Brookhaven electron analogue, 1953--1957

    International Nuclear Information System (INIS)

    Plotkin, M.

    1991-01-01

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary

  7. Studies of natural analogues and geological systems

    International Nuclear Information System (INIS)

    Brandberg, F.; Grundfelt, B.; Hoeglund, L.; Skagius K.; Karlsson, F.; Smellie, J.

    1993-04-01

    This review has involved studies of natural analogues and natural geological systems leading to the identification and quantification of processes and features of importance to the performance and safety of repositories for radioactive waste. The features and processes selected for the study comprise general geochemical issues related to the performance of the near- and far-field, the performance and durability of construction materials and the effects of glaciation. For each of these areas a number of potentially important processes for repository performance have been described, and evidence for their existence, as well as quantification of parameters of models describing the processes have been sought from major natural analogue studies and site investigations. The review has aimed at covering a relatively broad range of issues at the expense of in-depth analysis. The quantitative data presented are in most cases compilations of data from the literature; in a few cases results of evaluations made within the current project are included

  8. Doubly heavy baryon production at {gamma}{gamma} collider

    Energy Technology Data Exchange (ETDEWEB)

    Li Shiyuan [Department of Physics, Shandong University, Jinan 250100 (China)]. E-mail: lishy@sdu.edu.cn; Si Zongguo [Department of Physics, Shandong University, Jinan 250100 (China)]. E-mail: zgsi@sdu.edu.cn; Yang Zhongjuan [Department of Physics, Shandong University, Jinan 250100 (China)]. E-mail: yangzhongjuan@mail.sdu.edu.cn

    2007-05-10

    The inclusive production of doubly heavy baryons {xi}{sub cc} and {xi}{sub bb} at {gamma}{gamma} collider is investigated. It is found that the contribution from the heavy quark pair QQ in color triplet and color sextet are important.

  9. Natural analogue study on engineered barriers for underground disposal of radioactive wastes

    International Nuclear Information System (INIS)

    Araki, K.; Motegi, M.; Emoto, Y.; Kaji, Y.; Ikari, S.; Nada, T.; Watanabe, T.

    1989-01-01

    This is a report to develop the natural analogue methodology for the assessment of the life of the engineered barriers beyond the time period of normal experiments, 1000 years, for the disposal of low-level radioactive wastes with activity levels greater than those of wastes acceptable for shallow land burial in Japan. Geological and archeological events and objects available for the assessment of the possible life of each engineered barrier are surveyed. Taking heavy precipitation into account in Japan, a long-term, zero-release engineered barrier system using long-term durable materials based on the natural analogue events and objects is proposed along with the conventional type of water permeable engineered barrier system. The combination of the material quality and the environment that could be achieved within the repository is important for the long-term durability of the engineered barrier material. It is proposed that for the natural analogue study a physico-chemical methodology, which may be referred to as the physico-chemical natural history, is necessary to get parameters from the natural analogue events for the long-term assessment of the disposal system

  10. Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

    Energy Technology Data Exchange (ETDEWEB)

    Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

    2010-01-01

    Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.

  11. Fuzzy logic-based analogue forecasting and hybrid modelling of horizontal visibility

    Science.gov (United States)

    Tuba, Zoltán; Bottyán, Zsolt

    2018-04-01

    Forecasting visibility is one of the greatest challenges in aviation meteorology. At the same time, high accuracy visibility forecasts can significantly reduce or make avoidable weather-related risk in aviation as well. To improve forecasting visibility, this research links fuzzy logic-based analogue forecasting and post-processed numerical weather prediction model outputs in hybrid forecast. Performance of analogue forecasting model was improved by the application of Analytic Hierarchy Process. Then, linear combination of the mentioned outputs was applied to create ultra-short term hybrid visibility prediction which gradually shifts the focus from statistical to numerical products taking their advantages during the forecast period. It gives the opportunity to bring closer the numerical visibility forecast to the observations even it is wrong initially. Complete verification of categorical forecasts was carried out; results are available for persistence and terminal aerodrome forecasts (TAF) as well in order to compare. The average value of Heidke Skill Score (HSS) of examined airports of analogue and hybrid forecasts shows very similar results even at the end of forecast period where the rate of analogue prediction in the final hybrid output is 0.1-0.2 only. However, in case of poor visibility (1000-2500 m), hybrid (0.65) and analogue forecasts (0.64) have similar average of HSS in the first 6 h of forecast period, and have better performance than persistence (0.60) or TAF (0.56). Important achievement that hybrid model takes into consideration physics and dynamics of the atmosphere due to the increasing part of the numerical weather prediction. In spite of this, its performance is similar to the most effective visibility forecasting methods and does not follow the poor verification results of clearly numerical outputs.

  12. Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.

    Directory of Open Access Journals (Sweden)

    Leonie Harmse

    Full Text Available Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05. Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05, with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.

  13. Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.

    Science.gov (United States)

    Harmse, Leonie; Dahan-Farkas, Nurit; Panayides, Jenny-Lee; van Otterlo, Willem; Penny, Clement

    2015-01-01

    Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05). Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05), with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.

  14. Design and synthesis of biotin analogues reversibly binding with streptavidin.

    Science.gov (United States)

    Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

    2015-04-01

    Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. 18F-Labelled metomidate analogues as adrenocortical imaging agents

    International Nuclear Information System (INIS)

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Langstroem, Bengt

    2009-01-01

    Introduction: Two- and one-step syntheses of 18 F-labelled analogues of metomidate, such as 2-[ 18 F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[ 18 F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[ 18 F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[ 18 F]fluoroethyl 4-methylbenzenesulfonate or 3-[ 18 F]fluoropropyl 4-methylbenzenesulfonate. These were used as 18 F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46±3% and 79±30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  16. GammaSem Proceedings. A Nordic seminar for users of gamma spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Straalberg, E. (ed.) (Institute for Energy Technolgy (Norway)); Berg, K. (National Institute of Radiation Protection (Denmark)); Dowdall, M. (Norwegian Radiation Protection Authority (Norway)) (and others)

    2010-11-15

    The project GammaSem was proposed to the NKS in 2008. The aim of the project was to arrange two seminars for users of gamma spectrometry, in 2009 and 2010. The seminars were meant to provide a forum for discussions and sharing of information on practical issues concerning gamma spectrometry and initiate a network of gamma spectrometry users in the Nordic countries. Such a Nordic network should strengthen the collaboration between laboratories and improve all participants' competence in practical gamma spectrometry. Both seminars' focus was practical challenges met by the users themselves, rather than theoretical matters. Scientists and users of gamma spectrometry from all five Nordic countries were invited to the seminar, as well as scientist from the Baltic countries. A total of 65 people signed up for GammaSem 2010; representing 30 different universities, commercial companies, research institutes and authorities. The working group concept as presented at last year's GammaSem, has not worked out as intended. The reason for this is probably because most of the laboratories that signed up to join the working groups, signed up because they wanted to learn more about the different subjects. In combination with the fact that no funding was made available for the working groups, it was difficult to establish goals on what to achieve. None of the working groups applied for funding from the NKS (or elsewhere) to establish separate projects. There is a big need for more cooperation and for training within the field of gamma spectrometry. This fact has been proved through these two seminars, both by the many different topics that have been discussed, but also by the huge interest for participating in the suggested series of workshop. The GammaSem seminars have thus provided a much welcomed starting point for a broader Nordic collaboration. (Author)

  17. GammaSem Proceedings. A Nordic seminar for users of gamma spectrometry

    International Nuclear Information System (INIS)

    Straelberg, E.; Berg, K.; Dowdall, M.

    2010-11-01

    The project GammaSem was proposed to the NKS in 2008. The aim of the project was to arrange two seminars for users of gamma spectrometry, in 2009 and 2010. The seminars were meant to provide a forum for discussions and sharing of information on practical issues concerning gamma spectrometry and initiate a network of gamma spectrometry users in the Nordic countries. Such a Nordic network should strengthen the collaboration between laboratories and improve all participants' competence in practical gamma spectrometry. Both seminars' focus was practical challenges met by the users themselves, rather than theoretical matters. Scientists and users of gamma spectrometry from all five Nordic countries were invited to the seminar, as well as scientist from the Baltic countries. A total of 65 people signed up for GammaSem 2010; representing 30 different universities, commercial companies, research institutes and authorities. The working group concept as presented at last year's GammaSem, has not worked out as intended. The reason for this is probably because most of the laboratories that signed up to join the working groups, signed up because they wanted to learn more about the different subjects. In combination with the fact that no funding was made available for the working groups, it was difficult to establish goals on what to achieve. None of the working groups applied for funding from the NKS (or elsewhere) to establish separate projects. There is a big need for more cooperation and for training within the field of gamma spectrometry. This fact has been proved through these two seminars, both by the many different topics that have been discussed, but also by the huge interest for participating in the suggested series of workshop. The GammaSem seminars have thus provided a much welcomed starting point for a broader Nordic collaboration. (Author)

  18. [Ocular Surface Evaluation in Patients Treated with Prostaglandin Analogues Considering Preservative Agent].

    Science.gov (United States)

    Mlčáková, E; Mlčák, P; Karhanová, M; Langová, K; Marešová, K

    The aim of this study was to evaluate the ocular surface in patients treated with prostaglandin analogues considering contained preservative agent. 60 patients with glaucoma or ocular hypertension treated with prostaglandin analogue monotherapy were enrolled in this observational study. 20 patients with glaucoma suspect or ocular hypertension without local or systemic glaucoma medication formed the control group. Demographic data and medical history were recorded for each participant. Patients filled in the Ocular surface disease index© (OSDI) questionnaire and underwent an ophthalmological examination including assessment of conjunctival hyperaemia according to Efron, tear film break up time (BUT) and fluorescein staining according to the Oxford grading scheme. Treated participants were divided into 3 groups according to the preservative contained in the currently used prostaglandin analogue: the preservative-free group (18 patients), the polyquaternium group (17 patients) and the benzalkonium chloride (BAK) group (25 patients). The control group had significantly lower fluorescein staining than the preservative-free group (p=0.001), the polyquaternium group (p=0.007) and the BAK group (p=0.002). The conjunctival hyperaemia was significantly lower in the preservative-free group compared to the polyquaternium group (p=0.011). There was no significant difference among the other groups. The difference neither in the OSDI score nor in the BUT was statistically important. This study confirmed that the ocular surface is worse in patients treated with prostaglandin analogue monotherapy than in people without glaucoma medication. A significant difference among treated patients depending on a preservative agent was not proved.Key words: benzalkonium chloride, glaucoma, ocular surface disease, preservatives, prostaglandin analogues.

  19. Geological trainings for analogue astronauts: Lessons learned from MARS2013 expedition, Morocco

    Science.gov (United States)

    Orgel, C.; Achorner, I.; Losiak, A.; Gołębiowska, I.; Rampey, M.; Groemer, G.

    2013-09-01

    The Austrian Space Forum (OeWF) is a national organisation for space professionals and space enthusiasts. In collaboration with internal partner organisations, the OeWF focuses on Mars analogue research with their space volunteers and organises space-related outreach/education activities and conducts field tests with the Aouda.X and Aouda.S spacesuit simulators in Mars analogue environment. The main project of OeWF is called "PolAres" [1]. As the result of lessons learned from the Río Tinto 2011 expedition [4], we started to organise geological training sessions for the analogue astronauts. The idea was to give them basic geological background to perform more efficiently in the field. This was done in close imitation of the Apollo astronaut trainings that included theoretical lectures (between Jan. 1963-Nov. 1972) about impact geology, igneous petrology of the Moon, geophysics and geochemistry as well as several field trips to make them capable to collect useful samples for the geoscientists on Earth [3] [5]. In the last year the OeWF has organised three geoscience workshops for analogue astronauts as the part of their "astronaut" training. The aim was to educate the participants to make them understand the fundamentals in geology in theory and in the field (Fig. 1.). We proposed the "Geological Experiment Sampling Usefulness" (GESU) experiment for the MARS2013 simulation to improve the efficiency of the geological trainings. This simulation was conducted during February 2013, a one month Mars analogue research was conducted in the desert of Morocco [2] (Fig. 2.).

  20. Variation effect on the insecticide activity of DDT analogues. A chemometric approach

    Science.gov (United States)

    Itoh, S.; Nagashima, U.

    2002-08-01

    We investigated a variation effect on the insecticide activity of DDT analogues by using the first principles electronic structure calculations and the neural network analysis. It has been found that the charge distribution at the specific atomic sites in the DDT molecule is related to their toxicity. This approach can contribute to designing a new insecticide and a new harmlessness process of the DDT analogues.

  1. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    International Nuclear Information System (INIS)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

    1989-01-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides

  2. The Greenland analogue project. Yearly report 2010

    Energy Technology Data Exchange (ETDEWEB)

    Harper, J; Brinkerhoff, D; Johnson, J [University of Montana, Missoula (United States); Ruskeeniemi, T; Engstroem, J; Kukkonen, I [Geological Survey of Finland (Finland); and others

    2012-04-15

    A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

  3. The Greenland analogue project. Yearly report 2010

    International Nuclear Information System (INIS)

    Harper, J.; Brinkerhoff, D.; Johnson, J.; Ruskeeniemi, T.; Engstroem, J.; Kukkonen, I.

    2012-04-01

    A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

  4. Do GnRH analogues directly affect human endometrial epithelial cell gene expression?

    KAUST Repository

    Zhang, Xiaomei

    2010-03-04

    We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E2 and P4, and cyclic adenosine monophos-phate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5\\'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin2 and expressed ERa,ERb, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E2 and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A.E2 + P4 treatment for 4 days, alone or followed by GA, had no effect, but E2 + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endo-metrial epithelial cells in vitro. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.

  5. Cinnamoylated chloroquine analogues: A new structural class of antimalarial agents.

    Science.gov (United States)

    Gayam, Venkatareddy; Ravi, Subban

    2017-07-28

    A novel series of cinnamoylated chloroquine hybrid analogues were synthesized and evaluated as antimalarial agents. The trans cinnamic acid derivatives (3-8) were synthesized by utilizing substituted aldehydes and malanoic acid in DMF catalysed by DABCO. The final cinnamoylated chloroquine analogues (9-14) were synthesized by utilizing DCC coupling reagent. The amido chloroquine (17) was prepared from acid (16) and compound 2 in benzene using SOCl 2 as chlorinating agent. The corresponding ester (15) was prepared from 2-hydroxy acetophenone and 2-bromoacetates in actonitrile in presence of K 2 CO 3  as base followed by basic hydrolysis. The preparation of amide based chloroquine-chalcone analogues (18-22), were obtained by the combination of amido chloroquine (17) and aldehydes in 10% aq. KOH in methanol at room temperature. Further we prepared epichlorohydrin based chloroquine-chalcone analogues (25-28), by reacting the epoxide (24a, 24b and 24c) with 2 and methelenedioxy aniline. In vitro antimalarial activity against chloroquine sensitive strain 3D7, chloroquine resistant strain K1 of P. falciparum and in vitro cytotoxicity of compounds using VERO cell line was carried out. The synthesized molecules showed significant in vitro antimalarial activity especially against CQ resistant strain (K1). Among tested compounds, 13, 9 and 10 were found to be the most potent compounds of the series with IC 50 value of 44.06, 48.04 and 59.37 nM against chloroquine resistant K1 strain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Lysine-vasopressin analogues with glycoconjugates in position 8

    Czech Academy of Sciences Publication Activity Database

    Marcinkowska, A.; Borovičková, Lenka; Slaninová, Jiřina; Grzonka, Z.

    2006-01-01

    Roč. 80, č. 5 (2006), s. 759-766 ISSN 0137- 5083 Institutional research plan: CEZ:AV0Z40550506 Keywords : glycoconjugates * glycopeptides * lysine-vasopressin analogues Subject RIV: CC - Organic Chemistry Impact factor: 0.491, year: 2006

  7. An overview of gamma-hydroxybutyric acid: pharmacodynamics, pharmacokinetics, toxic effects, addiction, analytical methods, and interpretation of results.

    Science.gov (United States)

    Andresen, H; Aydin, B E; Mueller, A; Iwersen-Bergmann, S

    2011-09-01

    Abuse of gamma-hydroxybutyric acid (GHB) has been known since the early 1990's, but is not as widespread as the consumption of other illegal drugs. However, the number of severe intoxications with fatal outcomes is comparatively high; not the least of which is brought about by the consumption of the currently legal precursor substances gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). In regards to previous assumptions, addiction to GHB or its analogues can occur with severe symptoms of withdrawal. Moreover, GHB can be used for drug-facilitated sexual assaults. Its pharmacological effects are generated mainly by interaction with both GABA(B) and GHB receptors, as well as its influence on other transmitter systems in the human brain. Numerous analytical methods for determining GHB using chromatographic techniques were published in recent years, and an enzymatic screening method was established. However, the short window of GHB detection in blood or urine due to its rapid metabolism is a challenge. Furthermore, despite several studies addressing this problem, evaluation of analytical results can be difficult: GHB is a metabolite of GABA (gamma-aminobutyric acid); a differentiation between endogenous and exogenous concentrations has to be made. Apart from this, in samples with a longer storage interval and especially in postmortem specimens, higher levels can be measured due to GHB generation during this postmortem interval or storage time. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Development of a natural analogue database to support the safety case of the Korean radioactive waste disposal program

    International Nuclear Information System (INIS)

    Baik, M.H.; Park, T.J.; Kim, I.Y.; Jeong, J.; Choi, K.W.

    2015-01-01

    In this study, the status of natural analogue studies in Korea is briefly summarized and applicability of existing natural analogue information to the Korean safety case has been evaluated. To enable effective application of natural analogue information to the overall evaluation of long-term safety (the 'safety case') for the geological disposal of radioactive wastes, a natural analogue database has been developed by collecting, classifying, and evaluating relevant data. The natural analogue data collected were classified into categories based on site information, components/processes of the disposal system, properties/phenomena, reference, safety case application, application method, and suitability to a safety case. Suitability of the natural analogue data to a specific safety case was evaluated based upon the importance and the applicability to the Korean safety case. As a result, 75 natural analogue datasets were selected as important for the Korean safety case. The database developed can now be utilized in the RD and D (Research, Development, and Demonstration) program development for natural analogue studies. In addition, the methodology developed and the database compiled in this study may assist in the development of safety case including safety assessment for high-level radioactive waste disposal in Korea as well as in other countries. (authors)

  9. Development of a natural analogue database to support the safety case of the Korean radioactive waste disposal program

    Energy Technology Data Exchange (ETDEWEB)

    Baik, M.H.; Park, T.J.; Kim, I.Y.; Jeong, J. [Korea Atomic Research Institute, Yuseong-Gu, Daejeon (Korea, Republic of); Choi, K.W. [Korea Institute of Nuclear Safety, Yuseong-Gu, Daejeon (Korea, Republic of)

    2015-06-15

    In this study, the status of natural analogue studies in Korea is briefly summarized and applicability of existing natural analogue information to the Korean safety case has been evaluated. To enable effective application of natural analogue information to the overall evaluation of long-term safety (the 'safety case') for the geological disposal of radioactive wastes, a natural analogue database has been developed by collecting, classifying, and evaluating relevant data. The natural analogue data collected were classified into categories based on site information, components/processes of the disposal system, properties/phenomena, reference, safety case application, application method, and suitability to a safety case. Suitability of the natural analogue data to a specific safety case was evaluated based upon the importance and the applicability to the Korean safety case. As a result, 75 natural analogue datasets were selected as important for the Korean safety case. The database developed can now be utilized in the RD and D (Research, Development, and Demonstration) program development for natural analogue studies. In addition, the methodology developed and the database compiled in this study may assist in the development of safety case including safety assessment for high-level radioactive waste disposal in Korea as well as in other countries. (authors)

  10. Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression

    Science.gov (United States)

    Meylan, E M; Breuillaud, L; Seredenina, T; Magistretti, P J; Halfon, O; Luthi-Carter, R; Cardinaux, J-R

    2016-01-01

    Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1−/− mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1−/− mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1−/− prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin- and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1−/− mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D-aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1−/− mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression. PMID:27404284

  11. Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression

    KAUST Repository

    Meylan, E M

    2016-07-12

    Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1−/− mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1−/− mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1−/− prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin- and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1−/− mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D-aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1−/− mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression.

  12. Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis.

    Science.gov (United States)

    Goulding, N J; Knight, S M; Godolphin, J L; Guyre, P M

    1992-04-01

    The therapeutic potential of interferon gamma (IFN gamma) in a number of disease states is still being explored, but progress is hampered by the lack of a suitable measure of in vivo biological activity. To assess the in vivo biological effects of recombinant human IFN gamma (rhIFN gamma), 14 patients were studied in a randomised, prospective, double blind, placebo controlled trial of this cytokine for the treatment of rheumatoid arthritis. The levels of Fc gamma receptors on peripheral blood neutrophils were measured at baseline and after 21 days of once daily, subcutaneous injections of rhIFN gamma or placebo. An induction of neutrophil Fc gamma receptor type I (Fc gamma RI) was seen in the group of patients receiving recombinant human rhIFN gamma but not in those receiving placebo. No change in the expression of Fc gamma RII or Fc gamma RIII was detected. The amount of induction of Fc gamma RI detected on the neutrophils of patients receiving rhIFN gamma did not correlate with clinical measures of response at either 21 days or at the end of the study (24 weeks). No significant clinical responses were observed in the rhIFN gamma group at these times. These data confirm that the reported in vitro effect of IFN gamma on human neutrophil Fc receptor expression can be reproduced in vivo.

  13. Exploration of charge states of balanol analogues acting as ATP-competitive inhibitors in kinases.

    Science.gov (United States)

    Hardianto, Ari; Yusuf, Muhammad; Liu, Fei; Ranganathan, Shoba

    2017-12-28

    (-)-Balanol is an ATP mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is a tumour promoter, PKC isozymes act as tumour promoters or suppressors, depending on the cancer type. In particular, PKCε is frequently implicated in cancer promotion, making it a potential target for anticancer drugs. To improve isozyme selectivity of balanol, exhaustive structural and activity relationship (SAR) studies have been performed in the last two decades, but with limited success. More recently, fluorination on balanol has shown improved selectivity for PKCε, although the fluorine effect is not yet clearly understood. Understanding the origin to this fluorine-based selectivity will be valuable for designing better balanol-based ATP mimicking inhibitors. Computational approaches such as molecular dynamics (MD) simulations can decipher the fluorine effect, provided that correct charges have been assigned to a ligand. Balanol analogues have multiple ionisable functional groups and the effect of fluorine substitutions on the exact charge state of each analogue bound to PKA and to PKCε needs to be thoroughly investigated in order to design highly selective inhibitors for therapeutic applications. We explored the charge states of novel fluorinated balanol analogues using MD simulations. For different potential charge states of these analogues, Molecular Mechanics Generalized Born Surface Area (MMGBSA) binding energy values were computed. This study suggests that balanol and the most potent fluorinated analogue (5S fluorine substitution on the azepane ring), have charges on the azepane ring (N1), and the phenolic (C6''OH) and the carboxylate (C15''O 2 H) groups on the benzophenone moiety, when bound to PKCε as well as PKA. To the best our knowledge, this is the first study showing that the phenolate group is charged in balanol and its analogues binding to the ATP site of PKCε. Correct charge

  14. Potential of Resveratrol Analogues as Antagonists of Osteoclasts and Promoters of Osteoblasts

    DEFF Research Database (Denmark)

    Kupisiewicz, Katarzyna; Boissy, Patrice; Abdallah, Basem M

    2010-01-01

    The plant phytoalexin resveratrol was previously demonstrated to inhibit the differentiation and bone resorbing activity of osteoclasts, to promote the formation of osteoblasts from mesenchymal precursors in cultures, and inhibit myeloma cell proliferation, when used at high concentrations....... In the current study, we screened five structurally modified resveratrol analogues for their ability to modify the differentiation of osteoclasts and osteoblasts and proliferation of myeloma cells. Compared to resveratrol, analogues showed an up to 5,000-fold increased potency to inhibit osteoclast...... differentiation. To a lesser extent, resveratrol analogues also promoted osteoblast maturation. However, they did not antagonize the proliferation of myeloma cells. The potency of the best-performing candidate in vitro was tested in vivo in an ovariectomy-induced model of osteoporosis, but an effect on bone loss...

  15. The effect of synthetic ceramide analogues on gastritis and esophagitis in rats.

    Science.gov (United States)

    Kim, Sung Hyo; Um, Seung In; Nam, Yoonjin; Park, Sun Young; Dong, Je Hyun; Ko, Sung Kwon; Sohn, Uy Dong; Lee, Sang Joon

    2016-09-01

    The effects of ceremide analogues on esophagitis and gastritis in rats were examined. Gastritis induced by indomethacin was significantly reduced after CY3325 and CY3723 treatment, whereas other analogues had no effect. The amount of malondialdehyde in gastritis was significantly reduced by CY3325 or CY 3723. CY3325 or CY 3723 decreased the glutathione levels in gastritis. The myeloperoxidase level in gastritis is increased, and its increment was decreased by CY3325 and CY3723. In reflux esophagitis, the ulceration was decreased by CY3325, CY3723. The gastric volume and acid output are reduced, whereas the pH value is increased by CY3325 or CY3723 after esophagitis. These results suggest that ceramide analogues, CY3325 and CY3723, can prevent the development of gastritis and reflux esophagitis in rats.

  16. Upgrading of analogue cameras using modern PC based computer

    International Nuclear Information System (INIS)

    Pardom, M.F.; Matos, L.

    2002-01-01

    Aim: The use of computers along with analogue cameras enables them to perform tasks involving time-activity parameters. The INFORMENU system converts a modern PC computer into a dedicated nuclear medicine computer system with a total cost affordable to emerging economic countries, and easily adaptable to all existing cameras. Materials and Methods: In collaboration with nuclear medicine physicians, an application including hardware and software was developed by a private firm. The system runs smoothly on Windows 98 and its operation is very easy. The main features are comparable to the brand commercial computer systems; such as image resolution until 1024 x 1024, low count loss at high count rate, uniformity correction, integrated graphical and text reporting, and user defined clinical protocols. Results: The system is used in more than 20 private and public institutions. The count loss is less than 1% in all the routine work, improvement of uniformity correction of 3-5 times, improved utility of the analogue cameras. Conclusion: The INFORMENU system improves the utility of analogue cameras permitting the inclusion of dynamic clinical protocols and quantifications, helping the development of the nuclear medicine practice. The operation and maintenance costs were lowered. The end users improve their knowledge of modern nuclear medicine

  17. Cytotoxicity Study of Cyclopentapeptide Analogues of Marine Natural Product Galaxamide towards Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jignesh Lunagariya

    2017-01-01

    Full Text Available Herein, we report the cytotoxicity of cyclopentapeptide analogues of marine natural product galaxamide towards breast carcinoma cells and the underlying mechanisms. We examined the effect of the novel galaxamide analogues on cancer cell proliferation by MTT assay and also further examined the most active compound for morphological changes using Hoechst33342 staining technique, induction of apoptosis, cell cycle phases, mitochondrial membrane potential (MMP, and reactive oxygen species (ROS generation using flow cytometry in human breast cancer MCF-7 cells in vitro. Galaxamide and its analogues effectively induced toxicity in human hepatocellular carcinoma HepG2, human breast carcinoma MCF-7, human epitheloid cervix carcinoma HeLa, and human breast carcinoma MB-MDA-231 cell lines. Amongst them, compound 3 exhibited excellent toxicity towards MCF-7 cells. This galaxamide analogue significantly induced apoptosis in a dose-dependent manner in MCF-7 cells involves cell cycle arrest in the G1 phase, a reduction of MMP, and a marked increase in generation of ROS. Particularly, compound 3 of galaxamide analogues might be a potential candidate for the treatment of breast cancer.

  18. The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs.

    Science.gov (United States)

    Adriaens, E; Dierckens, K; Bauters, T G; Nelis, H J; van Goethem, F; Vanparys, P; Remon, J P

    2001-07-01

    The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism. The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs were measured. The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay. The antimicrobial activity of the different BAC analogues was also assessed. All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 or = BAC-C16 > BAC-C12. The BAC-C14 exhibited higher activity than the BAC-mix. The toxicity and activity of BAC analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered.

  19. Applications of natural analogue studies to Yucca Mountain as a potential high level radioactive waste repository

    International Nuclear Information System (INIS)

    1995-02-01

    The 5-member group convened in Las Vegas, Nov. 11-13, 1991, to clarify the extent to which studies of natural analogues can assist the Yucca Mountain site characterization (SC) project. This document is to provide guidance and recommendations to DOE for the implementation of natural analogue studies in the SC program. Performance assessment, integrity of engineered barriers, and communication to the public and the scientific community are stressed. The reference design being developed by Babcock ampersand Wilcox Fuel Company are reviewed. Guidelines for selecting natural analogues are given. Quality assurance is discussed. Recommendations are given for developing an effective natural analogue program within the SC program

  20. Natural Analogues of CO2 Geological Storage

    International Nuclear Information System (INIS)

    Perez del Villar, L.; Pelayo, M.; Recreo, F.

    2007-01-01

    Geological storage of carbon dioxide is nowadays, internationally considered as the most effective method for greenhouse gas emission mitigation, in order to minimize the global climate change universally accepted. Nevertheless, the possible risks derived of this long-term storage have a direct influence on its public acceptance. Among the favourable geological formations to store CO2, depleted oil and gas fields, deep saline reservoirs, and unamiable coal seams are highlighted. One of the most important objectives of the R and D projects related to the CO2 geological storage is the evaluation of the CO2 leakage rate through the above mentioned geological formations. Therefore, it is absolutely necessary to increase our knowledge on the interaction among CO2, storage and sealing formations, as well as on the flow paths and the physical resistance of the sealing formation. The quantification of the CO2 leakage rate is essential to evaluate the effects on the human and animal health, as well as for the ecosystem and water quality. To achieve these objectives, the study of the natural analogues is very useful in order to know the natural leakage rate to the atmosphere, its flow paths, the physical, chemical and mineralogical modifications due to the long term interaction processes among the CO2 and the storage and sealing formations, as well as the effects on the groundwaters and ecosystems. In this report, we have tried to summarise the main characteristics of the natural reservoirs and surficial sources of CO2, which are both natural analogues of the geological storage and CO2 leakage, studied in EEUU, Europe and Australia. The main objective of this summary is to find the possible applications for long-term risk prediction and for the performance assessment by means of conceptual and numerical modelling, which will allow to validate the predictive models of the CO2 storage behaviour, to design and develop suitable monitoring techniques to control the CO2 behaviour

  1. Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials.

    Science.gov (United States)

    Conroy, Trent; Guo, Jin T; Elias, Nabiha; Cergol, Katie M; Gut, Jiri; Legac, Jennifer; Khatoon, Lubna; Liu, Yang; McGowan, Sheena; Rosenthal, Philip J; Hunt, Nicholas H; Payne, Richard J

    2014-12-26

    Analogues of the natural product gallinamide A were prepared to elucidate novel inhibitors of the falcipain cysteine proteases. Analogues exhibited potent inhibition of falcipain-2 (FP-2) and falcipain-3 (FP-3) and of the development of Plasmodium falciparum in vitro. Several compounds were equipotent to chloroquine as inhibitors of the 3D7 strain of P. falciparum and maintained potent activity against the chloroquine-resistant Dd2 parasite. These compounds serve as promising leads for the development of novel antimalarial agents.

  2. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

    Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  3. Form factors of the transitions {gamma}{sup *}{pi}{sup 0} {r_arrow} {gamma} and {gamma}{sup *}{eta}{r_arrow}{gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Afanasev, A. [Continuous Electron Beam Accelerator Facility, Newport News, VA (United States)

    1994-04-01

    The author discusses possibilities to study {gamma}*{pi}{sup 0} and {gamma}*{eta} {r_arrow} {gamma} transition form factors at CEBAF energies. The author shows that for 4 GeV electron beam, these form factors can be measured at CEBAF for the 4-momentum transfers Q{sup 2} {le} 2.5 (GeV/c){sup 2} using virtual Compton scattering on the proton and nuclear target in the kinematic regime of low momentum transfers to the target. These measurements can be extended to Q{sup 2} {le} 4.0 (GeV/c){sup 2} using the electron beam with the energy 6 GeV.

  4. The Palmottu analogue project: overview for 1993

    International Nuclear Information System (INIS)

    Ruskeeniemi, T.; Blomqvist, R.; Suksi, J.; Niini, H.

    1994-01-01

    This article gives a summary of the activities carried out within the Palmottu analogue project in 1993. It consists of (1) an introductory part, followed by (2) a geological description of the site, and (3)an up-to-date summary of the results of the project. (orig.) (33 refs., 6 figs.)

  5. Efficient synthesis of RITA and its analogues: derivation of analogues with improved antiproliferative activity via modulation of p53/miR-34a pathway.

    Science.gov (United States)

    Lin, Jinshun; Jin, Xiuli; Bu, Yiwen; Cao, Deliang; Zhang, Nannan; Li, Shangfu; Sun, Qinsheng; Tan, Chunyan; Gao, Chunmei; Jiang, Yuyang

    2012-12-28

    A novel approach to synthesize RITA by practical palladium-catalyzed C-C bond-forming Suzuki reactions at room temperature was developed, which was used for deriving a series of substituted tricyclic α-heteroaryl (furan/thiophene) analogues of RITA under mild conditions. These novel analogues showed notable antiproliferative activity against cancer cell lines with wild-type p53 (i.e., HCT116, A549, MCF-7 and K562), but much less activity in HCT116/p53(-/-) cells. In particular, compound 1f demonstrated promising antiproliferative activity compared to RITA, with IC(50) = 28 nM in MCF-7 vs. 54 nM for RITA, and cancer cell selectivity. Compound 1f markedly activated p53 in HCT116 cells at 100 nM, triggering apoptosis. Importantly, we found that both RITA and compound 1f induced G(0)/G(1) cell cycle arrest by up-regulating miR-34a, which in turn down-regulated the expression of cell cycle-related proteins CDK4 and E2F1. In summary, this study reports an effective synthetic approach for RITA and its analogues, and elucidates a novel antiproliferative mechanism of these compounds.

  6. How Analogue Research Can Advance Descriptive Evaluation Theory: Understanding (and Improving) Stakeholder Dialogue

    Science.gov (United States)

    Campbell, Bernadette; Mark, Melvin M.

    2015-01-01

    Evaluation theories can be tested in various ways. One approach, the experimental analogue study, is described and illustrated in this article. The approach is presented as a method worthy to use in the pursuit of what Alkin and others have called descriptive evaluation theory. Drawing on analogue studies conducted by the first author, we…

  7. Ribosome-catalyzed formation of an abnormal peptide analogue

    International Nuclear Information System (INIS)

    Roesser, J.R.; Chorghade, M.S.; Hecht, S.M.

    1986-01-01

    The peptidyl-tRNA analogue N-(chloracetyl) phenylalanyl-tRNA/sup Phe/ was prepared by chemical aminoacylation and prebound to the P site of Escherichia coli ribosomes in response to poly(uridylic acid). Admixture of phenylalanyl-tRNA/sup Phe/ to the A site resulted in the formation of two dipeptides, one of which was found by displacement of chloride ion from the peptidyl-tRNA. This constitutes the first example of ribosome-mediated formation of a peptide of altered connectivity and suggests a need for revision of the current model of peptide bond formation. Also suggested by the present finding is the feasibility of utilizing tRNAs to prepare polypeptides of altered connectivity in an in vitro protein biosynthesizing system. [ 32 P]-oligo(rA), [ 3 H]- and [ 14 C] phenylalanines were used in the assay of the peptidye-tRNA analogue

  8. Fourth natural analogue working group meeting and Pocos de Caldas project final workshop

    International Nuclear Information System (INIS)

    Come, B.; Chapman, N.A.

    1991-01-01

    The fourth meeting of the CEC-sponsored natural analogue working group (NAWG) was held in Pitlochry, Scotland, from 18 to 22 June 1990, and also included the final workshop of the Pocos de Caldas (Brazil) natural analogue project, sponsored by Nagra (CH), SKB (S) UK-DOE and US-DOE. About 80 specialists attended this meeting, originating from EC Member States and also Australia, Brazil, Canada, Finland, Japan, Sweden, Switzerland and the USA. The IAEA and OCDE-NEA were also represented. This plenary meeting was the opportunity to review and discuss five years of progress and activities of natural analogues in central areas of performance assessment: waste forms and engineered barriers, geochemistry and radionuclide speciation, radionuclide migration and the overall geological context of radwaste disposal. In addition, a feedback session provided the opportunity for regulators and those individuals who had advisory roles to give their views and impressions on the significance of natural analogue research. These proceedings, divided into two sessions, contain 32 technical papers and 14 abstracts of published papers

  9. The $e^+ e^- \\to Z\\gamma\\gamma \\to q\\overline{q}\\gamma\\gamma$ Reaction at LEP and Constraints on Anomalous Quartic Gauge Boson Couplings

    CERN Document Server

    Achard, P; Aguilar-Benítez, M; Alcaraz, J; Alemanni, G; Allaby, James V; Aloisio, A; Alviggi, M G; Anderhub, H; Andreev, V P; Anselmo, F; Arefev, A; Azemoon, T; Aziz, T; Bagnaia, P; Bajo, A; Baksay, G; Baksay, L; Baldew, S V; Banerjee, S; Banerjee, Sw; Barczyk, A; Barillère, R; Bartalini, P; Basile, M; Batalova, N; Battiston, R; Bay, A; Becattini, F; Becker, U; Behner, F; Bellucci, L; Berbeco, R; Berdugo, J; Berges, P; Bertucci, B; Betev, B L; Biasini, M; Biglietti, M; Biland, A; Blaising, J J; Blyth, S C; Bobbink, Gerjan J; Böhm, A; Boldizsar, L; Borgia, B; Bottai, S; Bourilkov, D; Bourquin, Maurice; Braccini, S; Branson, J G; Brochu, F; Burger, J D; Burger, W J; Cai, X D; Capell, M; Cara Romeo, G; Carlino, G; Cartacci, A M; Casaus, J; Cavallari, F; Cavallo, N; Cecchi, C; Cerrada, M; Chamizo-Llatas, M; Chang, Y H; Chemarin, M; Chen, A; Chen, G; Chen, G M; Chen, H F; Chen, H S; Chiefari, G; Cifarelli, Luisa; Cindolo, F; Clare, I; Clare, R; Coignet, G; Colino, N; Costantini, S; de la Cruz, B; Cucciarelli, S; van Dalen, J A; De Asmundis, R; Déglon, P L; Debreczeni, J; Degré, A; Dehmelt, K; Deiters, K; Della Volpe, D; Delmeire, E; Denes, P; De Notaristefani, F; De Salvo, A; Diemoz, M; Dierckxsens, M; Dionisi, C; Dittmar, Michael; Doria, A; Dova, M T; Duchesneau, D; Echenard, B; Eline, A; El-Mamouni, H; Engler, A; Eppling, F J; Ewers, A; Extermann, Pierre; Falagán, M A; Falciano, S; Favara, A; Fay, J; Fedin, O; Felcini, Marta; Ferguson, T; Fesefeldt, H S; Fiandrini, E; Field, J H; Filthaut, Frank; Fisher, P H; Fisher, W; Fisk, I; Forconi, G; Freudenreich, Klaus; Furetta, C; Galaktionov, Yu; Ganguli, S N; García-Abia, P; Gataullin, M; Gentile, S; Giagu, S; Gong, Z F; Grenier, G; Grimm, O; Grünewald, M W; Guida, M; van Gulik, R; Gupta, V K; Gurtu, A; Gutay, L J; Haas, D; Hakobyan, R S; Hatzifotiadou, D; Hebbeker, T; Hervé, A; Hirschfelder, J; Hofer, H; Hohlmann, M; Holzner, G; Hou, S R; Hu, Y; Jin, B N; Jones, L W; de Jong, P; Josa-Mutuberria, I; Käfer, D; Kaur, M; Kienzle-Focacci, M N; Kim, J K; Kirkby, Jasper; Kittel, E W; Klimentov, A; König, A C; Kopal, M; Koutsenko, V F; Kräber, M H; Krämer, R W; Krenz, W; Krüger, A; Kunin, A; Ladrón de Guevara, P; Laktineh, I; Landi, G; Latt, J; Lebeau, M; Lebedev, A; Lebrun, P; Lecomte, P; Lecoq, P; Le Coultre, P; Le Goff, J M; Leiste, R; Levtchenko, M; Levchenko, P M; Li, C; Likhoded, S A; Lin, C H; Lin, W T; Linde, Frank L; Lista, L; Liu, Z A; Lohmann, W; Longo, E; Lü, Y S; Lübelsmeyer, K; Luci, C; Luminari, L; Lustermann, W; Ma Wen Gan; Malgeri, L; Malinin, A; Maña, C; Mangeol, D J J; Mans, J; Martin, J P; Marzano, F; Mazumdar, K; McNeil, R R; Mele, S; Merola, L; Meschini, M; Metzger, W J; Mihul, A; Milcent, H; Mirabelli, G; Mnich, J; Mohanty, G B; Muanza, G S; Muijs, A J M; Musicar, B; Musy, M; Nagy, S; Natale, S; Napolitano, M; Nessi-Tedaldi, F; Newman, H; Niessen, T; Nisati, A; Nowak, H; Ofierzynski, R A; Organtini, G; Palomares, C; Pandoulas, D; Paolucci, P; Paramatti, R; Passaleva, G; Patricelli, S; Paul, T; Pauluzzi, M; Paus, C; Pauss, Felicitas; Pedace, M; Pensotti, S; Perret-Gallix, D; Petersen, B; Piccolo, D; Pierella, F; Pioppi, M; Piroué, P A; Pistolesi, E; Plyaskin, V; Pohl, M; Pozhidaev, V; Pothier, J; Prokofiev, D O; Prokofev, D; Quartieri, J; Rahal-Callot, G; Rahaman, M A; Raics, P; Raja, N; Ramelli, R; Rancoita, P G; Ranieri, R; Raspereza, A V; Razis, P A; Ren, D; Rescigno, M; Reucroft, S; Riemann, S; Riles, K; Roe, B P; Romero, L; Rosca, A; Rosier-Lees, S; Roth, S; Rosenbleck, C; Roux, B; Rubio, Juan Antonio; Ruggiero, G; Rykaczewski, H; Sakharov, A; Saremi, S; Sarkar, S; Salicio, J; Sánchez, E; Sanders, M P; Schäfer, C; Shchegelskii, V; Schmidt-Kärst, S; Schmitz, D; Schopper, Herwig Franz; Schotanus, D J; Schwering, G; Sciacca, C; Servoli, L; Shevchenko, S; Shivarov, N; Shoutko, V; Shumilov, E; Shvorob, A V; Siedenburg, T; Son, D; Souga, C; Spillantini, P; Steuer, M; Stickland, D P; Stoyanov, B; Strässner, A; Sudhakar, K; Sultanov, G G; Sun, L Z; Sushkov, S V; Suter, H; Swain, J D; Szillási, Z; Tang, X W; Tarjan, P; Tauscher, Ludwig; Taylor, L; Tellili, B; Teyssier, D; Timmermans, C; Ting, Samuel C C; Ting, S M; Tonwar, S C; Tóth, J; Tully, C; Tung, K L; Ulbricht, J; Valente, E; Van de Walle, R T; Vásquez, R P; Veszpremi, V; Vesztergombi, G; Vetlitskii, I; Vicinanza, D; Viertel, Gert M; Villa, S; Vivargent, M; Vlachos, S; Vodopyanov, I; Vogel, H; Vogt, H; Vorobev, I; Vorobyov, A A; Wadhwa, M; Wallraff, W; Wang, X L; Wang, Z M; Weber, M; Wienemann, P; Wilkens, H; Wynhoff, S; Xia, L; Xu, Z Z; Yamamoto, J; Yang, B Z; Yang, C G; Yang, H J; Yang, M; Yeh, S C; Zalite, A; Zalite, Yu; Zhang, Z P; Zhao, J; Zhu, G Y; Zhu, R Y; Zhuang, H L; Zichichi, A; Zimmermann, B; Zöller, M

    2002-01-01

    The cross section of the process e^+ e^- -> Z \\gamma\\gamma -> qq~ \\gamma \\gamma is measured with 215 pb^-1 of data collected with the L3 detector during the final LEP run at centre-of-mass energies around 205 GeV and 207 GeV. No deviation from the Standard Model expectation is observed. The full data sample of 713 pb^-1, collected above the Z resonance, is used to constrain the coefficients of anomalous quartic gauge boson couplings to: -0.02 GeV^-2 < a_0/\\Lambda^2 < 0.03 GeV^-2 and -0.07 GeV^-2 < a_c/\\Lambda^2 < 0.05 GeV^-2, at 95% confidence level.

  10. Eco-Friendly Insecticide Discovery via Peptidomimetics: Design, Synthesis, and Aphicidal Activity of Novel Insect Kinin Analogues.

    Science.gov (United States)

    Zhang, Chuanliang; Qu, Yanyan; Wu, Xiaoqing; Song, Dunlun; Ling, Yun; Yang, Xinling

    2015-05-13

    Insect kinin neuropeptides are pleiotropic peptides that are involved in the regulation of hindgut contraction, diuresis, and digestive enzyme release. They share a common C-terminal pentapeptide sequence of Phe(1)-Xaa(2)-Yaa(3)-Trp(4)-Gly(5)-NH2 (where Xaa(2) = His, Asn, Phe, Ser, or Tyr; Yaa(3) = Pro, Ser, or Ala). Recently, the aphicidal activity of insect kinin analogues has attracted the attention of researchers. Our previous work demonstrated that the sequence-simplified insect kinin pentapeptide analogue Phe-Phe-[Aib]-Trp-Gly-NH2 could retain good aphicidal activity and be the lead compound for the further discovery of eco-friendly insecticides which encompassed a broad array of biochemicals derived from micro-organisms and other natural sources. Using the peptidomimetics strategy, we chose Phe-Phe-[Aib]-Trp-Gly-NH2 as the lead compound, and we designed and synthesized three series, including 31 novel insect kinin analogues. The aphicidal activity of the new analogues against soybean aphid was determined. The results showed that all of the analogues exhibited aphicidal activity. Of particular interest was the analogue II-1, which exhibited improved aphicidal activity with an LC50 of 0.019 mmol/L compared with the lead compound (LC50 = 0.045 mmol/L) or the commercial insecticide pymetrozine (LC50 = 0.034 mmol/L). This suggests that the analogue II-1 could be used as a new lead for the discovery of potential eco-friendly insecticides.

  11. QCD and $\\gamma\\,\\gamma$ studies at FCC-ee

    CERN Document Server

    Skands, Peter

    2016-10-20

    The Future Circular Collider (FCC) is a post-LHC project aiming at searches for physics beyond the SM in a new 80--100~km tunnel at CERN. Running in its first phase as a very-high-luminosity electron-positron collider (FCC-ee), it will provide unique possibilities for indirect searches of new phenomena through high-precision tests of the SM. In addition, by collecting tens of ab$^{-1}$ integrated luminosity in the range of center-of-mass energies $\\sqrt{s}$~=90--350~GeV, the FCC-ee also offers unique physics opportunities for precise measurements of QCD phenomena and of photon-photon collisions through, literally, billions of hadronic final states as well as unprecedented large fluxes of quasireal $\\gamma$'s radiated from the $\\rm e^+e^-$ beams. We succinctly summarize the FCC-ee perspectives for high-precision extractions of the QCD coupling, for detailed analyses of parton radiation and fragmentation, and for SM and BSM studies through $\\gamma\\gamma$ collisions.

  12. Genomic sequences of murine gamma B- and gamma C-crystallin-encoding genes: promoter analysis and complete evolutionary pattern of mouse, rat and human gamma-crystallins.

    Science.gov (United States)

    Graw, J; Liebstein, A; Pietrowski, D; Schmitt-John, T; Werner, T

    1993-12-22

    The murine genes, gamma B-cry and gamma C-cry, encoding the gamma B- and gamma C-crystallins, were isolated from a genomic DNA library. The complete nucleotide (nt) sequences of both genes were determined from 661 and 711 bp, respectively, upstream from the first exon to the corresponding polyadenylation sites, comprising more than 2650 and 2890 bp, respectively. The new sequences were compared to the partial cDNA sequences available for the murine gamma B-cry and gamma C-cry, as well as to the corresponding genomic sequences from rat and man, at both the nt and predicted amino acid (aa) sequence levels. In the gamma B-cry promoter region, a canonical CCAAT-box, a TATA-box, putative NF-I and C/EBP sites were detected. An R-repeat is inserted 366 bp upstream from the transcription start point. In contrast, the gamma C-cry promoter does not contain a CCAAT-box, but some other putative binding sites for transcription factors (AP-2, UBP-1, LBP-1) were located by computer analysis. The promoter regions of all six gamma-cry from mouse, rat and human, except human psi gamma F-cry, were analyzed for common sequence elements. A complex sequence element of about 70-80 bp was found in the proximal promoter, which contains a gamma-cry-specific and almost invariant sequence (crygpel) of 14 nt, and ends with the also invariant TATA-box. Within the complex sequence element, a minimum of three further features specific for the gamma A-, gamma B- and gamma D/E/F-cry genes can be defined, at least two of which were recently shown to be functional. In addition to these four sequence elements, a subtype-specific structure of inverted repeats with different-sized spacers can be deduced from the multiple sequence alignment. A phylogenetic analysis based on the promoter region, as well as the complete exon 3 of all gamma-cry from mouse, rat and man, suggests separation of only five gamma-cry subtypes (gamma A-, gamma B-, gamma C-, gamma D- and gamma E/F-cry) prior to species separation.

  13. Changes of imidazoline receptors in spontaneously hypertensive rats

    Science.gov (United States)

    Mar, Guang-Yuan; Chou, Ming-Ting; Chung, Hsien-Hui; Chiu, Nien-Hua; Chen, Mei-Fen; Cheng, Juei-Tang

    2013-01-01

    The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar–Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I1-receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (KATP) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I2-receptor, which is expressed more highly in SHRs. PMID:23176371

  14. Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation.

    Science.gov (United States)

    Grimm, Marcus O W; Thiel, Andrea; Lauer, Anna A; Winkler, Jakob; Lehmann, Johannes; Regner, Liesa; Nelke, Christopher; Janitschke, Daniel; Benoist, Céline; Streidenberger, Olga; Stötzel, Hannah; Endres, Kristina; Herr, Christian; Beisswenger, Christoph; Grimm, Heike S; Bals, Robert; Lammert, Frank; Hartmann, Tobias

    2017-12-19

    Alzheimer's disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D₂ and D₃ analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention.

  15. A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Rogier P.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Experimental Urology, Rotterdam (Netherlands); Mueller, Cristina; Melis, Marleen L.; Breeman, Wout A.P.; Blois, Erik de; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Reneman, Suzanne; Bangma, Chris H.; Weerden, Wytske M. van [Erasmus MC, Department of Experimental Urology, Rotterdam (Netherlands)

    2010-07-15

    Prostate-specific antigen (PSA)-based screening for prostate cancer (PC) has dramatically increased early diagnosis. Current imaging techniques are not optimal to stage early PC adequately. A promising alternative to PC imaging is peptide-based scintigraphy using radiolabelled bombesin (BN) analogues that bind to gastrin-releasing peptide receptors (GRPR) being overexpressed in PC. When labelled to appropriate radionuclides BN targeting of GRPRs may also provide applications for peptide radionuclide receptor therapy (PRRT). Assessment studies under identical experimental conditions allowing a reliable comparison of the potential of such analogues are lacking. This study was performed to evaluate and directly compare five promising radiolabelled BN analogues for their targeting efficacy for PC under standardised conditions. The BN agonists [{sup 111}In]DOTA-PESIN, [{sup 111}In]AMBA, [{sup 111}In]MP2346 and [{sup 111}In]MP2653 and one antagonist [{sup 99m}Tc]Demobesin-1 were evaluated in GRPR-overexpressing human PC-3 tumour-bearing mice to determine peptide stability in vivo, biodistribution and GRPR targeting potential by animal SPECT/CT imaging and ex vivo autoradiography. HPLC analysis of blood showed intact Demobesin-1 at 5 and 15 min after injection (64.1{+-}1.6% and 41.0{+-}01%, respectively) being much less for the other compounds. AMBA, the second most stable analogue, showed 36.1{+-}2.7% and 9.8{+-}1.1% intact peptide after 5 and 15 min. PC-3 tumour uptake at 1 h was comparable for Demobesin-1, AMBA, PESIN and MP2346 (3.0{+-}0.4, 2.7{+-}0.5, 2.3{+-}0.5 and 2.1{+-}0.9%ID/g, respectively), but very low for MP2653 (0.9 {+-} 0.2%ID/g). In addition, MP2346 showed undesirably high uptake in the kidneys (7.9{+-}1.9%ID/g) being significantly less for the other analogues. AMBA, MP2346 and PESIN revealed favourable increases in tumour to blood ratios over time while changes in tumour to kidney and pancreas ratios for Demobesin-1 from 1 to 24 h after injection were

  16. Watson-Crick Base Pairing, Electronic and Photophysical Properties of Triazole Modified Adenine Analogues: A Computational Study

    KAUST Repository

    Das, Shubhajit

    2015-09-17

    We employ first-principles Density Functional Theory (DFT) and time-dependent DFT (TDDFT) to elucidate structural, electronic and optical properties of a few recently reported triazole adenine nucleobase analogues. The results are compared against the findings obtained for both natural adenine nucleobase and available experimental data. The optical absorption of these adenine analogues are calculated both in gas-phase and in solvent (methanol) using Polarized Continuum Model (PCM). We find that all the analogues show a red-shifted absorption profile as compared to adenine. Our simulated emission spectra in solvent compare fairly well with experimentally observed results. We investigate base paring ability of these adenine analogues with thymine. The calculations on the intrinsic stability of these base pairs ascertain that all the adenine analogues form the hydrogen bonded Watson-Crick base pair with similar H-bonding energy as obtained for natural adenine-thymine base pair. In our study, we provide a microscopic origin of the low-energy absorption and emission peaks, observed experimentally.

  17. Watson-Crick Base Pairing, Electronic and Photophysical Properties of Triazole Modified Adenine Analogues: A Computational Study

    KAUST Repository

    Das, Shubhajit; Samanta, Pralok Kumar; Pati, Swapan

    2015-01-01

    We employ first-principles Density Functional Theory (DFT) and time-dependent DFT (TDDFT) to elucidate structural, electronic and optical properties of a few recently reported triazole adenine nucleobase analogues. The results are compared against the findings obtained for both natural adenine nucleobase and available experimental data. The optical absorption of these adenine analogues are calculated both in gas-phase and in solvent (methanol) using Polarized Continuum Model (PCM). We find that all the analogues show a red-shifted absorption profile as compared to adenine. Our simulated emission spectra in solvent compare fairly well with experimentally observed results. We investigate base paring ability of these adenine analogues with thymine. The calculations on the intrinsic stability of these base pairs ascertain that all the adenine analogues form the hydrogen bonded Watson-Crick base pair with similar H-bonding energy as obtained for natural adenine-thymine base pair. In our study, we provide a microscopic origin of the low-energy absorption and emission peaks, observed experimentally.

  18. The network to review natural analogue studies and their applications to repository safety assessment and public communication (NAnet)

    Energy Technology Data Exchange (ETDEWEB)

    Miller, W.M.; Hooker, P.J. [ENVIROS Consulting ltd, 61, the Shore Leith, UK-0 EH6 6RA Edinburgh (United Kingdom)

    2004-07-01

    Analogue information can increase our conceptual understanding of long-term repository behaviour in support of post-closure performance assessment (PA), provide quantitative data for PA models and provide ways of communicating safety information to non-specialist audiences. These functions of analogue studies have, however, received too little attention in PA reports and safety cases. Many analogue studies have been undertaken in the last two decades costing tens of millions of euros, and these have covered a wide range of phenomena such as uranium ore deposition, natural fission reactors, natural nuclide migration, contaminant containment by clays and sediments, preservation of ancient fossil trees and buried artefacts etc. The different uses of analogues would be easier to manage if a single database of quality approved analogue information were to be created. NAnet, a Thematic Network within the 5. EURATOM FP is aiming to promote more considered applications of analogues in performance and safety assessments and in audience dialogue. NAnet intends critically to review a number of analogue studies in terms of their relevance and limitations to different repository concepts and environments and with regard to their applications in performance assessments, safety cases and communication. On the basis of these reviews, a simple digital database is being developed for the PA community which will allow PA modelers to make quicker and wider use of natural analogue information in performance and safety assessments. It is expected that some of these tools will help radioactive waste institutions to make better use of natural analogue information for communication with different audiences, including the public. (authors)

  19. Revealing Television's Analogue Heroes

    Directory of Open Access Journals (Sweden)

    Vanessa Jackson

    2013-12-01

    Full Text Available In this article I will argue that we need to create new archival models in order to preserve and share knowledge of historical, ‘hidden’ television professions and production cultures. Oral history traditions of recording life stories give us a useful starting point. Engineering ‘encounters’ between skilled television technicians, and the now obsolete equipment they operated in the 1970s and 80s, is challenging for a myriad of reasons, but videoing the interaction of man and machine provides us with a rich insight into how analogue television was produced and broadcast. Social media enables us to disseminate these histories in new and innovative ways..

  20. Springer Measurements of the pp $\\to W\\gamma\\gamma$ and pp $\\to Z\\gamma\\gamma$ cross sections and limits on anomalous quartic gauge couplings at $ \\sqrt{s}=8 $ TeV

    CERN Document Server

    Sirunyan, A.M.; Adam, Wolfgang; Aşılar, Ece; Bergauer, Thomas; Brandstetter, Johannes; Brondolin, Erica; Dragicevic, Marko; Erö, Janos; Flechl, Martin; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Krammer, Natascha; Hrubec, Josef; Jeitler, Manfred; König, Axel; Krätschmer, Ilse; Liko, Dietrich; Matsushita, Takashi; Mikulec, Ivan; Rabady, Dinyar; Rad, Navid; Rahbaran, Babak; Rohringer, Herbert; Schieck, Jochen; Strauss, Josef; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Dvornikov, Oleg; Makarenko, Vladimir; Mossolov, Vladimir; Suarez Gonzalez, Juan; Zykunov, Vladimir; Shumeiko, Nikolai; Alderweireldt, Sara; De Wolf, Eddi A; Janssen, Xavier; Lauwers, Jasper; Van De Klundert, Merijn; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Abu Zeid, Shimaa; Blekman, Freya; D'Hondt, Jorgen; Daci, Nadir; De Bruyn, Isabelle; Deroover, Kevin; Lowette, Steven; Moortgat, Seth; Moreels, Lieselotte; Olbrechts, Annik; Python, Quentin; Skovpen, Kirill; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Parijs, Isis; Brun, Hugues; Clerbaux, Barbara; De Lentdecker, Gilles; Delannoy, Hugo; Fasanella, Giuseppe; Favart, Laurent; Goldouzian, Reza; Grebenyuk, Anastasia; Karapostoli, Georgia; Lenzi, Thomas; Léonard, Alexandre; Luetic, Jelena; Maerschalk, Thierry; Marinov, Andrey; Randle-conde, Aidan; Seva, Tomislav; Vander Velde, Catherine; Vanlaer, Pascal; Vannerom, David; Yonamine, Ryo; Zenoni, Florian; Zhang, Fengwangdong; Cornelis, Tom; Dobur, Didar; Fagot, Alexis; Gul, Muhammad; Khvastunov, Illia; Poyraz, Deniz; Salva Diblen, Sinem; Schöfbeck, Robert; Tytgat, Michael; Van Driessche, Ward; Verbeke, Willem; Zaganidis, Nicolas; Bakhshiansohi, Hamed; Bondu, Olivier; Brochet, Sébastien; Bruno, Giacomo; Caudron, Adrien; De Visscher, Simon; Delaere, Christophe; Delcourt, Martin; Francois, Brieuc; Giammanco, Andrea; Jafari, Abideh; Komm, Matthias; Krintiras, Georgios; Lemaitre, Vincent; Magitteri, Alessio; Mertens, Alexandre; Musich, Marco; Piotrzkowski, Krzysztof; Quertenmont, Loic; Vidal Marono, Miguel; Wertz, Sébastien; Beliy, Nikita; Aldá Júnior, Walter Luiz; Alves, Fábio Lúcio; Alves, Gilvan; Brito, Lucas; Hensel, Carsten; Moraes, Arthur; Pol, Maria Elena; Rebello Teles, Patricia; Belchior Batista Das Chagas, Ewerton; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; Da Silveira, Gustavo Gil; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Huertas Guativa, Lina Milena; Malbouisson, Helena; Matos Figueiredo, Diego; Mora Herrera, Clemencia; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Torres Da Silva De Araujo, Felipe; Vilela Pereira, Antonio; Ahuja, Sudha; Bernardes, Cesar Augusto; Dogra, Sunil; Tomei, Thiago; De Moraes Gregores, Eduardo; Mercadante, Pedro G; Moon, Chang-Seong; Novaes, Sergio F; Padula, Sandra; Romero Abad, David; Ruiz Vargas, José Cupertino; Aleksandrov, Aleksandar; Hadjiiska, Roumyana; Iaydjiev, Plamen; Rodozov, Mircho; Stoykova, Stefka; Sultanov, Georgi; Shopova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Fang, Wenxing; Gao, Xuyang; Ahmad, Muhammad; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Chen, Ye; Cheng, Tongguang; Jiang, Chun-Hua; Leggat, Duncan; Liu, Zhenan; Romeo, Francesco; Ruan, Manqi; Shaheen, Sarmad Masood; Spiezia, Aniello; Tao, Junquan; Wang, Chunjie; Wang, Zheng; Yazgan, Efe; Zhang, Huaqiao; Zhao, Jingzhou; Ban, Yong; Chen, Geng; Li, Qiang; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Xu, Zijun; Avila, Carlos; Cabrera, Andrés; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; González Hernández, Carlos Felipe; Ruiz Alvarez, José David; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Puljak, Ivica; Ribeiro Cipriano, Pedro M; Sculac, Toni; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Ferencek, Dinko; Kadija, Kreso; Mesic, Benjamin; Susa, Tatjana; Ather, Mohsan Waseem; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Rykaczewski, Hans; Finger, Miroslav; Finger Jr, Michael; Carrera Jarrin, Edgar; El-khateeb, Esraa; Elgammal, Sherif; Mohamed, Amr; Kadastik, Mario; Perrini, Lucia; Raidal, Martti; Tiko, Andres; Veelken, Christian; Eerola, Paula; Pekkanen, Juska; Voutilainen, Mikko; Härkönen, Jaakko; Jarvinen, Terhi; Karimäki, Veikko; Kinnunen, Ritva; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Talvitie, Joonas; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Favaro, Carlotta; Ferri, Federico; Ganjour, Serguei; Ghosh, Saranya; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Kucher, Inna; Locci, Elizabeth; Machet, Martina; Malcles, Julie; Rander, John; Rosowsky, André; Titov, Maksym; Abdulsalam, Abdulla; Antropov, Iurii; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Cadamuro, Luca; Chapon, Emilien; Charlot, Claude; Davignon, Olivier; Granier de Cassagnac, Raphael; Jo, Mihee; Lisniak, Stanislav; Lobanov, Artur; Miné, Philippe; Nguyen, Matthew; Ochando, Christophe; Orto