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Sample records for histamine h1 receptors

  1. Homologous histamine H1 receptor desensitization results in reduction of H1 receptor agonist efficacy

    NARCIS (Netherlands)

    Leurs, R; Smit, M J; Bast, A; Timmerman, H

    1991-01-01

    Prolonged exposure of the guinea-pig intestinal longitudinal smooth muscle to histamine caused homologous desensitization of the H1 receptor, which led to reduced H1 receptor-mediated production of [3H]inositol phosphates as well as to reduced H1 agonist-induced contractions. [3H]Mepyramine binding

  2. Characteristics of the mouse genomic histamine H1 receptor gene

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    Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others

    1996-08-15

    We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.

  3. Albizia lebbeck suppresses histamine signaling by the inhibition of histamine H1 receptor and histidine decarboxylase gene transcriptions.

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    Nurul, Islam Mohammed; Mizuguchi, Hiroyuki; Shahriar, Masum; Venkatesh, Pichairajan; Maeyama, Kazutaka; Mukherjee, Pulok K; Hattori, Masashi; Choudhuri, Mohamed Sahabuddin Kabir; Takeda, Noriaki; Fukui, Hiroyuki

    2011-11-01

    Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Histamine H1 receptors are expressed in mouse and frog semicircular canal sensory epithelia.

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    Botta, Laura; Tritto, Simona; Perin, Paola; Laforenza, Umberto; Gastaldi, Giulia; Zampini, Valeria; Zucca, Gianpiero; Valli, Stefano; Masetto, Sergio; Valli, Paolo

    2008-03-05

    Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. Their site and mechanism of action, however, are still poorly understood. To increase our knowledge of the histaminergic system in the vestibular organs, we have investigated the expression of H1 and H3 histamine receptors in the frog and mouse semicircular canal sensory epithelia. Analysis was performed by mRNA reverse transcriptase-PCR, immunoblotting and immunocytochemistry experiments. Our data show that both frog and mouse vestibular epithelia express H1 receptors. Conversely no clear evidence for H3 receptors expression was found.

  5. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways

    NARCIS (Netherlands)

    Zappia, C.D.; Granja-Galeano, G.; Fernández, N.; Shayo, C.; Davio, C.; Fitzsimons, C.P.; Monczor, F.

    2015-01-01

    Histamine H1 receptor (H1R) antagonists and glucocorticoid receptor (GR) agonists are used to treat inflammatory conditions such as allergic rhinitis, atopic dermatitis and asthma. Consistent with the high morbidity levels of such inflammatory conditions, these receptors are the targets of a vast

  6. Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

    Science.gov (United States)

    Rocha, Sandra M; Saraiva, Tatiana; Cristóvão, Ana C; Ferreira, Raquel; Santos, Tiago; Esteves, Marta; Saraiva, Cláudia; Je, Goun; Cortes, Luísa; Valero, Jorge; Alves, Gilberto; Klibanov, Alexander; Kim, Yoon-Seong; Bernardino, Liliana

    2016-06-04

    Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcγ or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) of mice. We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia

  7. Desipramine inhibits histamine H1 receptor-induced Ca2+ signaling in rat hypothalamic cells.

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    Ji-Ah Kang

    Full Text Available The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca(2+ evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca(2+ increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca(2+ increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants.

  8. Histamine Excites Rat Superior Vestibular Nuclear Neurons via Postsynaptic H1 and H2 Receptors in vitro

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    Qian-Xing Zhuang

    2012-09-01

    Full Text Available The superior vestibular nucleus (SVN, which holds a key position in vestibulo-ocular reflexes and nystagmus, receives direct hypothalamic histaminergic innervations. By using rat brainstem slice preparations and extracellular unitary recordings, we investigated the effect of histamine on SVN neurons and the underlying receptor mechanisms. Bath application of histamine evoked an excitatory response of the SVN neurons, which was not blocked by the low-Ca2+/high-Mg2+ medium, indicating a direct postsynaptic effect of the amine. Selective histamine H1 receptor agonist 2-pyridylethylamine and H2 receptor agonist dimaprit, rather than VUF8430, a selective H4 receptor agonist, mimicked the excitation of histamine on SVN neurons. In addition, selective H1 receptor antagonist mepyramine and H2 receptor antagonist ranitidine, but not JNJ7777120, a selective H4 receptor antagonist, partially blocked the excitatory response of SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly totally blocked the histamine-induced excitation. Immunostainings further showed that histamine H1 and H2 instead of H4 receptors existed in the SVN. These results demonstrate that histamine excites the SVN neurons via postsynaptic histamine H1 and H2 receptors, and suggest that the central histaminergic innervation from the hypothalamus may actively bias the SVN neuronal activity and subsequently modulate the SVN-mediated vestibular functions and gaze control.

  9. The Influence of histamine H1-receptor on liver functions in immunized rabbits.

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    Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Khan, Rahat Ali; Siddiqui, Mashiatullah; Mahdi, Abbas Ali

    2011-10-01

    This study was designed to investigate the functional roles of histamine and histamine H1-receptor agonist and antagonist in the development of liver function impairment in immunized rabbits. The study comprised of six groups containing 18 rabbits each. Group III-VI received histamine (100 μg/kg, s.c.), H1R-agonist (HTMT, 10 μg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R-antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 μg/kg, s.c.), respectively, b.i.d. for 10 days. Group I (negative control) and group II (positive control) received sterile distilled water intramuscularly b.i.d. for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1 × 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each experimental day, the mean values of serum enzymes and bilirubin in group I and group II showed no significant changes while in group III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p pheniramine, and combination of histamine + pheniramine cause hepatic function impairment in terms of altered serum enzymes and bilirubin levels. The present findings suggest that HTMT causes moderate liver function impairment while others show mild impairment.

  10. Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons.

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    Lundius, Ebba Gregorsson; Sanchez-Alavez, Manuel; Ghochani, Yasmin; Klaus, Joseph; Tabarean, Iustin V

    2010-03-24

    The preoptic area/anterior hypothalamus, a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase and was not dependent on synaptic activity. Furthermore, a population of non-GABAergic neurons was depolarized, and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca(2+) release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked, indicating that it represents a postsynaptic effect. Single-cell reverse transcription-PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons, while H1 receptors were expressed in non-GABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long-lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype-specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons that express H1 and H3 receptor subtypes, respectively.

  11. Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.

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    Grossmann, M; Jamieson, M J; Kirch, W

    1999-08-01

    Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods. Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions. Histamine was dosed cumulatively by iontophoresis to the forearm skin at 34 degrees C and 14 degrees C. Laser-Doppler flux (LDF) was measured at the same sites using customised probeholder/iontophoretic chambers with Peltier cooling elements. Finger mean arterial pressure (MAP) was measured and cutaneous vascular conductance calculated as LDF/MAP. Histamine vasodilation was reduced in cold skin. Cetirizine shifted the histamine dose-response at both temperatures: statistically significantly at 14 degrees C only. Combined H1- and H2-receptor antagonism shifted the response significantly at both temperatures. H1- and H2-receptors mediate histamine-induced skin vasodilation. The sensitivity of these receptors, particularly the H1- receptor, is attenuated at low skin temperature. Whether the reduced effect in cold skin represents specific receptor or postreceptor desensitization, or nonspecific attenuation of cutaneous vasodilation remains to be elucidated.

  12. Mutational analysis of the antagonist-binding site of the histamine H(1) receptor.

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    Wieland, K; Laak, A M; Smit, M J; Kühne, R; Timmerman, H; Leurs, R

    1999-10-15

    We combined in a previously derived three-dimensional model of the histamine H(1) receptor (Ter Laak, A. M., Timmerman, H., Leurs, H., Nederkoorn, P. H. J., Smit, M. J., and Donne-Op den Kelder, G. M. (1995) J. Comp. Aid. Mol. Design. 9, 319-330) a pharmacophore for the H(1) antagonist binding site (Ter Laak, A. M., Venhorst, J., Timmerman, H., and Donné-Op de Kelder, G. M. (1994) J. Med. Chem. 38, 3351-3360) with the known interacting amino acid residue Asp(116) (in transmembrane domain III) of the H(1) receptor and verified the predicted receptor-ligand interactions by site-directed mutagenesis. This resulted in the identification of the aromatic amino acids Trp(167), Phe(433), and Phe(436) in transmembrane domains IV and VI of the H(1) receptor as probable interaction points for the trans-aromatic ring of the H(1) antagonists. Subsequently, a specific interaction of carboxylate moieties of two therapeutically important, zwitterionic H(1) antagonists with Lys(200) in transmembrane domain V was predicted. A Lys(200) --> Ala mutation results in a 50- (acrivastine) to 8-fold (d-cetirizine) loss of affinity of these zwitterionic antagonists. In contrast, the affinities of structural analogs of acrivastine and cetirizine lacking the carboxylate group, triprolidine and meclozine, respectively, are unaffected by the Lys(200) --> Ala mutation. These data strongly suggest that Lys(200), unique for the H(1) receptor, acts as a specific anchor point for these "second generation" H(1) antagonists.

  13. Large-scale overproduction, functional purification and ligand affinities of the His-tagged human histamine H1 receptor.

    NARCIS (Netherlands)

    Ratnala, V.R.; Swarts, H.G.P.; Oostrum, J. van; Leurs, R.; Groot, H.J.M. de; Bakker, R.; Grip, W.J. de

    2004-01-01

    This report describes an efficient strategy for amplified functional purification of the human H1 receptor after heterologous expression in Sf9 cells. The cDNA encoding a C-terminally histidine-tagged (10xHis) human histamine H1 receptor was used to generate recombinant baculovirus in a Spodoptera

  14. Histamine acting on H1 receptor promotes inhibition of proliferation via PLC, RAC, and JNK-dependent pathways

    International Nuclear Information System (INIS)

    Notcovich, Cintia; Diez, Federico; Tubio, Maria Rosario; Baldi, Alberto; Kazanietz, Marcelo G.; Davio, Carlos; Shayo, Carina

    2010-01-01

    It is well established that histamine modulates cell proliferation through the activation of the histamine H1 receptor (H1R), a G protein-coupled receptor (GPCR) that is known to couple to phospholipase C (PLC) activation via Gq. In the present study, we aimed to determine whether H1R activation modulates Rho GTPases, well-known effectors of Gq/G 11 -coupled receptors, and whether such modulation influences cell proliferation. Experiments were carried out in CHO cells stably expressing H1R (CHO-H1R). By using pull-down assays, we found that both histamine and a selective H1R agonist activated Rac and RhoA in a time- and dose-dependent manner without significant changes in the activation of Cdc42. Histamine response was abolished by the H1R antagonist mepyramine, RGS2 and the PLC inhibitor U73122, suggesting that Rac and RhoA activation is mediated by H1R via Gq coupling to PLC stimulation. Histamine caused a marked activation of serum response factor activity via the H1R, as determined with a serum-responsive element (SRE) luciferase reporter, and this response was inhibited by RhoA inactivation with C3 toxin. Histamine also caused a significant activation of JNK which was inhibited by expression of the Rac-GAP β2-chimaerin. On the other hand, H1R-induced ERK1/2 activation was inhibited by U73122 but not affected by C3 or β2-chimaerin, suggesting that ERK1/2 activation was dependent on PLC and independent of RhoA or Rac. [ 3 H]-Thymidine incorporation assays showed that both histamine and the H1R agonist inhibited cell proliferation in a dose-dependent manner and that the effect was independent of RhoA but partially dependent on JNK and Rac. Our results reveal that functional coupling of the H1R to Gq-PLC leads to the activation of RhoA and Rac small GTPases and suggest distinct roles for Rho GTPases in the control of cell proliferation by histamine.

  15. Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

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    Kjell A Svensson

    2012-05-01

    Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

  16. Short-term desensitization of the histamine H1 receptor in human HeLa cells : involvement of protein kinase C dependent and independent pathways

    NARCIS (Netherlands)

    Smit, M J; Bloemers, S M; Leurs, R; Tertoolen, L G; Bast, A; de Laat, S W; Timmerman, H

    1992-01-01

    1. In this study we have investigated the effects of short-term exposure of cells to histamine on the subsequent H1 receptor responsiveness in HeLa cells, using Ca2+ fluorescence microscopy and video digital imaging. 2. In HeLa cells, histamine (100 microM) induces an immediate H1 receptor-mediated

  17. Evaluation of in vivo selective binding of [11C]doxepin to histamine H1 receptors in five animal species

    International Nuclear Information System (INIS)

    Ishiwata, Kiichi; Kawamura, Kazunori; Wang Weifang; Tsukada, Hideo; Harada, Norihiro; Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Iwata, Ren; Yanai, Kazuhiko

    2004-01-01

    The specific binding of [ 11 C]doxepin, which has been used as a radioligand for mapping histamine H 1 receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [ 11 C]doxepin uptake was reduced by treatment with cold doxepin and two H 1 receptor antagonists, but not with H 2 /H 3 antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H 1 antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig

  18. The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats

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    Karina H. Solís

    2017-12-01

    Full Text Available Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2 and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon

  19. Simplified PET measurement for evaluating histamine H1 receptors in human brains using [11C]doxepin

    International Nuclear Information System (INIS)

    Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Oda, Keiichi; Sasaki, Toru; Tashiro, Manabu; Yanai, Kazuhiko; Ishiwata, Kiichi

    2004-01-01

    The aim of this study was to develop simplified positron emission tomography measurement using [ 11 C]doxepin ([ 11 C]DOX) to evaluate histamine H 1 receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [ 11 C]DOX, estimated quantitatively with a two-compartment model, and the [ 11 C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [ 11 C]DOX-H1R binding

  20. Distinct signalling pathways of murine histamine H1- and H4-receptors expressed at comparable levels in HEK293 cells.

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    Silke Beermann

    Full Text Available Histamine (HA is recognized by its target cells via four G-protein-coupled receptors, referred to as histamine H1-receptor (H1R, H2R, H3R, and H4R. Both H1R and H4R exert pro-inflammatory functions. However, their signal transduction pathways have never been analyzed in a directly comparable manner side by side. Moreover, the analysis of pharmacological properties of the murine orthologs, representing the main targets of pre-clinical research, is very important. Therefore, we engineered recombinant HEK293 cells expressing either mouse (mH1R or mH4R at similar levels and analyzed HA-induced signalling in these cells. HA induced intracellular calcium mobilization via both mH1R and mH4R, with the mH1R being much more effective. Whereas cAMP accumulation was potentiated via the mH1R, it was reduced via the mH4R. The regulation of both second messengers via the H4R, but not the H1R, was sensitive to pertussis toxin (PTX. The mitogen-activated protein kinases (MAPKs ERK 1/2 were massively activated downstream of both receptors and demonstrated a functional involvement in HA-induced EGR-1 gene expression. The p38 MAPK was moderately activated via both receptors as well, but was functionally involved in HA-induced EGR-1 gene expression only in H4R-expressing cells. Surprisingly, in this system p38 MAPK activity reduced the HA-induced gene expression. In summary, using this system which allows a direct comparison of mH1R- and mH4R-induced signalling, qualitative and quantitative differences on the levels of second messenger generation and also in terms of p38 MAPK function became evident.

  1. Pharmacological and functional characterisation of the wild-type and site-directed mutants of the human H1 histamine receptor stably expressed in CHO cells.

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    Moguilevsky, N; Varsalona, F; Guillaume, J P; Noyer, M; Gillard, M; Daliers, J; Henichart, J P; Bollen, A

    1995-01-01

    A cDNA clone for the human histamine H1 receptor was isolated from a lung cDNA library and stably expressed in CHO cells. The recombinant receptor protein present in the cell membranes, displayed the functional and binding characteristics of histamine H1 receptors. Mutation of Ser155 to Ala in the fourth transmembrane domain did not significantly change the affinity of the receptor for histamine and H1 antagonists. However, mutation of the fifth transmembrane Asn198 to Ala resulted in a dramatic decrease of the affinity for histamine binding, and for the histamine-induced polyphosphoinositides breakdown, whereas the affinity towards antagonists was not significantly modified. In addition, mutation of another fifth transmembrane amino acid, Thr194 to Ala also diminished, but to a lesser extent, the affinity for histamine. These data led us to propose a molecular model for histamine interaction with the human H1 receptor. In this model, the amide moiety of Asn198 and the hydroxyl group of Thr194 are involved in hydrogen bonding with the nitrogen atoms of the imidazole ring of histamine. Moreover, mutation of Thr194 to Ala demonstrated that this residue is responsible for the discrimination between enantiomers of cetirizine.

  2. Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

    International Nuclear Information System (INIS)

    Kandasamy, S.B.; Hunt, W.A.

    1988-01-01

    Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration of disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia. 34 references, 5 figures, 2 tables

  3. C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling.

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    Hishinuma, Shigeru; Nozawa, Hiroki; Akatsu, Chizuru; Shoji, Masaru

    2016-11-01

    It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that G q/11 -protein-coupled human histamine H 1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H 1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H 1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [ 3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H 1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [ 3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H 1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H 1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. © 2016 International Society for Neurochemistry.

  4. Temporal responses of cutaneous blood flow and plasma catecholamine concentrations to histamine H1- or H2-receptor stimulation in man

    DEFF Research Database (Denmark)

    Knigge, U; Alsbjørn, B; Thuesen, B

    1988-01-01

    continuously with a laser Doppler flowmeter, and noradrenaline and adrenaline concentrations were determined in blood samples drawn every 15 min. The infusion of histamine caused an immediate and sustained vasodilatation. The Concomitant infusion of mepyramine prevented the immediate vasodilatation, but had...... noradrenaline, while the increase during concomitant H1-receptor blockade was delayed but achieved the level observed during the histamine infusion. The response to histamine during H2-receptor blockade was small and transient. The rise in plasma adrenaline was not significant. These findings suggest...

  5. Implication of prostaglandins and histamine H1 and H2 receptors in radiation-induced temperature responses of rats

    International Nuclear Information System (INIS)

    Kandasamy, S.B.; Hunt, W.A.; Mickley, G.A.

    1988-01-01

    Exposure of rats to 1-15 Gy gamma radiation ( 60 Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations

  6. Sedation and memory: studies with a histamine H-1 receptor antagonist.

    Science.gov (United States)

    Turner, Claire; Handford, Alison D F; Nicholson, Anthony N

    2006-07-01

    The influence of sedation on the effect of an H-1 receptor antagonist on various cognitive functions, including memory, were evaluated. Diphenhydramine (50, 75 and 100 mg) and lorazepam (0.5 and 1.5 mg) were given on single occasions to 12 healthy volunteers (six males, six females) aged 20-33 (mean 23.4) years. Subjective assessments of sedation, sleep latencies, digit symbol substitution, choice reaction time, sustained attention and memory recall were studied 1.0 h before and 0.5, 2.0 and 3.5 h after drug ingestion. The study was double blind, placebo controlled and with a crossover design. With all doses of diphenhydramine there was subjective sedation, reduced sleep latencies and impairments in performance on the digit symbol substitution, choice reaction time and sustained attention tasks. No effects were observed with 0.5 mg lorazepam. With 1.5 mg lorazepam there was subjective sedation, fewer digit symbol substitutions, slowed choice reaction time, impaired attention and memory, but no effect on sleep latencies. Contrast analysis of data measured at all time points showed that although there was no difference in the effect of diphenhydramine (100 mg) and lorazepam (1.5 mg) on those tasks without a memory component, response times were slower with lorazepam on those tasks with a memory component. However, both 100 mg diphenhydramine and 1.5 mg lorazepam impaired prompted recall measured at 2 h post-ingestion only. It is considered that impaired memory is not necessarily associated with sedation, and that impairment of memory with drugs that lead to sedation may be effected through neuronal systems independent of those that affect arousal.

  7. Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

    International Nuclear Information System (INIS)

    Gianlorenço, A.C.L.; Serafim, K.R.; Canto-de-Souza, A.; Mattioli, R.

    2014-01-01

    This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM

  8. Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Gianlorenço, A.C.L.; Serafim, K.R. [Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Canto-de-Souza, A. [Laboratório de Psicologia da Aprendizagem, Departamento de Psicologia, Centro de Educação e Ciências Humanas, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Psicologia da Aprendizagem, Departamento de Psicologia, Centro de Educação e Ciências Humanas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, SP (Brazil); Instituto de Neurociências e Comportamento, Universidade de São Paulo, Ribeirão Preto, SP, Brasil, Instituto de Neurociências e Comportamento, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattioli, R. [Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP, Brasil, Laboratório de Neurociências, Departamento de Fisioterapia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, SP (Brazil)

    2014-02-17

    This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

  9. Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

    Directory of Open Access Journals (Sweden)

    A.C.L. Gianlorenco

    2014-02-01

    Full Text Available This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM. The cerebellar vermis of male mice (Swiss albino was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2. Immediately after exposure to the EPM (T1, animals received a microinjection of saline (SAL or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2 under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE and spent less time in the open arms (%OAT in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

  10. Can human allergy drug fexofenadine, an antagonist of histamine (H1) receptor, be used to treat dog and cat? Homology modeling, docking and molecular dynamic Simulation of three H1 receptors in complex with fexofenadine.

    Science.gov (United States)

    Sader, Safaa; Cai, Jun; Muller, Anna C G; Wu, Chun

    2017-08-01

    Fexofenadine, a potent antagonist to human histamine 1 (H 1 ) receptor, is a non-sedative third generation antihistamine that is widely used to treat various human allergic conditions such as allergic rhinitis, conjunctivitis and atopic dermatitis. Encouragingly, it's been successfully used to treat canine atopic dermatitis, this supports the notion that it might have a great potential for treating other canine allergic conditions and other mammal pets such as dog. Regrettably, while there is a myriad of studies conducted on the interactions of antihistamines with human H 1 receptor, the similar studies on non-human pet H 1 are considerably scarce. The published studies using the first and second generation antihistamines drugs have shown that the antihistamine response is varied and unpredictable. Thus, to probe its efficacy on pet, the homology models of dog and cat H 1 receptors were built based on the crystal structure of human H 1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H 1 receptors. The docked complexes are then subjected to 1000ns molecular dynamics (MD) simulations with explicit membrane. Our calculated MM/GBSA binding energies indicated that fexofenadine binds comparably to the three receptors; and our MD data also showed the binding poses, structural and dynamic features among three receptors are very similar. Therefore, our data supported the application of fexofenadine to the H 1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H 1 receptors were also identified. Clearly, there is still a space to develop a more selective, potent and safe antihistamine alternatives such as Fexofenadine for dog or cat based on these differences. Our computation approach might provide a fast and economic way to predict if human antihistamine drugs can also be safely and efficaciously administered to animals. Copyright © 2017 Elsevier Inc

  11. Histamine type I (H1) receptor radioligand binding studies on normal T cell subsets, B cells, and monocytes

    International Nuclear Information System (INIS)

    Cameron, W.; Doyle, K.; Rocklin, R.E.

    1986-01-01

    A single, specific binding site for [ 3 H]pyrilamine on normal human T helper, T suppressor, B cells, and monocytes was documented. The binding of the radioligand to its receptor is reversible with cold H 1 antagonist, saturates at 40 to 60 nM, and binding equilibrium is achieved in 2 to 4 min. Using a computer program (Ligand), the authors calculated the dissociation constants, binding capacities, and numbers of receptors per cell for each of the different cell types. Monocytes were found to have the highest affinity for [ 3 H]pyrilamine, followed by T helper cells, B cells and T suppressor cells (K/sub D/ = 44.6 +/- 49.4 nM). T suppressor cells were found to express the higher number of H 1 receptors per cell followed by B cells, T helper cells, and monocytes. The binding affinity for [ 3 H]pyrilamine increased over a 48-hr period, whereas the number of receptors per T cell was essentially unchanged. In contrast, T cells stimulated with Con A or PHA were shown to have a greater than fourfold increase in the number of receptors per cell, whereas the binding affinity for [ 3 H]pyrilamine decreased over the 48-hr period. Although the function of H 1 receptors on T cells, B cells, and monocytes has not been completely defined, this receptor has the potential of playing an important role in the modulating the immune response

  12. [11C]Doxepin binding to histamine H1 receptors in living human brain in association with attentive waking and circadian rhythm

    Directory of Open Access Journals (Sweden)

    Kazuhiko eYanai

    2012-06-01

    Full Text Available Molecular imaging in neuroscience is a new research field that enables visualization of the impact of molecular events on brain structure and function in humans. While magnetic resonance-based imaging techniques can provide complex information at the level of system, positron emission tomography (PET enables determination of the distribution and density of receptor and enzyme in the human brain. Previous studies using [11C]raclopride revealed that the release of neuronal dopamine was increased in human brain by psychostimulants or reward stimuli. Following on from these previous studies, we examined whether the levels of neuronal release of histamine might change [11C]doxepin binding to the H1 receptors under the influence of physiological stimuli. The purpose of the present study was to evaluate the test-retest reliability of quantitative measurement of [11C]doxepin binding between morning and afternoon and between resting and attentive waking conditions in healthy human subjects. There was a trend for a decrease in [11C]doxepin binding during attentive calculation tasks compared with that in resting conditions, but the difference (approximately 10% was not significant. In contrast, the binding potential of [11C]doxepin in the anterior cingulate gyrus was significantly higher in the morning than that in the afternoon (approximately 19%, suggesting that higher histamine release in the morning would decrease the [11C]doxepin binding in the afternoon. This study suggests that non-invasive measurement of neuronal histamine release is feasible in humans by PET ligand-activation study, although the development of a tracer with better signal-to-noise properties is needed.

  13. Histamine facilitates GABAergic transmission in the rat entorhinal cortex: Roles of H1 and H2 receptors, Na+ -permeable cation channels, and inward rectifier K+ channels.

    Science.gov (United States)

    Cilz, Nicholas I; Lei, Saobo

    2017-05-01

    In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception, and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H 1 , H 2 , and H 3 ). We investigated the effects of HA on GABAergic transmission in the MEC and found that HA significantly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with an EC 50 of 1.3 µM, but failed to significantly alter sIPSC amplitude. HA-induced increases in sIPSC frequency were sensitive to tetrodotoxin (TTX), required extracellular Ca 2+ , and persisted when GDP-β-S, a G-protein inactivator, was applied postsynaptically via the recording pipettes, indicating that HA increased GABA release by facilitating the excitability of GABAergic interneurons in the MEC. Recordings from local MEC interneurons revealed that HA significantly increased their excitability as determined by membrane depolarization, generation of an inward current at -65 mV, and augmentation of action potential firing frequency. Both H 1 and H 2 receptors were involved in HA-induced increases in sIPSCs and interneuron excitability. Immunohistochemical staining showed that both H 1 and H 2 receptors are expressed on GABAergic interneurons in the MEC. HA-induced depolarization of interneurons involved a mixed ionic mechanism including activation of a Na + -permeable cation channel and inhibition of a cesium-sensitive inward rectifier K + channel, although HA also inhibited the delayed rectifier K + channels. Our results may provide a cellular mechanism, at least partially, to explain the roles of HA in the brain. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Antihistamines suppress upregulation of histidine decarboxylase gene expression with potencies different from their binding affinities for histamine H1 receptor in toluene 2,4-diisocyanate-sensitized rats

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mizuguchi

    2016-04-01

    Full Text Available Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription.

  15. Stimulation of cell proliferation by histamine H2 receptors in dimethylhdrazine-induced adenocarcinomata.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1978-03-01

    Cell proliferation in dimethylhydrazine-induced colonic carcinomata was stimulated by histamine and by the histamine H2 receptor agonist dimaprit and inhibited by the histamine H2 receptor antagonists Metiamide and Cimetidine but not by the histamine H1 receptor antagonist Mepyramine. In contrast histamine had no effect on colonic crypt cell proliferation in normal or dimethylhydrazine-treated rats.

  16. The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.

    Science.gov (United States)

    Poyurovsky, Michael; Pashinian, Artashes; Levi, Aya; Weizman, Ronit; Weizman, Abraham

    2005-03-01

    Histamine antagonism has been implicated in antipsychotic drug-induced weight gain. Betahistine, a histamine enhancer with H1 agonistic/H3 antagonistic properties (48 mg t.i.d.), was coadministered with olanzapine (10 mg/day) in three first-episode schizophrenia patients for 6 weeks. Body weight was measured at baseline and weekly thereafter. Clinical rating scales were completed at baseline and at week 6. All participants gained weight (mean weight gain 3.1+/-0.9 kg) and a similar pattern of weight gain was observed: an increase during the first 2 weeks and no additional weight gain (two patients) or minor weight loss (one patient) from weeks 3 to 6. None gained 7% of baseline weight, which is the cut-off for clinically significant weight gain. Betahistine was safe and well tolerated and did not interfere with the antipsychotic effect of olanzapine. Our findings justify a placebo-controlled evaluation of the putative weight-attenuating effect of betahistine in olanzapine-induced weight gain.

  17. H1-histamine receptors in the amygdala are involved in emotional memory but do not mediate anxiety-related behaviors in mice submitted to EPM testing.

    Science.gov (United States)

    Serafim, K R; Gianlorenço, A C L; Daher, F P; Mattioli, R

    2012-10-01

    This study investigated the role of amygdala H(1) receptors in state-dependent memory deficits induced by l-histidine (LH). Tests using an elevated plus-maze (EPM) were performed on two consecutive days: Trial 1 (T1) and Trial 2 (T2). Before each trial, mice were intraperitoneally (IP) injected with LH (500mg/kg). Two hours later, they were microinjected with the H(1) receptor antagonist, chlorpheniramine (CPA 0.016, 0.052, or 0.16 nmol/0.1μl), or saline (SAL) into the amygdala and submitted to the EPM. LH-CPA did not affect trial 1 performances in the EPM, which indicated that these drugs did not affect anxiety. Emotional memory, as revealed by a reduction in open arm exploration between both trials, was present in the SAL-SAL groups as well as in the SAL-CPA groups for the lower doses of CPA (0.016 and 0.052nmol). On the contrary, neither the LH-SAL group nor the LH-CPA groups exhibited this decrease in open arm activity between both trials, which reveals that LH impaired emotional memory. While intra-amygdalar CPA did not interact with LH effect, it impaired per se the emotional memory performances at the highest dose (0.16nmol). No significant changes were observed in the number of enclosed arm entries (EAE), an EPM index of general exploratory activity. These results may be attributed to a combined effect in the different nucleus of the amygdala. Taken together, these results suggest that the H(1) receptors in the amygdala are not implicated in anxiety-like behaviors but are involved in emotional states induced by the T1/T2 EPM protocol in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Antiallergic effects of H1-receptor antagonists.

    Science.gov (United States)

    Baroody, F M; Naclerio, R M

    2000-01-01

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

  19. In vitro study of histamine and histamine receptor ligands influence on the adhesion of purified human eosinophils to endothelium.

    Science.gov (United States)

    Grosicki, Marek; Wójcik, Tomasz; Chlopicki, Stefan; Kieć-Kononowicz, Katarzyna

    2016-04-15

    It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit

    Directory of Open Access Journals (Sweden)

    Yoshiaki Kitamura

    2015-11-01

    Full Text Available In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders.

  1. A new generation of anti-histamines : Histamine H4 receptor antagonists on their way to the clinic

    NARCIS (Netherlands)

    Engelhardt, Harald; Smits, Rogier A; Leurs, Rob; Haaksma, Eric E J; de Esch, Iwan J P

    At the turn of the millennium, the DNA sequence encoding the histamine H4 receptor (H4R) was identified in data from human genome databases. Considering the clinical importance of H1R and H2R ligands, and the clinical trials that are ongoing for H3R ligands, the latest addition to the histamine

  2. West syndrome associated with administration of a histamine H1 antagonist, oxatomide.

    Science.gov (United States)

    Yamashita, Yushiro; Isagai, Takeo; Seki, Yoshitaka; Ohya, Takashi; Nagamitsu, Shinichiro; Matsuishi, Toyojiro

    2004-01-01

    We report a 4-month-old female infant who developed West syndrome eleven days after administration of a histamine H1 antagonist, oxatomide, for atopic dermatitis. It has been reported that some histamine H1 antagonists induce seizures in epileptic patients. The age, the interval between oxatomide administration, and the onset of West syndrome and its clinical course were similar to two previously reported 3-month-old infants with West syndrome associated with ketotifen administration. We should be cautious in using the histamine H1 antagonists, oxatomide and ketotifen, in young infants because such agents could potentially disturb the anticonvulsive central histaminergic system.

  3. Presynaptic localization of histamine H3-receptors in rat brain

    International Nuclear Information System (INIS)

    Fujimoto, K.; Mizuguchi, H.; Fukui, H.; Wada, H.

    1991-01-01

    The localization of histamine H3-receptors in subcellular fractions from the rat brain was examined in a [3H] (R) alpha-methylhistamine binding assay and compared with those of histamine H1- and adrenaline alpha 1- and alpha 2-receptors. Major [3H](R) alpha-methylhistamine binding sites with increased specific activities ([3H]ligand binding vs. protein amount) were recovered from the P2 fraction by differential centrifugation. Minor [3H](R)alpha-methylhistamine binding sites with increased specific activities were also detected in the P3 fraction. Further subfractionation of the P2 fraction by discontinuous sucrose density gradient centrifugation showed major recoveries of [3H](R)alpha-methylhistamine binding in myelin (MYE) and synaptic plasma membrane (SPM) fractions. A further increase in specific activity was observed in the MYE fraction, but the SPM fraction showed no significant increase in specific activity. Adrenaline alpha 2-receptors, the pre-synaptic autoreceptors, in a [3H] yohimbine binding assay showed distribution patterns similar to histamine H3-receptors. On the other hand, post-synaptic histamine H1- and adrenaline alpha 1-receptors were closely localized and distributed mainly in the SPM fraction with increased specific activity. Only a negligible amount was recovered in the MYE fraction, unlike the histamine H3- and adrenaline alpha 2-receptors

  4. The Histamine H4 Receptor: From Orphan to the Clinic

    Directory of Open Access Journals (Sweden)

    Robin L. Thurmond

    2015-03-01

    Full Text Available The histamine H4 receptor (H4R was first noted as a sequence in genomic databases that had features of a G-protein coupled receptor. This putative receptor was found to bind histamine consistent with its homology to other histamine receptors and thus became the fourth member of the histamine receptor family. Due to the previous success of drugs that target the H1 and H2 receptors, an effort was made to understand the function of this receptor and determine if it represented a drug target. Taking advantage of the vast literature on histamine, a search for histamine activity that did not appear to be mediated by the other three histamine receptors was undertaken. From this asthma and pruritus emerged as areas of particular interest. Histamine has long been suspected to play a role in the pathogenesis of asthma, but antihistamines that target the H1 and H2 receptors have not been shown to be effective for this condition. The use of selective ligands in animal models of asthma has now potentially filled this gap by showing a role for the H4R in mediating lung function and inflammation. A similar story exists for chronic pruritus associated with conditions such as atopic dermatitis. Antihistamines that target the H1 receptor are effective in reducing acute pruritus, but are ineffective in pruritus experienced by patients with atopic dermatitis. As for asthma, animal models have now suggested a role for the H4R in mediating pruritic responses, with antagonists to the H4R reducing pruritus in a number of different conditions. The anti-pruritic effect of H4R antagonists has recently been shown in human clinical studies, validating the preclinical findings in the animal models. A selective H4R antagonist inhibited histamine-induced pruritus in health volunteers and reduced pruritus in patients with atopic dermatitis. The history to date of the H4R provides an excellent example of the deorphanization of a novel receptor and the translation of this into

  5. Modulation of in vivo immunoglobulin production by endogenous histamine and H1R and H2R agonists and antagonists.

    Science.gov (United States)

    Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Negi, Mahendra Pal Singh; Siddiqui, Mashiatullah; Khan, Rahat A

    2010-01-01

    The present study was designed to delineate the immunomodulatory role of histamine receptors (H1R and H2R) and their antibody generation in a rabbit model. Six groups containing 18 rabbits each received either vehicle (sterile distilled water, 1 ml/kg x b.i.d), histamine (100 μg/kg x b.i.d.), H1R agonist (HTMT, 10 μg/kg x b.i.d.), H2R agonist (amthamine, 10 μg/kg x b.i.d.), H1R antagonist (pheniramine, 10 mg/kg x b.i.d.) or H2R antagonist (ranitidine, 10 mg/kg x b.i.d.). All animals were subsequently immunized with an intravenous injection of sheep red blood cells (SRBC). Estimations of total serum immunoglobulins (Igs), immunoglobulin M (IgM) and immunoglobulin G (IgG) were performed by ELISA and hemagglutination assay (HA) at days 0 (pre-immunization), 7, 14, 21, 28 and 58 (post-immunization). Both the ELISA and the HA showed similar production of Igs, IgM and IgG but the results were found comparatively more significant by ELISA as opposed to HA. Results showed that histamine could influence a detectable antibody response to SRBC early (i.e., at day 7), which lasted until day 58. Immunomodulatory processes showed suppression of an Ig generation in the H1R-antagonist group with enhancement in the H2R-antagonist group. The H1R-agonist group showed an increased Ig production in comparison to the H2R-agonist group. The IgM production was inhibited in the H1R-antagonist group as compared to the H2R-antagonist group, and it was also suppressed in H1R-agonist group as compared to H2R-agonist group. IgG production was inhibited in the H1R-antagonist group as opposed to the H2R-antagonist group. In contrast, the H1R-agonist group increased IgG production as compared to the H2R-agonist group. All the results were found to be statistically significant (p < 0.05 or p < 0.01). In conclusion, histamine and its receptor (H1R and H2R) agonists enhance antibody production by triggering the histamine receptors (H1R and H2R), and both the H1R antagonist and the H2R antagonist

  6. Ophthalmic antihistamines and H1-H4 receptors.

    Science.gov (United States)

    Wade, Laurie; Bielory, Leonard; Rudner, Shara

    2012-10-01

    Antihistamines exert pharmacologic effects by binding to four histamine receptors (H1-H4) at different affinities, producing variable effects depending on the receptor they predominantly bind to. This review's purpose is to determine the relative potency of antihistamines by comparing their binding affinities to these receptors. Studies on binding affinities of antihistamines to histamine receptors were reviewed and the dissociation constant for inhibitor binding (Ki) analyzed to determine the most and least potent antihistamine for each receptor. We retrieved the binding affinities for nineteen antihistamines. For H1 receptors, pyrilamine exhibited the highest affinity (Ki = 0.8 nM), and thioperamide the lowest (Ki = 280, 000 nM). For H2 receptors, ranitidine exhibited the highest affinity (Ki = 187 nM), and olopatadine the lowest (Ki = 100 ,000 nM). For the recently discovered H3 and H4 receptors, thioperamide exhibited the highest affinity (Ki = 1.1 nM), and olopatadine exhibited the lowest (Ki = 79 ,400 nM), to H3. Data on binding affinities to the H4 receptor exist for: ketotifen, pheniramine, ranitidine, cimetidine and thioperamide. Of these, thioperamide exhibited the highest affinity (Ki = 27 nM), whereas cimetidine and ranitidine exhibited the lowest affinity (Ki = >10, 000 nM) for H4 receptors. This review summarizes the relative potency of antihistamines based on their binding affinities to the four histamine receptors. Although data on binding affinities of antihistamines to the H4 receptor are sparse, it is apparent that further research on these histamine subtypes may open new venues for more direct treatment with a higher therapeutic efficacy on allergic disorders including those affecting the ocular surface.

  7. Interaction of active compounds from Aegle marmelos CORREA with histamine-1 receptor

    Science.gov (United States)

    Nugroho, Agung Endro; Agistia, Dany Dwi; Tegar, Maulana; Purnomo, Hari

    2013-01-01

    The aim of this study is to determine the affinity of six active compounds of Aegle Marmelos Correa, they are (E, R)-Marmin, skimmianine, (S)-aegeline, aurapten, zeorin, and dustanin as antihistamines in histamine H1 receptor in comparison to cetirizin, diphenhydramine and chlorpheniramine as ligands comparison. Previously, in the in vitro study marmin obviously antagonized the histamine H1 receptor in a competitive manner. Methods: molecular docking to determine the interaction of ligand binding to its receptor. Lower docking score indicates more stable binding to that protein. Results: Marmin, skimmianine, aegeline, aurapten, zeorin, and dustanin were potential to develop as antihistamine agents, especially as histamine H1 receptor antagonists by interacting with amino acid residues, Asp107, Lys179, Lys191, Asn198, and Trp428 of histamine H1 receptor. Conclusions: Based on molecular docking, Amino acid residues involved in ligand protein interactions were Asp107, Lys179, Lys191, Asn198, and Trp428. PMID:23750086

  8. Vascular Effects of Histamine

    African Journals Online (AJOL)

    olayemitoyin

    effects of histamine are mediated via H1 and H2 receptors and the actions are modulated by H3 receptor subtype located on presynaptic ... neurotransmittion in the central nervous system and .... Autoinhibition of brain histamine release.

  9. Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes.

    Science.gov (United States)

    Neuhaus, Jochen; Weimann, Annett; Stolzenburg, Jens-Uwe; Dawood, Waled; Schwalenberg, Thilo; Dorschner, Wolfgang

    2006-06-01

    The potent inflammatory mediator histamine is released from activated mast cells in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes involved in the intracellular calcium response of cultured smooth muscle cells (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from human detrusor biopsies. The distribution of histamine receptor subtypes was addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a maximum of 92% of the cells (n=335), being more effective than carbachol (70%, n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant lower numbers of reacting cells (60, 48 and 54%). Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine-induced calcium increase is mediated by distinct histamine receptors. Thus, pre-therapeutic evaluation of histamine receptor expression in IC patients may help to optimize therapy by using a patient-specific cocktail of subtype-specific histamine receptor antagonists.

  10. In vitro H1-receptor antagonist activity of methanolic extract of tuber of Stephania glabra

    Directory of Open Access Journals (Sweden)

    Nisar Ahmad Khan

    2010-06-01

    Full Text Available In the present study, methanolic extract of tuber of Stephania glabra was evaluated for H1-bloker activity by employing in vitro screening models of guinea pig ileum and goat tracheal chain preparation. Goat isolated trachea and guinea pig ileum contracted to histamine in a dose-dependent manner while chlorpheniramine blocked this effect. The methanolic extract produced significant dose-dependent H1-receptor antagonist activity by blocking histamine-induced contraction.

  11. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-03-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor.

  12. Inhibition of radiation-induced polyuria by histamine receptor antagonists

    International Nuclear Information System (INIS)

    Donlon, M.A.; Melia, J.A.; Helgeson, E.A.; Wolfe, W.W.

    1986-01-01

    In previous studies the authors have demonstrated that gamma radiation results in polyuria, which is preceded by polydypsia. This suggests that the increased thirst elicited by radiation causes increased urinary volume (UV). Histamine, which is released following radiation exposure, also elicits drinking by nonirradiated rats when administered exogenously. In this study the authors have investigated both the role of water deprivation and the effect of histamine receptor antagonists (HRA) on radiation-induced polyuria. Sprague-Dawley rats were housed individually in metabolic cages. Water was allowed ad libitum except in deprivation experiments where water was removed for 24 hr immediately following radiation. Cimetidine (CIM), an H2 HRA, and dexbromopheniramine (DXB), an H1 HRA, were administered i.p. (16 and 1 mg/kg, respectively) 30 min prior to irradiation (950 rads from a cobalt source). UV was determined at 24-hr intervals for 3 days preceding irradiation and 24 hr postirradiation. UV in DXB treated rats was significantly reduced 24 hr postirradiation (CON = 427 +/- 54%; DXB = 247 +/- 39% of preirradiated CON) compared to postirradiation control values. CIM did not affect postirradiation UV. These data suggest that radiation-induced polyuria is caused by polydypsia which is, in part, mediated by histamine induced by an H1 receptor

  13. Modulation of Mast Cell Toll-Like Receptor 3 Expression and Cytokines Release by Histamine

    Directory of Open Access Journals (Sweden)

    Guogang Xie

    2018-05-01

    Full Text Available Background/Aims: As a major inflammatory molecule released from mast cell activation, histamine has been reported to regulate TLRs expression and cytokine production in inflammatory cells present in the microenvironment. In this study, we determined the ability of histamine to modulate TLRs expression and cytokine production in mast cells. Methods: HMC-1 and P815 cells were exposed to various concentrations of histamine in the presence or absence of histamine antagonist for 2, 6 or 16 h. The effect of histamine on the expression of TLR3 protein and mRNA was analyzed by flow cytometry、 RT-PCR and immunofluorescent microscopy. Furthermore, we also examined the effect of histamine on the secretion of MCP-1 and IL-13 from mast cells by ELISA. Results: The amplification of TLR3 mRNA and protein expression in mast cells was observed after incubation with histamine, which was accompanied by increasing secretion of IL-13 and MCP-1 via H1 receptor. The signaling pathways of PI3K/ Akt and Erk1/2/MAPK contributed to these induction effects. Conclusion: These results demonstrate that histamine up-regulates the expression of TLR3 and secretion of IL-13 and MCP-1 in mast cells, thus identifying a new mechanism for the histamine inducing allergic response.

  14. Syntheses of radiolabelled forms of a novel histamine H1 antagonist (SKandF 94944)

    International Nuclear Information System (INIS)

    Cashyap, M.M.; Mitchell, M.B.; Osborne, D.C.; Saunders, D.

    1985-01-01

    A novel histamine H 1 antagonist SKandF 93944, 2-[4-(5-bromo-3-methylpyrid-2-yl)butylamino]-5-(6-methylpyrid-3-yl-methyl)-4(3H)-pyrimidone, has been labelled with carbon-14 in two different positions for use in metabolism and pharmacokinetic studies. The four stage synthesis of [pyrimidone-2- 14 C] SKandF 93944 from barium [ 14 C]cyanamide is described. The overall radiochemical yield was 38%. [butylamino-4- 14 C] SKandF 93944 was synthesised in four steps from [ 14 C]methyl iodide. The key steps in this synthesis were alkylation of 2-lithio-3-methyl pyridine with [ 14 C]methyl iodide and the bromination of 4-(3-methyl-2-pyridyl)[4- 14 C]butylamine in a liquid sulphur trioxide/freon mixture. The overall radiochemical yield was 1.6% from [ 14 C]methyl iodide. (author)

  15. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar

    2016-05-01

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

  16. H1 antihistamines in allergic rhinitis: The molecular pathways of interleukin and toll - like receptor systems

    Directory of Open Access Journals (Sweden)

    Jonny Karunia Fajar

    2016-03-01

    Full Text Available The complex interaction between inflammatory mediators in allergic rhinitis (AR is determined by the role of genetic polymorphisms, including interleukin (IL and toll-like receptor (TLR genes. This study aimed to discuss the effects of H1-antihistamines on IL and TLR systems. Several ILs involved in AR pathogenesis are: IL-4 (rs2243250, rs1800925, rs1801275, rs2227284, rs2070874, IL-6 (rs1800795, rs1800797, IL-10 (rs1800871, rs1800872, IL-12R (rs438421, IL-13 (rs1800925, rs20541, IL-17 (rs3819024, IL-18 (rs360721, rs360718, rs360717, rs187238, IL-23R (rs7517847, and IL-27 (rs153109, rs17855750. In the IL system, histamines stimulate the IL production in Type 2 helper T (Th2 cells through protein kinase A (PKA, janus kinase-signal transducer and activator of transcription (JAK-STAT pathway, and the activation of H1-histamine receptor and histidine decarboxylase (HDC genes. On contrary, antihistamines down-regulate the H1-histamine receptor gene expression through the transcription suppression of HDC and IL genes and suppress histamine basal signaling through the inverse agonistic activity. TLRs involved in AR pathogenesis are TLR2 (rs4696480, rs3804099, rs5743708, TLR4 (rs4986790, TLR6 (rs2381289, TLR7 (rs179008, rs5935438, TRL8 (rs2407992, rs5741883, rs17256081, rs4830805, rs3788935, rs178998, and TLR10 (rs11466651. In the TLR system, histamines trigger the TLR expression by stimulating interferon-γ (IFN-γ to up-regulate mast cells and by stimulating receptor-interacting protein (RIP to activate IκB kinase-β. Contrastingly, antihistamines suppress TIR-domain-containing adaptor protein inducing IFN-β (TRIF and RIP protein and thus inhibit the expression of TLR. In addition, several studies indicated that H1-antihistamines inhibit the IL and TLR systems indirectly.

  17. Histamina, receptores de histamina e anti-histamínicos: novos conceitos Histamine, histamine receptors and antihistamines: new concepts

    Directory of Open Access Journals (Sweden)

    Paulo Ricardo Criado

    2010-04-01

    Full Text Available As drogas com ação anti-histamínica estão entre as medicações mais comumente prescritas na prática dermatológica diária, tanto em adultos como em crianças. Este artigo aborda os novos conceitos da função dos receptores de histamina (receptores H1 e discute os efeitos anti-inflamatórios dessas drogas. A segunda geração de anti-histamínicos difere da primeira geração devido a sua elevada especificidade e afinidade pelos receptores H1 periféricos e devido a seu menor efeito no sistema nervoso central, tendo como resultado menores efeitos sedativos. Embora a eficácia dos diferentes anti-histamínicos H1 (anti-H1 no tratamento de doentes alérgicos seja similar, mesmo quando se comparam anti-H1 de primeira e de segunda geração, eles são muito diferentes em termos de estrutura química, farmacologia e propriedades tóxicas. Consequentemente o conhecimento de suas características farmacocinéticas e farmacodinâmicas é importante para a melhor prática médica, especialmente em gestantes, crianças, idosos e doentes com comorbidades.Drugs with antihistamine action are the most commonly prescribed medication in daily dermatologic practice, both to adults and children. This article addresses new concepts of the role of histamine receptors (H1 receptors and discusses the anti-inflammatory effects of these drugs. Second generation antihistamines differs from first generation because of their high specificity and affinity for peripheral H1-receptors. Second generation antihistamines are also less likely to produce sedation because they have less effect on the central nervous system. Although the efficacy of the various H1-antihistamines in the treatment of allergic patients is similar, even when comparing first- and second-generation drugs, these drugs are still very different in terms of their chemical structure, pharmacology and toxic properties. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics

  18. Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.

    Science.gov (United States)

    Chen, Meiling; Xu, Shuhong; Zhou, Peipei; He, Guangwei; Jie, Qiong; Wu, Yulin

    2015-11-15

    Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Role of histamine receptors in the effects of histamine on the production of reactive oxygen species by whole blood phagocytes

    Czech Academy of Sciences Publication Activity Database

    Vašíček, Ondřej; Lojek, Antonín; Jančinová, V.; Nosál, R.; Číž, Milan

    2014-01-01

    Roč. 100, č. 1 (2014), s. 67-72 ISSN 0024-3205 R&D Projects: GA MŠk(CZ) LD11010 Institutional support: RVO:68081707 Keywords : Histamine * Histamine receptors * Reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 2.702, year: 2014

  20. Efficacy and safety of histamine-2 receptor antagonists

    NARCIS (Netherlands)

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

    2014-01-01

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

  1. Expression of histamine receptors in the human endolymphatic sac

    DEFF Research Database (Denmark)

    Møller, M Nue; Kirkeby, S; Vikeså, J.

    2016-01-01

    in 2012. This leaves betahistine (Betaserc) as the only drug for potential prevention of the incapacitating attacks of dizziness, tinnitus and hearing loss. However, the histamine receptors targeted by betahistine have never been demonstrated in the human ES. Accordingly, this study aims to investigate...

  2. The modulatory role of spinally located histamine receptors in the regulation of the blood glucose level in d-glucose-fed mice.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

    2014-02-01

    The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

  3. Histamine 1 Receptor Blockade Enhances Eosinophil-Mediated Clearance of Adult Filarial Worms.

    Directory of Open Access Journals (Sweden)

    Ellen Mueller Fox

    Full Text Available Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis and river blindness. The goal of this study was to characterize the role of histamine during Litomosoides sigmodontis infection of BALB/c mice, a murine model of filariasis. Time course studies demonstrated that while expression of histidine decarboxylase mRNA increases throughout 12 weeks of infection, serum levels of histamine exhibit two peaks-one 30 minutes after primary infection and one 8 weeks later. Interestingly, mice treated with fexofenadine, a histamine receptor 1 inhibitor, demonstrated significantly reduced worm burden in infected mice compared to untreated infected controls. Although fexofenadine-treated mice had decreased antigen-specific IgE levels as well as lower splenocyte IL-5 and IFNγ production, they exhibited a greater than fourfold rise in eosinophil numbers at the tissue site where adult L. sigmodontis worms reside. Fexofenadine-mediated clearance of L. sigmodontis worms was dependent on host eosinophils, as fexofenadine did not decrease worm burdens in eosinophil-deficient dblGATA mice. These findings suggest that histamine release induced by tissue invasive helminths may aid parasite survival by diminishing eosinophilic responses. Further, these results raise the possibility that combining H1 receptor inhibitors with current anthelmintics may improve treatment efficacy for filariae and other tissue-invasive helminths.

  4. Human eosinophils - potential pharmacological model applied in human histamine H4 receptor research.

    Science.gov (United States)

    Grosicki, Marek; Kieć-Kononowicz, Katarzyna

    2015-01-01

    Histamine and histamine receptors are well known for their immunomodulatory role in inflammation. In this review we describe the role of histamine and histamine H4 receptor on human eosinophils. In the first part of article we provide short summary of histamine and histamine receptors role in physiology and histamine related therapeutics used in clinics. We briefly describe the human histamine receptor H4 and its ligands, as well as human eosinophils. In the second part of the review we provide detailed description of known histamine effects on eosinophils including: intracellular calcium concentration flux, actin polymerization, cellular shape change, upregulation of adhesion proteins and cellular chemotaxis. We provide proofs that these effects are mainly connected with the activation of histamine H4 receptor. When examining experimental data we discuss the controversial results and limitations of the studies performed on isolated eosinophils. In conclusion we believe that studies on histamine H4 receptor on human eosinophils can provide interesting new biomarkers that can be used in clinical studies of histamine receptors, that in future might result in the development of new strategies in the treatment of chronic inflammatory conditions like asthma or allergy, in which eosinophils are involved.

  5. Histamine delays gastric emptying of solid food in man through histamine, receptors

    International Nuclear Information System (INIS)

    Sridhar, K.; Lange, R.; McCallum, R.W.

    1984-01-01

    The authors have shown that histamine (H) contracts the cat pylorus and duodenum through H/sub 1/ receptor mechanisms. The authors investigated the effect of H infusion on gastric emptying (GE) and the role of H/sub 1/ and H/sub 2/ receptor blockade in healthy volunteers. Radionuclide GE studies were performed using chicken liver labeled in vivo with /sup 99m/Technetium-sulfur colloid as a marker of solid food. Study days were as follows: a baseline GE study (Day 1); H infused continuously IV at a rate of 40 μg/kg/hr during the GE study (Day 2); an IV bolus of 50 mg of diphenhydramine (Day 3), or 300 mg cimetidine (Day 4) given just prior to the continuous infusion of H; a final day when cimetidine was given alone (Day 5). GE was monitored for 2 hours on each day. The results of days 1, 2 and 3 are summarized below (+p<0.05 vs baseline or Day 1). Pretreatment with cimetidine (Day 4) augmented the delay in GE induced by H infusion, while cimetidine without H (Day 5) had no effect on GE. The authors conclude that: 1) H given at a dose which elicits maximal acid secretory response in man significantly delays GE; and 2) H/sub 1/ receptor blockade but not H/sub 2/ blockade prevented this effect. Histamine may play a modulatory role in human gastric emptying through an H/sub 1/ receptor mechanism

  6. Characteristics in Molecular Vibrational Frequency Patterns between Agonists and Antagonists of Histamine Receptors

    Directory of Open Access Journals (Sweden)

    S. June Oh

    2012-06-01

    Full Text Available To learn the differences between the structure-activity relationship and molecular vibration-activity relationship in the ligand-receptor interaction of the histamine receptor, 47 ligands of the histamine receptor were analyzed by structural similarity and molecular vibrational frequency patterns. The radial tree that was produced by clustering analysis of molecular vibrational frequency patterns shows its potential for the functional classification of histamine receptor ligands.

  7. The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission : an in vivo electrophysiology and microdialysis study

    NARCIS (Netherlands)

    Flik, Gunnar; Dremencov, Eliyahu; Cremers, Thomas I. H. F.; Folgering, Joost H. A.; Westerink, Ben H. C.

    2011-01-01

    The current study aimed to investigate the effect of histamine-3 (H3) receptors, expressed in the tuberomammillary nucleus (TMN) of the hypothalamus and in the prefrontal cortex (PFC), on histamine neurotransmission in the rat brain. The firing activity of histamine neurons in the TMN was measured

  8. Receptor-independent, vacuolar ATPase-mediated cellular uptake of histamine receptor-1 ligands: Possible origin of pharmacological distortions and side effects

    International Nuclear Information System (INIS)

    Morissette, Guillaume; Lodge, Robert; Bouthillier, Johanne; Marceau, Francois

    2008-01-01

    The aims of this study were to investigate whether several histamine receptor agonists and antagonists are subjected to receptor-independent ion trapping into acidic organelles, and whether this sequestration influences their pharmacological or toxicological properties. Vacuolar (V)-ATPase-dependent intracellular sequestration of agonists was recognized as morphological alterations (large fluid-filled vacuoles for betahistine and 1-methylhistamine, granular uptake for fluorescent BODIPY FL histamine) prevented by the specific V-ATPase inhibitor bafilomycin A1 in rabbit vascular smooth muscle cells. Lipophilicity was the major determinant of these cellular effects (order of potency: BODIPY FL histamine > betahistine > 1-methylhistamine > histamine) that occurred at high concentrations. This ranking was dissociable from the potency order for H 1 receptor-mediated contraction of the rabbit aorta, a response uninfluenced by bafilomycin. Antihistamines are inherently more lipophilic and caused vacuolization of a proportion of cells at 5-500 μM. Agonist or antagonist-induced vacuoles were of macroautophagic nature (labeled with GFP-conjugated LC3, Rab7 and CD63; detection of LC3 II). Further, the 2 most lipophilic antihistamines tested, astemizole and terfenadine, were potentiated by V-ATPase blockade in the aortic contractility assay (13- and 3.6-fold more potent, respectively, pA 2 scale), suggesting that V-ATPase-mediated cation trapping sequesters these antagonists from the vicinity of H 1 receptors in the therapeutic concentration range. This potentiation did not apply to less lipophilic antagonists (pyrilamine, diphenhydramine). While some agonists and all tested antagonists of the histamine H 1 receptors induce the V-ATPase-dependent vacuolar and autophagic cytopathology, sequestration affects the pharmacology of only the most lipophilic antagonists, the ones prone to off-target arrhythmogenic side effects

  9. Histamine H4 receptor in oral lichen planus.

    Science.gov (United States)

    Salem, A; Al-Samadi, A; Stegajev, V; Stark, H; Häyrinen-Immonen, R; Ainola, M; Hietanen, J; Konttinen, Y T

    2015-04-01

    Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines. Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes. H4 R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4 R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs, whereas high histamine concentration and interferon-γ decreased HRH4 -gene transcripts. Healthy oral epithelial cells are equipped with H4 R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4 R. Cell culture experiments suggest a rapid H4 R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4 R synthesis. H4 R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Novel spirotetracyclic zwitterionic dual H(1)/5-HT(2A) receptor antagonists for the treatment of sleep disorders.

    Science.gov (United States)

    Gianotti, Massimo; Botta, Maurizio; Brough, Stephen; Carletti, Renzo; Castiglioni, Emiliano; Corti, Corrado; Dal-Cin, Michele; Delle Fratte, Sonia; Korajac, Denana; Lovric, Marija; Merlo, Giancarlo; Mesic, Milan; Pavone, Francesca; Piccoli, Laura; Rast, Slavko; Roscic, Maja; Sava, Anna; Smehil, Mario; Stasi, Luigi; Togninelli, Andrea; Wigglesworth, Mark J

    2010-11-11

    Histamine H(1) and serotonin 5-HT(2A) receptors mediate two different mechanisms involved in sleep regulation: H(1) antagonists are sleep inducers, while 5-HT(2A) antagonists are sleep maintainers. Starting from 9'a, a novel spirotetracyclic compound endowed with good H(1)/5-HT(2A) potency but poor selectivity, very high Cli, and a poor P450 profile, a specific optimization strategy was set up. In particular, we investigated the possibility of introducing appropriate amino acid moieties to optimize the developability profile of the series. Following this zwitterionic approach, we were able to identify several advanced leads (51, 65, and 73) with potent dual H(1)/5-HT(2A) activity and appropriate developability profiles. These compounds exhibited efficacy as hypnotic agents in a rat telemetric sleep model with minimal effective doses in the range 3-10 mg/kg po.

  11. En route to new blockbuster antihistamines:surveying the offspring of the expanding histamine receptor family

    NARCIS (Netherlands)

    Leurs, R.; Vischer, H.F.; Wijtmans, M.; De Esch, I.J.

    2011-01-01

    With the recognition of two new histamine receptors at the start of the new millennium, the field of histamine research has seen a clear revival. In the last 10 years, many academic and industrial groups have taken up the challenge to target these new members of the aminergic G-protein-coupled

  12. Characteristics of recombinantly expressed rat and human histamine H3 receptors.

    Science.gov (United States)

    Wulff, Birgitte S; Hastrup, Sven; Rimvall, Karin

    2002-10-18

    Human and rat histamine H(3) receptors were recombinantly expressed and characterized using receptor binding and a functional cAMP assay. Seven of nine agonists had similar affinities and potencies at the rat and human histamine H(3) receptor. S-alpha-methylhistamine had a significantly higher affinity and potency at the human than rat receptor, and for 4-[(1R*,2R*)-2-(5,5-dimethyl-1-hexynyl)cyclopropyl]-1H-imidazole (Perceptin) the preference was the reverse. Only two of six antagonists had similar affinities and potencies at the human and the rat histamine H(3) receptor. Ciproxifan, thioperamide and (1R*,2R*)-trans-2-imidazol-4 ylcyclopropyl) (cyclohexylmethoxy) carboxamide (GT2394) had significantly higher affinities and potencies at the rat than at the human histamine H(3) receptor, while for N-(4-chlorobenzyl)-N-(7-pyrrolodin-1-ylheptyl)guanidine (JB98064) the preference was the reverse. All antagonists also showed potent inverse agonism properties. Iodoproxyfan, Perceptin, proxyfan and GR175737, compounds previously described as histamine H(3) receptor antagonists, acted as full or partial agonists at both the rat and the human histamine H(3) receptor. Copyright 2002 Elsevier Science B.V.

  13. Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Sadek B

    2016-11-01

    Full Text Available Bassem Sadek,1 Ali Saad,1 Johannes Stephan Schwed,2,3 Lilia Weizel,2 Miriam Walter,2 Holger Stark2,3 1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 2Biocenter, Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt, Germany; 3Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Düsseldorf, Germany Abstract: Phenytoin (PHT, valproic acid, and modern antiepileptic drugs (AEDs, eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%–80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H3 receptors (H3Rs for epilepsy might be a promising therapeutic approach. To determine the potential of H3Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the (S-2-(4-(3-(piperidin-1-ylpropoxybenzylaminopropanamide (1. In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R-enantiomer, namely, (R-2-(4-(3-(piperidin-1-ylpropoxybenzylaminopropaneamide (2 and analogs thereof, in maximum electroshock (MES-, pentylenetetrazole (PTZ-, and strychnine (STR-induced convulsion models in rats having PHT and valproic acid (VPA as reference AEDs. Unlike the S-enantiomer (1, the results show that animals pretreated intraperitoneally (ip with the R-enantiomer 2 (10 mg/kg were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier (R-enantiomer (3

  14. Histamine-2 receptor antagonists as immunomodulators: new therapeutic views?

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1996-01-01

    Considerable evidence has emerged to suggest that histamine participates in the regulation of the inflammatory response, immune reaction, coagulation cascade, and cardiovascular function. Furthermore, histamine may play a major role in the growth of normal and malignant tissue as a regulator of p...

  15. Major advances in the development of histamine H4 receptor ligands.

    Science.gov (United States)

    Smits, Rogier A; Leurs, Rob; de Esch, Iwan J P

    2009-08-01

    The search for new and potent histamine H4 receptor ligands is leading to a steadily increasing number of scientific publications and patent applications. Several interesting and structurally diverse compounds have been found, but fierce IP competition for a preferred 2-aminopyrimidine scaffold is becoming apparent. Recent investigations into the role of the histamine H(4)R in (patho)physiology and the use of H4R ligands in in vivo disease models reveal enormous potential in the field of inflammation and allergy, among others. The development of ligands that display activity at two or more histamine receptor (HR) subtypes is another clinical opportunity that is currently being explored. Taken together, the histamine H4R field is gearing up for clinical studies and has the potential to deliver another generation of blockbuster drugs.

  16. Identification of amino acids involved in histamine potentiation of GABA(A receptors

    Directory of Open Access Journals (Sweden)

    Ulrike eThiel

    2015-05-01

    Full Text Available Histamine is a neurotransmitter involved in a number of physiological and neuronal functions. In mammals, such as humans and rodents, the histaminergic neurons found in the tuberomamillary nucleus (TMN project widely throughout the central nervous system (CNS. Histamine acts as positive modulator of GABA(A receptors (GABA(ARs and, in high concentrations (10 mM, as negative modulator of the strychnine-sensitive glycine receptor. However, the exact molecular mechanisms by which histamine acts on GABA(ARs are unknown. In our study, we aimed to identify amino acids potentially involved in the modulatory effect of histamine on GABA(ARs. We expressed GABA(ARs with 12 different point mutations in Xenopus laevis oocytes and characterized the effect of histamine on GABA-induced currents using the two-electrode voltage clamp technique. Our data demonstrate that the amino acid residues ß2(N265 and ß2(M286, which are important for modulation by propofol, are not involved in the action of histamine. However, we found that histamine modulation is dependent on the amino acid residues alpha1(R120, ß2(Y157, ß3(D163, ß3(V175 and ß3(Q185. We showed that the amino acid residues ß2(Y157 and ß3(Q185 mediate the positive modulatory effect of histamine on GABA-induced currents, whereas alpha1(R120 and ß2(D163 form a potential histamine interaction site in GABA(ARs.

  17. Identification of novel β-lactams and pyrrolidinone derivatives as selective Histamine-3 receptor (H3R) modulators as possible anti-obesity agents.

    Science.gov (United States)

    Ghoshal, Anirban; Kumar, Ajeet; Yugandhar, Doddapaneni; Sona, Chandan; Kuriakose, Sunu; Nagesh, Kommu; Rashid, Mamunur; Singh, Sandeep K; Wahajuddin, Muhammad; Yadav, Prem N; Srivastava, Ajay K

    2018-05-25

    Four series of structurally related β-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) were synthesized by utilizing post-Ugi modifications in one-pot, and their activity towards human histamine-3 receptor (H3R) was evaluated. Out of 94 compounds, screened against histamine-3 receptor (H3R), 21 compounds showed high H3R selective agonist property with EC 50 values ranging from 187 nM to 0.1 nM, whereas none of the compound was found to have the affinity towards other receptors of histamine family such as histamine H1, H2, and H4 receptor. All active compounds have no assay interference activity as determined by in-silico analysis and receptor independent luciferase assay and cell cytotoxicity assay. Given the important role of H3R in hypophagia, we also evaluated the in vivo effect of the representative compound 6k on the cumulative food intake in diet induce obese C57BL6/J mice. Interestingly, we observed that single dose administration (20 mg/kg, intraperitoneal injection) of 6k significantly suppressed cumulative food intake, while no significant effect was observed at 10 mg/kg. These results suggest that β-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) could be useful for the development of anti-obesity candidate drugs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    1998-02-01

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

  19. Simplified PET measurement for evaluating histamine H{sub 1} receptors in human brains using [{sup 11}C]doxepin

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Hideki [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Kimura, Yuichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)]. E-mail: ukimura@ieee.org; Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Oda, Keiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Sasaki, Toru [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan); Tashiro, Manabu [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Yanai, Kazuhiko [Department of Pharmacology, Tohoku University School of Medicine, Sendai, 980-8575 (Japan); Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0022 (Japan)

    2004-11-01

    The aim of this study was to develop simplified positron emission tomography measurement using [{sup 11}C]doxepin ([{sup 11}C]DOX) to evaluate histamine H{sub 1} receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [{sup 11}C]DOX, estimated quantitatively with a two-compartment model, and the [{sup 11}C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [{sup 11}C]DOX-H1R binding.

  20. TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch.

    Science.gov (United States)

    Jian, Tunyu; Yang, Niuniu; Yang, Yan; Zhu, Chan; Yuan, Xiaolin; Yu, Guang; Wang, Changming; Wang, Zhongli; Shi, Hao; Tang, Min; He, Qian; Lan, Lei; Wu, Guanyi; Tang, Zongxiang

    2016-01-01

    Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG) neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip)-a histamine H4 receptor special agonist under cutaneous injection-obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3-50 μM) could also induce a dose-dependent increase in intracellular Ca(2+) ([Ca(2+)]i) of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca(2+) responses. In addition, immepip-induced [Ca(2+)]i increase could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons' responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation.

  1. TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch

    Directory of Open Access Journals (Sweden)

    Tunyu Jian

    2016-01-01

    Full Text Available Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip—a histamine H4 receptor special agonist under cutaneous injection—obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3–50 μM could also induce a dose-dependent increase in intracellular Ca2+ (Ca2+i of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca2+ responses. In addition, immepip-induced Ca2+i increase could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons’ responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation.

  2. Autonomous control of phosphatidylinositol turnover by histamine and acetylcholine receptors in the NIE-115 neuron-like cell line

    International Nuclear Information System (INIS)

    Large, T.H.; Lambert, M.P.; Cohen, N.M.; Klein, W.L.

    1986-01-01

    Histamine was found to stimulate the turnover of phosphatidylinositol (PI) in cultures of neuron-like NE-115 cells. Turnover was measured by increased production of ( 3 H)inositol phosphates (breakdown) and by accelerated incorporation of 32 P into PI (resynthesis). Data were consistent with hydrolysis of polyphosphoinositides being the initial event in receptor-stimulated PI turnover. This response to histamine desensitized within 10 min. Receptor systems for histamine and acetylcholine were tested for possible interactions: PI turnover in response to dual stimulation was approximately equal to the sum of the individual responses while prior desensitization of the acetylcholine receptor system had no effect on subsequent stimulation of the histamine receptor system. These results are consistent with the hypothesis that components of acetylcholine and histamine receptor systems responsible for PI turnover are autonomously organised and regulated. (author)

  3. Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors

    Directory of Open Access Journals (Sweden)

    Zucca Gianpiero

    2009-06-01

    Full Text Available Abstract Background Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia. Results RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin. Conclusion The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.

  4. Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors.

    Science.gov (United States)

    Tritto, Simona; Botta, Laura; Zampini, Valeria; Zucca, Gianpiero; Valli, Paolo; Masetto, Sergio

    2009-06-29

    Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia. RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin. The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to) H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin.

  5. Localization and function of histamine H3 receptor in the nasal mucosa

    OpenAIRE

    Suzuki, Shinya; Takeuchi, Kazuhiko; Majima, Yuichi

    2008-01-01

    BACKGROUND: Histamine is an important chemical mediator of allergic rhinitis (AR). Histamine H3 receptors H3R are located on cholinergic and NANC neurons of the myenteric plexus, and activation of H3R regulates gastric acid secretion. However, little is known about the localization and function of H3R in the upper airway. OBJECTIVE: The objective of this study was to examine the localization and possible function of H3R in the nasal mucosa. METHODS: We extracted total RNA from the inferior tu...

  6. Antagonistic targeting of the histamine H3 receptor decreases caloric intake in higher mammalian species.

    Science.gov (United States)

    Malmlöf, Kjell; Hastrup, Sven; Wulff, Birgitte Schellerup; Hansen, Barbara C; Peschke, Bernd; Jeppesen, Claus Bekker; Hohlweg, Rolf; Rimvall, Karin

    2007-04-15

    The main purpose of this study was to examine the effects of a selective histamine H(3) receptor antagonist, NNC 38-1202, on caloric intake in pigs and in rhesus monkeys. The compound was given intragastrically (5 or 15 mg/kg), to normal pigs (n=7) and subcutaneously (1 or 0.1mg/kg) to obese rhesus monkeys (n=9). The energy intake recorded following administration of vehicle to the same animals served as control for the effect of the compound. In addition, rhesus monkey and pig histamine H(3) receptors were cloned from hypothalamic tissues and expressed in mammalian cell lines. The in vitro antagonist potencies of NNC 38-1202 at the H(3) receptors were determined using a functional GTPgammaS binding assay. Porcine and human H(3) receptors were found to have 93.3% identity at the amino acid level and the close homology between the monkey and human H(3) receptors (98.4% identity) was confirmed. The antagonist potencies of NNC 38-1202 at the porcine, monkey and human histamine H(3) receptors were high as evidenced by K(i)-values being clearly below 20 nM, whereas the K(i)-value on the rat H(3) receptor was significantly higher (56+/-6.0 nM). NNC 38-1202, given to pigs in a dose of 15 mg/kg, produced a significant (p<0.05) reduction (55%) of calorie intake compared with vehicle alone, (132.6+/-10.0 kcal/kgday versus 59.7+/-10.2 kcal/kgday). In rhesus monkeys administration of 0.1 and 1mg/kg decreased (p<0.05) average calorie intakes by 40 and 75%, respectively. In conclusion, the present study demonstrates that antagonistic targeting of the histamine H(3) receptor decreases caloric intake in higher mammalian species.

  7. Molecular and functional profiling of histamine receptor-mediated calcium ion signals in different cell lines.

    Science.gov (United States)

    Meisenberg, Annika; Kaschuba, Dagmar; Balfanz, Sabine; Jordan, Nadine; Baumann, Arnd

    2015-10-01

    Calcium ions (Ca(2+)) play a pivotal role in cellular physiology. Often Ca(2+)-dependent processes are studied in commonly available cell lines. To induce Ca(2+) signals on demand, cells may need to be equipped with additional proteins. A prominent group of membrane proteins evoking Ca(2+) signals are G-protein coupled receptors (GPCRs). These proteins register external signals such as photons, odorants, and neurotransmitters and convey ligand recognition into cellular responses, one of which is Ca(2+) signaling. To avoid receptor cross-talk or cross-activation with introduced proteins, the repertoire of cell-endogenous receptors must be known. Here we examined the presence of histamine receptors in six cell lines frequently used as hosts to study cellular signaling processes. In a concentration-dependent manner, histamine caused a rise in intracellular Ca(2+) in HeLa, HEK 293, and COS-1 cells. The concentration for half-maximal activation (EC50) was in the low micromolar range. In individual cells, transient Ca(2+) signals and Ca(2+) oscillations were uncovered. The results show that (i) HeLa, HEK 293, and COS-1 cells express sufficient amounts of endogenous receptors to study cellular Ca(2+) signaling processes directly and (ii) these cell lines are suitable for calibrating Ca(2+) biosensors in situ based on histamine receptor evoked responses. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Docking-based Screening of Ficus religiosa Phytochemicals as Inhibitors of Human Histamine H2 Receptor.

    Science.gov (United States)

    Chaudhary, Amit; Yadav, Birendra Singh; Singh, Swati; Maurya, Pramod Kumar; Mishra, Alok; Srivastva, Shweta; Varadwaj, Pritish Kumar; Singh, Nand Kumar; Mani, Ashutosh

    2017-10-01

    Ficus religiosa L. is generally known as Peepal and belongs to family Moraceae . The tree is a source of many compounds having high medicinal value. In gastrointestinal tract, histamine H2 receptors have key role in histamine-stimulated gastric acid secretion. Their over stimulation causes its excessive production which is responsible for gastric ulcer. This study aims to screen the range of phytochemicals present in F. religiosa for binding with human histamine H2 and identify therapeutics for a gastric ulcer from the plant. In this work, a 3D-structure of human histamine H2 receptor was modeled by using homology modeling and the predicted model was validated using PROCHECK. Docking studies were also performed to assess binding affinities between modeled receptor and 34 compounds. Molecular dynamics simulations were done to identify most stable receptor-ligand complexes. Absorption, distribution, metabolism, excretion, and screening was done to evaluate pharmacokinetic properties of compounds. The results suggest that seven ligands, namely, germacrene, bergaptol, lanosterol, Ergost-5-en-3beta-ol, α-amyrin acetate, bergapten, and γ-cadinene showed better binding affinities. Among seven phytochemicals, lanosterol and α-amyrin acetate were found to have greater stability during simulation studies. These two compounds may be a suitable therapeutic agent against histamine H2 receptor. This study was performed to screen antiulcer compounds from F. religiosa . Molecular modeling, molecular docking and MD simulation studies were performed with selected phytochemicals from F. religiosa . The analysis suggests that Lanosterol and α-amyrin may be a suitable therapeutic agent against histamine H2 receptor. This study facilitates initiation of the herbal drug discovery process for the antiulcer activity. Abbreviations used: ADMET: Absorption, distribution, metabolism, excretion and toxicity, DOPE: Discrete Optimized Potential Energy, OPLS: Optimized potential for liquid

  9. Determination of some histamine H1-receptor antagonists in dosage forms.

    Science.gov (United States)

    Gazy, Azza A; Mahgoub, Hoda; El-Yazbi, F A; El-Sayed, M A; Youssef, Rasha M

    2002-10-15

    Three simple and accurate methods are presented for determination of Cetirizine, Fexofenadine, Loratadine and Acrivastine in pure form and commercial dosage forms. The first method is based on the reaction of the above cited drugs with bromocresol purple dye to form ion-pair complex extractable with chloroform and subsequently measured spectrophotometrically. Secondly, eosin gives with these drugs ion-pair complex, measurable directly without extraction both spectrophotometrically and spectrofluorimetrically. The last method involves the base-catalysed condensation of mixed anhydrides of organic acids (citric acid/acetic anhydride) where as the tertiary amino group in the above-cited drugs acts as the basic catalyst. The product of condensation is measured spectrophotometrically. All the reaction conditions for the proposed methods have been studied. Copyright 2002 Elsevier Science B.V.

  10. Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H(3) receptor

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Goodman, M W; Burstein, E S

    2002-01-01

    The pharmacology of histamine H(3) receptors suggests the presence of distinct receptor isoforms or subtypes. We herein describe multiple, functionally distinct, alternatively spliced isoforms of the human H(3) receptor. Combinatorial splicing at three different sites creates at least six distinct...... receptor isoforms, of which isoforms 1, 2, and 4, encode functional proteins. Detailed pharmacology on isoforms 1 (unspliced receptor), and 2 (which has an 80 amino acid deletion within the third intracellular loop of the protein) revealed that both isoforms displayed robust responses to a series of known...... revealed a rank order of potency at both isoforms of clobenpropit>iodophenpropit>thioperamide, and these drugs are fivefold less potent at isoform 2 than isoform 1. To further explore the pharmacology of H(3) receptor function, we screened 150 clinically relevant neuropsychiatric drugs for H(3) receptor...

  11. Non-imidazole-based histamine H3 receptor antagonists with anticonvulsant activity in different seizure models in male adult rats

    Directory of Open Access Journals (Sweden)

    Sadek B

    2016-11-01

    Full Text Available Bassem Sadek,1 Ali Saad,1 Gniewomir Latacz,2 Kamil Kuder,2 Agnieszka Olejarz,2 Tadeusz Karcz,2 Holger Stark,3 Katarzyna Kieć-Kononowicz2 1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 2Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; 3Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Düsseldorf, Germany Abstract: A series of twelve novel non-imidazole-based ligands (3–14 was developed and evaluated for its in vitro binding properties at the human histamine H3 receptor (hH3R. The novel ligands were investigated for their in vivo protective effects in different seizure models in male adult rats. Among the H3R ligands (3–14 tested, ligand 14 showed significant and dose-dependent reduction in the duration of tonic hind limb extension in maximal electroshock (MES-induced seizure model subsequent to acute systemic administration (5, 10, and 20 mg/kg, intraperitoneally, whereas ligands 4, 6, and 7 without appreciable protection in MES model were most promising in pentylenetetrazole (PTZ model. Moreover, the protective effect observed for ligand 14 in MES model was lower than that observed for the reference drug phenytoin and was entirely abrogated when rats were co-administered with the brain-penetrant H1R antagonist pyrilamine (PYR but not the brain-penetrant H2R antagonist zolantidine (ZOL, demonstrating that histaminergic neurotransmission by activation of postsynaptically located H1Rs seems to be involved in the protective action. On the contrary, PYR and ZOL failed to abrogate the full protection provided by 4 in PTZ model and the moderate protective effect by 14 in strychnine (STR model. Moreover, the experimental and in silico estimation of properties such as metabolism was

  12. Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.

    Science.gov (United States)

    Quartulli, F; Pinelli, E; Broué-Chabbert, A; Gossart, S; Girard, V; Pipy, B

    1998-05-08

    Using the human lung epithelial WI26VA4 cell line, we investigated the capacity of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties, to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid formation. Histamine and a histamine H1 receptor agonist elicited a rapid and transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells. This response was antagonized by the histamine H1 receptor antagonist, diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid release, was responsible for the histamine-induced intracellular Ca2+ increase. In the second phase release (15-60 min), a sustained arachidonic acid release appeared to be associated with the formation of cyclooxygenase and lipoxygenase metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced arachidonic acid release. These results suggest that anti-inflammatory and antibronchoconstrictor properties of fenspiride may result from the inhibition of these effects of histamine.

  13. Structure-based prediction of subtype selectivity of histamine H3 receptor selective antagonists in clinical trials.

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    Kim, Soo-Kyung; Fristrup, Peter; Abrol, Ravinder; Goddard, William A

    2011-12-27

    Histamine receptors (HRs) are excellent drug targets for the treatment of diseases, such as schizophrenia, psychosis, depression, migraine, allergies, asthma, ulcers, and hypertension. Among them, the human H(3) histamine receptor (hH(3)HR) antagonists have been proposed for specific therapeutic applications, including treatment of Alzheimer's disease, attention deficit hyperactivity disorder (ADHD), epilepsy, and obesity. However, many of these drug candidates cause undesired side effects through the cross-reactivity with other histamine receptor subtypes. In order to develop improved selectivity and activity for such treatments, it would be useful to have the three-dimensional structures for all four HRs. We report here the predicted structures of four HR subtypes (H(1), H(2), H(3), and H(4)) using the GEnSeMBLE (GPCR ensemble of structures in membrane bilayer environment) Monte Carlo protocol, sampling ∼35 million combinations of helix packings to predict the 10 most stable packings for each of the four subtypes. Then we used these 10 best protein structures with the DarwinDock Monte Carlo protocol to sample ∼50 000 × 10(20) poses to predict the optimum ligand-protein structures for various agonists and antagonists. We find that E206(5.46) contributes most in binding H(3) selective agonists (5, 6, 7) in agreement with experimental mutation studies. We also find that conserved E5.46/S5.43 in both of hH(3)HR and hH(4)HR are involved in H(3)/ H(4) subtype selectivity. In addition, we find that M378(6.55) in hH(3)HR provides additional hydrophobic interactions different from hH(4)HR (the corresponding amino acid of T323(6.55) in hH(4)HR) to provide additional subtype bias. From these studies, we developed a pharmacophore model based on our predictions for known hH(3)HR selective antagonists in clinical study [ABT-239 1, GSK-189,254 2, PF-3654746 3, and BF2.649 (tiprolisant) 4] that suggests critical selectivity directing elements are: the basic proton

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

    Science.gov (United States)

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

    1995-05-01

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

  15. A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

    Science.gov (United States)

    Petri, Doris; Schlicker, Eberhard

    2016-07-01

    The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients*.

    Science.gov (United States)

    MacLaren, Robert; Campbell, Jon

    2014-04-01

    To examine the cost-effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Decision analysis model examining costs and effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Costs were expressed in 2012 U.S. dollars from the perspective of the institution and included drug regimens and the following outcomes: clinically significant stress-related mucosal bleed, ventilator-associated pneumonia, and Clostridium difficile infection. Effectiveness was the mortality risk associated with these outcomes and represented by survival. Costs, occurrence rates, and mortality probabilities were extracted from published data. A simulation model. A mixed adult ICU population. Histamine receptor-2 antagonist or proton pump inhibitor for 9 days of stress ulcer prophylaxis therapy. Output variables were expected costs, expected survival rates, incremental cost, and incremental survival rate. Univariate sensitivity analyses were conducted to determine the drivers of incremental cost and incremental survival. Probabilistic sensitivity analysis was conducted using second-order Monte Carlo simulation. For the base case analysis, the expected cost of providing stress ulcer prophylaxis was $6,707 with histamine receptor-2 antagonist and $7,802 with proton pump inhibitor, resulting in a cost saving of $1,095 with histamine receptor-2 antagonist. The associated mortality probabilities were 3.819% and 3.825%, respectively, resulting in an absolute survival benefit of 0.006% with histamine receptor-2 antagonist. The primary drivers of incremental cost and survival were the assumptions surrounding ventilator-associated pneumonia and bleed. The probabilities that histamine receptor-2 antagonist was less costly and provided favorable survival were 89.4% and 55.7%, respectively. A secondary analysis assuming equal rates of C. difficile infection showed a cost saving of $908 with histamine

  17. Histamine-2 receptor antagonist famotidine modulates cardiac stem cell characteristics in hypertensive heart disease

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    Sherin Saheera

    2017-10-01

    Full Text Available Background Cardiac stem cells (CSCs play a vital role in cardiac homeostasis. A decrease in the efficiency of cardiac stem cells is speculated in various cardiac abnormalities. The maintenance of a healthy stem cell population is essential for the prevention of adverse cardiac remodeling leading to cardiac failure. Famotidine, a histamine-2 receptor antagonist, is currently used to treat ulcers of the stomach and intestines. In repurposing the use of the drug, reduction of cardiac hypertrophy and improvement in cardiac function of spontaneously hypertensive rats (SHR was reported by our group. Given that stem cells are affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on CSC characteristics was investigated. Methods To examine whether famotidine has a positive effect on CSCs, spontaneously hypertensive rats (SHR treated with the drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. Six-month-old male SHRs were treated with famotidine (30 mg/kg/day for two months. The effect of famotidine treatment on migration, proliferation and survival of CSCs was compared with untreated SHRs and normotensive Wistar rats. Results Functional efficiency of CSCs from SHR was compromised relative to that in Wistar rat. Famotidine increased the migration and proliferation potential, along with retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative stress were also reduced. The expression of H2R was unaffected by the treatment. Discussion As anticipated, CSCs from SHRs were functionally impaired. Stem cell attributes of famotidine-treated SHRs was comparable to that of Wistar rats. Therefore, in addition to being cardioprotective, the histamine 2 receptor antagonist modulated cardiac stem cells characteristics. Restoration of stem cell efficiency by famotidine is possibly mediated by reduction of oxidative stress as the expression of H2R was unaffected by the treatment. Maintenance of

  18. Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

    Science.gov (United States)

    Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

    2018-01-01

    Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

  19. Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Lea Weber

    2018-05-01

    Full Text Available Olfactory receptors (ORs are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

  20. Comparison of the tumor inhibiting effects of three histamine H2-receptor antagonists.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1983-01-01

    Three histamine H2-receptor antagonists, Cimetidine, Metiamide and Ranitidine, were tested for their inhibitory effect on two experimental bowel cancer models. In the first model mitotic rates were measured in dimethylhydrazine-induced tumors of rat colon and in the second model volumetric changes in human large bowel cancer xenografts were assessed. In tumors of rat colon all three drugs were able to suppress mitotic activity, but the effects of Metiamide and Ranitidine were more prolonged than that of Cimetidine in each of two lines of human bowel cancer that were used. Metiamide and Ranitidine were also more effective growth inhibitors than was Cimetidine.

  1. Intra-cerebellar microinjection of histamine enhances memory consolidation of inhibitory avoidance learning in mice via H2 receptors.

    Science.gov (United States)

    Gianlorenço, A C L; Canto-de-Souza, A; Mattioli, R

    2013-12-17

    Studies have demonstrated the relationship between the histaminergic system and the cerebellum, and we intend to investigate the role of the cerebellar histaminergic system on memory consolidation. This study investigated the effect of intra-cerebellar microinjection of histamine on memory retention of inhibitory avoidance in mice, and the role of H1 and H2 receptors in it. The cerebellar vermis of male mice were implanted with guide cannulae, and after three days of recovery, the inhibitory avoidance test was performed. Immediately after a training session, animals received a microinjection of histaminergic drugs: in the experiment 1, saline (SAL) or histamine (HA 0.54, 1.36, 2.72 or 4.07 nmol); experiment 2, SAL or 1.36 nmol HA 5 min after a pretreatment with 0.16 nmol chlorpheniramine (CPA) or SAL; and experiment 3, SAL or 1.36 nmol HA 5 min after a pretreatment with 2.85 nmol ranitidine (RA) or SAL. Twenty-four hours later, a retention test was performed. The data were analyzed using one-way analysis of variance (ANOVA) and Duncan's tests. In experiment 1, animals microinjected with 1.36 nmol HA showed a higher latency to cross to the dark compartment compared to controls and to 2.72 and 4.07 nmol HA groups. In experiment 2, the combined infusions revealed difference between control (SAL+SAL) and SAL+HA and CPA+HA; while in the experiment 3 the analysis indicated differences in retention latency between mice injected with SAL+SAL and SAL+HA. The groups that received the H2 antagonist RA did not show difference compared to control. These results indicate that 1.36 nmol HA enhances memory consolidation of inhibitory avoidance learning in mice and that the pretreatment with H2 antagonist RA was able to prevent this effect. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. On the role of serotonin and histamine in neurohumoral mechanisms of postirradiation diarrhea in rats

    International Nuclear Information System (INIS)

    Legeza, V.I.; Shagoyan, M.G.; Markovskaya, I.V.; Vasil'eva, T.P.; Pozharisskaya, T.D.; Alekseeva, I.I.; Lokteva, O.I.

    1990-01-01

    In experiments with rats exposed to 200 Gy radiation it was shown that the diarrhea effect of serotonin under the effect of radiation is implemented via D- and M-type receptors, and that of histamine via H 1 and H 2 receptors. Serotonin and histamine, that were released under the effect of radiation from endocrine and mast cells of the digestive tract stimulated the propulsion activity of the intestine whereas histamine, in addition, inhibited the absorption process. It is suggested that serotonin and histamine antagonists should be used as means of preventing of radiation-induced diarrhea

  3. Histamine H3 receptor ligands in the group of (homo)piperazine derivatives.

    Science.gov (United States)

    Szczepanska, Katarzyna; Kuder, Kamil; Kiec-Kononowicz, Katarzyna

    2017-11-23

    Since its' discovery in 1983, followed by gene cloning in 1999, the histamine H3 receptor served as an outstanding target for drug discovery. The wide spectrum of possible therapeutic implications make H3R's one of the most researched areas in the vast GPCR ligands field - started from imidazole containing ligands, through various successful imidazole replacements, with recent introduction of Wakix® to pharmaceutical market. One of such replacements is piperazine moiety, a significant versatile scaffold in rational drug design for most of the GPCR ligands. Therefore, herein we review ligands built on piperazine, as well as its seven membered analogue azepine, that target H3R's and their potential therapeutical applications, in order to elucidate the current state of the art in this vast field. Due to a high level of structural divergence among compounds described herein, we decided to divide them into groups, where the key division element was the position of nitrogen basicity decreasing moieties in (homo)piperazine ring. Paying attention to a number of published structures and their overall high biological activity, one can realize that the (homo)piperazine scaffold bids a versatile template also for histamine H3 receptor ligands. With two possible substitution sites and therefore a number of possible structural combinations, piperazine derivatives stand as one of the largest group of high importance among H3R ligands. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri.

    Science.gov (United States)

    Gao, Chunxu; Major, Angela; Rendon, David; Lugo, Monica; Jackson, Vanessa; Shi, Zhongcheng; Mori-Akiyama, Yuko; Versalovic, James

    2015-12-15

    Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc(+) L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon. Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc(+) L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic

  5. Potentiation of the gastric antisecretory activity of histamine H2-receptor antagonists by clebopride.

    Science.gov (United States)

    Fernández, A G; Massingham, R; Roberts, D J

    1988-05-01

    The substituted benzamide, clebopride, at doses (0.03-3 mg kg-1 i.p.) that were without effect per se on the secretion of gastric acid in pylorus ligated (Shay) rats, potentiated the antisecretory effects of the histamine H2 receptor antagonists cimetidine and ranitidine in this model but not those of the muscarine receptor antagonist pirenzepine nor those of the proton pump inhibitor omeprazole. By contrast, clebopride was without influence on the inhibitory effects of cimetidine on pentagastrin-induced secretion in perfused stomach (Ghosh and Schild) preparations in anaesthetized rats. The significance of these findings is discussed in relation to the previously described potentiating effects of clebopride on the anti-ulcer activity of cimetidine in various experimental models, and the potential beneficial effects of such combined therapy in the clinic.

  6. Histamine and Antihistamines / Histamin i antihistamini

    Directory of Open Access Journals (Sweden)

    Stojković Nikola

    2015-03-01

    Full Text Available Poslednjih godina beleži se kontinuirani rast prevalencije alergijskih oboljenja. Alergijski imunski odgovor predstavlja jednu kompleksnu mrežu ćelijskih događaja u kojoj učestvuju mnogobrojne imunske ćelije i medijatori. On predstavlja interakciju urođenog i stečenog imunskog odgovora. Ključnu ulogu u imunološkoj kaskadi zauzima histamin, prirodni sastojak tela, koga u alergijskom inflamatornom odgovoru oslobađaju mastociti i bazofili. Cilj ovog rada bio je naglasiti ulogu histamina u alergijskim imunološkim događajima, njegov efekat na Th1 i Th2 subpopulaciju limfocita i produkciju odgovarajućih citokina, kao i ulogu blokatora histamina u tretmanu ovih stanja. Histamin ostvaruje svoj efekat vezivanjem za četiri tipa svojih receptora koji su široko distribuirani u organizmu. Blokatori histamina blokiraju mnogobrojne efekte histamina vezivanjem za ove receptore. Cetirizin, visoko selektivni antihistaminik druge generacije, ne ostvaruje svoje efekte samo vezivanjem za H1 receptore već dovodi do atenuisanja mnogobrojnih zbivanja tokom inflamacijskog procesa. Dobro poznavanje efekata histaminskih blokatora, među njima i cetirizina, može dovesti do pravog odabira terapije u tretmanu alergijskih oboljenja.

  7. Effects of a histamine H4 receptor antagonist on cisplatin-induced anorexia in mice.

    Science.gov (United States)

    Yamamoto, Kouichi; Okui, Rikuya; Yamatodani, Atsushi

    2018-04-12

    Cancer chemotherapy often induces gastrointestinal symptoms such as anorexia, nausea, and vomiting. Antiemetic agents are effective in inhibiting nausea and vomiting, but patients still experience anorexia. We previously reported that chemotherapeutic agent-induced anorexia is associated with an increase of inflammatory cytokines. Other studies also reported that antagonism of the histamine H 4 receptor is anti-inflammatory. In this study, we investigated the involvement of the H 4 receptor in the development of chemotherapy-induced anorexia in mice. Cisplatin-induced anorexia occurred within 24 h of its administration and continued for 3 days. The early phase (day 1), but not the delayed phase (days 2 and 3), of anorexia was inhibited by the daily injection of a 5-HT 3 receptor antagonist (granisetron). However, a corticosteroid (dexamethasone) or selective H 4 receptor antagonist (JNJ7777120) abolished the delayed phases of anorexia. Cisplatin significantly increased TNF-α mRNA expression in the hypothalamus and spleen, and the period of expression increase paralleled the onset period of anorexia. In addition, pretreatment with JNJ7777120 completely inhibited the increased expression. These results suggest that TNF-α mRNA expression via H 4 receptors may contribute to the development of cisplatin-induced anorexia, and that H 4 receptor antagonists are potentially useful treatments. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Effects of Bidens pilosa L. var. radiata SCHERFF treated with enzyme on histamine-induced contraction of guinea pig ileum and on histamine release from mast cells.

    Science.gov (United States)

    Matsumoto, Takayuki; Horiuchi, Masako; Kamata, Katsuo; Seyama, Yoshiyuki

    2009-06-01

    The medical mechanism against type I allergies is to block the release or production of chemical mediators from mast cells or to block the H(1)-receptor signaling. We previously reported that the anti-allergic action of the dry powder from Bidens pilosa L. var. radiata SCHERFF treated with the enzyme cellulosine (eMMBP) was dependent on the inhibition of histamine release from mast cells. Here, we investigate that the effect of fractions in eMMBP on the histamine-induced contraction in guinea pig ileum and on the release of histamine in rat peritoneal mast cells. The histamine-induced contraction in guinea pig ileum is dose-dependently inhibited by ketotifen, an antagonist of H(1)-receptor. Fractions contained caffeic acid, caffeoylquinic acid and fractions contained flavonoids such as hyperin and isoquercitrin in eMMBP inhibit histamine release from mast cells, but only flavonoids such as hyperin, isoquercitrin and rutin suppress the histamine-induced contraction in guinea pig ileum. Moreover, the histamine-induced contraction was not affected by caffeic acid, however, such contraction was significantly inhibited by rutin. These results suggest that the primary antagonists of H(1)- receptor are different from the components in eMMBP that inhibit histamine release, and that these components participate in the anti-allergic activity of eMMBP.

  9. Structural Characterization of the Hemagglutinin Receptor Specificity from the 2009 H1N1 Influenza Pandemic

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Rui; McBride, Ryan; Nycholat, Corwin M.; Paulson, James C.; Wilson, Ian A. (Scripps)

    2012-02-13

    Influenza virus hemagglutinin (HA) is the viral envelope protein that mediates viral attachment to host cells and elicits membrane fusion. The HA receptor-binding specificity is a key determinant for the host range and transmissibility of influenza viruses. In human pandemics of the 20th century, the HA normally has acquired specificity for human-like receptors before widespread infection. Crystal structures of the H1 HA from the 2009 human pandemic (A/California/04/2009 [CA04]) in complex with human and avian receptor analogs reveal conserved recognition of the terminal sialic acid of the glycan ligands. However, favorable interactions beyond the sialic acid are found only for {alpha}2-6-linked glycans and are mediated by Asp190 and Asp225, which hydrogen bond with Gal-2 and GlcNAc-3. For {alpha}2-3-linked glycan receptors, no specific interactions beyond the terminal sialic acid are observed. Our structural and glycan microarray analyses, in the context of other high-resolution HA structures with {alpha}2-6- and {alpha}2-3-linked glycans, now elucidate the structural basis of receptor-binding specificity for H1 HAs in human and avian viruses and provide a structural explanation for the preference for {alpha}2-6 siaylated glycan receptors for the 2009 pandemic swine flu virus.

  10. Histamine, mast cells, and the enteric nervous system in the irritable bowel syndrome, enteritis, and food allergies

    OpenAIRE

    Wood, J D

    2006-01-01

    There is altered expression of histamine H1 and H2 receptor subtypes in mucosal biopsies from the terminal ileum and large intestine of patients with symptoms of food allergy and/or irritable bowel syndrome

  11. Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

    Science.gov (United States)

    Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

    2018-04-15

    Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

  12. Efeito analgésico de antagonistas do receptor da histamina H1 em modelo de dor provocada por formalina em ratos Efecto analgésico de antagonistas del receptor de la histamina H1 en un modelo de dolor provocado por formalina en ratones Analgesic effects of H1 receptor antagonists in the rat model of formalin-induced pain

    Directory of Open Access Journals (Sweden)

    Hazem Adel Ashmawi

    2009-08-01

    sistema nervioso periférico. No queda claro si el efecto analgésico local es de clase específico o un fármaco específico. MÉTODO: Para responder a esa pregunta, utilizamos tres diferentes antagonistas del receptor H1 (pirilamina, prometazina y cetirizina, administrados directamente en la pata del ratón, por vía intraperitoneal o por bloqueo de nervio periférico en modelo de dolor inducido por formalina. Observamos el efecto de los fármacos en el comportamiento del número de elevaciones de la pata. RESULTADOS: En la fase I, la pirilamina local redujo el número de elevaciones de la pata de forma dosis dependiente. En la dosis más alta, la reducción fue de un 97,8%. Para la prometazina, la disminución fue de un 92% y para la cetizirina de 23.9%. En la fase II, la pirilamina redujo el número de elevaciones de la pata en un 93,5%, la prometazina, un 78,2% y la cetirizina un 80,1%. La administración de los fármacos por vía intraperitoneal no alteró el comportamiento doloroso. Cuando se usaron para bloqueo del nervio periférico en la fase I, la pirilamina redujo el número de elevaciones de la pata en un 96,7%, la prometazina en un 73,3% y la cetirizina en un 23,9%. En la fase II, la pirilamina redujo un 86,6%, la prometazina un 64,4% y la cetirizina un 19,9%. CONCLUSIONES: Los resultados mostraron que los antagonistas del receptor de la histamina H1 presentaron efectos analgésicos locales, diferentes del efecto sistémico, siendo uno de ellos antiinflamatorio y clase específico, y el otro específico para la prometazina y la pirilamina, parecido con el efecto clínico anestésico local.BACKGROUND AND OBJECTIVES: Histamine receptors mediate nociceptive pathways, especially in the central nervous system. Some studies have demonstrated the analgesic effects of histamine receptor antagonists in the peripheral nervous system. It is not clear whether the local analgesic effect is class-specific or drug-specific. METHODS: To answer this question, we used three

  13. Novel chalcone-based fluorescent human histamine H3 receptor ligands as pharmacological tools

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    Holger eStark

    2012-03-01

    Full Text Available Novel fluorescent chalcone-based ligands at human histamine H3 receptors (hH3R have been designed, synthesized and characterized. Compounds described are non-imidazole analogues of ciproxifan with a tetralone motif. Tetralones as chemical precursors and related fluorescent chalcones exhibit affinities at hH3R in the same concentration range like that of the reference antagonist ciproxifan (hH3R pKi value of 7.2. Fluorescence characterization of our novel ligands shows emission maxima about 570 nm for yellow fluorescent chalcones and ≥600 nm for the red fluorescent derivatives. Interferences to cellular autofluorescence could be excluded. All synthesized chalcone compounds could be taken to visualize hH3R proteins in stably transfected HEK-293 cells using confocal laser scanning fluorescence microscopy. These novel fluorescent ligands possess high potential to be used as pharmacological tools for hH3R visualization in different tissues.

  14. Histamine H3 receptor: A novel therapeutic target in alcohol dependence?

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    Pertti ePanula

    2012-05-01

    Full Text Available The brain histaminergic system is one of the diffuse modulatory neurotransmitter systems which regulate neuronal activity in many brain areas. Studies on both rats and mice indicate that histamine H3 receptor antagonists decrease alcohol drinking in several models, like operant alcohol administration and drinking in the dark paradigm. Alcohol-induced place preference is also affected by these drugs. Moreover, mice lacking H3R do not drink alcohol like their wild type littermates, and they do not show alcohol-induced place preference. Although the mechanisms of these behaviors are still being investigated, we propose that H3R antagonists are promising candidates for use in human alcoholics, as these drugs are already tested for treatment of other disorders like narcolepsy and sleep disorders.

  15. Waking action of ursodeoxycholic acid (UDCA involves histamine and GABAA receptor block.

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    Yevgenij Yanovsky

    Full Text Available Since ancient times ursodeoxycholic acid (UDCA, a constituent of bile, is used against gallstone formation and cholestasis. A neuroprotective action of UDCA was demonstrated recently in models of Alzheimer's disease and retinal degeneration. The mechanisms of UDCA action in the nervous system are poorly understood. We show now that UDCA promotes wakefulness during the active period of the day, lacking this activity in histamine-deficient mice. In cultured hypothalamic neurons UDCA did not affect firing rate but synchronized the firing, an effect abolished by the GABA(AR antagonist gabazine. In histaminergic neurons recorded in slices UDCA reduced amplitude and duration of spontaneous and evoked IPSCs. In acutely isolated histaminergic neurons UDCA inhibited GABA-evoked currents and sIPSCs starting at 10 µM (IC(50 = 70 µM and did not affect NMDA- and AMPA-receptor mediated currents at 100 µM. Recombinant GABA(A receptors composed of α1, β1-3 and γ2L subunits expressed in HEK293 cells displayed a sensitivity to UDCA similar to that of native GABA(A receptors. The mutation α1V256S, known to reduce the inhibitory action of pregnenolone sulphate, reduced the potency of UDCA. The mutation α1Q241L, which abolishes GABA(AR potentiation by several neurosteroids, had no effect on GABA(AR inhibition by UDCA. In conclusion, UDCA enhances alertness through disinhibition, at least partially of the histaminergic system via GABA(A receptors.

  16. Effect of acute aerobic exercise and histamine receptor blockade on arterial stiffness in African Americans and Caucasians.

    Science.gov (United States)

    Yan, Huimin; Ranadive, Sushant M; Lane-Cordova, Abbi D; Kappus, Rebecca M; Behun, Michael A; Cook, Marc D; Woods, Jeffrey A; Wilund, Kenneth R; Baynard, Tracy; Halliwill, John R; Fernhall, Bo

    2017-02-01

    African Americans (AA) exhibit exaggerated central blood pressure (BP) and arterial stiffness measured by pulse wave velocity (PWV) in response to an acute bout of maximal exercise compared with Caucasians (CA). However, whether potential racial differences exist in central BP, elastic, or muscular arterial distensibility after submaximal aerobic exercise remains unknown. Histamine receptor activation mediates sustained postexercise hyperemia in CA but the effect on arterial stiffness is unknown. This study sought to determine the effects of an acute bout of aerobic exercise on central BP and arterial stiffness and the role of histamine receptors, in AA and CA. Forty-nine (22 AA, 27 CA) young and healthy subjects completed the study. Subjects were randomly assigned to take either histamine receptor antagonist or control placebo. Central blood BP and arterial stiffness measurements were obtained at baseline, and at 30, 60, and 90 min after 45 min of moderate treadmill exercise. AA exhibited greater central diastolic BP, elevated brachial PWV, and local carotid arterial stiffness after an acute bout of submaximal exercise compared with CA, which may contribute to their higher risk of cardiovascular disease. Unexpectedly, histamine receptor blockade did not affect central BP or PWV in AA or CA after exercise, but it may play a role in mediating local carotid arterial stiffness. Furthermore, histamine may mediate postexercise carotid arterial dilation in CA but not in AA. These observations provide evidence that young and healthy AA exhibit an exaggerated hemodynamic response to exercise and attenuated vasodilator response compared with CA. NEW & NOTEWORTHY African Americans are at greater risk for developing cardiovascular disease than Caucasians. We are the first to show that young and healthy African Americans exhibit greater central blood pressure, elevated brachial stiffness, and local carotid arterial stiffness following an acute bout of submaximal exercise

  17. In vivo pharmacological profile of S 38093, a novel histamine H3 receptor inverse agonist.

    Science.gov (United States)

    Panayi, Fany; Sors, Aurore; Bert, Lionel; Martin, Brigitte; Rollin-Jego, Gaelle; Billiras, Rodolphe; Carrié, Isabelle; Albinet, Karine; Danober, Laurence; Rogez, Nathalie; Thomas, Jean-Yves; Pira, Luigi; Bertaina-Anglade, Valérie; Lestage, Pierre

    2017-05-15

    S 38093, a novel histamine H3 receptor inverse agonist, was tested in a series of neurochemical and behavioral paradigms designed to evaluate its procognitive and arousal properties. In intracerebral microdialysis studies performed in rats, S 38093 dose-dependently increased histamine extracellular levels in the prefrontal cortex and facilitated cholinergic transmission in the prefrontal cortex and hippocampus of rats after acute and chronic administration (10mg/kg i.p.). Acute oral administration of S 38093 at 0.1mg/kg significantly improved spatial working memory in rats in the Morris water maze test. The compound also displayed cognition enhancing properties in the two-trial object recognition task in rats, in a natural forgetting paradigm at 0.3 and 1mg/kg p.o. and in a scopolamine-induced memory deficit situation at 3mg/kg p.o. The property of S 38093 to promote episodic memory was confirmed in a social recognition test in rats at 0.3 and 1mg/kg i.p. Arousal properties of S 38093 were assessed in freely moving rats by using electroencephalographic recordings: at 3 and 10mg/kg i.p., S 38093 significantly reduced slow wave sleep delta power and induced at the highest dose a delay in sleep latency. S 38093 at 10mg/kg p.o. also decreased the barbital-induced sleeping time in rats. Taken together these data indicate that S 38093, a novel H3 inverse agonist, displays cognition enhancing at low doses and arousal properties at higher doses in rodents. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The histamine H₃ receptor as a therapeutic drug target for metabolic disorders: status, challenges and opportunities.

    Science.gov (United States)

    Plancher, Jean-Marc

    2011-01-01

    Since the histamine-3 receptor (H₃R) was cloned in 1999, huge efforts have been made by most of the key players in the pharmaceutical industry as well as in smaller biotech companies to increase the knowledge on this peculiar receptor, with the ultimate goal of bringing new drugs to the market. This review gives a survey on the most valuable chemical tools discovered so far and the significant pharmacological experiments on metabolic disease models published to date. Pharmacology of H₃R antagonists turns out to be very complex due to various functional activities, species selectivity, presence of H₃R isoforms and the poorly understood dichotomy in efficacy between CNS and metabolic disease models. Adding an extra layer of complexity, researchers have to cope with some recurrent safety concerns, some of them being tightly linked to the nature of the H₃R pharmacophore. Therefore this review also strives to summarize the major hurdles and some of the contradictions seen in the H₃R field, together with a brief overview of the clinical trials currently running.

  19. Glycosylation at Asn91 of H1N1 haemagglutinin affects binding to glycan receptors.

    Science.gov (United States)

    Jayaraman, Akila; Koh, Xiaoying; Li, Jing; Raman, Rahul; Viswanathan, Karthik; Shriver, Zachary; Sasisekharan, Ram

    2012-06-15

    The glycoprotein HA (haemagglutinin) on the surface of influenza A virus plays a central role in recognition and binding to specific host cell-surface glycan receptors and in fusion of viral membrane to the host nuclear membrane during viral replication. Given the abundance of HA on the viral surface, this protein is also the primary target for host innate and adaptive immune responses. Although addition of glycosylation sites on HA are a part of viral evolution to evade the host immune responses, there are specific glycosylation sites that are conserved during most of the evolution of the virus. In the present study, it was demonstrated that one such conserved glycosylation site at Asn(91) in H1N1 HA critically governs the glycan receptor-binding specificity and hence would potentially impinge on the host adaptation of the virus.

  20. QSAR study on the histamine (H3 receptor antagonists using the genetic algorithm: Multi parameter linear regression

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    Adimi Maryam

    2012-01-01

    Full Text Available A quantitative structure activity relationship (QSAR model has been produced for predicting antagonist potency of biphenyl derivatives as human histamine (H3 receptors. The molecular structures of the compounds are numerically represented by various kinds of molecular descriptors. The whole data set was divided into training and test sets. Genetic algorithm based multiple linear regression is used to select most statistically effective descriptors. The final QSAR model (N =24, R2=0.916, F = 51.771, Q2 LOO = 0.872, Q2 LGO = 0.847, Q2 BOOT = 0.857 was fully validated employing leaveone- out (LOO cross-validation approach, Fischer statistics (F, Yrandomisation test, and predictions based on the test data set. The test set presented an external prediction power of R2 test=0.855. In conclusion, the QSAR model generated can be used as a valuable tool for designing similar groups of new antagonists of histamine (H3 receptors.

  1. Cocaine Disrupts Histamine H3 Receptor Modulation of Dopamine D1 Receptor Signaling: σ1-D1-H3 Receptor Complexes as Key Targets for Reducing Cocaine's Effects

    Science.gov (United States)

    Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric

    2014-01-01

    The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455

  2. Histamine and tryptase in nasal lavage fluid after allergen challenge

    DEFF Research Database (Denmark)

    Jacobi, H H; Skov, P S; Poulsen, L K

    1999-01-01

    BACKGROUND: Antihistamines (H1-receptor antagonists) act by competitive antagonism of histamine at H1-receptors. In addition, high concentrations of some antihistamines inhibit allergen-induced histamine release from mast cells in vitro. OBJECTIVE: The purpose of this study was to determine...... the effect of intranasal azelastine or systemic cetirizine (both potent antihistamines) on the allergen-induced release of mast-cell mediators from the human nasal mucosa in vivo. METHODS: Patients allergic to birch pollen (n = 11) and control subjects not allergic to birch pollen (n = 5) were included......, nasal allergen challenges were performed, and the number of sneezes were counted. In addition, nasal lavage fluid was collected, and the levels of mast-cell mediators (histamine and tryptase) were measured. RESULTS: The allergen challenge of patients allergic to pollen produced sneezing...

  3. Progress in the development of histamine H3 receptor antagonists/inverse agonists: a patent review (2013-2017).

    Science.gov (United States)

    Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

    2018-03-01

    Since years, ligands blocking histamine H 3 receptor (H 3 R) activity (antagonists/inverse agonists) are interesting targets in the search for new cures for CNS disorders. Intensive works done by academic and pharmaceutical company researchers have led to many potent and selective H 3 R antagonists/inverse agonists. Some of them have reached to clinical trials. Areas covered: Patent applications from January 2013 to September 2017 and the most important topics connected with H 3 R field are analysed. Espacenet, Patentscope, Pubmed, GoogleScholar or Cochrane Library online databases were principially used to collect all the materials. Expert opinion: The research interest in histamine H 3 R field is still high although the number of patent applications has decreased during the past 4 years (around 20 publications). Complexity of histamine H 3 R biology e.g. many isoforms, constitutive activity, heteromerization with other receptors (dopamine D 2 , D 1 , adenosine A 2A ) and pharmacology make not easy realization and evaluation of therapeutic potential of anti-H 3 R ligands. First results from clinical trials have verified potential utility of histamine H 3 R antagonist/inverse agonists in some diseases. However, more studies are necessary for better understanding of an involvement of the histaminergic system in CNS-related disorders and helping more ligands approach to clinical trials and the market. Lists of abbreviations: hAChEI - human acetylcholinesterase inhibitor; hBuChEI - human butyrylcholinesterase inhibitor; hMAO - human monoamine oxidase; MAO - monoamine oxidase.

  4. Activation of adenosine low-affinity A3 receptors inhibits the enteric short interplexus neural circuit triggered by histamine.

    Science.gov (United States)

    Bozarov, Andrey; Wang, Yu-Zhong; Yu, Jun Ge; Wunderlich, Jacqueline; Hassanain, Hamdy H; Alhaj, Mazin; Cooke, Helen J; Grants, Iveta; Ren, Tianhua; Christofi, Fievos L

    2009-12-01

    eADO acts at low-affinity A3 receptors in addition to high-affinity A1 receptors to suppress coordinated responses triggered by immune-histamine H2 receptor activation. The short interplexus circuit activated by histamine involves adenosine, acetylcholine, substance P, and serotonin. We postulate that A3 receptor modulation may occur in gut inflammatory diseases or allergic responses involving mast cell and histamine release.

  5. [11C]TASP457, a novel PET ligand for histamine H3 receptors in human brain

    International Nuclear Information System (INIS)

    Kimura, Yasuyuki; Seki, Chie; Ikoma, Yoko; Ichise, Masanori; Kawamura, Kazunori; Takahata, Keisuke; Moriguchi, Sho; Nagashima, Tomohisa; Ishii, Tatsuya; Kitamura, Soichiro; Niwa, Fumitoshi; Endo, Hironobu; Yamada, Makiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya

    2016-01-01

    The histamine H 3 receptors are presynaptic neuroreceptors that inhibit the release of histamine and other neurotransmitters. The receptors are considered a drug target for sleep disorders and neuropsychiatric disorders with cognitive decline. We developed a novel PET ligand for the H 3 receptors, [ 11 C]TASP0410457 ([ 11 C]TASP457), with high affinity, selectivity and favorable kinetic properties in the monkey, and evaluated its kinetics and radiation safety profile for quantifying the H 3 receptors in human brain. Ten healthy men were scanned for 120 min with a PET scanner for brain quantification and three healthy men were scanned for radiation dosimetry after injection of 386 ± 6.2 MBq and 190 ± 7.5 MBq of [ 11 C]TASP457, respectively. For brain quantification, arterial blood sampling and metabolite analysis were performed using high-performance liquid chromatography. Distribution volumes (V T ) in brain regions were determined by compartment and graphical analyses using the Logan plot and Ichise multilinear analysis (MA1). For dosimetry, radiation absorbed doses were estimated using the Medical Internal Radiation Dose scheme. [ 11 C]TASP457 PET showed high uptake (standardized uptake values in the range of about 3 - 6) in the brain and fast washout in cortical regions and slow washout in the pallidum. The two-tissue compartment model and graphical analyses estimated V T with excellent identification using 60-min scan data (about 16 mL/cm 3 in the pallidum, 9 - 14 in the basal ganglia, 6 - 9 in cortical regions, and 5 in the pons), which represents the known distribution of histamine H 3 receptors. For parametric imaging, MA1 is recommended because of minimal underestimation with small intersubject variability. The organs with the highest radiation doses were the pancreas, kidneys, and liver. The effective dose delivered by [ 11 C]TASP457 was 6.9 μSv/MBq. [ 11 C]TASP457 is a useful novel PET ligand for the investigation of the density of histamine H 3

  6. Shifting physician prescribing to a preferred histamine-2-receptor antagonist. Effects of a multifactorial intervention in a mixed-model health maintenance organization.

    Science.gov (United States)

    Brufsky, J W; Ross-Degnan, D; Calabrese, D; Gao, X; Soumerai, S B

    1998-03-01

    This study was undertaken to determine whether a program of education, therapeutic reevaluation of eligible patients, and performance feedback could shift prescribing to cimetidine from other histamine-2 receptor antagonists, which commonly are used in the management of ulcers and reflux, and reduce costs without increasing rates of ulcer-related hospital admissions. This study used an interrupted monthly time series with comparison series in a large mixed-model health maintenance organization. Physicians employed in health centers (staff model) and physicians in independent medical groups contracting to provide health maintenance organization services (group model) participated. The comparative percentage prescribed of specific histamine-2 receptor antagonists (market share), total histamine-2 receptor antagonist prescribing, cost per histamine-2 receptor antagonist prescription, and the rate of hospitalization for gastrointestinal illness were assessed. In the staff model, therapeutic reevaluation resulted in a sudden increase in market share of the preferred histamine-2 receptor antagonist cimetidine (+53.8%) and a sudden decrease in ranitidine (-44.7%) and famotidine (-4.8%); subsequently, cimetidine market share grew by 1.1% per month. In the group model, therapeutic reevaluation resulted in increased cimetidine market share (+9.7%) and decreased prescribing of other histamine-2 receptor antagonists (ranitidine -11.6%; famotidine -1.2%). Performance feedback did not result in further changes in prescribing in either setting. Use of omeprazole, an expensive alternative, essentially was unchanged by the interventions, as were overall histamine-2 receptor antagonist prescribing and hospital admissions for gastrointestinal illnesses. This intervention, which cost approximately $60,000 to implement, resulted in estimated annual savings in histamine-2 receptor antagonist expenditures of $1.06 million. Annual savings in histamine-2 receptor antagonist expenditures

  7. Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

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    Ionov

    2015-05-01

    Full Text Available Background The decreased level of somatostatin and increased level of histamine are detected in the Parkinsonian brain. In old Wistar rats, the brain somatostatin deficiency can initiate catalepsy that suggests the pathogenic significance of this abnormality in Parkinson’s disease (PD. The ability of histamine to affect the somatostatin deficiency action is not studied. Objectives The current study aimed to examine if histamine alters the cataleptogenic activity of the brain somatostatin deficiency in Wistar rats. Materials and Methods The animals used in the study were 100 - 110 and 736 - 767 days old. Catalepsy was evaluated by the bar test. The inhibition of the brain somatostatin activity was simulated by I.C.V. administration of cyclosomatostatin (cycloSOM, a somatostatin receptor antagonist. Results CycloSOM (0.2, 1.0, and 5.0 µg and histamine (1.0 and 10.0 µg alone were ineffective in both young and old animals. In combination, however, cycloSOM and histamine initiated cataleptic response in old rats. Effect of the combination was inhibited by H1 and H2 but not H3 antagonists. Conclusions CycloSOM and histamine synergistically exert catalepsy in old rats. In light of these data, the combination of the decreased brain level of somatostatin and increased brain level of histamine may be of pathogenic relevance for extrapyramidal signs in PD.

  8. Prenatal Alcohol Exposure Increases Histamine H3 Receptor-Mediated Inhibition of Glutamatergic Neurotransmission in Rat Dentate Gyrus.

    Science.gov (United States)

    Varaschin, Rafael K; Allen, Nyika A; Rosenberg, Martina J; Valenzuela, C Fernando; Savage, Daniel D

    2018-02-01

    We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H 3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H 3 receptor number and function. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution 4 hours each day throughout gestation. This pattern of drinking, which produces a mean peak maternal serum ethanol concentration of 60.8 ± 5.8 mg/dl, did not affect maternal weight gain, litter size, or offspring birthweight. Radiohistochemical studies in adult offspring revealed that specific [ 3 H]-A349821 binding to histamine H 3 receptors was not different in PAE rats compared to controls. However, H 3 receptor-mediated G i /G o protein-effector coupling, as measured by methimepip-stimulated [ 35 S]-GTPγS binding, was significantly increased in cerebral cortex, cerebellum, and dentate gyrus of PAE rats compared to control. A LIGAND analysis of detailed methimepip concentration-response curves in dentate gyrus indicated that PAE significantly elevates receptor-effector coupling by a lower affinity H 3 receptor population without significantly altering the affinities of H 3 receptor subpopulations. In agreement with the [ 35 S]-GTPγS studies, a similar range of methimepip concentrations also inhibited electrically evoked field excitatory postsynaptic potential responses and increased paired-pulse ratio, a measure of decreased glutamate release, to a significantly greater extent in dentate gyrus slices from PAE rats than in controls. These results suggest that a PAE-induced elevation in H 3 receptor-mediated inhibition of glutamate release from

  9. Histamine H3 receptors and its antagonism as a novel mechanism for antipsychotic effect: a current preclinical & clinical perspective.

    Science.gov (United States)

    Mahmood, Danish

    2016-10-01

    Histamine H 3 receptors are present as autoreceptors on histaminergic neurons and as heteroreceptors on nonhistaminergic neurones. They control the release and synthesis of histamine and several other key neurotransmitters in the brain. H 3 antagonism may be a novel approach to develop a new class of antipsychotic medications given the gathering evidence reporting therapeutic efficacy in several central nervous system disorders. Several medications such as cariprazine, lurasidone, LY214002, bexarotene, rasagiline, raloxifene, BL-1020 and ITI-070 are being developed to treat the negative symptoms and cognitive impairments of schizophrenia. These medications works through diverse mechanisms which include agonism at metabotropic glutamate receptor (mGluR2/3), partial agonism at dopamine D 2 , D 3 and serotonin 5-HT 1A receptors, antagonism at D 2 , 5-HT 2A, 5-HT 2B and 5-HT 7 receptors, combined dopamine antagonism with GABA agonist activity, inhibition of monoamine oxidase-B, modulation of oestrogen receptor, and activation of nuclear retinoid X receptor. However, still specific safe therapy for psychosis remains at large. Schizophrenia is a severe neuropsychiatric disorder result both from hyper- and hypo-dopaminergic transmission causing positive and negative symptoms, respectively. Pharmacological stimulation of dopamine release in the prefrontal cortex has been a viable approach in treating negative symptoms and cognitive deficits of schizophrenia symptoms that are currently not well treated and continue to represent significant unmet medical challenges. Administration of H 3 antagonists/inverse agonists increase extracellular dopamine concentrations in rat prefrontal cortex, but not in the striatum suggesting that antagonism via H 3 receptor may be a potential target for treating negative symptoms and cognitive deficits associated with schizophrenia. Further, insights are emerging into the potential role of histamine H 3 receptors as a target of antiobesity

  10. Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans.

    Science.gov (United States)

    Ito, Takehito; Kimura, Yasuyuki; Seki, Chie; Ichise, Masanori; Yokokawa, Keita; Kawamura, Kazunori; Takahashi, Hidehiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya; Yamada, Makiko

    2018-06-14

    The histamine H 3 receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H 3 receptors are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H 3 receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H 3 receptors in the prefrontal cortex. Ten healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H 3 receptor density was measured with the selective PET radioligand [ 11 C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H 3 receptors in this region. Higher neural activity of working memory was associated with lower H 3 receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H 3 receptors in working memory and indicates the potential of H 3 receptors as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders.

  11. Activation of Microglia by Histamine and Substance P

    Directory of Open Access Journals (Sweden)

    Jin Zhu

    2014-08-01

    Full Text Available Background: Activated microglia perform many of the immune effector functions typically associated with macrophages. However, the regulators involved in microglial activation are not well defined. Because microglia play a pivotal role in immune surveillance of the CNS, we studied the effect of the neuromediators histamine and substance P on microglia. Methods: The induction of microglial activation by histamine and substance P was examined using primary cultured microglia. Fluorescent images were acquired with a confocal microscope. The levels of TNF-α and IL-6 were measured with a commercial ELISA kit. Intracellular reactive oxygen species (ROS levels were determined by dichlorodihydrofluorescein oxidation. The mitochondrial membrane potential was assessed with the MitoProbe™ JC-1 assay kit. Results: We found that the neuromediators histamine and substance P were able to stimulate microglial activation and the subsequent production of ROS and proinflammatory factors TNF-α and IL-6. These effects were partially abolished by antagonists of the histamine receptors H1 and H4 and of the substance P receptors NK-1, NK-2 and NK-3. Histamine induced mitochondrial membrane depolarization in microglia. Conclusions: These results indicate that the neuromediators histamine and SP can trigger microglial activation and release of pro-inflammatory factors from microglia, thus contributing to the development of microglia-mediated inflammation in the brain.

  12. The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Bahi, Amine; Sadek, Bassem; Nurulain, Syed M; Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

    2015-11-01

    It has become clear that histamine H3 receptors (H3R) have been implicated in modulating ethanol intake and preference in laboratory animals. The novel non-imidazole H3R antagonist DL77 with excellent selectivity profile shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 of 2.1 ± 0.2 mg/kg and pKi=8.08, respectively. In the present study, and applying an unlimited access two-bottle choice procedure, the anti-alcohol effects of the H3R antagonist, DL77 (0, 3, 10 and 30 mg/kg; i.p.), were investigated in adult mice. In this C57BL/6 line, effects of DL77 on voluntary alcohol intake and preference, as well as on total fluid intake were evaluated. Results have shown that DL77, dose-dependently, reduced both ethanol intake and preference. These effects were very selective as both saccharin and quinine, used to control for taste sensitivity, and intakes were not affected following DL77 pre-application. More importantly, systemic administration of DL77 (10 mg/kg) during acquisition inhibited ethanol-induced conditioned-place preference (EtOH-CPP) as measured using an unbiased protocol. The anti-alcohol activity observed for DL77 was abrogated when mice were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist pyrilamine (PYR) (10mg/kg). These results suggest that DL77 has a predominant role in two in vivo effects of ethanol. Therefore, signaling via H3R is essential for ethanol-related consumption and conditioned reward and may represent a novel therapeutic pharmacological target to tackle ethanol abuse and alcoholism. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Biosensor cell assay for measuring real-time aldosterone-induced release of histamine from mesenteric arteries

    DEFF Research Database (Denmark)

    Dalgaard, Emil G; Andersen, Kenneth; Svenningsen, Per

    2017-01-01

    as a sensitive biosensor assay for histamine release from isolated mouse mesenteric arteries. Activation of the H1 receptor by histamine was measured as an increased number of intracellular Ca(2+) transient peaks using fluorescence imaging RESULTS: The developed biosensor was sensitive to histamine...... in physiological relevant concentrations and responded to substances released by the artery preparation. Aldosterone treatment of mesenteric arteries from wild type mice for 50 minutes resulted in an increased number of intracellular Ca(2+) transient peaks in the biosensor cells, which was significantly inhibited...... by the histamine H1 blocker pyrilamine. Mesenteric arteries from mast cell deficient SASH mice induced similar pyrilamine-sensitive Ca(2+) transient response in the biosensor cells. Mesenteric arteries from wild type and SASH mice expressed histamine decarboxylase mRNA, indicating that mast cells are not the only...

  14. The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats

    Directory of Open Access Journals (Sweden)

    Nermin Eissa

    2018-02-01

    Full Text Available The role of Histamine H3 receptors (H3Rs in memory, and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD is well-accepted. For that reason, the procognitive effects of the H3R antagonist DL77 on cognitive impairments induced with MK801 were tested in an inhibitory passive avoidance paradigm (PAP and novel object recognition (NOR task in adult male rats, using donepezil (DOZ as a standard drug. Acute systemic pretreatment with DL77 (2.5, 5, and 10 mg/kg, i.p. significantly ameliorated memory deficits induced with MK801 in PAP (all P < 0.05, n = 7. The ameliorative effect of most promising dose of DL77 (5 mg/kg, i.p. was reversed when rats were co-injected with the H3R agonist R-(α-methylhistamine (RAMH, 10 mg/kg, i.p. (p = 0.701 for MK801-amnesic group vs. MK801+DL77+RAMH group, n = 6. In the NOR paradigm, DL77 (5 mg/kg, i.p. counteracted long-term memory (LTM deficits induced with MK801 (P < 0.05, n = 6–8, and the DL77-provided effect was similar to that of DOZ (p = 0.788, n = 6–8, and was reversed when rats were co-injected with RAMH (10 mg/kg, i.p. (p = 0.877, n = 6, as compared to the (MK801-amnesic group. However, DL77 (5 mg/kg, i.p. did not alter short-term memory (STM impairment in NOR test (p = 0.772, n = 6–8, as compared to (MK801-amnesic group. Moreover, DL77 (5 mg/kg failed to modify anxiety and locomotor behaviors of animals innate to elevated-plus maze (EPM (p = 0.67 for percentage of time spent exploring the open arms, p = 0.52 for number of entries into the open arms, p = 0.76 for percentage of entries into the open arms, and p = 0.73 number of closed arm entries as compared to saline-treated groups, all n = 6, demonstrating that the procognitive effects observed in PAP or NOR tests were unconnected to alterations in emotions or in natural locomotion of tested animals. These results signify the potential involvement of H3Rs in modulating

  15. Dynamic interactions of the asialoglycoprotein receptor subunits with coated pits. Enhanced interactions of H2 following association with H1.

    Science.gov (United States)

    Katzir, Z; Nardi, N; Geffen, I; Fuhrer, C; Henis, Y I

    1994-08-26

    Lateral mobility studies comparing native and mutated membrane proteins, combined with treatments that alter clathrin lattice structure, can measure membrane protein-coated pit interactions in intact cells (Fire, E., Zwart, D., Roth, M. G., and Henis, Y. I. (1991) J. Cell Biol. 115, 1585-1594). We applied this approach to study the interactions of the H1 and H2 human asialoglycoprotein receptor subunits with coated pits. The lateral mobilities of singly expressed and coexpressed H1 and H2B (the H2 species that reaches the cell surface) were measured by fluorescence photobleaching recovery. They were compared with mutant proteins, H1(5A) (Tyr-5 replaced by Ala) and H2(5A) (Phe-5 replaced by Ala). While the mobile fractions of H1, H2B, and their mutants were similar, the lateral diffusion rate (measured by D, the lateral diffusion coefficient) was significantly slower for H1, whether expressed alone or with H2B. Coexpression with H1 reduced D of H2B to that of H1. Disruption of the clathrin lattices by hypertonic medium elevated D of H1, H1(5A), H2B, and H2(5A) to the same final level, without affecting their mobile fractions. Cytosol acidification, which retains altered clathrin lattices attached to the membrane and prevents coated vesicle formation, immobilized part of the H1 molecules, reflecting stable entrapment in "frozen" coated pits. H1(5A), H2B, and H2(5A) were not affected; however, coexpression of H2B with H1 conferred the sensitivity to cytosol acidification on H2B. Our results suggest that H1 lateral mobility is inhibited by dynamic interactions with coated pits in which Tyr-5 is involved. H2B resembles H1(5A) rather than H1, and its interactions with coated pits are weaker; efficient interaction of H2B with coated pits depends on complex formation with H1.

  16. Effects of the histamine H₃ receptor antagonist ABT-239 on cognition and nicotine-induced memory enhancement in mice.

    Science.gov (United States)

    Kruk, Marta; Miszkiel, Joanna; McCreary, Andrew C; Przegaliński, Edmund; Filip, Małgorzata; Biała, Grażyna

    2012-01-01

    The strong correlation between central histaminergic and cholinergic pathways on cognitive processes has been reported extensively. However, the role of histamine H(3) receptor mechanisms interacting with nicotinic mechanisms has not previously been extensively investigated. The current study was conducted to determine the interactions of nicotinic and histamine H(3) receptor systems with regard to learning and memory function using a modified elevated plus-maze test in mice. In this test, the latency for mice to move from the open arm to the enclosed arm (i.e., transfer latency) was used as an index of memory. We tested whether ABT-239 (4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl), an H(3) receptor antagonist/inverse agonist, had influence on two different stages of memory, i.e., memory acquisition and consolidation (administered prior to or immediately after the first trial, respectively) and whether ABT-239 influenced nicotine-induced memory enhancement. Our results revealed that the acute administration of nicotine (0.035 and 0.175 mg/kg), but not of ABT-239 (0.1-3 mg/kg) reduced transfer latency in the acquisition and consolidation phases. In combination studies, concomitant administration of either ABT-239 (1 and 3 mg/kg) and nicotine (0.035 mg/kg), or ABT-239 (0.1 mg/kg) and nicotine (0.0175 mg/kg) further increased nicotine-induced improvement in both memory acquisition and consolidation. The present data confirm an important role for H(3) receptors in regulating nicotine-induced mnemonic effects since inhibition of H(3) receptors augmented nicotine-induced memory enhancement in mice.

  17. (11)C-MK-8278 PET as a tool for pharmacodynamic brain occupancy of histamine 3 receptor inverse agonists.

    Science.gov (United States)

    Van Laere, Koenraad J; Sanabria-Bohórquez, Sandra M; Mozley, David P; Burns, Donald H; Hamill, Terence G; Van Hecken, Anne; De Lepeleire, Inge; Koole, Michel; Bormans, Guy; de Hoon, Jan; Depré, Marleen; Cerchio, Kristine; Plalcza, John; Han, Lingling; Renger, John; Hargreaves, Richard J; Iannone, Robert

    2014-01-01

    The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity. Using PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y). The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further investigated in 15 healthy male volunteers (age, 18-40 y) with up to 3 PET scans and 3 subjects per dose level. The mean effective dose for (11)C-MK-8278 was 5.4 ± 1.1 μSv/MBq. Human brain kinetics showed rapid high uptake and fast washout. Binding potential values can be assessed using the pons as a reference region, with a test-retest repeatability of 7%. Drug RO data showed low interindividual variability per dose (mean RO SD, 2.1%), and a targeted 90% RO can be reached for both IAs at clinically feasible doses. (11)C-MK-8278 is a useful novel PET radioligand for determination of human cerebral H3 receptor binding and allows highly reproducible in vivo brain occupancy of H3-targeting drugs, hereby enabling the evaluation of novel compounds in early development to select doses and schedules.

  18. Cultured smooth muscle cells of the human vesical sphincter are more sensitive to histamine than are detrusor smooth muscle cells.

    Science.gov (United States)

    Neuhaus, Jochen; Oberbach, Andreas; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

    2006-05-01

    To compare histamine receptor expression in cultured smooth muscle cells from the human detrusor and internal sphincter using receptor-specific agonists. Smooth muscle cells from the bladder dome and internal sphincter were cultured from 5 male patients undergoing cystectomy for bladder cancer therapy. Calcium transients in cells stimulated with carbachol, histamine, histamine receptor 1 (H1R)-specific heptanecarboxamide (HTMT), dimaprit (H2R), and R-(alpha)-methylhistamine (H3R) were measured by calcium imaging. Histamine receptor proteins were detected by Western blot analysis and immunocytochemistry. H1R, H2R, and H3R expression was found in tissue and cultured cells. Carbachol stimulated equal numbers of detrusor and sphincter cells (60% and 51%, respectively). Histamine stimulated significantly more cells than carbachol in detrusor (100%) and sphincter (99.34%) cells. Calcium responses to carbachol in detrusor and sphincter cells were comparable and did not differ from those to histamine in detrusor cells. However, histamine and specific agonists stimulated more sphincter cells than did carbachol (P <0.001), and the calcium increase was greater in sphincter cells than in detrusor cells. Single cell analysis revealed comparable H2R responses in detrusor and sphincter cells, but H1R and H3R-mediated calcium reactions were significantly greater in sphincter cells. Histamine very effectively induces calcium release in smooth muscle cells. In sphincter cells, histamine is even more effective than carbachol regarding the number of reacting cells and the intracellular calcium increase. Some of the variability in the outcome of antihistaminic interstitial cystitis therapies might be caused by the ineffectiveness of the chosen antihistaminic or unintentional weakening of sphincteric function.

  19. Asymmetric binding of histone H1 stabilizes MMTV nucleosomes and the interaction of progesterone receptor with the exposed HRE.

    Science.gov (United States)

    Vicent, Guillermo P; Meliá, María J; Beato, Miguel

    2002-11-29

    Packaging of mouse mammary tumor virus (MMTV) promoter sequences in nucleosomes modulates access of DNA binding proteins and influences the interaction among DNA bound transcription factors. Here we analyze the binding of histone H1 to MMTV mononucleosomes assembled with recombinant histones and study its influence on nucleosome structure and stability as well as on progesterone receptor (PR) binding to the hormone responsive elements (HREs). The MMTV nucleosomes can be separated into three main populations, two of which exhibited precise translational positioning. Histone H1 bound preferentially to the 5' distal nucleosomal DNA protecting additional 27-28 nt from digestion by micrococcal nuclease. Binding of histone H1 was unaffected by prior crosslinking of protein and DNA in nucleosomes with formaldehyde. Neither the translational nor the rotational nucleosome positioning was altered by histone H1 binding, but the nucleosomes were stabilized as judged by the kinetics of nuclease cleavage. Unexpectedly, binding of recombinant PR to the exposed distal HRE-I in nucleosomes was enhanced in the presence of histone H1, as demonstrated by band shift and footprinting experiments. This enhanced PR affinity may contribute to the reported positive effect of histone H1 on the hormonal activation of MMTV reporter genes.

  20. Regulation of 1,25-dihydroxyvitamin D, receptors by [3H]-1,25-dihydroxyvitamin D3 in cultured cells (T-47D): evidence for receptor upregulation

    International Nuclear Information System (INIS)

    Reinhardt, T.A.; Horst, R.L.

    1986-01-01

    The authors examined the effect of 1,25-(OH) 2 D 3 on receptor concentration in cultured cells (T-47D). Two days prior to experiment, cells were fed with RPMI 1640 + 10% serum and 24-32 hours prior to experiment the media was replaced with RPMI 1640 + 25 mM Hepes + 1% serum. [ 3 H]-1,25-(OH) 2 D 3 +/- 100-fold molar excess cold hormone was used to treat the cells. Occupied receptors were measured in freshly prepared cytosols. Total receptors were measured following a 16-hour incubation of cytosols in the presence of 0.6 nM [ 3 H]-1,25-(OH) 2 D 3 +/- 100-fold molar excess of cold hormone at 4 0 C. Treatment of cell cultures for 16-18 hours with 0.5-1.0 nM [ 3 H]-1,25-(OH) 2 D 3 resulted in a 30-40% receptor occupancy by the hormone and a 2- to 3-fold increase in total cell receptor as compared to vehicle-treated controls. Time course studies showed a rapid increase in total receptors up to 16 hours post-treatment in the face of declining receptor occupancy. Actinomycin D blocked the [ 3 H]-1,25-(OH) 2 D 3 -dependent rise in cell receptor. The physiological significance of this receptor upregulation is not known nor is it known whether upregulation results from synthesis of new receptors and/or is the result of the activation of preformed receptors by a inducible activator protein

  1. Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer's Disease.

    Science.gov (United States)

    Rodríguez-Ruiz, Mar; Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Mallol, Josefa; Cortés, Antonio; Lluís, Carme; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Franco, Rafael

    2017-08-01

    Alzheimer's disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D 1 , histamine H 3 , and N-methyl-D-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by co-immunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H 3 receptor agonists, via negative cross-talk, and H 3 receptor antagonists, via cross-antagonism, decreased D 1 receptor agonist signaling determined by ERK1/2 or Akt phosphorylation, and counteracted D 1 receptor-mediated excitotoxic cell death. Both D 1 and H 3 receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D 1 -H 3 receptor heteromer function. Likely due to heteromerization, H 3 receptors act as allosteric regulator for D 1 and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D 1 or H 3 receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D 1 -H 3 -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H 3 receptor antagonists reduced NMDA or D 1 receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H 3 receptor antagonists reverted the toxicity induced by ß 1-42 -amyloid peptide. Thus, histamine H 3 receptors in D 1 -H 3 -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration.

  2. Acute exposure to high-peak-power pulsed microwaves affecting the histamine H3 receptor expression in rat hippocampus

    International Nuclear Information System (INIS)

    Yu Xiaodong; Li Bo; Li Dehua; He Qiyi; Yu Zhengping

    2006-01-01

    In the Morris Water test, high-peak-power pulsed microwave (MW)-exposed rats displayed some learning and memory behavior dysfunctions, and their escape time and swimming distance to the submerged platform were longer than those of the sham-exposed rats. to understand the molecular mechanism involved, the reverse transcription-polymerase chain reation (RT-PCR) and the Western-blotting technique were used for investigating the mRNA and protein expression patterns of the histamine H 3 receptor (H 3 R) in rat hippocampus. High-peak-power pulsed microwave-exposure did not remarkably lead to the change in expression of H 3 R mRNA in rat hippocampi; however, it promoted the up-regulatory expression of the H 3 R protein, which was possibly triggered through the mitogen-activated protein kinase (MAPK) pathways. Therefore, further investigation of the molecular mechanism of the MW effects on the learning and memory behaviors is required. (authors)

  3. Radioprotective effects of histamine H2 receptor antagonists famotidine and ranitidine on gamma ray induced chromosome damage

    International Nuclear Information System (INIS)

    Sharma, N.K.

    2013-01-01

    Histamine H2 receptor antagonist such as Cimetidine, Famotidine and Ranitidine are used in the clinical treatment of peptic ulcer. In vitro metaphase analysis and micronucleus assay were used to test the effects of famotidine and ranitidine on Cobalt 60 γ-ray induced clastogenic effects. Heparinised whole blood was obtained from healthy non-smoker volunteers. Blood samples were irradiated at a dose of 3Gy and incubated at 37 deg C for 1h. Lymphocyte cultures were initiated for metaphase chromosomes and cytochalasin B blocked micronucleus analysis. Aqueous solution of Famotidine (150 g/ml) and Ranitidine (500 g/ml) was added to the whole blood cultures at 0h and 24h. Cultures were harvested and processed at 48h and 72h for chromosome aberrations and micronucleus analysis respectively. Cultures treated with Famotidine at 0h and 24h after 3Gy γ-ray irradiation induce 60.90% and 56.52% inhibition in dicentrics, 48.70% and 43.61% inhibition in total aberrations. Ranitidine at 0h and 24h after 3Gy γ-ray irradiation induce 52.17% and 43.47% inhibition in dicentrics, 33.60% and 46.15% inhibition in total aberrations, when compared with 3Gy γ-ray irradiation alone. 43-54% inhibition in Binucleated cells with micronuclei and 47.72% inhibition in micronuclei at 0h treatment respectively. In conclusion radioprotective effects of Histamine H2 receptor antagonists famotidine and ranitidine on γ-ray induced chromosome damage is observed and the drugs effectively reduced the frequency of radiation induced chromosome aberrations and micronucleus. Famotidine was found to be more effective. The mechanism in which these drugs reduce clastogenic effect of γ-radiation is not fully understood. It might be due to their antioxidant and free radical-scavenging properties. (author)

  4. Effects of central histamine receptors blockade on GABA(A) agonist-induced food intake in broiler cockerels.

    Science.gov (United States)

    Morteza, Zendehdel; Vahhab, Babapour; Hossein, Jonaidi

    2008-02-01

    In this study, the effect of intracerebroventricular (i.c.v) injection of H1, H2 and H3 antagonists on feed intake induced by GABA(A) agonist was evaluated. In Experiment 1, the animals received chloropheniramine, a H1 antagonist and then muscimol, a GABA(A) agonist. In Experiment 2, chickens received famotidine, a H2 receptor antagonist, prior to injection of muscimol. Finally in Experiment 3, the birds were injected with thioperamide, a H3 receptor antagonist and muscimol. Cumulative food intake was measured 15, 30, 45, 60, 90, 120, 150 and 180 min after injections. The results of this study indicated that effects of muscimol on food intake inhibited by pretreatment with chloropheneramine maleate (p GABA(A) receptor interaction on food intake in broiler cockerels.

  5. Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

    International Nuclear Information System (INIS)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

    2016-01-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H 4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H 4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H 4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H 4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60

  6. Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan); Ozaki, Norio [Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Noda, Yukihiro, E-mail: ynoda@meijo-u.ac.jp [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan)

    2016-09-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation

  7. A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets.

    Directory of Open Access Journals (Sweden)

    Akila Jayaraman

    2011-03-01

    Full Text Available The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne transmission studies using the ferret model have shown that the transmission efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced transmission efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA to α2→6 sialylated glycan receptors (human receptors. Here we report that a single point mutation (Ile219→Lys; a base pair change in the glycan receptor-binding site (RBS of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and transmission efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses.

  8. H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anne-France Petit-Bertron

    Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

  9. Regional Differential Effects of the Novel Histamine H3 Receptor Antagonist 6-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) on Histamine Release in the Central Nervous System of Freely Moving Rats

    OpenAIRE

    Giannoni, Patrizia; Medhurst, Andrew D.; Passani, Maria Beatrice; Giovannini, Maria Grazia; Ballini, Chiara; Corte, Laura Della; Blandina, Patrizio

    2010-01-01

    After oral administration, the nonimidazole histamine H3 receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased histamine release from the tuberomammillary nucleus, where all histaminergic somata are localized, and from where their axons project to the entire brain. To further understand functional histaminergic circuitry in the brain, dual-probe microdialysis was used to pharmacologically block H3...

  10. The dual orexin receptor antagonist, DORA-22, lowers histamine levels in the lateral hypothalamus and prefrontal cortex without lowering hippocampal acetylcholine.

    Science.gov (United States)

    Yao, Lihang; Ramirez, Andres D; Roecker, Anthony J; Fox, Steven V; Uslaner, Jason M; Smith, Sean M; Hodgson, Robert; Coleman, Paul J; Renger, John J; Winrow, Christopher J; Gotter, Anthony L

    2017-07-01

    Chronic insomnia is defined as a persistent difficulty with sleep initiation maintenance or non-restorative sleep. The therapeutic standard of care for this condition is treatment with gamma-aminobutyric acid (GABA) A receptor modulators, which promote sleep but are associated with a panoply of side effects, including cognitive and memory impairment. Dual orexin receptor antagonists (DORAs) have recently emerged as an alternative therapeutic approach that acts via a distinct and more selective wake-attenuating mechanism with the potential to be associated with milder side effects. Given their distinct mechanism of action, the current work tested the hypothesis that DORAs and GABA A receptor modulators differentially regulate neurochemical pathways associated with differences in sleep architecture and cognitive performance induced by these pharmacological mechanisms. Our findings showed that DORA-22 suppresses the release of the wake neurotransmitter histamine in the lateral hypothalamus, prefrontal cortex, and hippocampus with no significant alterations in acetylcholine levels. In contrast, eszopiclone, commonly used as a GABA A modulator, inhibited acetylcholine secretion across brain regions with variable effects on histamine release depending on the extent of wakefulness induction. In normal waking rats, eszopiclone only transiently suppressed histamine secretion, whereas this suppression was more obvious under caffeine-induced wakefulness. Compared with the GABA A modulator eszopiclone, DORA-22 elicits a neurotransmitter profile consistent with wake reduction that does not impinge on neurotransmitter levels associated with cognition and rapid eye movement sleep. © 2017 International Society for Neurochemistry.

  11. Generation of a homology model of the human histamine H3 receptor for ligand docking and pharmacophore-based screening

    Science.gov (United States)

    Schlegel, Birgit; Laggner, Christian; Meier, Rene; Langer, Thierry; Schnell, David; Seifert, Roland; Stark, Holger; Höltje, Hans-Dieter; Sippl, Wolfgang

    2007-08-01

    The human histamine H3 receptor (hH3R) is a G-protein coupled receptor (GPCR), which modulates the release of various neurotransmitters in the central and peripheral nervous system and therefore is a potential target in the therapy of numerous diseases. Although ligands addressing this receptor are already known, the discovery of alternative lead structures represents an important goal in drug design. The goal of this work was to study the hH3R and its antagonists by means of molecular modelling tools. For this purpose, a strategy was pursued in which a homology model of the hH3R based on the crystal structure of bovine rhodopsin was generated and refined by molecular dynamics simulations in a dipalmitoylphosphatidylcholine (DPPC)/water membrane mimic before the resulting binding pocket was used for high-throughput docking using the program GOLD. Alternatively, a pharmacophore-based procedure was carried out where the alleged bioactive conformations of three different potent hH3R antagonists were used as templates for the generation of pharmacophore models. A pharmacophore-based screening was then carried out using the program Catalyst. Based upon a database of 418 validated hH3R antagonists both strategies could be validated in respect of their performance. Seven hits obtained during this screening procedure were commercially purchased, and experimentally tested in a [3H]Nα-methylhistamine binding assay. The compounds tested showed affinities at hH3R with K i values ranging from 0.079 to 6.3 μM.

  12. The effects of histamine and prostaglandin D2 on rat mast-cell cyclic AMP and mediator release

    International Nuclear Information System (INIS)

    Wescott, S.; Kaliner, M.

    1981-01-01

    The possibility that histamine may play a functional role in modulating mast-cell secretion, as has been suggested for basophil degranulation, has both physiologic and pharmacologic implications. Therefore the capacity of histamine to influence rat peritoneal mast-cell (RPMC) cyclic AMP levels and reversed anaphylatic degranulation as reflected in the release of 3H-serotonin (5-HT) was examined. To ascertain that RPMC were functionally responsive to exogenous hormonal stimulation, assessment of prostaglandin (PG) D2 effects on cyclic AMP and 5-HT release were determined in parallel. Although PGD2 (100 microM) increased cyclic AMP and inhibited 5-HT release in the presence of 50 microM aminophylline, histamine (up to 1000 microM) was ineffective was ineffective in both. However, 1000 microM histamine in the presence of 500 microM aminophylline was capable of transiently increasing RPMC cyclic AMP (for 15 to 30 sec) and under these conditions of suppressing 5-HT release. The receptor subtype involved in the suppressive actions of histamine appeared to be of the H-1 type as reflected in the capacity of specific H-1 agonists to reproduce the inhibition of 5-HT release, whereas neither H-2 agonists nor H-2 antagonists had any influence. Thus, under conditions in which phosphodiesterase enzymatic action is impaired, histamine in extremely high concentrations is able to modulate mast-cell secretion. However, it seems very unlikely that this action of histamine has any physiologic significance

  13. Hypertensive response to stress: the role of histaminergic H1 and H2 receptors in the medial amygdala.

    Science.gov (United States)

    de Almeida, Daniela Oliveira; Ferreira, Hilda Silva; Pereira, Luana Bomfim; Fregoneze, Josmara Bartolomei

    2015-05-15

    Different brain areas seem to be involved in the cardiovascular responses to stress. The medial amygdala (MeA) has been shown to participate in cardiovascular control, and acute stress activates the MeA to a greater extent than any of the other amygdaloid structures. It has been demonstrated that the brain histaminergic system may be involved in behavioral, autonomic and neuroendocrine responses to stressful situations. The aim of the present study was to investigate the role of the histaminergic receptors H1 and H2 in cardiovascular responses to acute restraint stress. Wistar rats (280-320g) received bilateral injections of cimetidine, mepyramine or saline into the MeA and were submitted to 45min of restraint stress. Mepyramine microinjections at doses of 200, 100 and 50nmol promoted a dose-dependent blockade of the hypertensive response induced by the restraint stress. Cimetidine (200 and 100nmol) promoted a partial blockade of the hypertensive response to stress only at the highest dose administered. Neither drugs altered the typical stress-evoked tachycardiac responses. Furthermore, mepyramine and cimetidine were unable to modify the mean arterial pressure or heart rate of freely moving rats under basal conditions (non-stressed rats). The data suggest that in the MeA the histaminergic H1 receptors appear to be more important than H2 receptors in the hypertensive response to stress. Furthermore, there appears to be no histaminergic tonus in the MeA controlling blood pressure during non-stress conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Acute exposure to high-peak-power pulsed microwaves affecting the histamine H3 receptor expression in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In the Morris Water Maze test, high-peak-power pulsed microwave (MW)-exposed rats displayed some learning and memory behavior dysfunctions, and their escape time and swimming distance to the submerged platform were longer than those of the sham-exposed rats. To understand the molecular mechanism involved, the reverse transcription-polymerase chain reaction (RT-PCR) and the Western-blotting technique were used for investigating the mRNA and protein expression patterns of the histamine H3 receptor (H3R) in rat hippocampus. High-peak-power pulsed microwave-exposure did not remarkably lead to the change in expression of H3R mRNA in rat hippocampi;however, it promoted the up-regulatory expression of the H3R protein, which was possibly triggered through the mitogen-activated protein kinase (MAPK) pathways. Therefore, further investigation of the molecular mechanism of the MW effects on the learning and memory behaviors is required.

  15. Structure-Based Prediction of Subtype Selectivity of Histamine H3 Receptor Selective Antagonists in Clinical Trials

    DEFF Research Database (Denmark)

    Kim, Soo-Kyung; Fristrup, Peter; Abrol, Ravinder

    2011-01-01

    applications, including treatment of Alzheimer’s disease, attention deficit hyperactivity disorder (ADHD), epilepsy, and obesity.(1) However, many of these drug candidates cause undesired side effects through the cross-reactivity with other histamine receptor subtypes. In order to develop improved selectivity...... and antagonists. We find that E2065.46 contributes most in binding H3 selective agonists (5, 6, 7) in agreement with experimental mutation studies. We also find that conserved E5.46/S5.43 in both of hH3HR and hH4HR are involved in H3/ H4 subtype selectivity. In addition, we find that M3786.55 in hH3HR provides...... additional hydrophobic interactions different from hH4HR (the corresponding amino acid of T3236.55 in hH4HR) to provide additional subtype bias. From these studies, we developed a pharmacophore model based on our predictions for known hH3HR selective antagonists in clinical study [ABT-239 1, GSK-189,254 2...

  16. Evaluation of in vivo selective binding of [{sup 11}C]doxepin to histamine H{sub 1} receptors in five animal species

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi E-mail: ishiwata@pet.tmig.or.jp; Kawamura, Kazunori; Wang Weifang; Tsukada, Hideo; Harada, Norihiro; Mochizuki, Hideki; Kimura, Yuichi; Ishii, Kenji; Iwata, Ren; Yanai, Kazuhiko

    2004-05-01

    The specific binding of [{sup 11}C]doxepin, which has been used as a radioligand for mapping histamine H{sub 1} receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [{sup 11}C]doxepin uptake was reduced by treatment with cold doxepin and two H{sub 1} receptor antagonists, but not with H{sub 2}/H{sub 3} antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H{sub 1} antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig.

  17. Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis.

    Science.gov (United States)

    Han, Song Hee; Hur, Min Seok; Kim, Min Jung; Kim, Bo Mi; Kim, Kyoung Woon; Kim, Hae Rim; Choe, Yong Beom; Ahn, Kyu Joong; Lee, Yang Won

    2017-10-01

    Previous studies have shown the expression of histamine H 4 receptor (H4R) on CD4 + T cells, especially human CD4 + T h 2-polarized T cells. This study aimed to investigate the role of H4R on these effector T cells in psoriasis. We enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4 + T cells. Then, we identified H4R expression in dermal CD4 + T cells. Furthermore, we investigated H4R expression after stimulating separated peripheral blood CD4 + T cells with several inflammatory cytokines. The results showed higher H4R expression in the active psoriasis group compared to the inactive psoriasis group. It was interesting that interleukin (IL)-23, which is a representative cytokine contributing to T h 17 cell differentiation, stimulated H4R expression significantly. After adding a selective H4R antagonist (JNJ-7777120) while the CD4 + T cells were polarized into T h 17 cells, we observed a tendency toward suppressed IL-17 secretion. Histamine stimulation influences the IL-17 pathway in psoriasis via the fourth histamine receptor subtype, H4R, on CD4 + T cells. The immunomodulatory roles of H4R suggest its potency as a new therapeutic target for obstinate psoriasis. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  18. The discovery of the benzazepine class of histamine H3 receptor antagonists.

    Science.gov (United States)

    Wilson, David M; Apps, James; Bailey, Nicholas; Bamford, Mark J; Beresford, Isabel J; Briggs, Michael A; Calver, Andrew R; Crook, Barry; Davis, Robert P; Davis, Susannah; Dean, David K; Harris, Leanne; Heightman, Tom D; Panchal, Terry; Parr, Christopher A; Quashie, Nigel; Steadman, Jon G A; Schogger, Joanne; Sehmi, Sanjeet S; Stean, Tania O; Takle, Andrew K; Trail, Brenda K; White, Trevor; Witherington, Jason; Worby, Angela; Medhurst, Andrew D

    2013-12-15

    This Letter describes the discovery of a novel series of H3 receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H3 receptor antagonists based on the benzazepine core. Employing an H3 driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice.

    Science.gov (United States)

    Kinbara, Masayuki; Bando, Kanan; Shiraishi, Daisuke; Kuroishi, Toshinobu; Nagai, Yasuhiro; Ohtsu, Hiroshi; Takano-Yamamoto, Teruko; Sugawara, Shunji; Endo, Yasuo

    2016-06-01

    We previously reported that allergic responses to nickel (Ni) were minimal in mice deficient in the histamine-forming enzyme histidine decarboxylase (HDC-KO), suggesting an involvement of histamine in allergic responses to Ni. However, it remains unclear how histamine is involved in the process of Ni allergy. Here, we examined the role of histamine in Ni allergy using a murine model previously established by us. Mice were sensitized to Ni by intraperitoneal injection of a NiCl2 -lipopolysaccharide (LPS) mixture. Ten days later, allergic inflammation was elicited by challenging ear-pinnas intradermally with NiCl2 . Then, ear-swelling was measured. Pyrilamine (histamine H1-receptor antagonist) or cromoglicate (mast cell stabilizer) was intravenously injected 1 h before the sensitization or the challenge. In cell-transfer experiments, spleen cells from Ni-sensitized donor mice were intravenously transferred into non-sensitized recipient mice. In both sensitized and non-sensitized mice, 1 mm or more NiCl2 (injected into ear-pinnas) induced transient non-allergic inflammation (Ni-TI) with accompanying mast cell degranulation. LPS did not affect the magnitude of this Ni-TI. Pyrilamine and cromoglicate reduced either the Ni-TI or the ensuing allergic inflammation when administered before Ni-TI (at either the sensitization or elicitation step), but not if administered when the Ni-TI had subsided. Experiments on HDC-KO and H1-receptor-KO mice, and also cell-transfer experiments using these mice, demonstrated histamine's involvement in both the sensitization and elicitation steps. These results suggest that mast cell histamine-mediated Ni-TI promotes subsequent allergic inflammatory responses to Ni, raising the possibility that control of Ni-TI by drugs may be effective at preventing or reducing Ni allergy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. One-step preparation of [2,3-{sup 3}H]1-aminocyclo-propanecarboxylic acid: a useful ligand for strychnine-insensitive glycine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lewin, A.H.; Lamb, P.B. [Research Triangle Inst., Research Triangle Park, NC (United States); Popik, P.; Skolnick, P. [National Insts. of Health, Bethesda, MD (United States)

    1994-11-01

    Catalytic hydrogenation of 1-aminocyclopropenecarboxylic acid under tritium gas afforded [2,3-{sup 3}H]1-aminocyclopropanecarboxylic acid with specific activity 26 Ci/mmol, determined by a combination of {sup 1}H and {sup 3}H NMR. Pilot radioligand binding assays indicate this compound will be a useful prove for the NMDA receptor-associated strychnine-insensitive glycine receptor. (author).

  1. Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

    Science.gov (United States)

    Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

    2013-05-01

    The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  2. Pneumonia prevention in intubated patients given sucralfate versus proton-pump inhibitors and/or histamine II receptor blockers.

    Science.gov (United States)

    Grindlinger, Gene A; Cairo, Sarah B; Duperre, Carole B

    2016-12-01

    Ventilator-associated pneumonia (VAP) is a common cause of infectious morbidity and mortality in the intensive care unit (ICU). The type of stress-ulcer prophylaxis (SUP) given to ventilated patients may, in part, be responsible. We observed an increase in VAP as ventilator bundle compliance increased and a decrease in VAP when bundle compliance decreased. We reasoned that SUP which raises gastric pH such as proton-pump inhibitors (PPIs) and histamine II (H2) receptor antagonists as opposed to SUP which does not raise pH such as sucralfate (S) may be responsible and also may alter the causative bacteria. This is a single-center retrospective cohort analysis of all intubated, adult surgical patients admitted to the surgical ICU between January and June during the 3-y period 2012-2014. Demographics, APACHE II, Injury Severity Score, VAP occurrence, culprit bacteria, ventilator days, and ICU days were recorded based on the type of SUP given. There were 45 instances of VAP in the 504 study patients, 33 in the PPI/H2 group, and 12 in the S group (P < 0.01). VAP per 1000 ventilator days were 10.2 for PPI/H2 and 3.7 for S (P < 0.01). Culprit bacteria were mostly Pseudomonas, gram-negative bacilli, and methicillin-resistant Staphylococcus aureus in PPI/H2 patients (n = 29) compared with oropharyngeal flora in S patients (n = 6; P < 0.001). There was a substantial difference in VAP occurrence and in the culprit bacteria between S and PPI/H2 treated patients due perhaps to gastric alkalization. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Activation of histamine H4 receptor inhibits TNFα/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells.

    Science.gov (United States)

    Stegajev, Vasili; Kouri, Vesa-Petteri; Salem, Abdelhakim; Rozov, Stanislav; Stark, Holger; Nordström, Dan C E; Konttinen, Yrjö T

    2014-12-01

    Apoptosis is involved in the pathogenesis of Sjögren's syndrome (SS), an autoimmune disease affecting exocrine glands. Our recent studies revealed diminished histamine H4 receptor (H₄R) expression and impaired histamine transport in the salivary gland epithelial cells in SS. The aim was now to test if nanomolar histamine and high-affinity H₄R signaling affect apoptosis of human salivary gland epithelial cell. Simian virus 40-immortalized acinar NS-SV-AC cells were cultured in serum-free keratinocyte medium ± histamine H₄R agonist HST-10. Expression and internalization of H₄R were studied by immunofluorescence staining ± clathrin inhibitor methyl-β-cyclodextrin (MβCD). Apoptosis induced using tumor necrosis factor-α with nuclear factor-κB inhibitor IMD-0354 was studied using phase contrast microscopy, Western blot, flow cytometry and polymerase chain reaction (qRT-PCR). HST-10-stimulated H₄R internalization was inhibited by MβCD. Western blotting revealed diminished phosphorylated c-Jun N-terminal kinase JNK, but unchanged levels of phosphorylated extracellular signal regulated kinase pERK1/2 in H₄R-stimulated samples compared to controls. qRT-PCR showed up-regulated expression of anti-apoptotic B cell lymphoma-extra large/Bcl-xL mRNAs and proteins, whereas pro-apoptotic Bcl-2-associated X protein/BAX remained unchanged in H4R-stimulated samples. H₄R stimulation diminished cleavage of PARP and flow cytometry showed significant dose-dependent inhibitory effect of H₄R stimulation on apoptosis. As far as we know this is the first study showing inhibitory effect of H₄R activation on apoptosis of human salivary gland cells. Diminished H₄R-mediated activation may contribute to loss of immune tolerance in autoimmune diseases and in SS in particular.

  4. Mast cell-derived histamine mediates cystitis pain.

    Directory of Open Access Journals (Sweden)

    Charles N Rudick

    2008-05-01

    Full Text Available Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC.Infection of mice with pseudorabies virus (PRV induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF, TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology.These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, and histamine receptors represent direct therapeutic targets for pain in IC and other chronic pain conditions.

  5. Regional differential effects of the novel histamine H3 receptor antagonist 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254) on histamine release in the central nervous system of freely moving rats.

    Science.gov (United States)

    Giannoni, Patrizia; Medhurst, Andrew D; Passani, Maria Beatrice; Giovannini, Maria Grazia; Ballini, Chiara; Corte, Laura Della; Blandina, Patrizio

    2010-01-01

    After oral administration, the nonimidazole histamine H(3) receptor antagonist, 6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride (GSK189254), increased histamine release from the tuberomammillary nucleus, where all histaminergic somata are localized, and from where their axons project to the entire brain. To further understand functional histaminergic circuitry in the brain, dual-probe microdialysis was used to pharmacologically block H(3) receptors in the tuberomammillary nucleus, and monitor histamine release in projection areas. Perfusion of the tuberomammillary nucleus with GSK189254 increased histamine release from the tuberomammillary nucleus, nucleus basalis magnocellularis, and cortex, but not from the striatum or nucleus accumbens. Cortical acetylcholine (ACh) release was also increased, but striatal dopamine release was not affected. When administered locally, GSK189254 increased histamine release from the nucleus basalis magnocellularis, but not from the striatum. Thus, defined by their sensitivity to GSK189254, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. Consistent with its effects on cortical ACh release, systemic administration of GSK189254 antagonized the amnesic effects of scopolamine in the rat object recognition test, a cognition paradigm with important cortical components.

  6. HISTAMINE H3 RECEPTOR INVERSE AGONISTS ON COGNITIVE AND MOTOR PROCESSES: RELEVANCE TO ALZHEIMER’S DISEASE, ADHD, SCHIZOPHRENIA AND DRUG ABUSE

    Directory of Open Access Journals (Sweden)

    Divya eVohora

    2012-10-01

    Full Text Available Histamine H3 receptor antagonists/ inverse agonists possess potential to treat diverse disease states of the central nervous system (CNS. Cognitive dysfunction and motor impairments are the hallmark of multifarious neurodegenerative and/or psychiatric disorders. This review presents the various neurobiological/ neurochemical evidences available so far following H3 receptor inverse agonists/ antagonists in the pathophysiology of Alzheimer’s disease (AD, attention-deficit hyperactivity disorder (ADHD, schizophrenia and drug abuse each of which is accompanied by deficits of some aspects of cognitive and/or motor functions. Whether the H3 receptor inverse agonism modulates the neurochemical basis underlying the disease condition or affects only the cognitive/motor component of the disease process is discussed with the aim to provide a rationale for their use in diverse disease states that are interlinked and are accompanied by some common motor, cognitive and attentional deficits.

  7. The extracellular loop 2 (ECL2 of the human histamine H4 receptor substantially contributes to ligand binding and constitutive activity.

    Directory of Open Access Journals (Sweden)

    David Wifling

    Full Text Available In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R shows extraordinarily high constitutive activity. In the extracellular loop (ECL, replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R.

  8. Cost-Effectiveness of Histamine2 Receptor Antagonists Versus Proton Pump Inhibitors for Stress Ulcer Prophylaxis in Critically Ill Patients.

    Science.gov (United States)

    Hammond, Drayton A; Kathe, Niranjan; Shah, Anuj; Martin, Bradley C

    2017-01-01

    To determine the cost-effectiveness of stress ulcer prophylaxis with histamine 2 receptor antagonists (H2RAs) versus proton pump inhibitors (PPIs) in critically ill and mechanically ventilated adults. A decision analytic model estimating the costs and effectiveness of stress ulcer prophylaxis (with H2RAs and PPIs) from a health care institutional perspective. Adult mixed intensive care unit (ICU) population who received an H2RA or PPI for up to 9 days. Effectiveness measures were mortality during the ICU stay and complication rate. Costs (2015 U.S. dollars) were combined to include medication regimens and untoward events associated with stress ulcer prophylaxis (pneumonia, Clostridium difficile infection, and stress-related mucosal bleeding). Costs and probabilities for complications and mortality from complications came from randomized controlled trials and observational studies. A base case scenario was developed with pooled data from an observational study and meta-analysis of randomized controlled trials. Scenarios based on observational and meta-analysis data alone were evaluated. Outcomes were expected and incremental costs, mortalities, and complication rates. Univariate sensitivity analyses were conducted to determine the influence of inputs on cost, mortality, and complication rates. Monte Carlo simulations evaluated second-order uncertainty. In the base case scenario, the costs, complication rates, and mortality rates were $9039, 17.6%, and 2.50%, respectively, for H2RAs and $11,249, 22.0%, and 3.34%, respectively, for PPIs, indicating that H2RAs dominated PPIs. The observational study-based model provided similar results; however, in the meta-analysis-based model, H2RAs had a cost of $8364 and mortality rate of 3.2% compared with $7676 and 2.0%, respectively, for PPIs. At a willingness-to-pay threshold of $100,000/death averted, H2RA therapy was superior or preferred 70.3% in the base case and 97.0% in the observational study-based scenario. PPI therapy

  9. Potent, nonsteroidal selective androgen receptor modulators (SARMs) based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones.

    Science.gov (United States)

    Higuchi, Robert I; Thompson, Anthony W; Chen, Jyun-Hung; Caferro, Thomas R; Cummings, Marquis L; Deckhut, Charlotte P; Adams, Mark E; Tegley, Christopher M; Edwards, James P; López, Francisco J; Kallel, E Adam; Karanewsky, Donald S; Schrader, William T; Marschke, Keith B; Zhi, Lin

    2007-10-01

    A series of androgen receptor modulators based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones was synthesized and evaluated in an androgen receptor transcriptional activation assay. The most potent analogues from the series exhibited single-digit nanomolar potency in vitro. Compound 18h demonstrated full efficacy in the maintenance of muscle weight, at 10 mg/kg, with reduced activity in prostate weight in an in vivo model of androgen action.

  10. Influence of the novel histamine H₃ receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice.

    Science.gov (United States)

    Bahi, Amine; Sadek, Bassem; Schwed, Stephan J; Walter, Miriam; Stark, Holger

    2013-07-01

    Growing evidence supports a role for the central histaminergic system to have a modulatory influence on drug addiction in general and alcohol-use disorders in particular through histamine H3 receptors (H3R). In the present study, the effects of systemic injection of the newly synthesized H3R antagonist ST1283 on ethanol (EtOH) voluntary intake and EtOH-conditioned reward in mice have been investigated. Oral EtOH, saccharin, and quinine intake was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol or tastant solutions. EtOH-induced place preference (CPP), EtOH-induced locomotor activity, and blood ethanol concentration (BEC) were also measured. Following administration of the H3R antagonist (2.5, 5, and 10 mg/kg, i.p.), there was a significant dose-dependent decrease in alcohol consumption and preference. Importantly, vehicle- and ST1283 (5 mg/kg)-treated mice showed similar consumption and preference to increasing concentration of both sweet and bitter tastes. More interestingly, systemic administration of ST1283 inhibited EtOH-CPP and EtOH-enhanced locomotion. This inhibition was blocked when mice were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (10 mg/kg). Finally, vehicle- and ST1283-treated mice had similar BECs. Our results show that ST1283 may decrease voluntary EtOH consumption and EtOH-CPP by altering its reinforcing effects, suggesting a novel role for histamine signaling in regulation of alcoholism. Lastly, the results add to the growing literature on H3R modulation in the pharmacotherapy of EtOH addiction.

  11. Pancreatic adenocarcinoma upregulated factor (PAUF) confers resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNA receptor-mediated signaling

    Energy Technology Data Exchange (ETDEWEB)

    Kaowinn, Sirichat; Cho, Il-Rae; Moon, Jeong; Jun, Seung Won; Kim, Chang Seok [BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736 (Korea, Republic of); Kang, Ho Young [Department of Microbiology, Pusan National University, Busan 609-736 (Korea, Republic of); Kim, Manbok [Department of Medical Science, Dankook University College of Medicine, Cheonan 330-714 (Korea, Republic of); Koh, Sang Seok [Department of Biological Sciences, Dong-A University, Busan 604-714 (Korea, Republic of); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736 (Korea, Republic of)

    2015-04-03

    Pancreatic adenocarcinoma upregulated factor (PAUF), a novel oncogene, plays a crucial role in the development of pancreatic cancer, including its metastasis and proliferation. Therefore, PAUF-expressing pancreatic cancer cells could be important targets for oncolytic virus-mediated treatment. Panc-1 cells expressing PAUF (Panc-PAUF) showed relative resistance to parvovirus H-1 infection compared with Panc-1 cells expressing an empty vector (Panc-Vec). Of interest, expression of type I IFN-α receptor (IFNAR) was higher in Panc-PAUF cells than in Panc-Vec cells. Increased expression of IFNAR in turn increased the activation of Stat1 and Tyk2 in Panc-PAUF cells compared with that in Panc-Vec cells. Suppression of Tyk2 and Stat1, which are important downstream molecules for IFN-α signaling, sensitized pancreatic cancer cells to parvovirus H-1-mediated apoptosis. Further, constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to parvovirus H-1 infection. Taken together, these results suggested that PAUF conferred resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNAR-mediated signaling. - Highlights: • PAUF confers resistance against oncolytic parvovirus H-1 infection. • PAUF enhances the expression of IFNAR in Panc-1 cells. • Increased activation of Tyk2 or Stat1 by PAUF provides resistance to parvovirus H-1-mediated apoptosis. • Constitutive inhibition of PAUF enhances parvovirus H-1-mediated oncolysis of Bxpc3 pancreatic cancer cells.

  12. Pancreatic adenocarcinoma upregulated factor (PAUF) confers resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNA receptor-mediated signaling

    International Nuclear Information System (INIS)

    Kaowinn, Sirichat; Cho, Il-Rae; Moon, Jeong; Jun, Seung Won; Kim, Chang Seok; Kang, Ho Young; Kim, Manbok; Koh, Sang Seok; Chung, Young-Hwa

    2015-01-01

    Pancreatic adenocarcinoma upregulated factor (PAUF), a novel oncogene, plays a crucial role in the development of pancreatic cancer, including its metastasis and proliferation. Therefore, PAUF-expressing pancreatic cancer cells could be important targets for oncolytic virus-mediated treatment. Panc-1 cells expressing PAUF (Panc-PAUF) showed relative resistance to parvovirus H-1 infection compared with Panc-1 cells expressing an empty vector (Panc-Vec). Of interest, expression of type I IFN-α receptor (IFNAR) was higher in Panc-PAUF cells than in Panc-Vec cells. Increased expression of IFNAR in turn increased the activation of Stat1 and Tyk2 in Panc-PAUF cells compared with that in Panc-Vec cells. Suppression of Tyk2 and Stat1, which are important downstream molecules for IFN-α signaling, sensitized pancreatic cancer cells to parvovirus H-1-mediated apoptosis. Further, constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to parvovirus H-1 infection. Taken together, these results suggested that PAUF conferred resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNAR-mediated signaling. - Highlights: • PAUF confers resistance against oncolytic parvovirus H-1 infection. • PAUF enhances the expression of IFNAR in Panc-1 cells. • Increased activation of Tyk2 or Stat1 by PAUF provides resistance to parvovirus H-1-mediated apoptosis. • Constitutive inhibition of PAUF enhances parvovirus H-1-mediated oncolysis of Bxpc3 pancreatic cancer cells

  13. Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata

    International Nuclear Information System (INIS)

    Aceves, J.; Young, J.M.; Arias-Montano, J.A.; Floran, B.; Garcia, M.

    1997-01-01

    The release of [ 3 H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K + from 6 to 15 mM in the presence of 10 μM sulpiride was inhibited by 73±3% by 1 μM SCH 23390, consistent with a large component of release dependent upon D 1 receptor activation. The histamine H 3 receptor-selective agonist immepip (1 μM) and the non-selective agonist histamine (100 μM) inhibited [ 3 H]GABA release by 78±2 and 80±2%, respectively. The inhibition by both agonists was reversed by the H 3 receptor antagonist thioperamide (1 μM). However, in the presence of 1 μM SCH 23390 depolarization-induced release of [ 3 H]GABA was not significantly decreased by 1 μM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [ 3 H]GABA, but in the presence of 1 μM SKF 38393, which produced a 7±1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 μM) also inhibited the depolarization-induced release of [ 3 H]dopamine from substantia nigra pars reticulata slices, by 38±3%.The evidence is consistent with the proposition that activation of histamine H 3 receptors leads to the selective inhibition of the component of depolarization-induced [ 3 H]GABA release in substantia nigra pars reticulata slices which is dependent upon D 1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [ 3 H]dopamine release. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  14. Generation of cell lines for drug discovery through random activation of gene expression: application to the human histamine H3 receptor.

    Science.gov (United States)

    Song, J; Doucette, C; Hanniford, D; Hunady, K; Wang, N; Sherf, B; Harrington, J J; Brunden, K R; Stricker-Krongrad, A

    2005-06-01

    Target-based high-throughput screening (HTS) plays an integral role in drug discovery. The implementation of HTS assays generally requires high expression levels of the target protein, and this is typically accomplished using recombinant cDNA methodologies. However, the isolated gene sequences to many drug targets have intellectual property claims that restrict the ability to implement drug discovery programs. The present study describes the pharmacological characterization of the human histamine H3 receptor that was expressed using random activation of gene expression (RAGE), a technology that over-expresses proteins by up-regulating endogenous genes rather than introducing cDNA expression vectors into the cell. Saturation binding analysis using [125I]iodoproxyfan and RAGE-H3 membranes revealed a single class of binding sites with a K(D) value of 0.77 nM and a B(max) equal to 756 fmol/mg of protein. Competition binding studies showed that the rank order of potency for H3 agonists was N(alpha)-methylhistamine approximately (R)-alpha- methylhistamine > histamine and that the rank order of potency for H3 antagonists was clobenpropit > iodophenpropit > thioperamide. The same rank order of potency for H3 agonists and antagonists was observed in the functional assays as in the binding assays. The Fluorometic Imaging Plate Reader assays in RAGE-H3 cells gave high Z' values for agonist and antagonist screening, respectively. These results reveal that the human H3 receptor expressed with the RAGE technology is pharmacologically comparable to that expressed through recombinant methods. Moreover, the level of expression of the H3 receptor in the RAGE-H3 cells is suitable for HTS and secondary assays.

  15. The ability of H1 or H2 receptor antagonists or their combination in counteracting the glucocorticoid-induced alveolar bone loss in rats.

    Science.gov (United States)

    Ezzat, Bassant A; Abbass, Marwa M S

    2014-02-01

    The aim of the present study was to compare between three possible osteoporotic treatments in prevention of glucocorticoid-induced alveolar bone loss. Fifty adult female Wistar rats with an average weight 150-200 g were randomized into five groups: group I (control) was intraperitoneally injected with saline. The other experimental groups (II & III, IV & V) were intraperitoneally injected with 200 µg/100 g body weight dexamethasone. The experimental groups III, IV and V received intraperitoneal injection of 10 mg/kg/day pheniramine maleate (H1 receptor antagonist), ranitidine hydrochloride (H2 receptor antagonist) and concomitant doses of both H1 & H2 receptor antagonists respectively. After 30 days, the rats have been sacrificed. The mandibles were examined histologically, histochemically and histomorphometrically. The bone mineral density was measured using dual-energy X-ray absorptiometry (DEXA). Histopathologically the glucocorticoid group showed wide medullary cavities with wide osteocytic lacunae. These marrow cavities were reduced in the prophylactic groups (III, IV) but increased in group V. Bone histomorphometric analysis revealed improvement in static bone parameters in groups III and IV and deterioration in group V in comparison to group II. The DEXA revealed significant reduction in the bone mineral density in all experimental groups compared to the control group. In a rat model, the administration of H1 or H2 receptor antagonists separately could minimize the alveolar bone loss caused by the administration of glucocorticoids while concomitant administration of both H1 and H2 receptor antagonists deteriorated the bone condition. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Histamine ameliorates spatial memory deficits induced by MK-801 infusion into ventral hippocampus as evaluated by radial maze task in rats

    Institute of Scientific and Technical Information of China (English)

    Li-sha XU; Li-xia YANG; Wei-wei HU; Xiao YU; Li MA; Lu-ying LIU; Er-qing WEI; Zhong CHEN

    2005-01-01

    Aim: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. Methods: An 8-arm radial maze (4arms baited) was used to assess spatial memory. Results: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 μg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 μg/site, ih) and the H2 antagonist cimetidine (2.5 μg/site,ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. Conclusion:The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.

  17. Identification and characterization of luekotriene C4 and D4 receptors on a cultured smooth muscle cell line, BC3H-1

    International Nuclear Information System (INIS)

    Tamura, N.; Agrawal, D.K.; Townley, R.G.

    1987-01-01

    The authors studied the characteristics of the leukotriene (LT) C 4 and D 4 receptors on a cultured smooth muscle cell line, BC3H-1. Specific [ 3 H]LTC 4 binding to the cell membrane was greater than 80% of total binding and saturable at a density of 3.96 +/- 0.39 pmol/mg protein, with an apparent dissociation constant(Kd) of 14.3 +/- 2.0 nM (n=9). The association and dissociation of [ 3 H]LTC 4 binding were rapid and apparent equilibrium conditions were established within 5 min. Calculated Kd value of [ 3 H]LTC binding from the kinetic analysis was 9.9 nM. From the competition analysis, calculated Ki value of unlabeled LTC 4 to compete for the specific binding of [ 3 H]LTC 4 was 9.2 nM and was in good agreement with the Kd value obtained from the Scatchard plots or kinetic analysis. The maximum number of binding sites (Bmax) of [ 3 H]LTD 4 in the membrane of BC3H-1 cell line was about 11 times lower than that of the [ 3 H]LTC 4 . The calculated values of Kd and Bmax of [ 3 H]LTD 4 binding were 9.3 +/- 0.8 nM and 0.37 +/- 0.04 pmol/mg proteins, respectively (n=3). These findings demonstrate that BC3H-1 cell line possess both LTC 4 and LTD 4 receptors with a predominance of LTC 4 receptors. Thus, BC3H-1 cell line is a good model to study the regulation of LTC 4 and LTD 4 receptors. 34 references, 5 figures, 1 table

  18. Histamine Regulates the Inflammatory Profile of SOD1-G93A Microglia and the Histaminergic System Is Dysregulated in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Savina Apolloni

    2017-11-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a late-onset motor neuron disease where activated glia release pro-inflammatory cytokines that trigger a vicious cycle of neurodegeneration in the absence of resolution of inflammation. Given the well-established role of histamine as a neuron-to-glia alarm signal implicated in brain disorders, the aim of this study was to investigate the expression and regulation of the histaminergic pathway in microglial activation in ALS mouse model and in humans. By examining the contribution of the histaminergic system to ALS, we found that particularly via H1 and H4 receptors, histamine promoted an anti-inflammatory profile in microglia from SOD1-G93A mice by modulating their activation state. A decrease in NF-κB and NADPH oxidase 2 with an increase in arginase 1 and P2Y12 receptor was induced by histamine only in the ALS inflammatory environment, but not in the healthy microglia, together with an increase in IL-6, IL-10, CD163, and CD206 phenotypic markers in SOD1-G93A cells. Moreover, histaminergic H1, H2, H3, and H4 receptors, and histamine metabolizing enzymes histidine decarboxylase, histamine N-methyltransferase, and diamine oxidase were found deregulated in spinal cord, cortex, and hypothalamus of SOD1-G93A mice during disease progression. Finally, by performing a meta-analysis study, we found a modulated expression of histamine-related genes in cortex and spinal cord from sporadic ALS patients. Our findings disclose that histamine acts as anti-inflammatory agent in ALS microglia and suggest a dysregulation of the histaminergic signaling in ALS.

  19. Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats

    International Nuclear Information System (INIS)

    Kandasamy, S.B.; Hunt, W.A.

    1990-01-01

    Exposure of rats to 1-15 Gy of gamma radiation induced hyperthermia, whereas exposure to 20-150 Gy produced hypothermia. Since radiation exposure induced the release of prostaglandins (PGs) and histamine, the role of PGs and histamine in radiation-induced temperature changes was examined. Radiation-induced hyper- and hypothermia were antagonized by pretreatment with indomethacin, a cyclooxygenase inhibitor. Intracerebroventricular administration of PGE2 and PGD2 induced hyper- and hypothermia, respectively. Administration of SC-19220, a specific PGE2 antagonist, attenuated PGE2- and radiation-induced hyperthermia, but it did not antagonize PGD2- or radiation-induced hypothermia. Consistent with an apparent role of histamine in hypothermia, administration of disodium cromoglycate (a mast cell stabilizer), mepyramine (H1-receptor antagonist), or cimetidine (H2-receptor antagonist) attenuated PGD2- and radiation-induced hypothermia. These results suggest that radiation-induced hyperthermia is mediated via PGE2 and that radiation-induced hypothermia is mediated by another PG, possibly PGD2, via histamine

  20. Hybrid approach to structure modeling of the histamine H3 receptor: Multi-level assessment as a tool for model verification.

    Directory of Open Access Journals (Sweden)

    Jakub Jończyk

    Full Text Available The crucial role of G-protein coupled receptors and the significant achievements associated with a better understanding of the spatial structure of known receptors in this family encouraged us to undertake a study on the histamine H3 receptor, whose crystal structure is still unresolved. The latest literature data and availability of different software enabled us to build homology models of higher accuracy than previously published ones. The new models are expected to be closer to crystal structures; and therefore, they are much more helpful in the design of potential ligands. In this article, we describe the generation of homology models with the use of diverse tools and a hybrid assessment. Our study incorporates a hybrid assessment connecting knowledge-based scoring algorithms with a two-step ligand-based docking procedure. Knowledge-based scoring employs probability theory for global energy minimum determination based on information about native amino acid conformation from a dataset of experimentally determined protein structures. For a two-step docking procedure two programs were applied: GOLD was used in the first step and Glide in the second. Hybrid approaches offer advantages by combining various theoretical methods in one modeling algorithm. The biggest advantage of hybrid methods is their intrinsic ability to self-update and self-refine when additional structural data are acquired. Moreover, the diversity of computational methods and structural data used in hybrid approaches for structure prediction limit inaccuracies resulting from theoretical approximations or fuzziness of experimental data. The results of docking to the new H3 receptor model allowed us to analyze ligand-receptor interactions for reference compounds.

  1. Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.

    Science.gov (United States)

    Higuchi, Robert I; Arienti, Kristen L; López, Francisco J; Mani, Neelakhanda S; Mais, Dale E; Caferro, Thomas R; Long, Yun Oliver; Jones, Todd K; Edwards, James P; Zhi, Lin; Schrader, William T; Negro-Vilar, Andrés; Marschke, Keith B

    2007-05-17

    Recent interest in orally available androgens has fueled the search for new androgens for use in hormone replacement therapy and as anabolic agents. In pursuit of this, we have discovered a series of novel androgen receptor modulators derived from 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. These compounds were synthesized and evaluated in competitive binding assays and an androgen receptor transcriptional activation assay. A number of compounds from the series demonstrated single-digit nanomolar agonist activity in vitro. In addition, lead compound (R)-16e was orally active in established rodent models that measure androgenic and anabolic properties of these agents. In this assay, (R)-16e demonstrated full efficacy in muscle and only partially stimulated the prostate at 100 mg/kg. These data suggest that these compounds may be utilized as selective androgen receptor modulators or SARMs. This series represents a novel class of compounds for use in androgen replacement therapy.

  2. Influenza human monoclonal antibody 1F1 interacts with three major antigenic sites and residues mediating human receptor specificity in H1N1 viruses.

    Directory of Open Access Journals (Sweden)

    Tshidi Tsibane

    Full Text Available Most monoclonal antibodies (mAbs to the influenza A virus hemagglutinin (HA head domain exhibit very limited breadth of inhibitory activity due to antigenic drift in field strains. However, mAb 1F1, isolated from a 1918 influenza pandemic survivor, inhibits select human H1 viruses (1918, 1943, 1947, and 1977 isolates. The crystal structure of 1F1 in complex with the 1918 HA shows that 1F1 contacts residues that are classically defined as belonging to three distinct antigenic sites, Sa, Sb and Ca(2. The 1F1 heavy chain also reaches into the receptor binding site (RBS and interacts with residues that contact sialoglycan receptors and determine HA receptor specificity. The 1F1 epitope is remarkably similar to the previously described murine HC63 H3 epitope, despite significant sequence differences between H1 and H3 HAs. Both antibodies potently inhibit receptor binding, but only HC63 can block the pH-induced conformational changes in HA that drive membrane fusion. Contacts within the RBS suggested that 1F1 may be sensitive to changes that alter HA receptor binding activity. Affinity assays confirmed that sequence changes that switch the HA to avian receptor specificity affect binding of 1F1 and a mAb possessing a closely related heavy chain, 1I20. To characterize 1F1 cross-reactivity, additional escape mutant selection and site-directed mutagenesis were performed. Residues 190 and 227 in the 1F1 epitope were found to be critical for 1F1 reactivity towards 1918, 1943 and 1977 HAs, as well as for 1I20 reactivity towards the 1918 HA. Therefore, 1F1 heavy-chain interactions with conserved RBS residues likely contribute to its ability to inhibit divergent HAs.

  3. IN VITRO INTERACTION OF INFLUENZA VIRUS A(H1N1pdm09 WITH MONOCYTIC MACROPHAGES: INDIVIDUAL RESPONSES OF TLR7 AND RIG1 RECEPTOR GENES

    Directory of Open Access Journals (Sweden)

    T. M. Sokolova

    2017-01-01

    Full Text Available In vitro differentiation of donor blood monocytes to macrophages (Mph following GM-CSF treatment was accompanied by a significant increase in the levels of gene transcription signaling receptors TLR7 or RIG1. The levels of intracellular viral RNA (M1 gene in Mph remained high upon infection by influenza virus A H1N1pdm (Moscow 2009 for 24-96 hours. The innate immunity reactions caused by influenza virus show individual features: they are decreased in Mph from donor 1 which had initially high level of endosomal TLR7 gene activity, and it increased by influenza virus in MPh from donor 2 who had a very low level of TLR7 gene expression. The influenza H1N1pdm virus weakly stimulated expression of gene RIG1 and production of inflammatory cytokines in Mf in donor 1. The differences may be connected with individual sensitivity of the donors to influenza infection.

  4. Envenenamento ofídico em crianças: frequência de reações precoces ao antiveneno em pacientes que receberam pré-tratamento com antagonistas H1 e H2 da histamina e hidrocortisona Snake envenomation in children: early reactions frequency at antivenom in patients pretreated with histamine antagonists HI and H2 and hydrocortisone

    Directory of Open Access Journals (Sweden)

    Fábio Bucarethi

    1994-10-01

    Full Text Available Foram estudadas 24 crianças, com idade entre 2 a 14 anos, de 1989 a 1993, vítimas de acidentes ofídicos, submetidas a pré-tratamento com antagonistas H1 (dextroclorfeniramina e H2 (cimetidine ou ranitidina da histamina e hidrocortisona, com objetivo de avaliar a frequência e o tipo de reações precoces (RP ao antiveneno (AV. Em nenhum paciente havia antecedente de atopia ou uso prévio de algum tipo de antiveneno ou antitoxina heteróloga. Das 24 crianças 15 receberam AV botrópico (RP em 5, 7 AV crotálico (RP em 5, 1 AV crotálico e AV botrópico-crotálico e 1 AV elapídico (RP. Foram observadas RP graves em 3 crianças, as 3 classificadas como acidente crotálico grave. A análise dos resultados sugere que o pré-tratamento realizado não ofereceu uma proteção segura quanto ao aparecimento de RP.Type and frequency of early reactions (ER were studied in 24 children aging 2-14 years victims of snake bites who received pretreatment with histamine antagonists H1 (dextrochlorfenirarnine and H2 (cimetidine or ranitidine and hydrocortisone from 1989 to 1993. None of them had atopy nor received any type of anti-venoms(AV and antitoxins before. Of 24 children, 15 received bothropic AV (ER in 5, 7 crotalic AV (ER in 5, 1 crotalic plus crotalic-bothropic AV, and 1 elapidic AV (ER in 1. In 3 children severe early reactions were observed and they were classified as severe crotalic accident. Results suggest that pre-treatment did not offer safety protection at the appearance of early reactions.

  5. Effect of FRG-8813, a new-type histamine H(2)-receptor antagonist, on the recurrence of gastric ulcer after healing by drug treatment in rats.

    Science.gov (United States)

    Ajioka, H; Miyake, H; Matsuura, N

    2000-08-01

    We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (+/-)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H(2)-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p. o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days' administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy. Copyright 2000 S. Karger AG, Basel

  6. PPI versus Histamine H2 Receptor Antagonists for Prevention of Upper Gastrointestinal Injury Associated with Low-Dose Aspirin: Systematic Review and Meta-analysis.

    Directory of Open Access Journals (Sweden)

    Chen Mo

    Full Text Available This study compared proton pump inhibitors (PPIs and histamine H2 receptor antagonists (H2RAs for prevention of low-dose aspirin (LDA-related gastrointestinal (GI erosion, ulcer and bleeding. Electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Data were searched from the date of their establishment to December 31, 2013. Randomized controlled trials comparing PPIs and H2RAs for prevention of GI injury associated with low-dose aspirin (LDA were collected. Two reviewers independently abstracted studies and patient characteristics and appraised study quality using the Cochrane risk-of-bias tool. Meta-analysis was performed using RevMan 5.1 software. We included nine RCTs involving 1047 patients. The meta-analysis showed that PPIs were superior to H2RAs for prevention of LDA-associated GI erosion/ulcer [odds ratio (OR=0.28, 95% confidence interval (CI: 0.16-0.50] and bleeding (OR=0.28, 95% CI: 0.14-0.59. In conclusion, PPIs were superior to H2RAs for prevention of LDA-related GI erosion/ulcer and bleeding. Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs.

  7. The histamine system in human brain. Changes in neurological and psychiatric disorders

    International Nuclear Information System (INIS)

    Goodchild, R.E.

    1999-09-01

    Autoradiographical examination of the distribution of H 1 - and H 3 - histamine receptor subtypes, using [ 3 H]-mepyramine and [ 3 H]-R-(α) methylhistamine respectively, found high H 1 -receptor binding densities in neocortex, dentate gyrus and basolateral amygdala, with low binding in all subdivisions of the thalamus and other subcortical areas. H 3 -receptor binding was enriched within the nucleus accumbens, globus pallidus and substantia nigra, whilst was low in the hippocampus, subthalamic nucleus, temporal cortex, motor and somatosensory thalamic areas and basolateral amygdala. In situ hybridisation found H 2 -receptor mRNA located in the striatum, thalamus, hippocampal pyramidal cell layer and dentate gyrus, and specific laminae of neocortex. Comparison of autoradiographically determined H 1 -, H 2 - and H 3 -receptor binding densities between normal and pathological cases found significantly decreased (p 3 -receptor binding in Huntington's disease (HD), with unaltered binding in the insular cortex. A significant correlation (p 1 -receptor was increased (p 2 - (measured using [ 125 I]-iodoaminopotentidine) and H 3 -receptor binding densities were normal in all areas examined. H 1 -receptor binding was also increased in the hippocampus of Lewy-body dementia (DLB) cases (p 2 -receptor binding densities were decreased in DLB, together with Alzheimer's disease (AD) (p 3 -receptor binding was increased in the insular cortex and decreased in the temporal cortex of DLB, but not AD, cases (p 1 -receptor binding to tissue from patients with schizophrenia was significantly reduced in all cortical (p 2 -receptor binding was unaltered in all areas, however H 3 -receptor binding was increased in the posterior putamen (p < 0.05), and highly significantly decreased (p < 0.005, Students two-tailed T-Test) in the external globus pallidus in schizophrenia. (author)

  8. Are basophil histamine release and high affinity IgE receptor expression involved in asymptomatic skin sensitization?

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Assing, K; Jensen, Lone Hummelshøj

    2006-01-01

    Immunoglobulin (Ig)E-sensitized persons with positive skin prick test, but no allergy symptoms, are classified as being asymptomatic skin sensitized (AS). The allergic type 1 disease is dependant on IgE binding to the high affinity IgE-receptor (FcepsilonRI) expressed on basophils and mast cells....

  9. Histamine fish poisoning revisited.

    Science.gov (United States)

    Lehane, L; Olley, J

    2000-06-30

    Histamine (or scombroid) fish poisoning (HFP) is reviewed in a risk-assessment framework in an attempt to arrive at an informed characterisation of risk. Histamine is the main toxin involved in HFP, but the disease is not uncomplicated histamine poisoning. Although it is generally associated with high levels of histamine (> or =50 mg/100 g) in bacterially contaminated fish of particular species, the pathogenesis of HFP has not been clearly elucidated. Various hypotheses have been put forward to explain why histamine consumed in spoiled fish is more toxic than pure histamine taken orally, but none has proved totally satisfactory. Urocanic acid, like histamine, an imidazole compound derived from histidine in spoiling fish, may be the "missing factor" in HFP. cis-Urocanic acid has recently been recognised as a mast cell degranulator, and endogenous histamine from mast cell degranulation may augment the exogenous histamine consumed in spoiled fish. HFP is a mild disease, but is important in relation to food safety and international trade. Consumers are becoming more demanding, and litigation following food poisoning incidents is becoming more common. Producers, distributors and restaurants are increasingly held liable for the quality of the products they handle and sell. Many countries have set guidelines for maximum permitted levels of histamine in fish. However, histamine concentrations within a spoiled fish are extremely variable, as is the threshold toxic dose. Until the identity, levels and potency of possible potentiators and/or mast-cell-degranulating factors are elucidated, it is difficult to establish regulatory limits for histamine in foods on the basis of potential health hazard. Histidine decarboxylating bacteria produce histamine from free histidine in spoiling fish. Although some are present in the normal microbial flora of live fish, most seem to be derived from post-catching contamination on board fishing vessels, at the processing plant or in the

  10. Ciproxifan, a histamine H{sub 3} receptor antagonist and inverse agonist, presynaptically inhibits glutamate release in rat hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Cheng-Wei; Lin, Tzu-Yu [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan (China); Chang, Chia-Ying [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Department of Chemistry, Fu Jen Catholic University, No. 510, Chung-Cheng Road, Hsin-Chuang District, New Taipei City 24205, Taiwan (China); Huang, Shu-Kuei [Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan (China); Wang, Su-Jane, E-mail: med0003@mail.fju.edu.tw [School of Medicine, Fu Jen Catholic University, No. 510, Chung-Cheng Rd., Hsin-Chuang, New Taipei 24205, Taiwan (China); Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan (China)

    2017-03-15

    Ciproxifan is an H{sub 3} receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca{sup 2+}-dependent glutamate release and cytosolic Ca{sup 2+} concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Ca{sub v}2.2 (N-type) and Ca{sub v}2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, but was not affected by the intracellular Ca{sup 2+}-release inhibitors dantrolene and CGP37157. Furthermore, the phospholipase A{sub 2} (PLA{sub 2}) inhibitor OBAA, prostaglandin E{sub 2} (PGE{sub 2}), PGE2 subtype 2 (EP{sub 2}) receptor antagonist PF04418948, and extracellular signal-regulated kinase (ERK) inhibitor FR180204 eliminated the inhibitory effect of ciproxifan on glutamate release. Ciproxifan reduced the 4-AP-evoked phosphorylation of ERK and synapsin I, a presynaptic target of ERK. The ciproxifan-mediated inhibition of glutamate release was prevented in synaptosomes from synapsin I-deficient mice. Moreover, ciproxifan reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that ciproxifan, acting through the blockade of Gi/Go protein-coupled H{sub 3} receptors present on hippocampal nerve terminals, reduces voltage-dependent Ca{sup 2+} entry by diminishing PLA{sub 2}/PGE{sub 2}/EP{sub 2} receptor pathway, which subsequently suppresses the ERK/synapsin I cascade to decrease the evoked glutamate release. - Highlights: • Ciproxifan presynaptically reduces glutamate release in the hippocampus in vitro. • Decrease in voltage-dependent Ca{sup 2+} influx is involved. • A role for the PLA{sub 2}/PGE{sub 2}/EP{sub 2} pathway in the action of

  11. Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Constanza Ballesteros-Martinez

    2017-10-01

    Full Text Available Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1 is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF, and epinephrine in primary human vein (HV-/artery (HA-derived endothelial cells (ECs and human dermal microvascular ECs (HMVEC-D. Vascular permeability was analyzed in vitro in human ECs with forced Rcan1 expression using Transwell migration assays and in vivo using Rcan1 knockout mice. Histamine, but neither PAF nor epinephrine, induced Rcan1-4 mRNA and protein expression in primary HV-ECs, HA-ECs, and HMVEC-D through histamine receptor 1 (H1R. These effects were prevented by pharmacological inhibition of calcineurin with cyclosporine A. Moreover, intravenous histamine administration increased Rcan1 expression in lung tissues of mice undergoing experimental anaphylaxis. Functional in vitro assays showed that overexpression of Rcan1 promotes barrier integrity, suggesting a role played by this molecule in vascular permeability. Consistent with these findings, in vivo models of subcutaneous and intravenous histamine-mediated fluid extravasation showed increased response in skin, aorta, and lungs of Rcan1-deficient mice compared with wild-type animals. These findings reveal that endothelial Rcan1 is synthesized in response to histamine through a calcineurin-sensitive pathway and may reduce barrier breakdown, thus contributing to the strengthening of the endothelium and resistance to anaphylaxis. These new insights underscore its potential role as a regulator of sensitivity to anaphylaxis in humans.

  12. On histamine and appetites

    Directory of Open Access Journals (Sweden)

    Fernando eTorrealba

    2012-07-01

    Full Text Available Brain histamine may influence a variety of different behavioral and physiological functions, but its responsibility in waking up has casted a long shadow on other important functions of this neurotransmitter. Here we review evidence indicating a central role of brain histamine in motivation, emphasizing its differential involvement in the appetitive and consummatory phases of motivated behaviors. We discuss the inputs that control the histaminergic neurons of the tuberomamillary nucleus of the hypothalamus, which determine the distinct role of these neurons in appetitive behavior, sleep/wake cycles and in food anticipatory activity. We review evidence supporting a dysfunction of histamine neurons and its cortical input in certain forms of decreased motivation (apathy. We finally discuss the relationship between the histamine system and drug addiction as a dysfunction of motivation.

  13. Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists

    DEFF Research Database (Denmark)

    Hansen, Kasper Bø; Mullasseril, Praseeda; Dawit, Sara

    2010-01-01

    N-Methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that mediate a slow, Ca(2+)-permeable component of excitatory synaptic transmission in the central nervous system and play a pivotal role in synaptic plasticity, neuronal development, and several neurological diseases. We describe...... a fluorescence-based assay that measures NMDA receptor-mediated changes in intracellular calcium in a BHK-21 cell line stably expressing NMDA receptor NR2D with NR1 under the control of a tetracycline-inducible promoter (Tet-On). The assay selectively identifies allosteric modulators by using supramaximal...

  14. 11C-labeled and 18F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain

    NARCIS (Netherlands)

    Funke, U.; Vugts, D.J.; Janssen, B.; Spaans, A.; Kruijer, P.S.; Lammertsma, A.A.; Perk, L.R.; Windhorst, A.D.

    2013-01-01

    The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and

  15. Effect of histamine-2-receptor antagonists versus sucralfate on stress ulcer prophylaxis in mechanically ventilated patients: a meta-analysis of 10 randomized controlled trials.

    Science.gov (United States)

    Huang, Jiahao; Cao, Yunfei; Liao, Cun; Wu, Liucheng; Gao, Feng

    2010-01-01

    We conducted a meta-analysis in order to investigate the effect of histamine-2-receptor antagonists (H2RA) versus sucralfate on stress ulcer prophylaxis in mechanically ventilated patients in the intensive care unit (ICU). A systematic literature search of Medline, EMBASE, Cochrane Central Register of Controlled Trials (1966 to January 2010) was conducted using specific search terms. A review of Web of Science and a manual review of references were also performed. Eligible studies were randomized control trials (RCTs) that compared H2RA and sucralfate for the prevention of stress ulcer in mechanically ventilated patients. Main outcome measures were rates of overt bleeding, clinically important gastrointestinal (GI) bleeding, ventilator-associated pneumonia, gastric colonization and ICU mortality. Ten RCTs with 2,092 participants on mechanical ventilation were identified. Meta-analysis showed there was a trend toward decreased overt bleeding when H2RA was compared with sucralfate (OR = 0.87, 95% CI: 0.49 to 1.53). A total of 12 clinically important GI bleeding events occurred among 667 patients (1.8%) in the H2RA group compared with 26 events among 673 patients (3.9%) in the sucralfate groups. Prophylaxis with sucralfate decreased the incidence of gastric colonization (OR = 2.03, 95% CI: 1.29 to 3.19) and ventilator-associated pneumonia (OR = 1.32, 95% CI: 1.07 to 1.64). Subgroup analysis showed H2RA was not superior to sucralfate in reducing early-onset pneumonia (OR = 0.62, 95%CI: 0.36 to 1.07) but had a higher late-onset pneumonia rate (OR = 4.36, 95%CI: 2.09 to 9.09) relative to sucralfate. No statistically significant reduction was observed in mortality of ICU between groups (OR = 1.08, 95% CI: 0.86 to 1.34). In patients with mechanical ventilation, H2RA resulted in no differential effectiveness in treating overt bleeding, but had higher rates of gastric colonization and ventilator-associated pneumonia. Additional RCTs of stress ulcer prophylaxis with H2RA and

  16. Potentiodynamic formation of gold nanoparticles film on glassy carbon electrode using aminophenyl diazonium cations grafted gold nanoparticles: Determination of histamine H2 receptor antagonist

    International Nuclear Information System (INIS)

    Kesavan, Srinivasan; Revin, S. Brillians; John, S. Abraham

    2014-01-01

    Graphical abstract: - Highlights: • Grafting based AuNPs were synthesized in aqueous medium by spontaneous grafting. • GC/ITO electrode was modified with AuNPs film by potentiodynamic method. • AuNPs film modified electrode was characterized by XPS, AFM and CV. • Simultaneous determination of ranitidine and paracetamol was demonstrated. • Practical application was demonstrated in commercial drugs. - Abstract: The aminophenyl (AP) functionalized AuNPs (AP-AuNPs) were synthesized in aqueous medium by spontaneous grafting method and were used for the formation of AuNPs film on glassy carbon (GC) and indium tin oxide (ITO) surfaces by potentiodynamic method. The formed AP-AuNPs film modified electrodes were characterized by cyclic voltammetry (CV), atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS), and X-ray photoelectron spectroscopy (XPS). EIS studies show that the electron transfer reaction of [Fe(CN) 6 ] 3-/4− was higher at the AP-AuNPs film modified electrode (1.58 × 10 −4 cm s −1 ) than at bare (3.78 × 10 −5 cm s −1 ) GC electrode. The surface coverage of the AP-AuNPs film modified electrode was found to be 4.4 × 10 −10 mol cm −2 . The film formation takes place via -NH 2 groups of AP-AuNPs, which was confirmed by XPS from the observed peaks corresponding to =N-H (396.7 eV), -N-H (399.2 eV), -N = N- (400.2 eV) and -N + -H (403.3 eV). The AP-AuNPs film modified electrode was successfully utilized for the determination of histamine H 2 receptor antagonist ranitidine (RA). Further, the AP-AuNPs film modified electrode was effectively used for the selective determination of RA in the presence of 40-fold excess paracetamol. The present method was successfully used to determine the concentration of RA in commercial drugs

  17. Stress-induced release of anterior pituitary hormones: Effect of H3 receptor-mediated inhibition of histaminergic activity or posterior hypothalamic lesion

    DEFF Research Database (Denmark)

    Knigge, U.; Søe-Jensen, P.; Jørgensen, Henrik

    1999-01-01

    Histamine receptors, corticotropin, *Gb-endorphin, prolactin, adrenal steroids, stress, endotoxin, serotonin......Histamine receptors, corticotropin, *Gb-endorphin, prolactin, adrenal steroids, stress, endotoxin, serotonin...

  18. Histamine and Tyramine in Food.

    Science.gov (United States)

    1985-05-01

    FISH PRODUCTS 44 ON THE JAPANESE MARKET TABLE 4-9 TYRAMINE AND HISTAMINE IN FRUITS, 48 VEGETABLES AND THEIR PRODUCTS TABLE 5-1 SCOMBROTOXIN (HISTAMINE...Products The histamine and tyramine content of fruits, vegetables and their products is shown in Table 4-9. The fruits of avocado , lemon, and...VEGETABLES, AND THEIR PRODUCTS (ug/g) ITEM HISTAMINE TYRAMINE REFERENCE Apple 0 6 Avocado 23 78 Bananas 7 79, 80, 81, 82 Banana Peel - 65 81 Barley - 10

  19. Radiosynthesis and biodistribution of a histamine H{sub 3} receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[{sup 11}C]benzyl]-morpholine: evaluation of a potential PET ligand

    Energy Technology Data Exchange (ETDEWEB)

    Airaksinen, Anu J. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Jablonowski, Jill A. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Mey, Margreet van der [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Barbier, Ann J. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Klok, Rob P. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Verbeek, Joost [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Schuit, Robert [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Herscheid, Jacobus D.M. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Leysen, Josee E. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Carruthers, Nicholas I. [Johnson and Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121 (United States); Lammertsma, Adriaan A. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands); Windhorst, Albert D. [Department of Nuclear Medicine and PET Research, Location Radionuclide Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam (Netherlands)]. E-mail: bwindhorst@rnc.vu.nl

    2006-08-15

    The potent histamine H{sub 3} receptor antagonist JNJ-10181457 () was successfully labeled with {sup 11}C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28{+-}8%) and high specific radioactivity (56{+-}26 GBq/{mu}mol). The binding of [{sup 11}C] to H{sub 3} receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [{sup 11}C] in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H{sub 3} antagonists, JNJ-5207852 () and unlabeled Compound (), in a concentration-dependent manner. The biodistribution of [{sup 11}C] in rats was measured at 5, 10, 30 and 60 min. The uptake of [{sup 11}C] in regions rich in H{sub 3} receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [{sup 11}C] in the rat brain could not be blocked by pretreatment with either Compound () (30 min or 24 h pretreatment) or cold Compound () (30-min pretreatment). The biodistribution of [{sup 11}C] in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H{sub 3}(-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [{sup 11}C] could not specifically label H{sub 3} receptors in rodent brain in vivo. Possible causes are discussed.

  20. Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand

    International Nuclear Information System (INIS)

    Airaksinen, Anu J.; Jablonowski, Jill A.; Mey, Margreet van der; Barbier, Ann J.; Klok, Rob P.; Verbeek, Joost; Schuit, Robert; Herscheid, Jacobus D.M.; Leysen, Josee E.; Carruthers, Nicholas I.; Lammertsma, Adriaan A.; Windhorst, Albert D.

    2006-01-01

    The potent histamine H 3 receptor antagonist JNJ-10181457 () was successfully labeled with 11 C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28±8%) and high specific radioactivity (56±26 GBq/μmol). The binding of [ 11 C] to H 3 receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [ 11 C] in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H 3 antagonists, JNJ-5207852 () and unlabeled Compound (), in a concentration-dependent manner. The biodistribution of [ 11 C] in rats was measured at 5, 10, 30 and 60 min. The uptake of [ 11 C] in regions rich in H 3 receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [ 11 C] in the rat brain could not be blocked by pretreatment with either Compound () (30 min or 24 h pretreatment) or cold Compound () (30-min pretreatment). The biodistribution of [ 11 C] in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H 3 (-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [ 11 C] could not specifically label H 3 receptors in rodent brain in vivo. Possible causes are discussed

  1. Measurement of plasma histamine: description of an improved method and normal values

    International Nuclear Information System (INIS)

    Dyer, J.; Warren, K.; Merlin, S.; Metcalfe, D.D.; Kaliner, M.

    1982-01-01

    The single isotopic-enzymatic assay of histamine was modified to increase its sensitivity and to facilitate measurement of plasma histamine levels. The modification involved extracting 3 H-1-methylhistamine (generated by the enzyme N-methyltransferase acting on histamine in the presence of S-[methyl- 3 H]-adenosyl-L-methionine) into chloroform and isolating the 3 H-1-methylhistamine by thin-layer chromatography (TLC). The TLC was developed in acetone:ammonium hydroxide (95:10), and the methylhistamine spot (Rf . 0.50) was identified with an o-phthalaldehyde spray, scraped from the plate, and assayed in a scintillation counter. The assay in plasma demonstrated a linear relationship from 200 to 5000 pg histamine/ml. Plasma always had higher readings than buffer, and dialysis of plasma returned these values to the same level as buffer, suggesting that the baseline elevations might be attributable to histamine. However, all histamine standard curves were run in dialyzed plasma to negate any additional influences plasma might exert on the assay. The arithmetic mean (+/- SEM) in normal plasma histamine was 318.4 +/- 25 pg/ml (n . 51), and the geometric mean was 280 +/- 35 pg/ml. Plasma histamine was significantly elevated by infusion of histamine at 0.05 to 1.0 micrograms/kg/min or by cold immersion of the hand of a cold-urticaria patient. Therefore this modified isotopic-enzymatic assay of histamine is extremely sensitive, capable of measuring fluctuations in plasma histamine levels within the normal range, and potentially useful in analysis of the role histamine plays in human physiology

  2. Involvement of prostaglandins and histamine in nickel wire-induced acute inflammation in mice.

    Science.gov (United States)

    Hirasawa, Noriyasu; Goi, Yoshiaki; Tanaka, Rina; Ishihara, Kenji; Ohtsu, Hiroshi; Ohuchi, Kazuo

    2010-06-15

    The irritancy of Nickel (Ni) ions has been well documented clinically. However, the chemical mediators involved in the acute inflammation induced by solid Ni are not fully understood. We used the Ni wire-implantation model in mice and examined roles of prostaglandins and histamine in plasma leakage in the acute phase. The subcutaneous implantation of a Ni wire into the back of mice induced plasma leakage from 8 to 24 h and tissue necrosis around the wire at 3 days, whereas the implantation of an aluminum wire induced no such inflammatory responses. An increase in the mRNA for cyclooxygenase (COX)-2 and HDC in cells around the Ni wire was detected 4 h after the implantation. The leakage of plasma at 8 h was inhibited by indomethacin in a dose-dependent manner. Dexamethasone and the p38 MAP kinase inhibitor SB203580 also inhibited the exudation of plasma consistent with the inhibition of the expression of COX-2 mRNA. Furthermore, plasma leakage was partially but siginificantly reduced in histamine H1 receptor knockout mice and histidine decarboxylase (HDC) knockout mice but not in H2 receptor knockout mice. These results suggested that the Ni ions released from the wire induced the expression of COX-2 and HDC, resulting in an increase in vascular permeability during the acute phase of inflammation. (c) 2009 Wiley Periodicals, Inc.

  3. Pharmacological Characterization of 5-Substituted 1-[(2,3-dihydro-1-benzofuran-2-ylmethyl]piperazines: Novel Antagonists for the Histamine H3 and H4 Receptors with Anti-inflammatory Potential

    Directory of Open Access Journals (Sweden)

    Michelle F. Corrêa

    2017-11-01

    Full Text Available The histamine receptors (HRs are traditional G protein-coupled receptors of extensive therapeutic interest. Recently, H3R and H4R subtypes have been targeted in drug discovery projects for inflammation, asthma, pain, cancer, Parkinson’s, and Alzheimer’s diseases, which includes searches for dual acting H3R/H4R ligands. In the present work, nine 1-[(2,3-dihydro-1-benzofuran-2-ylmethyl]piperazine (LINS01 series molecules were synthesized and evaluated as H3R and H4R ligands. Our data show that the N-allyl-substituted compound LINS01004 bears the highest affinity for H3R (pKi 6.40, while the chlorinated compound LINS01007 has moderate affinity for H4R (pKi 6.06. In addition, BRET assays to assess the functional activity of Gi1 coupling indicate that all compounds have no intrinsic activity and act as antagonists of these receptors. Drug-likeness assessment indicated these molecules are promising leads for further improvements. In vivo evaluation of compounds LINS01005 and LINS01007 in a mouse model of asthma showed a better anti-inflammatory activity of LINS01007 (3 g/kg than the previously tested compound LINS01005. This is the first report with functional data of these compounds in HRs, and our results also show the potential of their applications as anti-inflammatory.

  4. Molecular Regulation of Histamine Synthesis

    Directory of Open Access Journals (Sweden)

    Hua Huang

    2018-06-01

    Full Text Available Histamine is a critical mediator of IgE/mast cell-mediated anaphylaxis, a neurotransmitter and a regulator of gastric acid secretion. Histamine is a monoamine synthesized from the amino acid histidine through a reaction catalyzed by the enzyme histidine decarboxylase (HDC, which removes carboxyl group from histidine. Despite the importance of histamine, transcriptional regulation of HDC gene expression in mammals is still poorly understood. In this review, we focus on discussing advances in the understanding of molecular regulation of mammalian histamine synthesis.

  5. Design and synthesis of novel platelet fibrinogen receptor antagonists with 2H-1,4-benzoxazine-3(4H)-one scaffold. A systematic study.

    Science.gov (United States)

    Anderluh, Marko; Cesar, Jozko; Stefanic, Petra; Kikelj, Danijel; Janes, Damjan; Murn, Jernej; Nadrah, Kristina; Tominc, Mojca; Addicks, Elisabeth; Giannis, Athanassios; Stegnar, Mojca; Dolenc, Marija Sollner

    2005-01-01

    New platelet glycoprotein IIb/IIIa (GP IIb/IIIa, integrin alpha(IIb)beta3) antagonists were prepared on a 2H-1,4-benzoxazine-3(4H)-one scaffold. Their anti-aggregatory activities in human platelet rich plasma and their affinity towards alpha(IIb)beta3 and alpha(V)beta3 integrins were assessed. Various substitution positions and side chain variations were studied. In contrast to the generally accepted model, compounds containing ethyl esters as aspartate mimetics were in general more active than the corresponding free acids. We suggest an explanation for the observed behaviour of these new compounds.

  6. BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.

    Science.gov (United States)

    Ligneau, X; Perrin, D; Landais, L; Camelin, J-C; Calmels, T P G; Berrebi-Bertrand, I; Lecomte, J-M; Parmentier, R; Anaclet, C; Lin, J-S; Bertaina-Anglade, V; la Rochelle, C Drieu; d'Aniello, F; Rouleau, A; Gbahou, F; Arrang, J-M; Ganellin, C R; Stark, H; Schunack, W; Schwartz, J-C

    2007-01-01

    Histamine H3 receptor inverse agonists are known to enhance the activity of histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Its in vitro potency was approximately 6 times lower at the rodent receptor. In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days. In rats, the drug enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states and also enhanced fast cortical rhythms of the electroencephalogram, known to be associated with improved vigilance. On the two-trial object recognition test in mice, a promnesiant effect was shown regarding either scopolamine-induced or natural forgetting. These preclinical data suggest that BF2.649 is a valuable drug candidate to be developed in wakefulness or memory deficits and other cognitive disorders.

  7. Loss of Melanopsin Photoreception and Antagonism of the Histamine H3 Receptor by Ciproxifan Inhibit Light-Induced Sleep in Mice.

    Directory of Open Access Journals (Sweden)

    Fanuel Muindi

    Full Text Available Light has direct effects on sleep and wakefulness causing arousal in diurnal animals and sleep in nocturnal animals. In the present study, we assessed the modulation of light-induced sleep by melanopsin and the histaminergic system by exposing mice to millisecond light flashes and continuous light respectively. First, we show that the induction of sleep by millisecond light flashes is dose dependent as a function of light flash number. We found that exposure to 60 flashes of light occurring once every 60 seconds for 1-h (120-ms of total light over an hour induced a similar amount of sleep as a continuous bright light pulse. Secondly, the induction of sleep by millisecond light flashes was attenuated in the absence of melanopsin when animals were presented with flashes occurring every 60 seconds over a 3-h period beginning at ZT13. Lastly, the acute administration of a histamine H3 autoreceptor antagonist, ciproxifan, blocked the induction of sleep by a 1-h continuous light pulse during the dark period. Ciproxifan caused a decrease in NREMS delta power and an increase in theta activity during both sleep and wake periods respectively. The data suggest that some form of temporal integration occurs in response to millisecond light flashes, and that this process requires melanopsin photoreception. Furthermore, the pharmacological data suggest that the increase of histaminergic neurotransmission is sufficient to attenuate the light-induced sleep response during the dark period.

  8. The H1 detector

    International Nuclear Information System (INIS)

    Cozzika, G.

    1992-11-01

    The H1 detector presently operating at the HERA e-p collider is described. A general overview of the detector is given with particular emphasis on the calorimeters, the main element of which is a liquid Argon calorimeter enclosed within a large radius solenoid. Calorimetry in the proton direction, close to the beam-pipe is provided by a copper-silicon pad hadronic calorimeter. In the electron direction a lead-scintillator electromagnetic calorimeter closes the solid angle between the rear part of the liquid Argon calorimeter and the beam-pipe. An iron limited streamer tube tail catcher using the return yoke of the solenoid as absorber completes the calorimetry of the detector. The hardware triggers derived from the calorimeters are also described and some performance details of the calorimeters are given

  9. Time-dependent histamine release from stored human blood products

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K

    1996-01-01

    storage. Whole blood (six units), plasma-reduced whole blood (six units), and plasma- and buffy coat-reduced (saline-adenine-glucose-mannitol) (SAGM) blood (six units) from unpaid healthy donors were stored in the blood bank for 35 days at 4 degrees C. Plasma histamine and total cell-bound histamine......Perioperative transfusion of whole blood has been shown to amplify trauma-induced immunosuppression, which could be attenuated by perioperative administration of histamine2 receptor antagonists. Supernatants from different blood products were, therefore, analysed for histamine content during.......0 (range 176.0-910.0) nmol/l in whole blood and 475.0 (range 360.0-1560.0) nmol/l in plasma-reduced whole blood, while it was undetectable in SAGM blood. Spontaneous histamine release increased in a time-dependent manner from a median of 6.7 (range 2.2-17.4) nmol/l at the time of storage to 175.0 (range 33...

  10. Stimulation of phospholipase C in cultured microvascular endothelial cells from human frontal lobe by histamine, endothelin and purinoceptor agonists.

    Science.gov (United States)

    Purkiss, J. R.; West, D.; Wilkes, L. C.; Scott, C.; Yarrow, P.; Wilkinson, G. F.; Boarder, M. R.

    1994-01-01

    1. Cultures of endothelial cells derived from the microvasculature of human frontal lobe have been investigated for phospholipase C (PLC) responses to histamine, endothelins and purinoceptor agonists. 2. Using cells prelabelled with [3H]-inositol and measuring total [3H]-inositol (poly)phosphates, histamine acting at H1 receptors stimulated a substantial response with an EC50 of about 10 microM. 3. Endothelin-1 also gave a clear stimulation of phosphoinositide-specific phospholipase C. Both concentration-response curves and binding curves showed effective responses and binding in the rank order of endothelin-1 > sarafotoxin S6b > endothelin-3, suggesting an ETA receptor. 4. Assay of total [3H]-inositol (poly)phosphates showed no response to the purinoceptor agonists, 2-methylthioadenosine 5'-trisphosphate (2MeSATP), adenosine 5'-O-(3-thiotrisphosphate) (ATP gamma S) or beta,gamma-methylene ATP. Both ATP and UTP gave a small PLC response. 5. Similarly, when formation of [32P]-phosphatidic acid from cells prelabelled with 32Pi was used as an index of both PLC and phospholipase D, a small response to ATP and UTP was seen but there was no response to the other purinoceptor agonists tested. 6. Study by mass assay of stimulation by ATP of inositol (1,4,5) trisphosphate accumulation revealed a transient response in the first few seconds, a decline to basal, followed by a small sustained response. 7. These results show that human brain endothelial cells in culture are responsive to histamine and endothelins in a manner which may regulate brain capillary permeability. Purines exert a lesser influence. PMID:8032588

  11. TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

    Science.gov (United States)

    Vu, Michael T; Du, Guizhi; Bayliss, Douglas A; Horner, Richard L

    2015-10-07

    Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K(+) current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASK(f/f) mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30-50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30-50 Hz activity in ChAT-Cre:TASK(f/f) mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain

  12. The histamine content of oriental foods.

    Science.gov (United States)

    Chin, K W; Garriga, M M; Metcalfe, D D

    1989-05-01

    Several of the symptoms of scombroid poisoning (i.e. histamine toxicity) resemble those observed in people suffering from Chinese restaurant syndrome. Therefore, the histamine content of representative Chinese cuisine, which included 31 common dishes, 12 condiments and 12 basic ingredients from several sources, was measured using a sensitive and specific radioenzymatic assay. A further enzymatic procedure involving diamine oxidase was used to verify that the substance measured was histamine. A total of 184 assays were performed on 57 samples in the study. High levels of histamine were found in the cheeses, which were used as positive controls (863.6 micrograms histamine/g blue cheese and 107.4 micrograms histamine/g Parmesan cheese), and in some common condiments, including tamari (2392.2 micrograms histamine/g sample) and one brand of soy sauce (220.4 micrograms histamine/g sample). The histamine content of four condiments and three common dishes was over 10 micrograms histamine/g sample, while four condiments and 16 common dishes contained less than 1 microgram histamine/g sample. Calculations involving representative amounts of food that can be consumed at a typical oriental meal suggest that, in some cases, histamine intake may approach toxic levels. The results are discussed with regard to the possible role of histamine in reactions associated with restaurant meals.

  13. Effects of histamine and 5-hydroxytryptamine on the growth rate of xenografted human bronchogenic carcinomas.

    Science.gov (United States)

    Sheehan, P F; Baker, T; Tutton, P J; Barkla, D H

    1996-01-01

    1. The influence of histamine and 5-hydroxytryptamine (5-HT) antagonists and agonists on the volume doubling times (Td) of human bronchogenic carcinomas propagated as s.c. xenografts in immunosuppressed mice was examined. 2. The H2-receptor antagonists, cimetidine and ranitidine, increased Td. 3. Treatment with the H2-receptor agonist, 4-methyl histamine, had no effect on Td. 4. Co-administration of 4-methyl histamine and cimetidine abolished the effects of cimetidine. 5. The 5-HT2-receptor antagonists, cinanserin and ketanserin, both increased Td. 6. Treatment with the 5-HT1/2-receptor agonist quipazine (0.1 mg/kg, reflecting 5-HT2 agonist activity) decreased Td, while a higher dose (10.0 mg/kg) had no effect. 7. The 5-HT1/2-receptor antagonist, methiothepin, decreased Td. 8. The 5-HT uptake inhibitor, fluoxetine, increased Td in one tumour line but not in another, while the 5-HT releaser/depletor, fenfluramine, increased Td. 9. Histamine may stimulate tumour growth through the histamine H2-receptor, while the dominant effect of 5-HT is 5-HT1-receptor inhibition. 10. Tumour growth in some bronchogenic carcinomas may involve 5-HT uptake mechanisms.

  14. 7-Phenoxy-Substituted 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides as Positive Allosteric Modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors with Nanomolar Potency

    DEFF Research Database (Denmark)

    Goffin, Eric; Drapier, Thomas; Larsen, Anja Probst

    2018-01-01

    We report here the synthesis of 7-phenoxy-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides and their evaluation as AMPA receptor positive allosteric modulators (AMPApams). The impact of substitution on the phenoxy ring and on the nitrogen atom at the 4-position was examined. At GluA2......-ray scattering (SAXS) experiments using isolated GluA2 ligand-binding domain (GluA2-LBD) are consistent with binding of one molecule of 11m per dimer interface, contrary to most benzothiadiazine dioxides developed to date. This observation was confirmed by the X-ray structure of 11m bound to GluA2-LBD and by NMR......(Q) expressed in HEK293 cells (calcium flux experiment), the most potent compound was 11m (4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide, EC50 = 2.0 nM). The Hill coefficient in the screening and the shape of the dimerization curve in small-angle X...

  15. H1 at HERA Exhibition

    CERN Multimedia

    2000-01-01

    H1 is one of the two large detectors installed at HERA, the first electron-proton accelerator, located at DESY in Hamburg. The H1 collaboration regroups physicists from 32institutes of 11countries all over the world.

  16. Individual receptor profiling as a novel tool to support diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC).

    Science.gov (United States)

    Neuhaus, Jochen; Schulte-Baukloh, Heinrich; Stolzenburg, Jens-Uwe; Speroni di Fenizio, Pietro; Horn, Lars-Christian; Rüffert, Henrik; Hartenstein, Siegurd; Burger, Maximilian; Schulze, Matthias; Schwalenberg, Thilo

    2012-10-01

    Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor. Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n = 44; age 60.64 ± 13.78, mean ± SD) and carcinoma patients (n = 11; age 58.91 ± 12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1-3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR). M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2 > M3 and M3 > M2) were observed, which differed in associated purinergic and histamine receptor expression. M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.

  17. Sickle erythrocytes enhance phenylephrine and histamine ...

    African Journals Online (AJOL)

    Sickle erythrocytes enhance phenylephrine and histamine contractions of isolated rabbit carotid arteries. ... enhancement of histamine contractions, compared with phenylephrine (in AS and SS), suggests a possible role for histamine in the increased vascular tone and vaso-occlusive crisis in sickle cell disease.

  18. Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

    LENUS (Irish Health Repository)

    Gong, H

    1990-03-01

    The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

  19. Comparison of methods for intestinal histamine application

    DEFF Research Database (Denmark)

    Vind, S; Søondergaard, I; Poulsen, L K

    1991-01-01

    The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast ...... conclude that oral administration of enterosoluble capsules is an easy and appropriate method for intestinal histamine challenge. Fast and histamine-restrictive diets are not necessary, but subjects should record unexpected responses in a food and symptom diary.......The study was conducted to investigate whether introduction of histamine in enterosoluble capsules produced the same amount of urinary histamine metabolites as that found after application of histamine through a duodeno-jejunal tube. Secondly, to examine whether a histamine-restrictive or a fast...... all other intervals did not differ significantly between the two challenge regimens. Fast (water only) and histamine-restrictive diet versus non-restrictive diet did not affect the urinary MIAA. MIAA was significantly higher overall during the first 24 h after challenge than in any other fraction. We...

  20. Histamine 50-skin-prick test: a tool to diagnose histamine intolerance.

    Science.gov (United States)

    Kofler, Lukas; Ulmer, Hanno; Kofler, Heinz

    2011-01-01

    Background. Histamine intolerance results from an imbalance between histamine intake and degradation. In healthy persons, dietary histamine can be sufficiently metabolized by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the key enzyme in degradation. Histamine elicits a wide range of effects. Histamine intolerance displays symptoms, such as rhinitis, headache, gastrointestinal symptoms, palpitations, urticaria and pruritus. Objective. Diagnosis of histamine intolerance until now is based on case history; neither a validated questionnaire nor a routine test is available. It was the aim of this trial to evaluate the usefullness of a prick-test for the diagnosis of histamine intolerance. Methods. Prick-testing with 1% histamine solution and wheal size-measurement to assess the relation between the wheal in prick-test, read after 20 to 50 minutes, as sign of slowed histamine degradation as well as history and symptoms of histamine intolerance. Results. Besides a pretest with 17 patients with HIT we investigated 156 persons (81 with HIT, 75 controls): 64 out of 81 with histamine intolerance(HIT), but only 14 out of 75 persons from the control-group presented with a histamine wheal ≥3 mm after 50 minutes (P < .0001). Conclusion and Clinical Relevance. Histamine-50 skin-prickt-test offers a simple tool with relevance.

  1. Second generation H1 - antihistamines interaction with food and alcohol-A systematic review.

    Science.gov (United States)

    Paśko, Paweł; Rodacki, Tomasz; Domagała-Rodacka, Renata; Palimonka, Krzysztof; Marcinkowska, Monika; Owczarek, Danuta

    2017-09-01

    Histamine is a mediator of many physiological processes. It plays an important role in modulating allergy reactions and immune system responses. H1 receptor is a therapeutic target for drugs applied in allergic diseases such as allergic rhinoconjunctivitis, urticarial, or atopic dermatitis. H1-antihistamines display different chemical structures, pharmacokinetics and a potential for drug-drug and drug-food interactions. Drug-food interactions are known to reduce therapeutic effects of the medicine, as well as to induce a potent adverse drug reactions. Considering it all, a systematic review was conducted to investigate the importance of drug-food interaction for H1-antihistamine drugs. As non-sedating second generation H1-antihistamines remain to be drugs of choice in treating allergic conditions, the review has been focused on this particular class of medicines. The aim of this paper is to examine the evidence of food-drug and food-alcohol interactions for second generation H1-antihistamine drugs. A systematic literature queries were performed in the following databases: Medline (via PubMed), Cochrane Library, Embase and Web of Science (all from their inception date till October 2016). The queries covered nine specific names of second generation anthistamine drugs, namely bilastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mizolastine, and rupatadine, in combinations with such terms as "food", "juice", "grapefruit", "fruits", "alcohol", "pharmacokinetics", and "meal". Additional publications were found by checking all the reference lists. Where none data on drug-food interaction could be found within the investigated databases, a specific drug prescribing information was used. 2326 publications were identified with the database queries. Articles were subjected to analysis by reviewing their title, abstract and full text; duplicated papers were removed. Having collected a complete set of data, a critical review was undertaken

  2. Studies on the role of central histamine in the acquisition of a radiation-induced conditioned taste aversion

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1982-01-01

    The experiments described in this report were designed to test two hypotheses about how exposure to low-level radiation can affect the behavior of an organism: first, tht radiation effects on behavior are mediated by a radiation-induced release of histamine; and second, that this radiation-induced histamine release can exert relatively direct effects on the central nervous system. The results of the first experiment showed that microinjection of histamine directly into the fourth ventricle of rats produced a taste aversion to a novel sucrose solution. Pretreating rats with intraventricular H 1 or H 2 blockers was not effective in preventing the acquisition of the radiation-induced aversion, although the H 1 blocker did prevent the acquisition of a histamine-induced taste aversion. It also was not possible to establish a cross-tolerance between centrally administered histamine and radiation. The results are interpreted as not supporting the hypothesis that a radiation-induced release of central histamine mediates the acquisition of a conditioned taste aversion following exposure to low-level radiation

  3. Facilitating effect of histamine on spatial memory deficits induced by dizocilpine as evaluated by 8-arm radial maze in SD rats%组胺对地佐环平诱发的SD大鼠八臂迷宫空间记忆障碍的改善作用

    Institute of Scientific and Technical Information of China (English)

    黄育文; 陈忠; 胡薇薇; 张力三; 吴炜; 应力阳; 魏尔清

    2003-01-01

    AIM: To investigate whether or not histamine is involved in spatial memory deficits induced by dizocilpine (MK 801) as evaluated by 8-arm radial maze of rats. METHODS: 8-Arm (4-arm baited) radial maze was used to measure spatial memory in rats. RESULTS: Bilaterally intrahippocampal (ih) injection of MK-801 (0.3 μg/site) impaired working memory and reference memory in rats. Both histamine (50, 100 ng/site, ih) and intraperitoneal (ip) injection of histidine (100, 200 mg/kg) markedly improved the spatial memory deficits induced by MK-801. On the other hand, the ameliorating effect of histidine (100 mg/kg, ip) was completely antagonized by αfluoromethylhistidine (α-FMH, 5 μg/site, ih), a potent and selective histidine decarboxylase (HDC) inhibitor, and H1-antagonist pyrilamine (1 μg/site, ih), but not by H2-antagonist cimetidine, even at a high dose (2.5 μg/site, ih).CONCLUSION: The hippocampal histamine plays an important role in the ameliorating effect on MK-801-induced spatial memory deficits, and its action is mediated through postsynaptic H1-receptor.

  4. Validation of basophil histamine release against the autologous serum skin test and outcome of serum-induced basophil histamine release studies in a large population of chronic urticaria patients

    DEFF Research Database (Denmark)

    Platzer, M H; Grattan, C E H; Poulsen, Lars K.

    2005-01-01

    the immunoglobulin E (IgE) or the high affinity IgE receptor (FcepsilonRI) and serum-induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine-releasing assay (the HR-Urtikaria test) in a group of well-characterized CU patients...... and subsequently determined the frequency of HR-Urticaria-positive sera from a larger population of CU patients....

  5. H1 in RSA galaxies

    Science.gov (United States)

    Richter, OTTO-G.

    1993-01-01

    The original Revised Shapley-Ames (RSA) galaxy sample of almost 1300 galaxies has been augmented with further bright galaxies from the RSA appendix as well as newer galaxy catalogs. A complete and homogeneous, strictly magnitude-limited all-sky sample of 2345 galaxies brighter than 13.4 in apparent blue magnitude was formed. New 21 cm H1 line observations for more than 600 RSA galaxies have been combined with all previously available H1 data from the literature. This new extentise data act allows detailed tests of widely accepted 'standard' reduction and analysis techniques.

  6. Fluorometric determination of histamine in cheese.

    Science.gov (United States)

    Chambers, T L; Staruszkiewicz, W F

    1978-09-01

    Thirty-one samples of cheese obtained from retail outlets were analyzed for histamine, using an official AOAC fluorometric method. The types of cheese analyzed and the ranges of histamine found were: colby, 0.3--2.8; camembert, 0.4--4.2; cheddar, 1.2--5.8; gouda, 1.3--2.4; provolone, 2.0--23.5; roquefort, 1.0--16.8; mozzarella 1.6--5.0; and swiss, 0.4--250 mg histamine/100 g. Ten of the 12 samples of swiss cheese contained less than 16 mg histamine/100 g. The remaining 2 samples which contained 116 and 250 mg histamine/100 g were judged organoleptically to be of poor quality. An investigation of one processing facility showed that the production of histamine in swiss cheese may have been a result of a hydrogen peroxide/low temperature treatment of the milk supply. Recovery of histamine added to methanol extracts of cheese ranged from 93 to 105%. Histamine content was confirmed by high pressure liquid chromatographic analysis of the methanol extracts.

  7. Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P.

    Science.gov (United States)

    Smith, Ewan St John; Blass, Gregory R C; Lewin, Gary R; Park, Thomas J

    2010-05-24

    Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber) and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG) neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP) in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

  8. Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P

    Directory of Open Access Journals (Sweden)

    Lewin Gary R

    2010-05-01

    Full Text Available Abstract Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

  9. Different perception levels of histamine-induced itch sensation in young adult mice.

    Science.gov (United States)

    Ji, Yeounjung; Jang, Yongwoo; Lee, Wook Joo; Yang, Young Duk; Shim, Won-Sik

    2018-05-01

    Itch is an unpleasant sensation that evokes behavioral responses such as scratching the skin. Interestingly, it is conceived that the perception of itch sensation is influenced by age. Indeed, accumulating evidence supports the idea that even children or younger adults show distinctive itch sensation depending on age. This evidence implies the presence of a mechanism that regulates the perception of itch sensation in an age-dependent fashion. Therefore, the purpose of the present study was to investigate a putative mechanism for the age-dependent perception of itch sensation by comparing histamine-induced scratching behaviors in 45-day old (D45) and 75-day old male "young adult" mice. The results indicated that, following histamine administration, the D75 mice spent a longer time scratching than D45 mice. However, the intensity of the calcium influx induced by histamine in primary culture of dorsal root ganglia (DRG) neurons was not different between D45 and D75 mice. Moreover, no apparent difference was observed in mRNA levels of a characteristic His-related receptor and ion channel. In contrast, the mRNA levels of Toll-Like Receptor 4 (TLR4) were increased approximately by two-fold in D75 DRG compared with D45 DRG. Additionally, D75-derived DRG neurons exhibited enhanced intracellular calcium increase by lipopolysaccharide (LPS, a TLR4 agonist) than those of D45 mice. Furthermore, intensities of calcium influx induced by histamine were significantly potentiated when co-treated with LPS in D75 DRG neurons, but not in those of D45 mice. Thus, it appears that D75 mice showed enhanced histamine-induced scratching behaviors not by increased expression levels of histamine-related genes, but probably due to augmented TLR4 expression in DRG neurons. Consequently, the current study found that different perception levels of histamine-induced itch sensation are present in different age groups of young adult mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. H1 antihistamines and driving

    OpenAIRE

    Florin-Dan, Popescu

    2008-01-01

    Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion, Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and...

  11. Symptoms of pseudoallergy and histamine metabolism disorders

    Directory of Open Access Journals (Sweden)

    Joanna Kacik

    2016-09-01

    Full Text Available Histamine intolerance is a poorly investigated type of hypersensitivity responsible for a number of often serious symptoms, erroneously interpreted as food allergy. Endogenous histamine originates from the histidine amino acid with the help of the histidine decarboxylase enzyme. Apart from the endogenous production histamine may be supplied to the body with food. Slow-maturing and fermenting products are characterised by particularly high levels of histamine. Some food products stimulate excessive release of histamine from stores in the body as well as containing significant amounts of it. These products include spices, herbs, dried fruits and a large group of food additives. Histamine intolerance is considered to be a condition in which the amount of histamine in the body exceeds its tolerance threshold, which leads to the development of adverse reactions. These reactions primarily include skin symptoms (pruritus, urticaria, skin reddening, acne lesions, angioedema, respiratory symptoms (nasal obstruction and watery discharge, sneezing, coughing, wheezing, gastrointestinal symptoms (abdominal cramps, diarrhoea, bloating, nervous system symptoms (headaches, fatigue, irritability, anxiety, panic attacks, cardiovascular symptoms (tachycardia, hypotension, chest pain, primary dysmenorrhoea and many more. It is estimated that nearly 1% of society is susceptible to histamine intolerance. The diagnosis of this disorder is based on observing at least two characteristic symptoms and their disappearance or improvement following histamine-free diet. A new, although not easily accessible diagnostic tool is assay for serum diamine oxidase activity, which correlates to a significant extent with symptoms of histamine intolerance. Normal activity of diamine oxidase is considered to be the amount of >80 HDU/mL, decreased activity – 40–80 HDU/mL and severely decreased activity – <40 HDU/mL. Currently the option of diamine oxidase supplementation is

  12. The role of the central histaminergic receptors in the exercise-induced improvements of the spatial learning and memory in rats.

    Science.gov (United States)

    Taati, Majid; Moghaddasi, Mehrnoush; Esmaeili, Masoumeh; Pourkhodadad, Soheila; Nayebzadeh, Hassan

    2014-10-31

    While it is well known that exercise can improve cognitive performance, the underlying mechanisms are not fully understood. There is now evidence that histamine can modulate learning and memory in different types of behavioral tasks. The present study was designed to examine the possible role of central histamine H1 and H2 receptors in forced treadmill running-induced enhancement of learning and memory in rats. For this purpose the animals received intracerebroventricularly chlorpheniramine (H1 receptor blocker) and cimetidine (H2 receptor blocker) before each day of fifteen consecutive days of exercise. Then their learning and memory were tested on the water maze task using a four-trial-per-day for 4 consecutive days. A probe trial was performed after the last training day. Our data showed that cimetidine reversed the exercise-induced improvement in learning and memory in rats; however, this was not the case regarding chlorpheniramine. Our findings indicate that central histamine H2 receptors play an important role in mediating the beneficial effects of forced exercise on learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. H1 antihistamines and driving.

    Science.gov (United States)

    Popescu, Florin Dan

    2008-01-01

    Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion. Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one.

  14. Degradation of Histamine by Lactobacillus plantarum Isolated from Miso Products.

    Science.gov (United States)

    Kung, Hsien-Feng; Lee, Yi-Chen; Huang, Ya-Ling; Huang, Yu-Ru; Su, Yi-Cheng; Tsai, Yung-Hsiang

    2017-10-01

    Histamine is a toxic chemical and is the causative agent of food poisoning. This foodborne toxin may be degraded by the oxidative deamination activity of certain microorganisms. In this study, we isolated four histamine-degrading Lactobacillus plantarum bacteria from miso products. Among them, L. plantarum D-103 exhibited 100% degradation of histamine in de Man Rogosa Sharpe (MRS) broth containing 50 ppm of histamine after 24 h of incubation at 30°C. The optimal growth, histamine oxidase, and histamine-degrading activity of L. plantarum D-103 were observed in histamine MRS broth at pH 7.0, 3% NaCl, and 30°C. It also exhibited tolerance to broad ranges of pH (4 to 10) and salt concentrations (0 to 12%) in histamine MRS broth. Therefore, the histamine-degrading L. plantarum D-103 might be used as an additive culture to prevent histamine accumulation in miso products during fermentation.

  15. UVB-induced systemic immunosuppression: role of mast cells and histamine

    International Nuclear Information System (INIS)

    Hart, P.H.; Grimbaldeston, M.A.; Finlay-Jones, J.J.

    1999-01-01

    Full text: UVB radiation (290-320 nm) is immunosuppressive by multiple mechanisms allowing the outgrowth of UV-induced tumours in both mouse and man. Furthermore, patients with non-melanoma skin cancers have a higher risk of death from other cancers which could be explained by UV-induced immunomodulation. The mechanism(s) of suppression by UVB depend on whether the sensitising antigen is applied to the irradiated site ('local') or to non-irradiated sites ('systemic'). In the former, the activity of UV-induced TNFα is important as it affects the migration of Langerhans cells to draining lymph nodes. In contrast, histamine from dermal mast cells is critical to the early events by which UVB can suppress systemic immune responses. The prevalence of dermal mast cells in 7 strains and substrains of mice correlates directly with their susceptibility to UVB-induced systemic immunosuppression. Furthermore, mast cell depleted mice (Wf/Wf) are resistant to UVB-induced systemic immunomodulation. However, they become susceptible after reconstitution of the site to be irradiated with bone marrow derived mast cell precursors. The mice also gain susceptibility to cis-urocanic acid-induced systemic immunomodulation. There is considerable evidence that histamine is the mast cell product critical to downstream immunosuppressive events. Firstly, physiological concentrations of histamine suppress contact hypersensitivity responses. Secondly, histamine receptor antagonists halve UVB-induced systemic immunosuppression. Thirdly, mice with different UVB-susceptibilities are equally susceptible to histamine-induced immunosuppression, and finally, histamine can suppress contact hypersensitivity responses in Wf/Wf mice. We suggest that histamine may be immunomodulatory by multiple pathways. Histamine can induce the production of immunosuppressive prostanoids from keratinocytes. A lymphocyte-derived, histamine-induced suppressor factor was reported in the 1970's. More recently histamine has

  16. A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells

    Directory of Open Access Journals (Sweden)

    Chen Eric Y

    2012-01-01

    Full Text Available Abstract Background Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca2+ signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO2 NPs, a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain. Results TiO2 NP exposure increased both histamine secretion and cytosolic Ca2+ concentration ([Ca2+]C in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca2+ levels resulted primarily from an extracellular Ca2+ influx via membrane L-type Ca2+ channels. Unspecific Ca2+ entry via TiO2 NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO2 NPs also contributed to cytosolic Ca2+ signaling. The PLC-IP3-IP3 receptor pathways and endoplasmic reticulum (ER were responsible for the sustained elevation of [Ca2+]C and histamine secretion. Conclusion Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO2 NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.

  17. Simultaneous detection of pH changes and histamine release from oxyntic glands in isolated stomach.

    Science.gov (United States)

    Bitziou, Eleni; O'Hare, Danny; Patel, Bhavik Anil

    2008-11-15

    Real-time simultaneous detection of changes in pH and levels of histamine over the oxyntic glands of guinea pig stomach have been investigated. An iridium oxide pH microelectrode was used in a potentiometric mode to record the pH decrease associated with acid secretion when the sensor approached the isolated tissue. A boron-doped diamond (BDD) microelectrode was used in an amperometric mode to detect histamine when the electrode was placed over the tissue. Both sensors provided stable and reproducible responses that were qualitatively consistent with the signaling mechanism for acid secretion at the stomach. Simultaneous measurements in the presence of pharmacological treatments produced significant variations in the signals obtained by both sensors. As the H2 receptor antagonist cimetidine was perfused to the tissue, histamine levels increased that produced an increase in the signal of the BDD electrode whereas the pH sensor recorded a decrease in acid secretion as expected. Addition of acetylcholine (ACh) stimulated additional acid secretion detected with the pH microelectrode whereas the BDD sensor recorded the histamine levels decreasing significantly. This result shows that the primary influence of ACh is directly on the parietal cell receptors rather then the ECL cell receptors of the oxyntic glands. These results highlight the power of this simultaneous detection technique in the monitoring and diagnosis of physiological significant signaling mechanisms and pathways.

  18. Histamine intolerance as a cause of chronic digestive complaints in pediatric patients

    Directory of Open Access Journals (Sweden)

    Antonio Rosell-Camps

    2013-04-01

    Full Text Available Introduction: histamine intolerance (HI is a poorly described disease in gastroenterology that may present with predominant digestive complaints. The goals of this study include a report of two cases diagnosed in a pediatric gastroenterology clinic. Material and methods: observational, retrospective study of patients diagnosed with HI from September 2010 to December 2011 at the pediatric gastroenterology clinic of a tertiary hospital. They were deemed to have a diagnosis of HI in the presence of 2 or more characteristic digestive complaints, decreased diamino oxidase (DAO levels and/or response to a low histamine diet with negative IgE-mediated food allergy tests. Results: sixteen patients were diagnosed. Males predominated versus females (11/5. Mean age at symptom onset was 4 years (6 months vs. 13 years and 6 months and mean age at diagnosis was 6 years and 6 months (17 months vs. 13 years and 11 months, with an interval of 2 years and 1 month between symptom onset and diagnosis (5 months vs. 4 years. Predominant symptoms included diffuse abdominal pain (16/16, intermittent diarrhea (10/16, headache (5/16, intermittent vomiting (4/16, and skin rash (2/16. The diagnosis was established by measuring plasma diamino oxidase levels, which were below 10 kU/L (normal > 10 kU/L in 14 cases, and symptom clearance on initiating a low histamine diet. In two patients DAO levels were above 10 kU/L but responded to diet. Treatment was based on a diet low in histamine-contaning food, and antihistamines H1 y H2 had to be added for two cases. Conclusions: histamine intolerance is a little known disease with a potentially relevant incidence. Predominant complaints include diffuse abdominal pain, diarrhea, headache, and chronic intermittent vomiting. Its diagnosis is based on clinical suspicion, plasma DAO measurement, and response to a low histamine diet. Management with the latter provides immediate improvement.

  19. Nettle extract (Urtica dioica) affects key receptors and enzymes associated with allergic rhinitis.

    Science.gov (United States)

    Roschek, Bill; Fink, Ryan C; McMichael, Matthew; Alberte, Randall S

    2009-07-01

    A nettle (Urtica dioica) extract shows in vitro inhibition of several key inflammatory events that cause the symptoms of seasonal allergies. These include the antagonist and negative agonist activity against the Histamine-1 (H(1)) receptor and the inhibition of mast cell tryptase preventing degranulation and release of a host of pro-inflammatory mediators that cause the symptoms of hay fevers. The nettle extract also inhibits prostaglandin formation through inhibition of Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), and Hematopoietic Prostaglandin D(2) synthase (HPGDS), central enzymes in pro-inflammatory pathways. The IC(50) value for histamine receptor antagonist activity was 251 (+/-13) microg mL(-1) and for the histamine receptor negative agonist activity was 193 (+/-71) microg mL(-1). The IC(50) values for inhibition of mast cell tryptase was 172 (+/-28) microg mL(-1), for COX-1 was 160 (+/-47) microg mL(-1), for COX-2 was 275 (+/-9) microg mL(-1), and for HPGDS was 295 (+/-51) microg mL(-1). Through the use of DART TOF-MS, which yields exact masses and relative abundances of compounds present in complex mixtures, bioactives have been identified in nettle that contribute to the inhibition of pro-inflammatory pathways related to allergic rhinitis. These results provide for the first time, a mechanistic understanding of the role of nettle extracts in reducing allergic and other inflammatory responses in vitro. Copyright 2009 John Wiley & Sons, Ltd.

  20. Mapping of the receptor protein-tyrosine kinase 10 to human chromosome 1q21-q23 and mouse chromosome 1H1-5 by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Edelhoff, S.; Disteche, C.M. [Univ. of Washington School of Medicine, Seattle, WA (United States); Lai, C. [Scripps Research Inst., LaJolla, CA (United States)

    1995-01-01

    Receptor protein-tyrosine kinases (PTKs) play a critical role in the transduction of signals important to cell growth, differentiation, and survival. Mutations affecting the expression of receptor PTK genes have been associated with a number of vertebrate and invertebrate developmental abnormalities, and the aberrant regulation of tyrosine phosphorylation is implicated in a variety of neoplasias. One estimate suggests that approximately 100 receptor PTK genes exist in the mammalian genome, about half of which have been identified. The tyro-10 receptor protein-tyrosine kinase, first identified in a PCR-based survey for novel tyrosine kinases in the rat nervous system, defines a new subfamily of PTKs. It exhibits a catalytic domain most closely related to those found in the trk PTK receptor subfamily, which transduces signals for nerve growth factor and the related molecules brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4 (NT-3 and NT-4). Trk and the related PTK receptors trkB and trkC play a critical role in the neurotrophin-dependent survival of subsets of sensory and motor neurons. The predicted tyro-10 extracellular region is, however, distinct from that of the trk subfamily and is unique except for a domain shared with the blood coagulation factors V and VIII, thought to be involved in phospholipid binding. Although tyro-10 RNA is most abundant in heart and skeletal muscle in the adult rat, it is expressed in a wide variety of tissues, including the developing and mature brain. Tyro-10 appears identical to the murine TKT sequence reported by Karn et al. and exhibits a high degree of similarity with the CaK, DDR, and Nep PTKs. A ligand for tyro-10 has not yet been identified. 10 refs., 1 fig.

  1. Histamine (Scombroid) Fish Poisoning: a Comprehensive Review.

    Science.gov (United States)

    Feng, Charles; Teuber, Suzanne; Gershwin, M Eric

    2016-02-01

    Histamine fish poisoning, also known as scombroid poisoning, is the most common cause of ichythyotoxicosis worldwide and results from the ingestion of histamine-contaminated fish in the Scombroidae and Scomberesocidae families, including mackerel, bonito, albacore, and skipjack. This disease was first described in 1799 in Britain and re-emerged in the medical literature in the 1950s when outbreaks were reported in Japan. The symptoms associated with histamine fish poisoning are similar to that of an allergic reaction. In fact, such histamine-induced reactions are often misdiagnosed as IgE-mediated fish allergy. Indeed, histamine fish poisoning is still an underrecognized disease. In this review, we discuss the epidemiology, pathophysiology, evaluation, and treatment of scombroid disease. Because more than 80% of fish consumed in the USA is now imported from other countries, the disease is intimately linked with the global fish trade (National Marine Fisheries Service, 2012). Preventing future scombroid outbreaks will require that fishermen, public health officials, restaurant workers, and medical professionals work together to devise international safety standards and increase awareness of the disease. The implications of scombroid poisoning go far beyond that of fish and have broader implications for the important issues of food safety.

  2. Determination of histamine in Iranian cheese using enzyme-linked ...

    African Journals Online (AJOL)

    john

    enzyme-linked immunosorbent assay (ELISA) method. Mojtaba ... Histamine is a simple chemical substance created during processing of the amine acid histidine. Histamine is also an .... Institute of environment Health and Forensic. Sciences ...

  3. Prognosis of hospitalized patients with 2009 H1N1 influenza in Spain: influence of neuraminidase inhibitors

    Science.gov (United States)

    Delgado-Rodríguez, Miguel; Castilla, Jesús; Godoy, Pere; Martín, Vicente; Soldevila, Nuria; Alonso, Jordi; Astray, Jenaro; Baricot, Maretva; Cantón, Rafael; Castro, Ady; Gónzález-Candelas, Fernando; Mayoral, José María; Quintana, José María; Pumarola, Tomás; Tamames, Sonia; Sáez, Marc; Domínguez, Angela

    2012-01-01

    Background The H1N1 influenza pandemic strain has been associated with a poor prognosis in hospitalized patients. The present report evaluates the factors influencing prognosis. Methods A total of 813 patients hospitalized with H1N1 influenza in 36 hospitals (nationwide) in Spain were analysed. Detailed histories of variables preceding hospital admission were obtained by interview, validating data on medications and vaccine with their attending physicians. Data on treatment and complications during hospital stay were recorded. As definition of poor outcome, the endpoints of death and admission to intensive care were combined; and as a further outcome, length of stay was used. Results The mean age was 38.5 years (SD 22.8 years). There were 10 deaths and 79 admissions to intensive care (combined, 88). The use of neuraminidase inhibitors was reported by 495 patients (60.9%). The variables significantly associated with a poor outcome were diabetes (OR = 2.21, 95% CI = 1.21–4.02), corticosteroid therapy (OR = 3.37, 95% CI = 1.39–8.20) and use of histamine-2 receptor antagonists (OR = 2.68, 95% CI = 1.14–6.36), while the use of neuraminidase inhibitors (OR = 0.57, 95% CI = 0.34–0.94) was protective. Neuraminidase inhibitors within the first 2 days after the influenza onset reduced hospital stay by a mean of 1.9 days (95% CI = 4.7–6.6). Conclusions The use of neuraminidase inhibitors decreases the length of hospital stay and admission to intensive care and/or death. PMID:22467633

  4. Histamine and the regulation of body weight

    DEFF Research Database (Denmark)

    Jørgensen, Emilie A; Knigge, Ulrich; Warberg, Jørgen

    2007-01-01

    Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter. In the p......Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter...

  5. Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

    Directory of Open Access Journals (Sweden)

    Sachiko Chikahisa

    Full Text Available Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS. Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v mice. No significant difference was found in the basal amount of sleep/wake between W/W(v mice and their wild-type littermates (WT, although W/W(v mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v mice. Injection of H1 antagonists (triprolidine and mepyramine significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v mice. W/W(v mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

  6. Synergistic antitumor activity of histamine plus melphalan in isolated limb perfusion: preclinical studies.

    Science.gov (United States)

    Brunstein, Flavia; Hoving, Saske; Seynhaeve, Ann L B; van Tiel, Sandra T; Guetens, Gunther; de Bruijn, Ernst A; Eggermont, Alexander M M; ten Hagen, Timo L M

    2004-11-03

    We have previously shown how tumor response of isolated limb perfusion (ILP) with melphalan was improved when tumor necrosis factor alpha (TNF-alpha) was added. Taking into account that other vasoactive drugs could also improve tumor response to ILP, we evaluated histamine (Hi) as an alternative to TNF-alpha. We used a rat ILP model to assess the combined effects of Hi and melphalan (n = 6) on tumor regression, melphalan uptake (n = 6), and tissue histology (n = 2) compared with Hi or melphalan alone. We also evaluated the growth of BN-175 tumor cells as well as apoptosis, necrosis, cell morphology, and paracellular permeability of human umbilical vein endothelial cells (HUVECs) after Hi treatment alone and in combination with melphalan. The antitumor effect of the combination of Hi and melphalan in vivo was synergistic, and Hi-dependent reduction in tumor volume was blocked by H1 and H2 receptor inhibitors. Tumor regression was observed in 66% of the animals treated with Hi and melphalan, compared with 17% after treatment with Hi or melphalan alone. Tumor melphalan uptake increased and vascular integrity in the surrounding tissue was reduced after ILP treatment with Hi and melphalan compared with melphalan alone. In vitro results paralleled in vivo results. BN-175 tumor cells were more sensitive to the cytotoxicity of combined treatment than HUVECs, and Hi treatment increased the permeability of HUVECs. Hi in combination with melphalan in ILP improved response to that of melphalan alone through direct and indirect mechanisms. These results warrant further evaluation in the clinical ILP setting and, importantly, in organ perfusion.

  7. H1N1 influenza (Swine flu)

    Science.gov (United States)

    Swine flu; H1N1 type A influenza ... The H1N1 virus is now considered a regular flu virus. It is one of the three viruses included in the regular (seasonal) flu vaccine . You cannot get H1N1 flu virus from ...

  8. H1-antihistamines in pregnancy and lactation.

    Science.gov (United States)

    Schatz, Michael

    2002-01-01

    Antihistamines may be used for the treatment of allergic rhinitis, upper respiratory infections, urticaria/angioedema, atopic dermatitis, and, rarely, as adjunctive treatment for anaphylaxis, during pregnancy. Because these illnesses may affect maternal comfort and safety as well as threaten the fetus directly (anaphylaxis) or indirectly, they often require therapy during pregnancy. Based on the information available to date, in this chapter we have attempted to provide rational guidelines for the gestational use of H1-receptor antagonists in a manner that will lead to the optimal well-being of both the mother and her infant. As more information becomes available, the recommendations herein may require modification. Although this chapter has dealt specifically with gestational management, a case can be made for considering this information when making therapeutic decisions in all women of childbearing potential. First, most pregnancies are unplanned, and the peak period of fetal vulnerability to drug-induced teratogenesis begins the day a woman's period is due. Second, during gestation, substantial alterations in a previously successful but not optimal-for-pregnancy chronic therapeutic regimen may be psychologically threatening to the patient and may lead to either uncontrolled disease or unanticipated side effects. Thus, pregnancy-appropriate regimens should ideally be discussed with all women of childbearing age as part of the informed therapeutic decision-making process.

  9. Brain Activation by H1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in Suncus murinus (House Musk Shrew

    Directory of Open Access Journals (Sweden)

    Longlong Tu

    2017-06-01

    Full Text Available Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, Suncus murinus was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant, and cetirizine (non-brain penetrant, along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pKb values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p. and scopolamine (10 mg/kg, i.p., but not cetirizine (10 mg/kg, i.p., significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c

  10. Sickle erythrocytes enhance phenylephrine and histamine

    African Journals Online (AJOL)

    Dr Olaleye

    the influence of sickle erythrocyte on contractile responses induced by phenylephrine and histamine. ... obtained from subjects of different haemoglobin (Hb) genotypes (AA, AS and SS), under ... the sixth position of the β-chain of the hemoglobin S. Address for ... blood pressure values in sickle cell anaemia subjects as.

  11. Histamine metabolism in cluster headache and migraine. Catabolism of /sup 14/C histamine

    Energy Technology Data Exchange (ETDEWEB)

    Sjaastad, O; Sjaastad, O V

    1977-09-12

    Various parameters of histamine metabolism were studied in patients with migraine, cluster headache and chronic paroxysmal hemicrania. These included urinary excretion of radioactivity and of /sup 14/C histamine and its metabolites, exhaled /sup 14/CO/sub 2/ and fecal radioactivity after oral as well as subcutaneous administration of radioactive histamine. No marked deviation from the normal was found except in one patient with the cluster headache variant, chronic paroxysmal hemicrania, in whom an aberration in /sup 14/C histamine degradation seemed to be present. Only minute quantities of the /sup 14/C histamine metabolite C14 imidazoleacetic acid riboside seemed to be formed during a period with severe paraxysms. During a symptom-free period no deviation from normal was observed. The most likely explanation for this finding seems to be a defect in the conversion of imidazoleacetic acid to its riboside. This defect may possibly explain the increased urinary excretion of histamine in this particular patient. The relationship of this metabolic aberration to the production of headache still remains dubious for various reasons.

  12. The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1

    Science.gov (United States)

    Qin, Liuliang; Zhao, Dezheng; Xu, Jianfeng; Ren, Xianghui; Terwilliger, Ernest F.; Parangi, Sareh; Lawler, Jack; Dvorak, Harold F.

    2013-01-01

    Angiogenesis plays an important role in cancer and in many other human diseases. Vascular endothelial growth factor-A (VEGF-A), the best known angiogenic factor, was originally discovered as a potent vascular permeability factor (VPF), suggesting that other vascular permeabilizing agents, such as histamine and serotonin, might also have angiogenic activity. We recently demonstrated that, like VEGF-A, histamine and serotonin up-regulate the orphan nuclear receptor and transcription factor TR3 (mouse homolog Nur77) and that TR3/Nur77 is essential for their vascular permeabilizing activities. We now report that histamine and serotonin are also angiogenic factors that, at low micromolar concentrations, induce endothelial cell proliferation, migration and tube formation in vitro, and angiogenesis in vivo. All of these responses are mediated through specific histamine and serotonin receptors, are independent of VEGF-A, and are directly dependent on TR3/Nur77. Initially, the angiogenic response closely resembled that induced by VEGF-A, with generation of “mother” vessels. However, after ∼10 days, mother vessels began to regress as histamine and serotonin, unlike VEGF-A, up-regulated the potent angiogenesis inhibitor thrombospondin-1, thereby triggering a negative feedback loop. Thus, histamine and serotonin induce an angiogenic response that fits the time scale of acute inflammation. PMID:23315169

  13. Potential negative effects of anti-histamines on male reproductive function.

    Science.gov (United States)

    Mondillo, Carolina; Varela, María Luisa; Abiuso, Adriana María Belén; Vázquez, Ramiro

    2018-05-01

    Histamine (HA) is a pleiotropic biogenic amine synthesized exclusively by histidine decarboxylase (HDC) in most mammalian tissues. The literature on the role of HA within the male gonad has expanded over the last years, attracting attention to potential unexpected side-effects of anti-histamines on testicular function. In this regard, HA receptors (HRH1, HRH2 and HRH4) have been described in Leydig cells of different species, including human. Via these receptors, HA has been reported to trigger positive or negative interactions with the LH/hCG signaling pathway depending upon its concentration, thereby contributing to the local control of testicular androgen levels. It should then be considered that anti-histamines may affect testicular homeostasis by increasing or decreasing steroid production. Additionally, HRH1 and HRH2 receptors are present in peritubular and germ cells, and HRH2 antagonists have been found to negatively affect peritubular cells and reduce sperm viability. The potential negative impact of anti-histamines on male reproduction becomes even more dramatic if we consider that HA has also been associated with human sexual behavior and penile erection. What is more, although testicular mast cells are the major source of locally produced HA, recent studies have described HDC expression in macrophages, Leydig cells and germ cells, revealing the existence of multiple sources of HA within the testis. Undoubtedly, the more we learn about the testicular histaminergic system, the more opportunities there will be for rational design of drugs aimed at treating HA-related pathologies, with minimum or nule negative impact on fertility. © 2018 Society for Reproduction and Fertility.

  14. Histamine Enhances Theta-Coupled Spiking and Gamma Oscillations in the Medial Entorhinal Cortex Consistent With Successful Spatial Recognition.

    Science.gov (United States)

    Chen, Quanhui; Luo, Fenlan; Yue, Faguo; Xia, Jianxia; Xiao, Qin; Liao, Xiang; Jiang, Jun; Zhang, Jun; Hu, Bo; Gao, Dong; He, Chao; Hu, Zhian

    2017-06-07

    Encoding of spatial information in the superficial layers of the medial entorhinal cortex (sMEC) involves theta-modulated spiking and gamma oscillations, as well as spatially tuned grid cells and border cells. Little is known about the role of the arousal-promoting histaminergic system in the modification of information encoded in the sMEC in vivo, and how such histamine-regulated information correlates with behavioral functions. Here, we show that histamine upregulates the neural excitability of a significant proportion of neurons (16.32%, 39.18%, and 52.94% at 30 μM, 300 μM, and 3 mM, respectively) and increases local theta (4-12 Hz) and gamma power (low: 25-48 Hz; high: 60-120 Hz) in the sMEC, through activation of histamine receptor types 1 and 3. During spatial exploration, the strength of theta-modulated firing of putative principal neurons and high gamma oscillations is enhanced about 2-fold by histamine. The histamine-mediated increase of theta phase-locking of spikes and high gamma power is consistent with successful spatial recognition. These results, for the first time, reveal possible mechanisms involving the arousal-promoting histaminergic system in the modulation of spatial cognition. Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. Radioenzymatic assay for measurement of tissue concentrations of histamine: adaptation to correct for adherence of histamine to mechanical homogenizers

    International Nuclear Information System (INIS)

    Brown, J.K.; Frey, M.J.; Reed, B.R.; Leff, A.R.; Shields, R.; Gold, W.M.

    1984-01-01

    Because adherence of histamine to glass is well-known, we tested for its adherence to a mechanical homogenizer commonly used in the extraction of histamine from tissue samples. During 60 sec of homogenization, 15% to 17% of the histamine originally present in the samples ''disappeared,'' and the reason for the disappearance was reversible binding of histamine to the homogenizer. Adding trace amounts of [ 14 C]histamine to each sample before homogenization and measuring the disappearance of radioactivity during homogenization permitted correction for binding to the homogenizer. This technique for correction was validated by the measurement of endogenous concentrations of histamine in the tracheal posterior membranes of six dogs (range of mean concentrations: 0.63 to 1.51 ng/mg wet weight) followed by the measurement of known amounts of exogenous histamine added before homogenization to tracheal tissue samples from the same dogs. In the latter samples, 96 +/- 13% (mean +/- SEM) of the histamine added was measured by our technique. We conclude that binding of histamine to mechanical homogenizers may be an important cause of inaccuracy of the enzymatic assay for the measurement of histamine concentrations in tissue but that such binding may but that such binding may be easily corrected for

  16. Histamine, carbachol, and serotonin induce hyperresponsiveness to ATP in guinea pig tracheas: involvement of COX-2 pathway.

    Science.gov (United States)

    Montaño, Luis M; Carbajal, Verónica; Vargas, Mario H; García-Hernández, Luz M; Díaz-Hernández, Verónica; Checa, Marco; Barajas-López, Carlos

    2013-08-01

    Extracellular ATP promotes an indirect contraction of airway smooth muscle via the secondary release of thromboxane A2 (TXA2) from airway epithelium. Our aim was to evaluate if common contractile agonists modify this response to ATP. Tracheas from sensitized guinea pigs were used to evaluate ATP-induced contractions before and after a transient contraction produced by histamine, carbachol, or serotonin. Epithelial mRNA for COX-1 and COX-2 was measured by RT-PCR and their expression assessed by immunohistochemistry. Compared with the initial response, ATP-induced contraction was potentiated by pretreatment with histamine, carbachol, or serotonin. Either suramin (antagonist of P2X and P2Y receptors) plus RB2 (antagonist of P2Y receptors) or indomethacin (inhibitor of COX-1 and COX-2) annulled the ATP-induced contraction, suggesting that it was mediated by P2Y receptor stimulation and TXA2 production. When COX-2 was inhibited by SC-58125 or thromboxane receptors were antagonized by SQ-29548, just the potentiation was abolished, leaving the basal response intact. Airway epithelial cells showed increased COX-2 mRNA after stimulation with histamine or carbachol, but not serotonin, while COX-1 mRNA was unaffected. Immunochemistry corroborated this upregulation of COX-2. In conclusion, we showed for the first time that histamine and carbachol cause hyperresponsiveness to ATP by upregulating COX-2 in airway epithelium, which likely increases TXA2 production. Serotonin-mediated hyperresponsiveness seems to be independent of COX-2 upregulation, but nonetheless is TXA2 dependent. Because acetylcholine, histamine, and serotonin can be present during asthmatic exacerbations, their potential interactions with ATP might be relevant in its pathophysiology.

  17. A new crystal structure fragment-based pharmacophore method for G protein-coupled receptors

    DEFF Research Database (Denmark)

    Fidom, Kimberley; Isberg, Vignir; Hauser, Alexander Sebastian

    2015-01-01

    and receptor residue pairs, from crystal structure complexes. We describe the procedure to collect a library with more than 250 fragments covering 29 residue positions within the generic transmembrane binding pocket. We describe how the library fragments are recombined and inferred to build pharmacophores...... for new targets. A validating retrospective virtual screening of histamine H1 and H3 receptor pharmacophores yielded area-under-the-curves of 0.88 and 0.82, respectively. The fragment-based method has the unique advantage that it can be applied to targets for which no (homologous) crystal structures...... or ligands are known. 47% of the class A G protein-coupled receptors can be targeted with at least four-element pharmacophores. The fragment libraries can also be used to grow known ligands or for rotamer refinement of homology models. Researchers can download the complete fragment library or a subset...

  18. 3H-histamine release from human leukocytes

    International Nuclear Information System (INIS)

    Stahl Skov, P.; Norn, S.; Weeke, B.

    1979-01-01

    A rapid, simple, and inexpensive method for large scale screening of patients suspected of type I allergy has been developed. The method is based on in vitro incorporation of 3 H-histamine in the leukocytes of the patient, whereafter release of labelled histamine is measured after provocation of the cells with the suspected allergen. The new method was compared with the conventional basophil histamine release technique by in vitro provocation of six asthmatic patients under suspicion of type I allergy against animal dander, house dust, and mite, and an almost identical release of histamine was observed in both assays. (author)

  19. Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

    Science.gov (United States)

    Vita, N; Oury-Donat, F; Chalon, P; Guillemot, M; Kaghad, M; Bachy, A; Thurneyssen, O; Garcia, S; Poinot-Chazel, C; Casellas, P; Keane, P; Le Fur, G; Maffrand, J P; Soubrie, P; Caput, D; Ferrara, P

    1998-11-06

    The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

  20. The symbiotic star H1-36

    International Nuclear Information System (INIS)

    Allen, D.A.

    1983-01-01

    Optical and infrared spectrophotometry is presented of the high-excitation emission-line star H1-36. The presence of a variable M giant is established: H1-36 may therefore be classified as a symbiotic star. The observations are interpreted in terms of the usual binary model for symbiotic stars, namely that an unseen star is heated by accretion of gas from its companion M giant. (author)

  1. Serum diamine oxidase activity in patients with histamine intolerance.

    Science.gov (United States)

    Manzotti, G; Breda, D; Di Gioacchino, M; Burastero, S E

    2016-03-01

    Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients. We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated. We found that 10 out of 14 patients had serum DAO activityintolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (±SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04±6.90 U/mL compared to 39.50±18.16 U/mL in 34 healthy controls (P=0.0031). In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy. © The Author(s) 2015.

  2. DETERMINATION OF HISTAMINE IN FISH USING ELISA TECHNIQUE

    NARCIS (Netherlands)

    KRUGER, C; SEWING, U; STENGEL, G; KEMA, [No Value; WESTERMANN, J; MANZ, B

    1995-01-01

    The analysis of histamine in fish and fish products via competitive ELISA is described. The advantages of this method are easy sample preparation and handling, screening capabilities, and low costs. Automation enables the performance of the assay with higher series of samples. The Histamine-ELISA is

  3. Histamine release from cord blood basophils

    DEFF Research Database (Denmark)

    Nielsen, Bent Windelborg; Damsgaard, Tine Engberg; Herlin, Troels

    1990-01-01

    The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng...... of less than 0.5 IU/ml, although sensitivity to anti-IgE was universally increased. Preincubation with pharmacologic agents modulating the IgE-mediated HR produced effects generally similar to previous findings in adult blood. However, the effects of inhibiting the cyclooxygenase pathway in cord blood...

  4. The H1 Data Preservation Project

    International Nuclear Information System (INIS)

    South, D M; Steder, M

    2012-01-01

    The H1 data preservation project was started in 2009 as part of the global data preservation initiative in high-energy physics, DPHEP. In order to retain the full potential for future improvements, the H1 Collaboration aims for level 4 of the DPHEP recommendations, which requires the full simulation and reconstruction chain as well as the data to be preserved for future analysis. A major goal of the H1 project is therefore to provide secure, long-lived and validated access to the H1 data and analysis software, which is realised in collaboration with DESY-IT using virtualisation techniques. By implementing such a system, it is hoped that the lifetime of the unique ep collision data from HERA will be extended, providing the possibility for novel analysis in the future. The preservation of the data and software is performed alongside a consolidation programme of digital and non-digital documentation, some of which dates back to the early 1980s. A new organisational model of the H1 Collaboration, reflecting the change to the long term phase, is to be adopted in July 2012.

  5. The role of histamine in estradiol-induced conditioned consumption reductions.

    Science.gov (United States)

    Hintiryan, Houri; Hayes, Unja L; Chambers, Kathleen C

    2005-01-31

    Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.

  6. Histamine poisoning and control measures in fish and fishery products

    Directory of Open Access Journals (Sweden)

    Pierina eVisciano

    2014-09-01

    Full Text Available Histamine poisoning is one of the most common form of intoxication caused by the ingestion of fish and fishery products. Cooking, canning or freezing cannot reduce the levels of histamine because this compound is heat stable. All humans are susceptible to histamine and its effects can be described as intolerance or intoxication depending on the severity of the symptoms. The amount of histamine in food, the individual sensitivity and the detoxification activity in human organism represent the main factors affecting the toxicological response in consumers. Histamine is the only biogenic amine with regulatory limits set by European Legislation, up to a maximum of 200 mg/kg in fresh fish and 400 mg/kg in fishery products treated by enzyme maturation in brine.

  7. The Effect of Schinus terebinthifolius Raddi (Anacardiaceae) Bark Extract on Histamine-Induced Paw Edema and Ileum Smooth Muscle Contraction.

    Science.gov (United States)

    Nunes-Neto, Paulo Alexandre; Peixoto-Sobrinho, Tadeu José da Silva; da Silva Júnior, Edilson Dantas; Leopoldina da Silva, Jamilka; Rodrigo da Silva Oliveira, Alisson; Pupo, André Sampaio; Araújo, Alice Valença; da Costa-Silva, João Henrique; Wanderley, Almir Gonçalves

    2017-01-01

    Schinus terebinthifolius Raddi (Anacardiaceae), popularly known as red aroeira, is used in traditional medicine to treat inflammatory, gastric, and respiratory disorders. The aim of this study was to evaluate the antihistaminic activity of S. terebinthifolius (St) bark extract by using in vivo and in vitro experimental models. The effects of St were investigated on contractions induced by histamine, carbachol, and potassium chloride in isolated guinea pig ileum. St was also studied in response to hind paw edema induced by histamine in rats. Experiments revealed that although St (250, 500, and 1,000  µ g/mL) reduced the histamine-induced contractions by 9.1 ± 1.8, 50.2 ± 2.0, and 68.9 ± 2.0%, respectively, it did not inhibit contractions induced by carbachol or KCl. The association of St (250 and 500  µ g/mL) with hydroxyzine, an H 1 -antihistamine (0.125 and 0.250  µ M), increased the inhibitory effect to 67.0 ± 3.2 and 85.1 ± 2.1%, respectively. Moreover, St (100, 200, and 400 mg/kg) decreased paw edema from its peak by 33.9, 48.4, and 54.8%, respectively, whereas hydroxyzine (70 mg/kg) inhibited the peak edema by 56.5%. Altogether, the results suggest that the bark extract of S. terebinthifolius has an antihistaminic effect (H 1 ).

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  9. Chronic effects of fluoxetine, a selective inhibitor of serotonin uptake, on neurotransmitter receptors

    International Nuclear Information System (INIS)

    Wong, D.T.; Reid, L.R.; Bymaster, F.P.; Threlkeld, P.G.

    1985-01-01

    Fluoxetine administration to rats dose of 10mg/kg i.p. daily up to 12 or 24 days failed to change the concentration-dependent binding of [ 3 H]WB4101, [ 3 H]clonidine and [ 3 H]dihydroalprenolol to α 1 -, α 2 - and β-adrenergic receptors, respectively; [ 3 H]quinuclidinyl benzilate to muscarinic receptors; [ 3 H]pyrilamine to histamine H 1 receptors and [ 3 H]naloxone to opiate receptors. Persistent and significant decreases in receptor number (Bsub(max) value) without changes in the dissociation constant (Ksub(D) value) of [ 3 H]5-HT binding in cortical membranes were observed upon chronic treatment with fluoxetine administered either by intraperitoneal injection or incorporation in the diet. A detectable reduction of 5-HT 1 receptor number occured after once-daily injections of fluoxetine at 10mg/kg i.p. within 49 hours. After pretreatment for 3 days with p-chlorophenylalanine, an inhibitor of 5-HT synthesis, followed by repeated administration of fluoxetine, 5-HT 1 receptor numbers were higher than those of normal rats, suggesting a dependence on synaptic concentration of 5-HT for fluoxetine to affect a receptor down-regulation. These studies provide further evidence for the selectivity of fluoxetine as an inhibitor of 5-HT reuptake, resulting in a selective down-regulation of 5-HT 1 receptors in the cerebal cortex of rat brain. (Author)

  10. Antiviral Prophylaxis and H1N1

    Centers for Disease Control (CDC) Podcasts

    2011-07-14

    Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1.  Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 7/18/2011.

  11. Pandemic influenza A (H1N1)

    African Journals Online (AJOL)

    ... in Port Shepstone, South Africa. Introduction. Influenza A (H1N1) 2009 'swine flu' variant is currently a global pandemic.1 The infection associated with this virus is usually a mild, self-limiting illness. However, it may progress to severe pneumonia requiring intensive care unit (ICU) therapy in 31% of patients.2 This may.

  12. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    Science.gov (United States)

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

  13. Distinct functional characteristics of levocabastine sensitive rat neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

    Science.gov (United States)

    Yamada, M; Yamada, M; Lombet, A; Forgez, P; Rostène, W

    1998-01-01

    Neurotensin has been shown to produce pharmacological effects both in brain and periphery. Several of these effects are mediated by a high-affinity neurotensin NT1 receptor. On the other hand, a low-affinity levocabastine-sensitive neurotensin NT2 receptor was molecularly cloned from rodent brain recently. In this study, in contrast to NT1 receptor, levocabastine (a histamine H1 receptor antagonist) and SR48692 (an antagonist for NT1 receptor) strongly stimulated intracellular Ca2+ mobilization in transfected Chinese hamster ovary cells expressing rat NT2 receptor, thus acting as potent NT2 receptor. Furthermore, despite of their affinities for NT2 receptor, the Ca2+ responses to potent NT1 agonists, neurotensin or JMV449 ([Lys8-(CH2NH)-Lys9]Pro-Tyr-Ile-Leu, a peptidase resistant analogue of neurotensin) were much smaller than that observed with SR48692. These findings suggest that NT1 and NT2 receptors present distinct functional characteristics and that SR48692 may act as a potent agonist for NT2 receptor.

  14. Interactions of the histamine and hypocretin systems in CNS disorders.

    Science.gov (United States)

    Shan, Ling; Dauvilliers, Yves; Siegel, Jerome M

    2015-07-01

    Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system.

  15. The Effect of Histamine on the Rat Oestrous Cycle | Anuka | West ...

    African Journals Online (AJOL)

    Triprolidine (50 mg/kg; ip), a H1-receptor antagonist, showed no changes in the oestrous rhythm ... changement dans le cycle œstral alors que le chlorpheniramine(50mg/kg,ip) un autre recepteur H1 ... EMAIL FULL TEXT EMAIL FULL TEXT

  16. Histamine formation in flying fish contaminated with Staphylococcus xylosus

    Directory of Open Access Journals (Sweden)

    Hsien-Feng Kung

    2016-06-01

    Full Text Available Abstract Histamine is the main causative agent of scombroid poisoning. However, unlike scombroid fish, histamine poisoning due to consumption of flying fish has never been reported. In this study, the white muscle of flying fish had high levels of free histidine at approximately 423.9 mg/100 g, and was inoculated with Staphylococcus xylosus Q2 isolated from dried flying fish at 5.0 log CFU/g and stored at −20 to 35°C to investigate histamine-related quality. The histamine contents quickly increased to higher than 50 mg/100 g in samples stored at 25 and 35°C within 12 h as well as stored at 15°C within 48 h. However, bacterial growth and histamine formation were controlled by cold storage of the samples at 4°C or below. Once the frozen flying fish samples stored at −20°C for 2 months were thawed and stored at 25°C after 24 h, histamine started to accumulate rapidly (>50 mg/100 g of fish. Therefore, flying fish muscle was a good substrate for histamine formation by bacterial histidine decarboxylation at elevated temperatures (>15°C when it is contaminated with S. xylosus. In conclusion, since the improperly contaminated flying fish muscle with S. xylosus could lead to production of hazardous levels of histamine over time when stored at temperatures >15°C, the flying fish should be stored below 4 °C or below to control proliferation of S. xylosus, and TVBN and histamine production.

  17. Antifungal properties of wheat histones (H1-H4) and purified wheat histone H1

    Science.gov (United States)

    Wheat (Triticum sp.) histones H1, H2, H3, and H4 were extracted. H1 was further purified. Their activities against fungi with varying degrees of wheat pathogenicity were determined. They included Aspergillus flavus, A. fumigatus, A. niger, F. oxysporum, F. verticillioides, F. solani, F. graminearu...

  18. Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls.

    Science.gov (United States)

    Pinzer, T C; Tietz, E; Waldmann, E; Schink, M; Neurath, M F; Zopf, Y

    2018-04-01

    Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls. We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory chemical parameters were evaluated. Twenty-four percent (8 of 33) suspected histamine-intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food-allergic and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine-intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance. We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine-intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms and strongly suggests the presence of histamine intolerance. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  19. OCCURANCE OF HISTAMINE IN FISH PRODUCTS ON MARKET

    Directory of Open Access Journals (Sweden)

    R. Mancusi

    2012-08-01

    Full Text Available Histamine fish poisoning is quite common and occur in consequence of microbial decarboxylase whose activity begin early in the post-mortem but are triggered in consequence of abuse in the shelf life of fish products. In this study forty-eight samples of tuna, mackerel, anchovies, sardines, fresh or processed were sampled from fish shops and supermarkets in the City of Bologna in the period from January to July 2010. Concentration of histamine was assessed using ELISA quantitative test and presence of psicrotrophic histamine forming bacteria was searched using a modified Niven agar medium which allow detection of suspect colonies that were confirmed by PCR for detecting the presence of the histidine decarboxylase genes in their DNA. The positive colonies were then identified on the basis of their morphology, Gram reaction and biochemical characteristics with API20E. The differential capability of the Niven agar was found to be low and approximately one fifth of the suspect colonies were confirmed by the PCR test, which however included both strong and weak histamine producing strains. The presence of Morganella morganii was associated with concentration of histamine 460 mg∙kg-1 above the allowed limit in a sample of tuna sampled from a fish shop. The same bacterium was found in samples of Atlantic horse mackerel (Trachurus trachurus. High histamine concentration (between 258 and > 300 mg∙kg-1 were observed in salted European pilchard and European anchovy (228 mg∙kg-1 sold loose in supermarkets. Because temperature abuse could occur when Tuna (fresh/defrozen are hold on chopping board to sell fresh cuts and during shelf life of salted pilchard and pickled anchovies held in opened cans in chilled display cabinets for extended period, which might results in very high histamine concentration, controls on time and temperature at the retail, in addition to those done during the harvest and processing are needed. The studies aiming at

  20. The H1 silicon vertex detector

    International Nuclear Information System (INIS)

    Pitzl, D.; Behnke, O.; Biddulph, M.; Boesiger, K.; Eichler, R.; Erdmann, W.; Gabathuler, K.; Gassner, J.; Haynes, W.J..; Horisberger, R.; Kausch, M.; Lindstroem, M.; Niggli, H.; Noyes, G.; Pollet, P.; Steiner, S.; Streuli, S.; Szeker, K.; Truoel, P.

    2000-01-01

    The design, construction and performance of the H1 silicon vertex detector is described. It consists of two cylindrical layers of double-sided, double-metal silicon sensors read out by a custom designed analog pipeline chip. The analog signals are transmitted by optical fibres to a custom-designed ADC board and are reduced on PowerPC processors. Details of the design and construction are given and performance figures from the first data-taking periods are presented

  1. Symbiotic star H1-36

    Energy Technology Data Exchange (ETDEWEB)

    Allen, D A

    1983-01-01

    It is suggested that H1-36 should be classified as a symbiotic star rather than a planetary nebula. Evidence of a cool giant now exists and the high-excitation emission-line spectrum resembles the spectra of many symbiotic stars. The optical spectrum, radio spectrum, high spectral index of +0.9 and computed mass-loss rate are among the features discussed.

  2. The symbiotic star H1-36

    International Nuclear Information System (INIS)

    Allen, D.A.

    1983-01-01

    It is suggested that H1-36 should be classified as a symbiotic star rather than a planetary nebula. Evidence of a cool giant now exists and the high-excitation emission-line spectrum resembles the spectra of many symbiotic stars. The optical spectrum, radio spectrum, high spectral index of +0.9 and computed mass-loss rate are among the features discussed

  3. The histamine content of dried flying fish products in Taiwan and the isolation of halotolerant histamine-forming bacteria.

    Science.gov (United States)

    Kung, Hsien-Feng; Huang, Chun-Yung; Lin, Chia-Min; Liaw, Lon-Hsiu; Lee, Yi-Chen; Tsai, Yung-Hsiang

    2015-06-01

    Thirty dried flying fish products were purchased from fishing village stores in Taiwan and tested to detect the presence of histamine and histamine-forming bacteria. Except for histamine and cadaverine, the average content of various biogenic amines in the tested samples was less than 3.5 mg/100 g. Eight (26.6%) dried flying fish samples had histamine levels greater than the United States Food and Drug Administration guideline of 5 mg/100 g for scombroid fish and/or scombroid products, whereas four (13.3%) samples contained more than the hazard action level of 50 mg/100 g. One histamine-producing bacterial isolate was identified as Staphylococcus xylosus by 16S rDNA sequencing with polymerase chain reaction amplification. This isolate was capable of producing 507.8 ppm of histamine in trypticase soy broth supplemented with 1.0% l-histidine (TSBH). The S. xylosus isolate was a halotolerant bacterium that had a consistent ability to produce more than 300 ppm of histamine at 3% sodium chloride concentration in TSBH medium after 72 hours. Copyright © 2015. Published by Elsevier B.V.

  4. The histamine content of dried flying fish products in Taiwan and the isolation of halotolerant histamine-forming bacteria

    Directory of Open Access Journals (Sweden)

    Hsien-Feng Kung

    2015-06-01

    Full Text Available Thirty dried flying fish products were purchased from fishing village stores in Taiwan and tested to detect the presence of histamine and histamine-forming bacteria. Except for histamine and cadaverine, the average content of various biogenic amines in the tested samples was less than 3.5 mg/100 g. Eight (26.6% dried flying fish samples had histamine levels greater than the United States Food and Drug Administration guideline of 5 mg/100 g for scombroid fish and/or scombroid products, whereas four (13.3% samples contained more than the hazard action level of 50 mg/100 g. One histamine-producing bacterial isolate was identified as Staphylococcus xylosus by 16S rDNA sequencing with polymerase chain reaction amplification. This isolate was capable of producing 507.8 ppm of histamine in trypticase soy broth supplemented with 1.0% l-histidine (TSBH. The S. xylosus isolate was a halotolerant bacterium that had a consistent ability to produce more than 300 ppm of histamine at 3% sodium chloride concentration in TSBH medium after 72 hours.

  5. The H1 liquid argon calorimeter system

    International Nuclear Information System (INIS)

    Andrieu, B.; Babayev, A.; Ban, J.

    1993-06-01

    The liquid argon calorimeter of the H1 detector presently taking data at the HERA ep - collider at DESY, Hamburg, is described here. The main physics requirements and the most salient design features relevant to this calorimeter are given. The aim to have smooth and hermetic calorimetric coverage over the polar angular range 4 ≤ θ ≤ 154 is achieved by a single liquid argon cryostat containing calorimeter stacks structured in wheels and octants for easy handling. The absorber materials used are lead in the electromagnetic part and stainless steel in the hadronic part. The read-out system is pipelined to reduce the dead time induced by the high trigger rate expected at the HERA collider where consecutive bunches are separated in time by 96 ns. The main elements of the calorimeter, such as the cryostat, with its associated cryogenics, the stack modules, the read-out, calibration and trigger electronics as well as the data acquisition system are described. Performance results from data taken in calibration runs with full size H1 calorimeter stacks at a CERN test beam, as well as results from data collected with the complete H1 detector using cosmic rays during the initial phase of ep operations are presented. The observed energy resolutions and linearities are well in agreement with the requirements. (orig.)

  6. Modulation of neutrophil oxidative burst via histamine receptors

    Czech Academy of Sciences Publication Activity Database

    Číž, Milan; Lojek, Antonín

    2013-01-01

    Roč. 170, č. 1 (2013), s. 17-22 ISSN 0007-1188 R&D Projects: GA MŠk(CZ) LD11010 Institutional support: RVO:68081707 Keywords : neutrophil * oxidative burst * reactive oxygen species Subject RIV: BO - Biophysics Impact factor: 4.990, year: 2013

  7. Effect of crude methanol leaf extract of Combretum racemosum on histamine-stimulated gastric secretion in rats

    Directory of Open Access Journals (Sweden)

    Chukwugozie Nwachukwu Okwuosa

    2017-02-01

    Full Text Available Objective: To investigate the effect of crude methanolic extract of Combretum racemosum (C. racemosum leaves on histamine-stimulated gastric secretion in rats. Methods: Phytochemical and acute toxicity tests were performed. Anti-secretory activity of C. racemosum extract was investigated in pyloric ligated rats administered histamine. Gastric juice was collected from all the animals and the volume, titratable acidity, pH and mucus content were measured. The effect of C. racemosum extract on calcium chloride induced contractions of the guinea-pig ileum suspended in high potassium, calcium-deficient depolarizing solution was investigated. The H2 receptor antagonistic potency was also evaluated using the isolated non-gravid rat uterus. Results: Phytochemistry revealed the presence of abundant amounts of saponins and moderate amounts of glycosides, terpenoids, proteins, reducing sugar, resins, alkaloids, flavonoids and carbohydrates. The oral LD50 of the extract was greater than 8 000 mg/kg body weight in mice. Pretreatment of pyloric ligated rats with C. racemosum prior to histamine administration significantly reduced (P < 0.001 the volume of gastric juice and titratable acidity, and significantly increased (P < 0.001 gastric pH and gastric mucus when compared to the negative control. Both doses of C. racemosum protected rats significantly (P < 0.001 from histamine-induced ulceration. C. racemosum potently inhibited contractions evoked by calcium chloride in a dose-dependent and reversible manner with an IC50 of 1 132 µg/mL. It also antagonized the relaxant effect of histamine on the isolated rat uterus in a manner comparable to cimetidine. Conclusions: The leaves of C. racemosum possess gastric anti-secretory and anti-ulcer effects and justify its use in traditional medicine in South-East Nigeria for the treatment of peptic ulcer disease.

  8. In Vivo Histamine Optical Nanosensors

    Directory of Open Access Journals (Sweden)

    Heather A. Clark

    2012-08-01

    Full Text Available In this communication we discuss the development of ionophore based nanosensors for the detection and monitoring of histamine levels in vivo. This approach is based on the use of an amine-reactive, broad spectrum ionophore which is capable of recognizing and binding to histamine. We pair this ionophore with our already established nanosensor platform, and demonstrate in vitro and in vivo monitoring of histamine levels. This approach enables capturing rapid kinetics of histamine after injection, which are more difficult to measure with standard approaches such as blood sampling, especially on small research models. The coupling together of in vivo nanosensors with ionophores such as nonactin provide a way to generate nanosensors for novel targets without the difficult process of designing and synthesizing novel ionophores.

  9. Hypothermia in mouse is caused by adenosine A1 and A3 receptor agonists and AMP via three distinct mechanisms.

    Science.gov (United States)

    Carlin, Jesse Lea; Jain, Shalini; Gizewski, Elizabeth; Wan, Tina C; Tosh, Dilip K; Xiao, Cuiying; Auchampach, John A; Jacobson, Kenneth A; Gavrilova, Oksana; Reitman, Marc L

    2017-03-01

    Small mammals have the ability to enter torpor, a hypothermic, hypometabolic state, allowing impressive energy conservation. Administration of adenosine or adenosine 5'-monophosphate (AMP) can trigger a hypothermic, torpor-like state. We investigated the mechanisms for hypothermia using telemetric monitoring of body temperature in wild type and receptor knock out (Adora1 -/- , Adora3 -/- ) mice. Confirming prior data, stimulation of the A 3 adenosine receptor (AR) induced hypothermia via peripheral mast cell degranulation, histamine release, and activation of central histamine H 1 receptors. In contrast, A 1 AR agonists and AMP both acted centrally to cause hypothermia. Commonly used, selective A 1 AR agonists, including N 6 -cyclopentyladenosine (CPA), N 6 -cyclohexyladenosine (CHA), and MRS5474, caused hypothermia via both A 1 AR and A 3 AR when given intraperitoneally. Intracerebroventricular dosing, low peripheral doses of Cl-ENBA [(±)-5'-chloro-5'-deoxy-N 6 -endo-norbornyladenosine], or using Adora3 -/- mice allowed selective stimulation of A 1 AR. AMP-stimulated hypothermia can occur independently of A 1 AR, A 3 AR, and mast cells. A 1 AR and A 3 AR agonists and AMP cause regulated hypothermia that was characterized by a drop in total energy expenditure, physical inactivity, and preference for cooler environmental temperatures, indicating a reduced body temperature set point. Neither A 1 AR nor A 3 AR was required for fasting-induced torpor. A 1 AR and A 3 AR agonists and AMP trigger regulated hypothermia via three distinct mechanisms. Published by Elsevier Ltd.

  10. Anti-histaminic potentials of Cnidoscolus aconitifolius in the ...

    African Journals Online (AJOL)

    Similarly, the observable significant reduction in the paw size was comparable to the Ibuprofen (100 mg/kg). Different concentrations of EECA (0.025, 0.05, 0.1 and 0.2 mg/kg) were assessed on the histamine release from the mast cells. The rats administered with 0.2mg/kg had the most profound effects on the histamine ...

  11. The H1 forward muon spectrometer

    International Nuclear Information System (INIS)

    Kenyon, I.R.; Phillips, H.; Cronstroem, H.I.; Hedberg, V.; Jacobsson, C.; Joensson, L.; Lohmander, H.; Nyberg, M.; Biddulph, P.; Finnegan, P.; Foster, J.; Gilbert, S.; Hilton, C.; Ibbotson, M.; Mehta, A.; Sutton, P.; Stephens, K.; Thompson, R.

    1993-02-01

    The H1 detector started taking data at the electron- proton collider HERA in the beginning of 1992. In HERA 30 GeV electrons collide with 820 GeV protons giving a strong boost of the centre-of-mass system in the direction of the proton, also called the forward region. For the detection of high momentum muons in this region a muon spectrometer has been constructed, consisting of six drift chamber planes, three either side of a toroidal magnet. A first brief description of the system and its main parameters as well as the principles for track reconstruction and Τ 0 determination is given. (orig.)

  12. Photoperiod-H1 (Ppd-H1) Controls Leaf Size1[OPEN

    Science.gov (United States)

    Digel, Benedikt; Tavakol, Elahe; Verderio, Gabriele; Xu, Xin

    2016-01-01

    Leaf size is a major determinant of plant photosynthetic activity and biomass; however, it is poorly understood how leaf size is genetically controlled in cereal crop plants like barley (Hordeum vulgare). We conducted a genome-wide association scan for flowering time, leaf width, and leaf length in a diverse panel of European winter cultivars grown in the field and genotyped with a single-nucleotide polymorphism array. The genome-wide association scan identified PHOTOPERIOD-H1 (Ppd-H1) as a candidate gene underlying the major quantitative trait loci for flowering time and leaf size in the barley population. Microscopic phenotyping of three independent introgression lines confirmed the effect of Ppd-H1 on leaf size. Differences in the duration of leaf growth and consequent variation in leaf cell number were responsible for the leaf size differences between the Ppd-H1 variants. The Ppd-H1-dependent induction of the BARLEY MADS BOX genes BM3 and BM8 in the leaf correlated with reductions in leaf size and leaf number. Our results indicate that leaf size is controlled by the Ppd-H1- and photoperiod-dependent progression of plant development. The coordination of leaf growth with flowering may be part of a reproductive strategy to optimize resource allocation to the developing inflorescences and seeds. PMID:27457126

  13. Photoperiod-H1 (Ppd-H1) Controls Leaf Size.

    Science.gov (United States)

    Digel, Benedikt; Tavakol, Elahe; Verderio, Gabriele; Tondelli, Alessandro; Xu, Xin; Cattivelli, Luigi; Rossini, Laura; von Korff, Maria

    2016-09-01

    Leaf size is a major determinant of plant photosynthetic activity and biomass; however, it is poorly understood how leaf size is genetically controlled in cereal crop plants like barley (Hordeum vulgare). We conducted a genome-wide association scan for flowering time, leaf width, and leaf length in a diverse panel of European winter cultivars grown in the field and genotyped with a single-nucleotide polymorphism array. The genome-wide association scan identified PHOTOPERIOD-H1 (Ppd-H1) as a candidate gene underlying the major quantitative trait loci for flowering time and leaf size in the barley population. Microscopic phenotyping of three independent introgression lines confirmed the effect of Ppd-H1 on leaf size. Differences in the duration of leaf growth and consequent variation in leaf cell number were responsible for the leaf size differences between the Ppd-H1 variants. The Ppd-H1-dependent induction of the BARLEY MADS BOX genes BM3 and BM8 in the leaf correlated with reductions in leaf size and leaf number. Our results indicate that leaf size is controlled by the Ppd-H1- and photoperiod-dependent progression of plant development. The coordination of leaf growth with flowering may be part of a reproductive strategy to optimize resource allocation to the developing inflorescences and seeds. © 2016 American Society of Plant Biologists. All rights reserved.

  14. Blood histamine release: A new allergy blood test

    International Nuclear Information System (INIS)

    Faraj, B.A.; Gottlieb, G.R.; Camp, V.M.; Lollies, P.

    1985-01-01

    Allergen-mediated histamine release from human leukocytes represents an important model for in vitro studies of allergic reactions. The purpose of this study was to determine whether the measurement of histamine released in allergic patients (pts) by radioenzymatic assay following mixing of their blood with common allergens represents a reliable index for diagnosis of atopic allergy. Three categories of allergies were used: (1) housedust and mite; (2) cat and dog dander; (3) trees and grasses and ragweed mixture. The presence of allergy was established by intradermal skin testing in the study group of 82 pts. Significant atopy was defined as ≥ 3+ (overall range 0-4 +, negative to maximum) on skin testing. The test was carried out in tubes with 0.5 ml heparinized blood, 0.5 ml tris albumin buffer, and one of the allergens (60-100 PNU/ml). In 20 controls without allergy, there always was ≤ 4% histamine release (normal response). A significant allergen-mediated histamine release, ranging from 12 to 30% of the total blood histamine content, was observed in 96% of the pts with skin test sensitivity of ≥ 3+. There was good agreement between skin testing and histamine release in terms of the allergen causing the response. Thus, measurement of histamine release in blood in response to allergen challenge represents a clinically useful in vitro test for the diagnosis of atopic allergy. Because data can be obtained from a single sample and are highly quantitative, this new method should have application to the longitudinal study of allergic pts and to the assessment of interventions

  15. Enhanced incorporation of fatty acid into phosphatidyl choline that parallels histamine discharge in mast cells

    International Nuclear Information System (INIS)

    Castle, J.D.; Castle, A.M.; Ma, A.K.; Stukenbrok, H.

    1984-01-01

    Purified rat peritoneal and pleural mast cells preincubated briefly with radioactively labeled fatty acid were treated with A23187, which bypasses primary receptors in stimulating exocytosis. An enhanced incorporation of fatty acid into phosphatidyl choline (PC) that occurred in parallel with histamine release at 24-25 degrees C was observed and was initially proportional to the total amount of histamine discharged. Enhanced PC labeling and histamine secretion were also proportional at temperatures ranging from 17-37 degrees C. Both radioactive linoleic and palmitic acids were incorporated selectively at the beta-position of the glycerol backbone of PC. PC labeling by [3H]choline was not detectably different in control and stimulated cells, and phosphatidic acid did not exhibit selectively enhanced beta-acylation. Thus, the stimulated labeling in A23187-treated cells may occur secondary to the action of a phospholipase A2 that favors PC as a substrate. Other peritoneal cell types exhibit a very similar A23187-stimulated selective labeling of PC. Therefore, autoradiography has been used to provide a direct demonstration that in purified preparations, mast cells are the principal cell type engaged in A23187-elicited incorporation of fatty acid into PC. The efficacy of this approach has relied on special procedures devised to obtain significantly different autoradiographic grain densities between control and stimulated preparations that can be attributed to differences in the level of [3H]palmitate-labeled PC. Preliminary tests using compound 48/80 as a secretory stimulus for mast cells have identified a similar selectively enhanced PC labeling. In either case, however, consideration of possible relationships between PC metabolism and the secretory process are premature since they have not been tested directly

  16. PENINGKATAN KADAR HISTAMIN PADA IKAN LAUT YANG SUDAH DIOLAH

    Directory of Open Access Journals (Sweden)

    Djarismawati Djarismawati

    2012-10-01

    Full Text Available  It was very difficult to recover the condition of people·s nutntion especially among the children during the economic crisis, even though that problem could be overcome by consuming protein especially from sea-fish. But handling food originated from sea-fish was very difficult, because sea-fish could be easily contaminated by toxins. In this study the histamine contents in fresh and processed sea-fish will be analized. The objective of the study was to test the best way of fish cooking to minimize the histamine content. The limiting time of the fish remain fresh after taken from the market was also studied. The result showed that the time taken to bring the fish from the sampling points to the laboratory and the way of fish cooking would influence the histamine content in cooked fish. We also found that cooking fish with coconut milk has resulted the lowest histamine content as compared with frying or roasting. Keywords: histamine, sea fish, nutrition

  17. Evolutionary trends of A(H1N1 influenza virus hemagglutinin since 1918.

    Directory of Open Access Journals (Sweden)

    Jun Shen

    2009-11-01

    Full Text Available The Pandemic (H1N1 2009 is spreading to numerous countries and causing many human deaths. Although the symptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreak in subsequent months. As the primary immunity-eliciting antigen, hemagglutinin (HA is the major agent for host-driven antigenic drift in A(H3N2 virus. However, whether and how the evolution of HA is influenced by existing immunity is poorly understood for A(H1N1. Here, by analyzing hundreds of A(H1N1 HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1 HAs. Among a subgroup of human A(H1N1 HAs between 1918 approximately 2008, we found strong diversifying (positive selection at HA(1 156 and 190. We also analyzed the evolutionary trends at HA(1 190 and 225 that are critical determinants for receptor-binding specificity of A(H1N1 HA. Different A(H1N1 viruses appeared to favor one of these two sites in host-driven antigenic drift: epidemic A(H1N1 HAs favor HA(1 190 while the 1918 pandemic and swine HAs favor HA(1 225. Thus, our results highlight the urgency to understand the interplay between antigenic drift and receptor binding in HA evolution, and provide molecular signatures for monitoring future antigenically drifted 2009 pandemic and seasonal A(H1N1 influenza viruses.

  18. Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuo

    2013-01-01

    Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  19. The Effects of Electrical Stimuli on Calcium Change and Histamine Release in Rat Basophilic Leukemia Mast Cells

    Science.gov (United States)

    Zhu, Dan; Wu, Zu-Hui; Chen, Ji-Yao; Zhou, Lu-Wei

    2013-06-01

    We apply electric fields at different frequencies of 0.1, 1, 10 and 100 kHz to the rat basophilic leukemia (RBL) mast cells in calcium-containing or calcium-free buffers. The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine. The [Ca2+]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz, and then decreases when the frequency further increases from 10 kHz to 100 kHz, showing a peak at 100 kHz. A similar frequency dependence of the histamine release is also found. The [Ca2+]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation. The ruthenium red (RR), an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane, is used in the experiment to check whether the electric field stimuli act on the TRPV channels. Under an electric field of 10 kHz, the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation, while the [Ca2+]i in a calcium-free buffer is only about 2.2 times. Similar behavior is also found for the histamine release. RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment. This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli. Under this condition, the histamine is also released following a similar way. We suggest that, as far as an electric stimulation is concerned, an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells, and this would cause a significant calcium influx resulting in a significant histamine release, which could be one of the mechanisms for electric therapy.

  20. Influence of histamine and serotonin antagonists on the growth of xenografted human colorectal tumors.

    Science.gov (United States)

    Barkla, D H; Tutton, P J

    1981-12-01

    Four lines of human colorectal cancer were established and serially propagated as subcutaneous xenographs in immunosuppressed inbred CBA/Lac mice. Established xenografts were then used to investigate the influence of a serotonin antagonist (BW 501c) and a histamine H2 receptor antagonists (Cimetidine) on xenograft growth. The growth of each of the four tumor lines was significantly inhibited by BW 501c throughout the treatment, whereas the growth of only two tumor lines was significantly inhibited by Cimetidine treatment. The response of individual tumor lines was not predictable on the basis of either tumor histopathology or the natural growth rate of the untreated xenograft. A number of alternative, but not mutually exclusive, hypotheses are suggested to explain the results. One hypothesis proposes that colorectal tumors are composed of subpopulations of tumor cells that are variously dependent on or independent of amine hormones. Another hypothesis is that tumor cells exhibit temporal changes in hormone sensitivity to amine hormones during treatment. Finally, it is suggested that serotonin and/or histamine H2 antagonists may be useful in preventing the repopulation of colorectal carcinomas following antineoplastic therapy with the use of conventional drugs.

  1. Redox regulation of mast cell histamine release in thioredoxin-1 (TRX) transgenic mice.

    Science.gov (United States)

    Son, Aoi; Nakamura, Hajime; Kondo, Norihiko; Matsuo, Yoshiyuki; Liu, Wenrui; Oka, Shin-ichi; Ishii, Yasuyuki; Yodoi, Junji

    2006-02-01

    Thioredoxin-1 (TRX) is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE (FcepsilonRI) was significantly suppressed in TRX transgenic (TRX-tg) mice compared to wild type (WT) mice. Intracellular reactive oxygen species (ROS) of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production of cytokines (IL-6 and TNF-alpha) from mast cells in response to 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper (Th) 2 dominant in primary immune response, although there was no difference in the population of dendritic cells (DCs) and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.

  2. Histamine is not released in acute thermal injury in human skin in vivo: a microdialysis study

    DEFF Research Database (Denmark)

    Petersen, Lars Jelstrup; Pedersen, Juri Lindy; Skov, Per Stahl

    2009-01-01

    BACKGROUND: Animal models have shown histamine to be released from the skin during the acute phase of a burn injury. The role of histamine during the early phase of thermal injuries in humans remains unclear. PURPOSE: The objectives of this trial were to study histamine release in human skin during...

  3. PENGGUNAAN EKSTRAK TEH HIJAU (Camellia sinensis) SEBAGAI PENGHAMBAT PEMBENTUKAN HISTAMIN PADA IKAN SEBELUM DIOLAH

    OpenAIRE

    Endang Sri Heruwati; Farida Ariyani; Radestya Triwibowo; Novalia Rachmawati; Irma Hermana

    2009-01-01

    Penelitian penggunaan ekstrak teh hijau (Camellia sinensis) sebagai penghambat pembentukan histamin pada ikan telah dilakukan. Ikan, terutama dari jenis skombroid, sangat rentan mengalami kerusakan karena terjadinya perubahan asam amino histidin yang terkandung dalam ikan menjadi senyawa histamin yang bersifat alergen, yang dikatalisasi oleh enzim histamin dekarboksilase (HDC). Teh hijau diketahui mengandung polifenol berupa senyawa epigalokatekingalat (EGCG) yang merupakan penghambat enzim H...

  4. Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri.

    Science.gov (United States)

    Hemarajata, P; Gao, C; Pflughoeft, K J; Thomas, C M; Saulnier, D M; Spinler, J K; Versalovic, J

    2013-12-01

    Human microbiome-derived strains of Lactobacillus reuteri potently suppress proinflammatory cytokines like human tumor necrosis factor (TNF) by converting the amino acid l-histidine to the biogenic amine histamine. Histamine suppresses mitogen-activated protein (MAP) kinase activation and cytokine production by signaling via histamine receptor type 2 (H2) on myeloid cells. Investigations of the gene expression profiles of immunomodulatory L. reuteri ATCC PTA 6475 highlighted numerous genes that were highly expressed during the stationary phase of growth, when TNF suppression is most potent. One such gene was found to be a regulator of genes involved in histidine-histamine metabolism by this probiotic species. During the course of these studies, this gene was renamed the Lactobacillus reuteri-specific immunoregulatory (rsiR) gene. The rsiR gene is essential for human TNF suppression by L. reuteri and expression of the histidine decarboxylase (hdc) gene cluster on the L. reuteri chromosome. Inactivation of rsiR resulted in diminished TNF suppression in vitro and reduced anti-inflammatory effects in vivo in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of acute colitis. A L. reuteri strain lacking an intact rsiR gene was unable to suppress colitis and resulted in greater concentrations of serum amyloid A (SAA) in the bloodstream of affected animals. The PhdcAB promoter region targeted by rsiR was defined by reporter gene experiments. These studies support the presence of a regulatory gene, rsiR, which modulates the expression of a gene cluster known to mediate immunoregulation by probiotics at the transcriptional level. These findings may point the way toward new strategies for controlling gene expression in probiotics by dietary interventions or microbiome manipulation.

  5. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    Science.gov (United States)

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

    2016-07-19

    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The histamine system in human brain. Changes in neurological and psychiatric disorders

    Energy Technology Data Exchange (ETDEWEB)

    Goodchild, R.E

    1999-09-01

    Autoradiographical examination of the distribution of H{sub 1}- and H{sub 3}- histamine receptor subtypes, using [{sup 3}H]-mepyramine and [{sup 3}H]-R-({alpha}) methylhistamine respectively, found high H{sub 1}-receptor binding densities in neocortex, dentate gyrus and basolateral amygdala, with low binding in all subdivisions of the thalamus and other subcortical areas. H{sub 3}-receptor binding was enriched within the nucleus accumbens, globus pallidus and substantia nigra, whilst was low in the hippocampus, subthalamic nucleus, temporal cortex, motor and somatosensory thalamic areas and basolateral amygdala. In situ hybridisation found H{sub 2}-receptor mRNA located in the striatum, thalamus, hippocampal pyramidal cell layer and dentate gyrus, and specific laminae of neocortex. Comparison of autoradiographically determined H{sub 1}-, H{sub 2}- and H{sub 3}-receptor binding densities between normal and pathological cases found significantly decreased (p < 0.005, ANOVA) striatal and pallidal H{sub 3}-receptor binding in Huntington's disease (HD), with unaltered binding in the insular cortex. A significant correlation (p < 0.01) was present between binding in the internal globus pallidus and HD grade. Binding to the striatal H{sub 1}-receptor was increased (p < 0.05, ANOVA) in Parkinson's disease (PD), whilst H{sub 2}- (measured using [{sup 125}I]-iodoaminopotentidine) and H{sub 3}-receptor binding densities were normal in all areas examined. H{sub 1}-receptor binding was also increased in the hippocampus of Lewy-body dementia (DLB) cases (p < 0.05, Students two-tailed T-Test), whilst hippocampal and cortical H{sub 2}-receptor binding densities were decreased in DLB, together with Alzheimer's disease (AD) (p < 0.05, ANOVA). H{sub 3}-receptor binding was increased in the insular cortex and decreased in the temporal cortex of DLB, but not AD, cases (p < 0.05, ANOVA). H{sub 1}-receptor binding to tissue from patients with schizophrenia was

  7. Down-regulation of histamine-induced endothelial cell activation as potential anti-atherosclerotic activity of peptides from Spirulina maxima.

    Science.gov (United States)

    Vo, Thanh-Sang; Kim, Se-Kwon

    2013-10-09

    Histamine, a potent inflammatory mediator, has been known to cause the pathogenesis of atherosclerosis. In this sense, two bioactive peptides P1 (LDAVNR; 686Da) and P2 (MMLDF; 655Da) purified from gastric enzymatic hydrolysate of Spirulina maxima were examined for their protective effects against early atherosclerotic responses induced by histamine in EA.hy926 endothelial cells. Interestingly, both P1 and P2 exhibited inhibitory activities on the production and expression of IL-6 and MCP-1. Furthermore, P1 and P2 inhibited the production of adhesion molecules including P-selectin and E-selectin, and thus reducing in vitro cell adhesion of monocyte onto endothelial cells. In addition, the production of intracellular reactive oxygen species was observed to reduce in the presence of P1 or P2. Notably, the inhibitory activities of P1 and P2 were found due to down-regulating Egr-1 expression via histamine receptor and PKCδ-dependent MAPKs activation pathway. These results suggest that peptides P1 and P2 from S. maxima are effective to suppress histamine-induced endothelial cell activation that may contribute to the prevention of early atherosclerosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Fisetin inhibits IL-31 production in stimulated human mast cells: Possibilities of fisetin being exploited to treat histamine-independent pruritus.

    Science.gov (United States)

    Che, Denis Nchang; Cho, Byoung Ok; Shin, Jae Young; Kang, Hyun Ju; Kim, Young-Soo; Jang, Seon Il

    2018-05-15

    Interleukin-31 (IL-31) is a recently discovered cytokine that is tightly linked to the pathogenesis of pruritus seen in atopic dermatitis. Flavonoids, like fisetin, are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. the present study sought to investigate whether fisetin modulates IL-31 and histamine release in human mast cells (HMC-1). HMC-1 cells were pretreated with fisetin at various doses and stimulated with phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PI) for different time intervals. We evaluated IL-31 production and histamine release and signaling mechanism of the action of fisetin on IL-31 production. We also investigated the effects of fisetin on scratching behaviors in mice. Fisetin decreased PI-stimulated mRNA expression and production of IL-31 in HMC-1 cells. Fisetin inhibited PI-induced phosphorylation of mitogen-activated protein kinases that further suppressed nuclear factor (NF-κB) activation and translocation to the nucleus through the inhibition of IκB-α phosphorylation. Fisetin also prevented mast cell release of histamine in HMC-1 cells. Mice in-vivo studies show that fisetin reduced scratching behaviors in mice. These pharmacological actions of fisetin provide new suggestions that fisetin can be of potential use for the treatment of pruritus that cannot be treated with histamine receptor blockers alone. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Cytopathology and exocrine dysfunction induced in ex vivo rabbit lacrimal gland acinar cell models by chronic exposure to histamine or serotonin.

    Science.gov (United States)

    McDonald, Michelle L; Wang, Yanru; Selvam, Shivaram; Nakamura, Tamako; Chow, Robert H; Schechter, Joel E; Yiu, Samuel C; Mircheff, Austin K

    2009-07-01

    Lacrimal immunohistopathology has diverse clinical presentations, suggesting that inflammatory mediators exert diverse influences. Chronic exposure to agonistic acetylcholine receptor autoantibodies has been studied previously; the present work addressed mediators that signal through other G protein-coupled receptors. Acinus-like structures and reconstituted acinar epithelial monolayers from rabbit lacrimal glands were exposed to varying concentrations of histamine or 5-hydroxytryptamine (5-HT) for 20 hours. Net and vectorial beta-hexosaminidase secretion, cytosolic Ca(2+) (Ca(i)) elevation, apical recruitment of p150(Glued), actin microfilament meshwork organization, and ultrastructure were assessed. Histamine and 5-HT acutely stimulated beta-hexosaminidase secretion at lower, but not higher, concentrations. Neither of them acutely elevated Ca(i) levels. Both recruited p150(Glued) at concentrations that failed to induce secretion. Chronic exposure to 10 mM histamine inhibited carbachol (CCh)-induced beta-hexosaminidase secretion and prevented the formation of continuous monolayers; 1 mM 5-HT partially inhibited secretion at the apical medium. Neither altered secretion to the basal medium. Chronic exposure to histamine or 5-HT partially decreased CCh induced Ca(i) elevations and p150(Glued) recruitment, even at concentrations that did not inhibit secretion. Both expanded acinar lumina and thickened microfilament meshworks, and both caused homotypic fusion of secretory vesicles and formation of aqueous vacuoles in the apical and basal cytoplasm. Chronic exposure to forskolin, which activates adenylyl cyclase, induced similar cytopathologic changes but impaired secretion modestly and only at the highest concentration tested. Inflammatory mediators that signal through G protein-coupled receptors cause acinar cell cytopathology and dose-dependent reductions of CCh-induced beta-hexosaminidase secretion. Although agonistic acetylcholine receptor autoantibodies may cause

  10. Influence of nitric oxide on histamine and carbachol – induced ...

    African Journals Online (AJOL)

    The study aimed to determine the influence of nitric oxide (NO) on the action of histamine and carbachol on acid secretion in the common African toad – Bufo regularis. Gastric acidity was determined by titration method. The acid secretion was determined when nitric oxide was absent following administration of NO synthase ...

  11. Digoxigenin-histamine conjugates and their use in digoxin measurement

    International Nuclear Information System (INIS)

    1979-01-01

    A method for measuring the digoxin content of a serum comprises adding to digoxin antibody coated tubes a mixture of a radiolabelled histamine derivative of digoxegenin and a sample, incubating the mixture to bind the antibody, separating the bound, labelled digoxin and measuring the radioactivity. (U.K.)

  12. Challenges in Developing a Biochip for Intact Histamine Using Commercial Antibodies

    Directory of Open Access Journals (Sweden)

    Leena Mattsson

    2017-12-01

    Full Text Available This study describes the development and the challenges in the development of an on-chip immunoassay for histamine using commercially available antibodies. Histamine can be used as an indicator of food freshness and quality, but it is also a relevant marker in clinical diagnostics. Due to its low molecular weight, simple structure and thus low immunogenicity production of high specificity and affinity antibodies is difficult. From six commercial anti-histamine antibodies tested, only two bound the histamine free in the solution. A fluorescent on-chip immunoassay for histamine was established with a dynamic range of 8–111 µg/mL using polyclonal anti-histamine antibody H7403 from Sigma (Mendota Heights, MN, USA. The anti-histamine antibodies described and used in published literature are thoroughly reviewed and the quality of commercial antibodies and their traceability and quality issues are highlighted and extensively discussed.

  13. 2009 H1N1 Flu Vaccine Facts

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Flu 2009 H1N1 Flu Vaccine Facts Past Issues / Fall 2009 Table of ... the H1N1 flu vaccine. 1 The 2009 H1N1 flu vaccine is safe and well tested. Clinical trials ...

  14. Histamine poisoning from insect consumption: an outbreak investigation from Thailand.

    Science.gov (United States)

    Chomchai, Summon; Chomchai, Chulathida

    2018-02-01

    Insect consumption is a common practice in the Asian culture and all over the world. We are reporting an outbreak investigation of histamine poisoning from ingestion of fried insects. On 24 July 2014, a group of students at a seminar presented to Angthong Provincial Hospital, Thailand, with pruritic rash after ingesting snacks consisting of fried insects from a vendor. We initiated an outbreak investigation with retrospective cohort design and collected samples of remaining foods for analyses. Attack rates, relative risks and their confidence intervals (CI) were calculated. Out of 227 students, 28 developed illnesses that were consistent with our case definition which included, flushing, pruritus, urticarial rashes, headache, nausea, vomiting, diarrhea, dyspnea and bronchospasm. Two children were hospitalized for progressive bronchospasm overnight without serious complications. The types of food ingested included a lunch that was provided at the seminar for all students and snacks that 41 students bought from the only vendor in the vicinity. The snacks included fried grasshoppers, silkworm pupae, common green frogs, bamboo borers, crickets and meat balls. The attack rates were highest (82.6 and 85.0%) among students who ingested fried grasshoppers and silkworm pupae and lowest (4.4 and 5.3%) among those who did not ingest them, with relative risk of 18.7 (95% CI 9.6-36.4) for grasshoppers and 16.0 (95% CI 8.8-29.3) for silkworm pupae. Histamine concentrations in the fried grasshoppers and silkworm pupae were 9.73 and 7.66 mg/100g, respectively. Through epidemiological analysis and laboratory confirmation, we have illustrated that histamine poisoning can occur from ingestion of fried insects. We postulate that histidine, which is present in high concentration in grasshoppers and silkworm pupae, is decarboxylated by bacteria to histamine, a heat stable toxin. The ingestion of histamine is responsible for the clinical pictures being reported.

  15. Evaluation of the Histamine Content and Potential Toxicity of Some of Consumable food

    Directory of Open Access Journals (Sweden)

    M Zarei

    2017-02-01

    Full Text Available ABSTRACT Background & aim: Consuming high amounts of histamine with food causes histamine poisoning among its consumers. Much information about the content of histamine in various food products is not available in the country. In the present study, the amount of histamine in food samples consumed in human diet which are based on existing data sources can contain histamine were measured. Methods: In the present study, 240 samples of 16 different types of food consumed in the human diet were examined. Histamine was extracted with 75 % ethanol- 0.4 N HCl in fresh and canned fish samples and extracted in other samples with  0.1 N HCl. After passing the extracts through ion exchange chromatography, the fluorescence derivative of histamine which was generated by O-phthaldialdehyde and the amount of fluorescent light was measured at excitation wavelength of 350 nm and emission wavelength of 444 nm respectively. Data were analyzed using descriptive statistics. Results: Spinach, fresh fish, canned fish and aubergine samples showed the high level of histamine with the mean levels of 5.04, 3.83, 2.77 and 2.64 mg/100g respectively. All samples tested contains histamine but 53.3, 20.0, 13.3 and 13.3 percent of the samples of these foods contains higher amounts histamine (5mg/100gr  respectively.Low levels of histamine was observed in a number of samples including tomato, pickles, nuts, bananas, oranges, melons, cheese, curd, yogurt and dough but no detectable histamine was found  olive and tea. Conclusion: In addition to confirming the fact that fish and seafood products have a high risk of histamine poisoning, but it showed that the risk of histamine poisoning in humans after consumption of fish and its products will not be less than spinach and aubergine.

  16. Identification of 6H1 as a P2Y purinoceptor: P2Y5.

    Science.gov (United States)

    Webb, T E; Kaplan, M G; Barnard, E A

    1996-02-06

    We have determined the identity of the orphan G-protein coupled receptor cDNA, 6H1, present in activated chicken T cells, as a subtype of P2Y purinoceptor. This identification is based on first on the degree of sequence identity shared with recently cloned members of the P2Y receptor family and second on the pharmacological profile. Upon transient expression in COS-7 cells the 6H1 receptor bound the radiolabel [35S]dATP alpha S specifically and with high affinity (Kd, 10 nM). This specific binding could be competitively displaced by a range of ligands active at P2 purinoceptors, with ATP being the most active (K (i)), 116 nM). Such competition studies have established the following rank order of activity: ATP ADP 2-methylthioATP alpha, beta-methylene ATP, UTP, thus confirming 6H1 as a member of the growing family of P2Y purinoceptors. As the fifth receptor of this type to be identified we suggest that it be named P2Y5.

  17. Luminosity measurement in H1; Mesure de la luminosite pour l'experience H1

    Energy Technology Data Exchange (ETDEWEB)

    Frisson, T

    2006-10-15

    At HERA, luminosity is determined on-line and bunch by bunch by measuring the Bremsstrahlung spectrum from e-p collisions. The Hl collaboration has built a completely new luminosity system in order to sustain the harsh running conditions after the fourfold luminosity increase. Namely, the higher synchrotron radiation doses and the increased event pile-up have governed the design of the two major components, a radiation resistant quartz-fibre electro-magnetic calorimeter, and a fast read-out electronic with on-line energy histogram loading at a rate of 500 kHz. The group was in charge of the electronic and the on-line data analysis of the new luminosity system. In this thesis, I present analysis tools and methods to improve the precision of the luminosity measurement. The energy scale and acceptance calculation methods set out in this thesis permit these values to be determined every four minutes, to an accuracy of 0.5 parts per thousand for the energy scale and 2 parts per thousand for the acceptance. From these results, the degree of accuracy obtained on the luminosity measurement is between 6.5 and 9.5 parts per thousand. These results are currently undergoing validation, with the aim of becoming the standard H1 method. I also studied quasi-elastic Compton events to cross-check the luminosity measurement using the 2003- 2004 and 2005 data. Indeed, this process has a well calculable cross section and a clear experimental signature. The leptonic final state consists of a coplanar e-gamma system, both observable in the central H1 detector. (author)

  18. Tryptase potentiates enteric nerve activation by histamine and serotonin: Relevance for the effects of mucosal biopsy supernatants from irritable bowel syndrome patients.

    Science.gov (United States)

    Ostertag, D; Annahazi, A; Krueger, D; Michel, K; Demir, I E; Ceyhan, G O; Zeller, F; Schemann, M

    2017-09-01

    We previously showed that mucosal biopsy supernatants from irritable bowel syndrome patients activated neurons despite low concentrations of tryptase, histamine, and serotonin which individually would not cause spike discharge. We studied the potentiating responses between these mediators on excitability of enteric neurons. Calcium-imaging was performed using the calcium-sensitive dye Fluo-4 AM in human submucous plexus preparations from 45 individuals. Histamine, serotonin, and tryptase were applied alone and in combinations to evaluate nerve activation which was assessed by analyzing increase in intracellular Ca 2+ ([Ca 2+ ] i ), the proportion of responding neurons and the product of both defined as Ca-neuroindex (NI). Protease activated receptor (PAR) 2 activating peptide, PAR2 antagonist and the serine protease-inhibitor FUT-175 were used to particularly investigate the role of proteases. Histamine or serotonin (1 μmol/L each) evoked only few small responses (median NI [25%/75%]: 0 [0/148]; 85 [0/705] respectively). Their combined application evoked statistically similar responses (216 [21/651]). Addition of the PAR2 activator tryptase induced a significantly higher Ca-NI (1401 [867/4075]) compared to individual application of tryptase or to coapplied histamine and serotonin. This synergistic potentiation was neither mimicked by PAR2 activating peptide nor reversed by the PAR2 antagonist GB83, but abolished by FUT-175. We observed synergistic potentiation between histamine, serotonin, and tryptase in enteric neurons, which is mediated by proteolytic activity rather than PAR2 activation. This explained neuronal activation by a cocktail of these mediators despite their low concentrations and despite a relatively small PAR2-mediated response in human submucous neurons. © 2017 John Wiley & Sons Ltd.

  19. PENGGUNAAN EKSTRAK TEH HIJAU (Camellia sinensis SEBAGAI PENGHAMBAT PEMBENTUKAN HISTAMIN PADA IKAN SEBELUM DIOLAH

    Directory of Open Access Journals (Sweden)

    Endang Sri Heruwati

    2009-12-01

    Full Text Available Penelitian penggunaan ekstrak teh hijau (Camellia sinensis sebagai penghambat pembentukan histamin pada ikan telah dilakukan. Ikan, terutama dari jenis skombroid, sangat rentan mengalami kerusakan karena terjadinya perubahan asam amino histidin yang terkandung dalam ikan menjadi senyawa histamin yang bersifat alergen, yang dikatalisasi oleh enzim histamin dekarboksilase (HDC. Teh hijau diketahui mengandung polifenol berupa senyawa epigalokatekingalat (EGCG yang merupakan penghambat enzim HDC, sehingga dekarboksilasi histidin menjadi histamin dapat dicegah. Perendaman ikan tongkol dalarn ekstrak teh hijau pada konsentrasi 0, 2, dan 4% dilakukan selama 30 menit, diikuti dengan pernindangan dalam larutan gararn 15% selama 30 menit diteruskan dengan penyimpanan ikan pindang pada suhu kamar. Pengambilan sampel dilakukan setiap hari selarna 4 hari penyimpanan untuk diamati perubahan mutu kimiawi (TVB dan kadar histarnin, mikrobiologi JPC dan bakteri pembentuk histamin, serta organoleptik (kenampakan, bau, tekstur, lendir, rasa. Hasil penelitian menunjukkan bahwa ikan yang direndam dalam ekstrak teh 4% mempunyai kadar histamin 21,3 ppm, jauh lebih rendah dibandingkan dengan ikan yang direndam dalam ekstrak teh 2% dan 0% yang masing-masing mencapai 64,4 pprn dan 101,4 ppm. Penghambatan pembentukan histamin oleh ekstrak teh hijau masih terjadi selama penyimpanan, yang terlihat dari rendahnya jumlah bakteri pembentuk histarnin dan kadar histamin dibandingkan dengan kontrol. Pada penyimpanan hari ke-3, penghambatan pembentukan histamin oleh ekstrak teh hijau tidak efektif, kemungkinan karena terlalu tingginya jurnlah bakteri pembentuk histamin, yaitu mencapai 108 cfu/g.

  20. Study to investigate the difference in reaction to intracutaneously and orally administered histamine between suspected histamine-intolerant patients and healthy volunteers

    NARCIS (Netherlands)

    den Broeder E; Kortboyer JM; Koers WJ; Bruijnzeel-Koomen CAFM; de Haan-Brand A; Wolthers BG; Breukelman H; Meulenbelt J; NVIC; ARO; afdeling Dermatologie en Allergologie (Academisch Ziekenhuis Utrecht); afdeling KCSB (Academisch Ziekenhuis Groningen)

    1996-01-01

    In een dubbelblinde placebo gecontroleerde, vergelijkende studie werd aan 16 histamine intolerante patienten en aan 16 gezonde proefpersonen histamine toegediend. Het doel van de studie was het ontwikkelen van een relatief simpele en betrouwbare test voor het stellen van de diagnose

  1. Histone h1 depletion impairs embryonic stem cell differentiation.

    Science.gov (United States)

    Zhang, Yunzhe; Cooke, Marissa; Panjwani, Shiraj; Cao, Kaixiang; Krauth, Beth; Ho, Po-Yi; Medrzycki, Magdalena; Berhe, Dawit T; Pan, Chenyi; McDevitt, Todd C; Fan, Yuhong

    2012-01-01

    Pluripotent embryonic stem cells (ESCs) are known to possess a relatively open chromatin structure; yet, despite efforts to characterize the chromatin signatures of ESCs, the role of chromatin compaction in stem cell fate and function remains elusive. Linker histone H1 is important for higher-order chromatin folding and is essential for mammalian embryogenesis. To investigate the role of H1 and chromatin compaction in stem cell pluripotency and differentiation, we examine the differentiation of embryonic stem cells that are depleted of multiple H1 subtypes. H1c/H1d/H1e triple null ESCs are more resistant to spontaneous differentiation in adherent monolayer culture upon removal of leukemia inhibitory factor. Similarly, the majority of the triple-H1 null embryoid bodies (EBs) lack morphological structures representing the three germ layers and retain gene expression signatures characteristic of undifferentiated ESCs. Furthermore, upon neural differentiation of EBs, triple-H1 null cell cultures are deficient in neurite outgrowth and lack efficient activation of neural markers. Finally, we discover that triple-H1 null embryos and EBs fail to fully repress the expression of the pluripotency genes in comparison with wild-type controls and that H1 depletion impairs DNA methylation and changes of histone marks at promoter regions necessary for efficiently silencing pluripotency gene Oct4 during stem cell differentiation and embryogenesis. In summary, we demonstrate that H1 plays a critical role in pluripotent stem cell differentiation, and our results suggest that H1 and chromatin compaction may mediate pluripotent stem cell differentiation through epigenetic repression of the pluripotency genes.

  2. Time-dependent histamine release from stored human blood products

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Edvardsen, L; Vangsgaard, K

    1996-01-01

    .0 (range 176.0-910.0) nmol/l in whole blood and 475.0 (range 360.0-1560.0) nmol/l in plasma-reduced whole blood, while it was undetectable in SAGM blood. Spontaneous histamine release increased in a time-dependent manner from a median of 6.7 (range 2.2-17.4) nmol/l at the time of storage to 175.0 (range 33...

  3. Effect of methylmercury on histamine release from rat mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Graevskaya, Elizabeth E.; Rubin, Andrew B. [Moscow State University, Biological Faculty, Department of Biophysics, 119899, Vorobjovy Gory, Moscow (Russian Federation); Yasutake, Akira; Aramaki, Ryoji [National Institute for Minamata Disease, 4058-18 Hama, Minamata, Kumamoto 867-0008 (Japan)

    2003-01-01

    Methylmercury chloride (MeHgCl) is well known as a significant environmental hazard, particularly as a modulator of the immune system. As it is acknowledged that the critical effector cells in the host response participating in various biological responses are mast cells, we tried to define the possible contribution of mast cells in the development of methylmercury-evoked effects. We investigated the effects of methylmercury on the rat mast cell degranulation induced by non-immunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. Using the cells prepared from methylmercury-intoxicated rats through a 5-day treatment of MeHgCl (10 mg/kg/day), we observed the suppression of calcium ionophore A23187- and 48/80-induced histamine release, which was enhanced with time after treatment. Similar suppression was observed in the ionophore-stimulated release, when cells were prepared from rat with a single treatment of MeHgCl (20 mg/kg). It should be noted that when cells from the control rat were pre-incubated with methylmercury in vitro at a 10{sup -8} M concentration for 10 min, A23187 and compound 48/80-stimulated histamine release was significantly enhanced. However, when the pre-incubation period was prolonged to 30 min, the release was suppressed. An increase in the methylmercury concentration to 10{sup -6} M also suppressed the histamine release. These results show that methylmercury treatment can modify mast cell function depending on concentration and time, and might provide an insight into the role of mast cells in the development of methylmercury-stimulated effects. (orig.)

  4. Measuring histamine and cytokine release from basophils and mast cells

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Falkencrone, Sidsel; Skov, Per S

    2014-01-01

    Basophils and mast cells are known for their capability to release both preformed and newly synthesized inflammatory mediators. In this chapter we describe how to stimulate and detect histamine released from basophils in whole blood, purified basophils, in vitro cultured mast cells, and in situ...... skin mast cells. We also give an example of an activation protocol for basophil and mast cell cytokine release and discuss approaches for cytokine detection....

  5. Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes.

    Science.gov (United States)

    DeVries, Zachary C; Santangelo, Richard G; Barbarin, Alexis M; Schal, Coby

    2018-01-01

    Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust) and significantly higher than in control homes not infested with bed bugs (mean emergent contaminant and pose a serious health risk in the indoor environment.

  6. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  7. [Outbreak due to butterfish consumption: keriorrhea and histamine poisoning].

    Science.gov (United States)

    Fariñas Cabrero, Maria Azucena; Berbel Hernández, Clara; Allué Tango, Marta; Díez Hillera, Margarita; Herrero Marcos, Juan Antonio

    2015-01-01

    The consumption of butterfish is spreading in our country; if appropriate standards of conservation and preparation of this type of food are not met may cause poisoning. The objective is to describe an outbreak of histamine poisoning and double cerous esters after consumption butterfish. A descriptive study of the double intoxication at a banquet held in July 2013 in Valladolid. It was studied by filling a specific survey, by phone or by the medical centers who treated the guests. The database and subsequent descriptive statistical analyzes were performed with Microsoft Excel Professional Plus 2010 program. Of the 27 cases reported in 24 we obtained information on symptoms. The attack rate was 22.5 %, with a clinical picture in which predominant diarrhea (75%), headache (46%), abdominal pain (38%) and sweating (38%), highlighting its specificity itching/burning of mouth (29%). Four patients had orange and oily stools (keriorrhea). The average time from the start of dinner to onset of symptoms was 119 minutes. The mean duration of symptoms was 14 hours. Analytical served fish showed histamine levels above 2,000 mg / kg. A double poisoning (histamine and cerous esters) was produced by consumption of butterfish. The picture was mild and self-limiting. You need to know this type of poison to properly handle avoiding unnecessary tests, and to notify the health authority for investigation and subsequent adoption of appropriate measures.

  8. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

    of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein...

  9. Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy.

    Science.gov (United States)

    Wang, Wenjun; Wang, Qing; Wan, Danyang; Sun, Yue; Wang, Lin; Chen, Hong; Liu, Chengyu; Petersen, Robert B; Li, Jianshuang; Xue, Weili; Zheng, Ling; Huang, Kun

    2017-05-04

    Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C overexpression also promotes inflammation and cell toxicity in vitro. Knockdown of histone HIST1H1C reduces both the basal and stresses (including high glucose)-induced autophagy, and inhibits high glucose induced inflammation and cell toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the retinas leads to increased autophagy, inflammation, glial activation and neuron loss, similar to the pathological changes identified in the early stage of diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the retinas of diabetic mice significantly attenuated the diabetes-induced autophagy, inflammation, glial activation and neuron loss. These results indicate that histone HIST1H1C may offer a novel therapeutic target for preventing diabetic retinopathy.

  10. Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X.

    Science.gov (United States)

    Okuwaki, Mitsuru; Abe, Mayumi; Hisaoka, Miharu; Nagata, Kyosuke

    2016-11-01

    Linker histones play important roles in the genomic organization of mammalian cells. Of the linker histone variants, H1.X shows the most dynamic behavior in the nucleus. Recent research has suggested that the linker histone variants H1.X and H1.0 have different chromosomal binding site preferences. However, it remains unclear how the dynamics and binding site preferences of linker histones are determined. Here, we biochemically demonstrated that the DNA/nucleosome and histone chaperone binding activities of H1.X are significantly lower than those of other linker histones. This explains why H1.X moves more rapidly than other linker histones in vivo Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. Our results also suggest that the N-terminal domain (NTD), GD, and CTD cooperatively determine the preferential binding sites, and the contribution of each domain for this determination is different depending on the target genes. We also found that linker histones accumulate in the nucleoli when the nucleosome binding activities of the GDs are weak. Our results contribute to understanding the molecular mechanisms of dynamic behaviors, binding site selection, and localization of linker histones. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Epidemiological characteristics of Pandemic Influenza A (H1N1 ...

    African Journals Online (AJOL)

    Background: A novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in ...

  12. Epidemiological characteristics of Pandemic Influenza A (H1N1 ...

    African Journals Online (AJOL)

    ... novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in Zhanjiang, China ...

  13. (H1N1) Influenza in Saurashtra, India

    African Journals Online (AJOL)

    Mexico in April, 2009,[1] and then in United States (US).[2,3]. This was originally ... duration of hospital stay of such patients was 2‑32 days. All admitted A (H1N1) .... Because of limited resources, only 2009 A (H1N1) influenza virus was tested ...

  14. Histamine as an emergent indoor contaminant: Accumulation and persistence in bed bug infested homes.

    Directory of Open Access Journals (Sweden)

    Zachary C DeVries

    Full Text Available Histamine is used in bronchial and dermal provocation, but it is rarely considered an environmental risk factor in allergic disease. Because bed bugs defecate large amounts of histamine as a component of their aggregation pheromone, we sought to determine if histamine accumulates in household dust in bed bug infested homes, and the effects of bed bug eradication with spatial heat on histamine levels in dust. We collected dust in homes and analyzed for histamine before, and up to three months after bed bug eradication. Histamine levels in bed bug infested homes were remarkably high (mean = 54.6±18.9 μg/100 mg of sieved household dust and significantly higher than in control homes not infested with bed bugs (mean < 2.5±1.9 μg/100 mg of sieved household dust. Heat treatments that eradicated the bed bug infestations failed to reduce histamine levels, even three months after treatment. We report a clear association between histamine levels in household dust and bed bug infestations. The high concentrations, persistence, and proximity to humans during sleep suggest that bed bug-produced histamine may represent an emergent contaminant and pose a serious health risk in the indoor environment.

  15. Induction of histamine release in vitro from rat peritoneal mast cells by extracts of grain dust.

    Science.gov (United States)

    Warren, C P; Holford-Strevens, V

    1986-01-01

    The ability of extracts of grain dust and wheat to induce histamine release from rat peritoneal cells was investigated. Some grain dusts, with a high endotoxin content, were found to produce cytotoxic histamine release. Extract of wheat dust, with a low endotoxin release, produced noncytotoxic histamine release from peritoneal cells but not from purified mast cells. This reaction was dependent on the presence of phosphatidyl serine. The agent did not appear to be a lectin because histamine release was not enhanced by passive sensitization of mast cells with IgE. The activity occurred only over a narrow range of concentrations of the extract of wheat. The cause was unclear. PMID:2423321

  16. Comparison of in vitro histamine release by ionic and nonionic radiographyic contrast media

    International Nuclear Information System (INIS)

    Faraj, B.A.; Martin, L.G.

    1989-01-01

    This paper discusses a study whose results showed that in 53 hospitalized patients undergoing cardiovascular catheterization, incubation of their blood samples with varying concentrations of an ionic contrast medium (Angiovist-370, 60--631 mM) induced a significant (P < .005) amount of histamine release from whole blood (3.5%--10%), as compared with the histamine release following incubation with a nonionic contrast medium. Data suggest that the use of nonionic contrast media may induce minimal histamine release and thereby involve less patient risk from the histamine-mediated allergic and hemodynamic side effects associated with radiographic contrast media procedures

  17. Extended-gate organic field-effect transistor for the detection of histamine in water

    Science.gov (United States)

    Minamiki, Tsukuru; Minami, Tsuyoshi; Yokoyama, Daisuke; Fukuda, Kenjiro; Kumaki, Daisuke; Tokito, Shizuo

    2015-04-01

    As part of our ongoing research program to develop health care sensors based on organic field-effect transistor (OFET) devices, we have attempted to detect histamine using an extended-gate OFET. Histamine is found in spoiled or decayed fish, and causes foodborne illness known as scombroid food poisoning. The new OFET device possesses an extended gate functionalized by carboxyalkanethiol that can interact with histamine. As a result, we have succeeded in detecting histamine in water through a shift in OFET threshold voltage. This result indicates the potential utility of the designed OFET devices in food freshness sensing.

  18. Histone H1(0) mapping using monoclonal antibodies.

    Science.gov (United States)

    Dousson, S; Gorka, C; Gilly, C; Lawrence, J J

    1989-06-01

    Monoclonal antibodies (mAb) to ox liver histone H1 degree were produced and characterized. Two sets of mice were immunized either with pure H1(0) or with an H1(0)-yeast tRNA complex. Eleven hybridomas of various clonal origin were selected. Typing of the antibodies indicated that all but three IgM belonged to the IgG1 class and contained kappa light chains. Immunoblotting experiments using peptides derived from H1(0) or H5 treated by various proteolytic agents (trypsin, N-bromosuccinimide, cyanogen bromide, acetic acid), revealed that nine of the mAb reacted with the globular part of H1(0). More advanced characterization of the antigenic determinants allowed us to determine distinct regions within this globular part which are involved in the antigenic recognition. The peptopes could be subdivided into two groups. Three mAb bound to residues 24-27 and were specific for H1(0). Six mAb bound to residues 27-30 and were specific for H1(0) except one of them which strongly cross-reacted with H5 and GH5. Two mAb reacted with the entire histone H1(0) but failed to react with any of the peptides, suggesting that the corresponding epitope is a conformational antigenic determinant. In order to confirm the localization of the two distinct regions which are involved in the antigenic recognition, a synthetic decapeptide corresponding to the beginning of human H1(0) globular part (from residue 19 to residue 28) was synthesized. Inhibition experiments of the reaction between H1(0) and the various IgG1 mAb by increasing amounts of peptide-bovine serum albumin conjugates were then performed.

  19. Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

    Science.gov (United States)

    Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

    2011-09-28

    Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Synthesis and pharmacological evaluation of thiopyran analogues of the dopamine D-3 receptor-selective agonist (4aR,10bR)-(+)-trans-3,4,4a,10b-tetrahydro-4-n-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol (PD 128907)

    NARCIS (Netherlands)

    van Vliet, LA; Rodenhuis, N; Dijkstra, D; Wikstrom, H; Pugsley, TA; Serpa, KA; Meltzer, LT; Heffner, TG; Wise, LD; Lajiness, ME; Huff, RM; Svensson, K; Sundell, S; Lundmark, M

    2000-01-01

    Benzopyranoxazine (+)-7 (PD 128907) is the most dopamine (DA) D-3 receptor-selective agonist presently known. The only structural feature which distinguishes 7 from the analogous nonselective naphthoxazines is an oxygen atom in the 6-position. To extend this series of tricyclic DA agonists we used a

  1. 77 FR 3284 - Comment Request for Information Collection for the H-1B Technical Skills Training (H-1B) and the...

    Science.gov (United States)

    2012-01-23

    ... concerning the collection of data about H-1B Technical Skills Training (H-1B) [SGA/DFA PY-10-13] and H-1B... DEPARTMENT OF LABOR Comment Request for Information Collection for the H-1B Technical Skills Training (H-1B) and the H-1B Jobs and Innovation Accelerator Challenge (JIAC) Grant Programs, New...

  2. Sleep and Sedative States Induced by Targeting the Histamine and Noradrenergic Systems

    Directory of Open Access Journals (Sweden)

    Xiao Yu

    2018-01-01

    Full Text Available Sedatives target just a handful of receptors and ion channels. But we have no satisfying explanation for how activating these receptors produces sedation. In particular, do sedatives act at restricted brain locations and circuitries or more widely? Two prominent sedative drugs in clinical use are zolpidem, a GABAA receptor positive allosteric modulator, and dexmedetomidine (DEX, a selective α2 adrenergic receptor agonist. By targeting hypothalamic neuromodulatory systems both drugs induce a sleep-like state, but in different ways: zolpidem primarily reduces the latency to NREM sleep, and is a controlled substance taken by many people to help them sleep; DEX produces prominent slow wave activity in the electroencephalogram (EEG resembling stage 2 NREM sleep, but with complications of hypothermia and lowered blood pressure—it is used for long term sedation in hospital intensive care units—under DEX-induced sedation patients are arousable and responsive, and this drug reduces the risk of delirium. DEX, and another α2 adrenergic agonist xylazine, are also widely used in veterinary clinics to sedate animals. Here we review how these two different classes of sedatives, zolpidem and dexmedetomideine, can selectively interact with some nodal points of the circuitry that promote wakefulness allowing the transition to NREM sleep. Zolpidem enhances GABAergic transmission onto histamine neurons in the hypothalamic tuberomammillary nucleus (TMN to hasten the transition to NREM sleep, and DEX interacts with neurons in the preoptic hypothalamic area that induce sleep and body cooling. This knowledge may aid the design of more precise acting sedatives, and at the same time, reveal more about the natural sleep-wake circuitry.

  3. Influenza A (H1N1) organising pneumonia.

    Science.gov (United States)

    Torrego, Alfons; Pajares, Virginia; Mola, Anna; Lerma, Enrique; Franquet, Tomás

    2010-04-27

    In November 2009, countries around the world reported confirmed cases of pandemic influenza H1N1, including over 6000 deaths. No peak in activity has been seen. The most common causes of death are pneumonia and acute respiratory distress syndrome. We report a case of a 55-year-old woman who presented with organising pneumonia associated with influenza A (H1N1) infection confirmed by transbronchial lung biopsy. Organising pneumonia should also be considered as a possible complication of influenza A (H1N1) infection, given that these patients can benefit from early diagnosis and appropriate specific management.

  4. Novel 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives: a patent review (2008 - 2011).

    Science.gov (United States)

    Ferreira, Vitor F; da Rocha, David R; da Silva, Fernando C; Ferreira, Patrícia G; Boechat, Núbia A; Magalhães, Jorge L

    2013-03-01

    The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms. Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds. In this review, the authors explored aspects of patents for the 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011. The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities. More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases. This review emphasizes recent perspective and advances in the therapeutically active 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals. Many studies have focused on these compounds as target structures and evaluated them in several biological targets. The preparation of 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives brings to light several issues. There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability. New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these

  5. Clebopride enhances contractility of the guinea pig stomach by blocking peripheral D2 dopamine receptor and alpha-2 adrenoceptor.

    Science.gov (United States)

    Takeda, K; Taniyama, K; Kuno, T; Sano, I; Ishikawa, T; Ohmura, I; Tanaka, C

    1991-05-01

    The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10(-8) M to 10(-5) M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: 1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. 2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility.

  6. Clebopride enhances contractility of the guinea pig stomach by blocking peripheral D2 dopamine receptor and alpha-2 adrenoceptor

    International Nuclear Information System (INIS)

    Takeda, K.; Taniyama, K.; Kuno, T.; Sano, I.; Ishikawa, T.; Ohmura, I.; Tanaka, C.

    1991-01-01

    The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10 - 8 M to 10 - 5 M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: (1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. (2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility

  7. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1.

    Science.gov (United States)

    Josupeit, Rafael; Bender, Sebastian; Kern, Sonja; Leuchs, Barbara; Hielscher, Thomas; Herold-Mende, Christel; Schlehofer, Jörg R; Dinsart, Christiane; Witt, Olaf; Rommelaere, Jean; Lacroix, Jeannine

    2016-05-19

    Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG). A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV) in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6), including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Cytotoxic effects induced by the virus have been observed in all HGG neurospheres at half maximal inhibitory concentration (IC50) doses of input virus between 1 and 10 plaque forming units per cell. H-1PV infection at this dose range was able to prevent tumorigenicity of NCH421k glioblastoma multiforme (GBM) "stem-like" cells in NOD/SCID mice. Interestingly NCH421R, an isogenic subclone with equal capacity of xenograft formation, but resistant to H-1PV infection could be isolated from the parental NCH421k culture. To reveal changes in gene expression associated with H-1PV resistance we performed a comparative gene expression analysis in these subclones. Several dysregulated genes encoding receptor proteins, endocytosis factors or regulators innate antiviral responses were identified and represent intriguing candidates for to further study molecular mechanisms of H-1PV resistance.

  8. Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

    Directory of Open Access Journals (Sweden)

    Simon Thebault

    Full Text Available Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03 vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR and contactin-associated protein 2 (CASPR2, both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054 in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6. In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

  9. Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

    Science.gov (United States)

    Thebault, Simon; Waters, Patrick; Snape, Matthew D; Cottrell, Dominic; Darin, Niklas; Hallböök, Tove; Huutoniemi, Anne; Partinen, Markku; Pollard, Andrew J; Vincent, Angela

    2015-01-01

    Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

  10. Production, purification, crystallization and structure determination of H-1 Parvovirus

    International Nuclear Information System (INIS)

    Halder, Sujata; Nam, Hyun-Joo; Govindasamy, Lakshmanan; Vogel, Michèle; Dinsart, Christiane; Salomé, Nathalie; McKenna, Robert; Agbandje-McKenna, Mavis

    2012-01-01

    The production, purification, crystallization and crystallographic analysis of H-1 Parvovirus, a gene-therapy vector, are reported. Crystals of H-1 Parvovirus (H-1PV), an antitumor gene-delivery vector, were obtained for DNA-containing capsids and diffracted X-rays to 2.7 Å resolution using synchrotron radiation. The crystals belonged to the monoclinic space group P2 1 , with unit-cell parameters a = 255.4, b = 350.4, c = 271.6 Å, β = 90.34°. The unit cell contained two capsids, with one capsid per crystallographic asymmetric unit. The H-1PV structure has been determined by molecular replacement and is currently being refined

  11. H-1NF: Australian national fusion plasma research facility

    International Nuclear Information System (INIS)

    Blackwell, B.D.; Borg, G.G.; Dewar, R.L.; Howard, J.; Gardner, H.J.; Rudakov, D.L.; Sharp, L.E.; Shats, M.G.; Warr, G.B.

    1997-01-01

    The H-1 heliac is a helical axis stellarator of moderate size and novel, flexible configuration. Since commissioning, H-1 has operated in quasi-continuous mode at low magnetic field. For higher fields ≤1T an ECRH heating system (28GHz, 200kW) has been installed under a collaborative agreement between ANU and NIFS. H-1 has recently been promoted to national facility status (H-1NF), which will include upgrades of the rf and ech heating systems to megawatt powers, and power supply and diagnostic and data system enhancements. This facilitates collaborative research locally (through the Australian Fusion Research Group consortium) and internationally. Results of a number of basic experiments in quasi-continuous mode are presented. (author)

  12. Adrenergic receptors and gastric acid secretion in dogs. The influence of beta 2-receptors

    DEFF Research Database (Denmark)

    Gottrup, F; Hovendal, C; Bech, K

    1984-01-01

    the characteristics of a non-competitive mechanism, while the weaker inhibition of histamine induced acid output seemed to follow a competitive mechanism. The inhibitory effect was not mediated through a decreased gastrin release. Dopamine receptor blockade was found to be without any influence on the inhibitory...

  13. Early Detection of Pandemic (H1N1) 2009, Bangladesh

    Science.gov (United States)

    Rahman, Mustafizur; Al Mamun, Abdullah; Haider, Mohammad Sabbir; Zaman, Rashid Uz; Karmakar, Polash Chandra; Nasreen, Sharifa; Muneer, Syeda Mah-E; Homaira, Nusrat; Goswami, Doli Rani; Ahmed, Be-Nazir; Husain, Mohammad Mushtuq; Jamil, Khondokar Mahbuba; Khatun, Selina; Ahmed, Mujaddeed; Chakraborty, Apurba; Fry, Alicia; Widdowson, Marc-Alain; Bresee, Joseph; Azim, Tasnim; Alamgir, A.S.M.; Brooks, Abdullah; Hossain, Mohamed Jahangir; Klimov, Alexander; Rahman, Mahmudur; Luby, Stephen P.

    2012-01-01

    To explore Bangladesh’s ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June–July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population. PMID:22257637

  14. Measurement of electric fields in the H-1NF heliac

    International Nuclear Information System (INIS)

    James, B.W.; Howard, J.

    1999-01-01

    There are a number of laser induced fluorescence techniques which can be used to measure internal plasma electric fields. It is planned to use a technique based on Stark mixing of energy levels in a supersonic beam containing metastable helium atoms to measure radial electric fields in H-1NF. Enhanced values of radial electric field are associated with improved confinement modes in H-1NF and other magnetically confined plasmas

  15. Data logging and online reconstruction in H1

    International Nuclear Information System (INIS)

    Fuhrmann, P.; Gerhards, R.; Kruener-Marquis, U.; Olsson, J.E.; Szkutnik, Z.

    1994-01-01

    In spring 1992, the H1 detector at the HERA electron proton collider at DESY came into operation. The high bunch crossing rate and, correspondingly, the large data volumes are placing demanding requirements on the data logging and event reconstruction. Both tasks are performed on an SGI Challenge series computer. This note reviews the development and the experience with the data logging and online reconstruction in H1

  16. Le dosage de l'histamine plasmatique lors de réactions anaphylactoïdes chez le sujet anesthésié: Influence des méthodes de prélèvement et de la préparation du plasma sur l'histaminémie mesurée [Plasma histamine assay in anaphylactoid reactions of the anesthetized subject. Effects of collection methods and plasma preparation on measured histamine

    OpenAIRE

    Lorenz, Wilfried; Neugebauer, E.; Schmal, A.

    1982-01-01

    Plasma histamine assay in man is indicated for the diagnosis of histamine release, as well as the elucidation of the mechanisms of adverse drug reactions, and the identification of clinical situations in anaesthesia and surgery where a pathological plasma histamine level may occur. Normal and pathological plasma histamine levels vary considerably in the literature. Data from various studies, especially one involving 300 patients in Heidelberg (G.F.R.), allow us to define the normal range for ...

  17. Fusion plasma physics research on the H-1 national facility

    International Nuclear Information System (INIS)

    Harris, J.

    1998-01-01

    Full text: Australia has a highly leveraged fusion plasma research program centred on the H-1 National Facility device at the ANU. H-1 is a heliac, a novel helical axis stellarator that was experimentally pioneered in Australia, but has a close correlation with the worldwide research program on toroidal confinement of fusion grade plasma. Experiments are conducted on H-1 by university researchers from the Australian Fusion Research Group (comprising groups from the ANU, the Universities of Sydney, Western Sydney, Canberra, New England, and Central Queensland University) under the aegis of AINSE; the scientists also collaborate with fusion researchers from Japan and the US. Recent experiments on H-1 have focused on improved confinement modes that can be accessed at very low powers in H-1, but allow the study of fundamental physics effects seen on much larger machines at higher powers. H-1 is now being upgraded in magnetic field and heating power, and will be able to confine hotter plasmas beginning in 1999, offering greatly enhanced research opportunities for Australian plasma scientists and engineers, with substantial spillover of ideas from fusion research into other areas of applied physics and engineering

  18. Germline-specific H1 variants: the "sexy" linker histones.

    Science.gov (United States)

    Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando

    2016-03-01

    The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.

  19. Molecular treatment of the ion-pair formation reaction in H(1s) + H(1s) collisions

    International Nuclear Information System (INIS)

    Borondo, F.; Martin, F.; Yaez, M.

    1987-01-01

    All the available theoretical calculations of the cross section for the ion-pair formation reaction H(1s)+H(1s)→H + H - (1s 2 ) have been performed using methods that are only valid at high collision energies. They get good agreement with the experiments for impact energies greater than 25 keV, but fail completely at smaller energies. In this work we report the cross section for this reaction at impact energies less than 10 keV, calculated in the framework of the impact-parameter approximation and using the molecular method with a common translation factor

  20. [A preliminary study on the role of substance P in histamine-nasal-spray-induced allergic conjunctivitis in guinea pigs].

    Science.gov (United States)

    Li, Tong; Zhao, Changqing

    2015-10-01

    To investigate the effect of the non adrenergic non cholinergic nerve (NANC) and substance P (SP) in allergic rhinoconjunctivitis by observing histamine nasal provocation induced conjunctivitis in guinea pigs. Forty male guinea pigs were randomly divided into five groups with each group consisting of eight guinea pigs. All anesthetized guinea pigs were exposed either to histamine (0.2%, 5 µl) (group B~E) or saline (5 µl, group A) via unilateral nostril. No pretreatment was done in group A and B while pretreatment was done in groups C~E through injection into the unilateral common carotid artery with cholinergic nerve inhibitor (atropine, 1 mg/kg, group C), cholinergic nerve inhibitor plus adrenergic nerve inhibitors (atropine, 1 mg/kg, phentolamine, 1 mg/kg plus Esmolol, 1 mg/kg, group D) and cholinergic nerve inhibitor, adrenergic nerve inhibitors plus SP receptor antagonist (the same treatment with group D plus D-SP 10(-6) mol/L, 1 µl/g, group E), respectively. To assess the ipsilateral conjunctival inflammatory reaction, conjunctiva leakage with Evans blue dye assessments and HE staining of conjunctival tissues were performed. The SP expression in ipsilateral conjunctival tissue in different groups of guinea pigs were assessed by immunofluorescence and RT-PCR. The activity of eosinophils was assessed by eosinophil major basic protein 1 (MBP1) with RT-PCR, meanwhile, the activity of mast cells was assessed by tryptase with RT-PCR. SPSS 17.0 software was used to analyze the data. At 30 min after nasal application of histamine, ipsilateral conjunctivitis was successfully induced as shown by the change of conjunctiva leakage and histology. The content of Evans blue in ipsilateral conjunctival tissue of group A~E was (13.78 ± 2.48), (29.62 ± 3.31), (19.03 ± 1.47), (18.42 ± 2.52), (14.83 ± 2.14) µg/ml, respectively. There was statistically significant difference between group A and B (t = -10.66, P 0.05). Histamine nasal provocation induced allergic

  1. [Effect of nociceptin on histamine and serotonin release in the central nervous system].

    Science.gov (United States)

    Gyenge, Melinda; Hantos, Mónika; Laufer, Rudolf; Tekes, Korniléa

    2006-01-01

    Role in pain sensation of both nociceptin (NC), the bioactive heptadecapeptide sequence of preproorphaninFQ and of histamine has been widely evidenced in the central nervous system (CNS). In the current series of experiments effect of intracerebroventricularly (i.c.v.) administered NC (5.5 nmol/rat) on histamine and serotonin levels in blood plasma, CSF and brain areas (hypothalamus and hippocampus) was studies and compared to the effect of the mast cell degranulator Compound 48/80(100microg/kg, i.c.v.) and the neuroactive peptide Substance P (50nmol/rat, i.c.v.). It was found that all the three compounds increased the histamine level in the CNS, however their activity concerning the mast cell-, and neuronal histamine release is different. NC could release histamine from both the mast cells and the neurons and it decreased CNS serotonin levels. Substance P was found the most potent in increasing CNS histamine levels. Compound 48/80 treatment resulted in elevated histamine levels both in the CNS and blood plasma. It is concluded that the histamine releasing effects of i.c.v. administered NC and SP are limited to the CNS, but in the effect of Compound 48/80 its blood-brain barrier impairing activity is also involved. Data also demonstrate that NC has significant effect on both the histaminergic and serotonergic neurotransmission in the CNS.

  2. A facile molecularly imprinted polymer-based fluorometric assay for detection of histamine

    DEFF Research Database (Denmark)

    Feng, Xiaotong; Ashley, Jon; Zhou, Tongchang

    2018-01-01

    urgently needed. In this paper, we developed a facile and cost-effective molecularly imprinted polymer (MIP)-based fluorometric assay to directly quantify histamine. Histamine-specific MIP nanoparticles (nanoMIPs) were synthesized using a modified solid-phase synthesis method. They were then immobilized...

  3. Bacteria-induced histamine release from human bronchoalveolar cells and blood leukocytes

    DEFF Research Database (Denmark)

    Clementsen, P; Milman, N; Struve-Christensen, E

    1991-01-01

    23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria...

  4. Mastocytosis and adverse reactions to biogenic amines and histamine-releasing foods : what is the evidence?

    NARCIS (Netherlands)

    Viieg-Boerstra, BJ; van der Heide, S; Elberink, JNGO; Kluin-Nelemans, JC; Dubois, AEJ

    2005-01-01

    Background: It has been suggested that normal concentrations of biogenic amines and 'histamine-releasing foods' may exacerbate symptoms in mastocytosis. The purpose of this study was to look for scientific evidence in the literature on diets restricted in biogenic amines and histamine-releasing

  5. Validation of the method spectrophotometer in the histamine determination in fresh tuna (Thunnus Tunna)

    International Nuclear Information System (INIS)

    Chacon Silva, F.

    1998-01-01

    The objective of this study was to validate the spectrophotometer method described by Bateman et al. (1994) for the histamine determination in fresh tuna (Thunnus Tunna) and to evaluate the histamine concentration in samples of fresh tuna. To fulfill the recently exposed objectives, the figures of merit were determined like they are it: recovery limits of detection, sensibility and repetitive of the method spectrophotometry and applied the analysis at twenty samples of fresh tuna for copy of the Metropolitan area and three sample like reference of fresh tuna stored 4 degree centigrade by 15 days. The histamine recovery you determines enriching seven ours of fresh tuna with histamine to two levels different 0.613 mg/L and 2.21 mg/L. three samples were left without enriching and you subtract the average to the native histamine. You determines the one it limits of detection using the standard deviation to three levels of concentration of histamine 1.37 mg/L, 2.22 mg/L and 3.22 mg/L, the minimum quantity of hi stamina that you can determine for the method spectrophotometry settling down. The repetitive you determines using the standard deviation for 100 among the average of the histamine values, in seven you replies independent of the same sample. You determines the histamine content, in the fresh tuna Thunnus Tunna of the expends of the Metropolitan Area and in samples of reference stored 4 degrees centigrade by 15 days [es

  6. Immunochemical cross-reactivity between albumin and solid-phase adsorbed histamine

    DEFF Research Database (Denmark)

    Poulsen, L K; Nolte, H; Søndergaard, I

    1990-01-01

    For production of an antibody against histamine, this was coupled to human serum albumin (HSA) and used for immunization of rabbits. To test the antiserum, an immunoradiometric assay was developed comprising solid-phase bound histamine, antisera and radiolabelled protein A. Titration and inhibition...

  7. Effect of terfenadine on nasal, eustachian tube, and pulmonary function after provocative intranasal histamine challenge.

    Science.gov (United States)

    Skoner, D P; Doyle, W J; Boehm, S; Fireman, P

    1991-12-01

    Previous studies have documented that intranasal histamine challenge results in nasal and eustachian tube obstruction (ETO) in human volunteers. The purpose of the present study was to assess the effect of pretreatment with terfenadine, a nonsedating antihistamine on the pathophysiologic consequences of intranasal histamine challenge. Fifteen subjects with allergic rhinitis were challenged intranasally with saline and increasing histamine doses (0.01, 0.1, 0.5, 1.0, 5.0, and 10.0 mg) before pretreatment (baseline) and after 1 week of pretreatment with terfenadine, 60 mg b.i.d., terfenadine, 120 mg b.i.d., and placebo. Nasal conductance as measured by posterior rhinomanometry showed a dose-dependent, monotonic decrease following sequential administration of the histamine solutions, but there were no apparent differences in the average responses among the four challenge sessions. The frequency of ETO after histamine challenge was decreased by pretreatment with both doses of terfenadine, although this was not significant. Histamine-induced sneezing and rhinorrhea, but not congestion, were significantly reduced by terfenadine pretreatment. There was no evidence of extension of the histamine effects to the lower airway. The results of the present study suggest that terfenadine, a nonsedating antihistamine, had a favorable effect on sneezing and rhinorrhea after provocative intranasal histamine challenge, but did not significantly attenuate the subjective or objective nasal and ET obstructive responses.

  8. Bronchial histamine challenge. A combined interrupter-dosimeter method compared with a standard method

    DEFF Research Database (Denmark)

    Pavlovic, M; Holstein-Rathlou, N H; Madsen, F

    1985-01-01

    We compared the provocative concentration (PC) values obtained by two different methods of performing bronchial histamine challenge. One test was done on an APTA, an apparatus which allows simultaneous provocation with histamine and measurement of airway resistance (Rtot) by the interrupter metho...

  9. Nitroglycerin-induced headache is not dependent on histamine release

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg; Olesen, J

    1994-01-01

    The molecular mechanisms of migraine pain have not yet been clarified. Monoamine and the peptide neurotransmitters involved in neurogenic inflammation do not cause significant head pain. Our previous studies of glyceryl trinitrate (GTN) and histamine-induced headaches have suggested that nitric...... in the cascade of intracellular reactions triggered by NO. These novel observations change current views on vascular headache mechanisms and the importance of NO as an initiator of the migraine attacks dictates new approaches to the pharmacological treatment of migraine and other vascular headaches....

  10. Signaling transduction pathways involved in basophil adhesion and histamine release

    DEFF Research Database (Denmark)

    Sha, Quan; Poulsen, Lars K.; Gerwien, Jens

    2006-01-01

    Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles...... of beta1 and beta2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK) 1/2 in basophil adhesion and histamine release (HR)....

  11. Spatial changes in acid secretion from isolated stomach tissue using a pH-histamine sensing microarray.

    Science.gov (United States)

    Bitziou, Eleni; O'Hare, Danny; Patel, Bhavik Anil

    2010-03-01

    The acid secretion mechanism can be studied by measuring a series of metabolic markers and neurotransmitters from in vitro isolated tissue. A microelectrode array was used to monitor proton concentration and histamine levels from isolated guinea pig stomach tissue. The device was partially modified using iridium oxide to form a series of pH sensors, whereas unmodified gold microelectrodes were used to measure the level of histamine in the gut. Real-time measurements in the presence of the H2-receptor antagonist ranitidine produced significant decreases in the overall Delta pH response, as expected. Also, a significant variation in the Delta pH response in between pH sensors was observed in the presence of pharmacological treatment due to structural features of the tissue. No significant differences in Delta i(H) were detected in the presence of ranitidine as expected. More significantly, clear variations in Delta pH responses between animals in control conditions and those in the presence of ranitidine was observed highlighting possible variation in parietal cell density and/or variations in tissue activity. These results identify great possibilities in applying these multi-sensing devices as a long-term stable personalised diagnostic tool for pharmacological screening and disease status.

  12. Indian red scorpion venom-induced augmentation of cardio-respiratory reflexes and pulmonary edema involve the release of histamine.

    Science.gov (United States)

    Dutta, Abhaya; Deshpande, Shripad B

    2011-02-01

    Pulmonary edema is a consistent feature of Mesobuthus tamulus (MBT) envenomation. Kinins, prostaglandins and other inflammatory mediators are implicated in it. Since, histamine also increases capillary permeability, this study was undertaken to evaluate whether MBT venom utilizes histamine to produce pulmonary edema and augmentation of cardio-respiratory reflexes evoked by phenylbiguanide (PBG). Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. Injection of PBG (10 μg/kg) produced apnoea, hypotension and bradycardia and the responses were augmented after exposure to venom (100 μg/kg). There was increased pulmonary water content in these animals. Pretreatment with pheniramine maleate (H₁ antagonist, 3 mg/kg) blocked both venom-induced augmentation of PBG response and pulmonary edema. In another series, compound 48/80 (mast cell depletor) was treated for 4 days then the PBG responses were elicited as before. At the end of the experiments, mast cells were counted from the peritoneal fluid. The venom-induced pulmonary edema and the augmentation of PBG reflex were not observed in compound 48/80 treated animals. Further, mast cells in the peritoneal fluid were absent in this group as compared to vehicle treated group (29 ± 7.9 cells/mm³). These observations indicate that venom-induced pulmonary edema and augmentation of PBG reflexe are mediated through mast cells by involving H₁ receptors. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Histamine is a modulator of metamorphic competence in Strongylocentrotus purpuratus (Echinodermata: Echinoidea

    Directory of Open Access Journals (Sweden)

    Sutherby Josh

    2012-04-01

    Full Text Available Abstract Background A metamorphic life-history is present in the majority of animal phyla. This developmental mode is particularly prominent among marine invertebrates with a bentho-planktonic life cycle, where a pelagic larval form transforms into a benthic adult. Metamorphic competence (the stage at which a larva is capable to undergo the metamorphic transformation and settlement is an important adaptation both ecologically and physiologically. The competence period maintains the larval state until suitable settlement sites are encountered, at which point the larvae settle in response to settlement cues. The mechanistic basis for metamorphosis (the morphogenetic transition from a larva to a juvenile including settlement, i.e. the molecular and cellular processes underlying metamorphosis in marine invertebrate species, is poorly understood. Histamine (HA, a neurotransmitter used for various physiological and developmental functions among animals, has a critical role in sea urchin fertilization and in the induction of metamorphosis. Here we test the premise that HA functions as a developmental modulator of metamorphic competence in the sea urchin Strongylocentrotus purpuratus. Results Our results provide strong evidence that HA leads to the acquisition of metamorphic competence in S. purpuratus larvae. Pharmacological analysis of several HA receptor antagonists and an inhibitor of HA synthesis indicates a function of HA in metamorphic competence as well as programmed cell death (PCD during arm retraction. Furthermore we identified an extensive network of histaminergic neurons in pre-metamorphic and metamorphically competent larvae. Analysis of this network throughout larval development indicates that the maturation of specific neuronal clusters correlates with the acquisition of metamorphic competence. Moreover, histamine receptor antagonist treatment leads to the induction of caspase mediated apoptosis in competent larvae. Conclusions We

  14. High-performance liquid chromatographic determination of histamine in biological samples: the cerebrospinal fluid challenge--a review.

    Science.gov (United States)

    Wang, Zhaopin; Wu, Juanli; Wu, Shihua; Bao, Aimin

    2013-04-24

    Histamine, a neurotransmitter crucially involved in a number of basic physiological functions, undergoes changes in neuropsychiatric disorders. Detection of histamine in biological samples such as cerebrospinal fluid (CSF) is thus of clinical importance. The most commonly used method for measuring histamine levels is high performance liquid chromatography (HPLC). However, factors such as very low levels of histamine, the even lower CSF-histamine and CSF-histamine metabolite levels, especially in certain neuropsychiatric diseases, rapid formation of histamine metabolites, and other confounding elements during sample collection, make analysis of CSF-histamine and CSF-histamine metabolites a challenging task. Nonetheless, this challenge can be met, not only with respect to HPLC separation column, derivative reagent, and detector, but also in terms of optimizing the CSF sample collection. This review aims to provide a general insight into the quantitative analyses of histamine in biological samples, with an emphasis on HPLC instruments, methods, and hyphenated techniques, with the aim of promoting the development of an optimal and practical protocol for the determination of CSF-histamine and/or CSF-histamine metabolites. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Cold urticaria: inhibition of cold-induced histamine release by doxantrazole.

    Science.gov (United States)

    Bentley-Phillips, C B; Eady, R A; Greaves, M W

    1978-10-01

    Thirteen patients with cold urticaria were studied to assess the effect of the systemic drug doxantrazole, which has actions resembling disodium cromoglycate, on cold evoked histamine release. The patients, all of whom developed an immediate local whealing response after cooling of the forearm, demonstrated release of histamine into venous blood draining that forearm. Following doxantrazole treatment, significant suppression of histamine release occurred. In some but not all patients this was accompanied by diminution of urtication in response to cooling. A double-blind study was carried out in 3 subjects, all of whom showed diminished cold-stimulated histamine release after doxantrazole. Two of these showed clinical improvement. Doxantrazole had no effect on erythema due to intradermal histamine, but did suppress the erythematous reaction to intradermal injection of compound 48/80. Our results suggest that doxantrazole or related anti-allergic agents might be useful in the treatment of cold urticaria.

  16. Cold urticaria. Dissociation of cold-evoked histamine release and urticara following cold challenge.

    Science.gov (United States)

    Keahey, T M; Greaves, M W

    1980-02-01

    Nine patients with acquired cold urticaria were studied to assess the effects of beta-adrenergic agents, xanthines, and corticosteroids on cold-evoked histamine release from skin in vivo. The patients, in all of whom an immediate urticarial response developed after cooling of the forearm, demonstrated release of histamine into the venous blood draining that forearm. Following treatment with aminophylline and albuterol in combination or prednisone alone, suppression of histamine release occurred in all but one patient. In some patients, this was accompanied by a subjective diminution in pruritus or buring, but there was no significant improvement in the ensuing edema or erythema. In one patient, total suppression of histamine release was achieved without any effect on whealing and erythema in response to cold challenge. Our results suggest that histamine is not central to the pathogenesis of vascular changes in acquired cold urticaria.

  17. Comparative analysis of the in vitro cytotoxicity of the dietary biogenic amines tyramine and histamine.

    Science.gov (United States)

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

    2016-04-15

    Tyramine and histamine, the most toxic biogenic amines (BA), are often found in high concentrations in certain foods. Prompted by the limited knowledge of BA toxicity, and increasing awareness of the risks associated with high intakes of dietary BA, the in vitro cytotoxicity of tyramine and histamine was investigated. Tyramine and histamine were toxic for HT29 intestinal cell cultures at concentrations commonly found in BA-rich food, as determined by real-time cell analysis. Surprisingly, tyramine had a stronger and more rapid cytotoxic effect than histamine. Their mode of action was also different, while tyramine caused cell necrosis, histamine induced apoptosis. To avoid health risks, the BA content of foods should be reduced and legal limits established for tyramine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

    DEFF Research Database (Denmark)

    Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

    1998-01-01

    OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

  19. The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs

    DEFF Research Database (Denmark)

    Lassen, L H; Christiansen, I; Iversen, Helle Klingenberg

    2003-01-01

    -decrease in MCA blood velocity, or dilatation of neither the temporal nor the radial artery. L-NMMA constricted the temporal artery by 8% before histamine infusion, whereas the radial artery was unaffected. The temporal artery dilated 4-5 times more than the radial artery during histamine infusion. In conclusion...... the use of a NOS inhibitor in the highest possible dose did not block the histamine-induced headache response or arterial dilatation. Either the concentration of L-NMMA reaching the smooth muscle cell was insufficient or, histamine dilates arteries and causes headache via NO independent mechanisms. Our...... results showed for the first time a craniospecificity for the vasodilating effect of histamine and for the arterial effects of NOS inhibition....

  20. Existence of carcinine, a histamine-related compound, in mammalian tissues

    International Nuclear Information System (INIS)

    Flancbaum, L.; Brotman, D.N.; Fitzpatrick, J.C.; Van Es, Theodorus; Kasziba, E.; Fisher, H.

    1990-01-01

    Carcinine (β-alanylhistamine) was synthesized in vitro from histamine and β-alanine. It was detected quantitatively using an HPLC method previously described for the quantification of the related compounds histamine, histidine, carnosine and 3-methylhistamine. Carcinine was identified in several tissues of the rat, guinea pig, mouse and human, and was then shown to be metabolically related in vivo to histamine, histidine, carnosine and 3-methylhistamine through radioisotopic labeling. The results demonstrate that carcinine may be concurrently quantitated using the same HPLC method as that used to measure histamine, histidine, carnosine and 3-methylhistamine. These findings suggest a role for carcinine in the carnosine-histidine-histamine metabolic pathway and the mammalian physiologic response to stress

  1. Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

    DEFF Research Database (Denmark)

    Brookes, Sharon M; Nunez, Alejandor; Choudhury, Bhudipa

    2010-01-01

    The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment...... and evolution within swine worldwide [3]. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations [4]. We performed an infection and transmission study in pigs with A/California/07/09. In combination......, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic [5]....

  2. Ion chemistry of 1H-1,2,3-triazole.

    Science.gov (United States)

    Ichino, Takatoshi; Andrews, Django H; Rathbone, G Jeffery; Misaizu, Fuminori; Calvi, Ryan M D; Wren, Scott W; Kato, Shuji; Bierbaum, Veronica M; Lineberger, W Carl

    2008-01-17

    A combination of experimental methods, photoelectron-imaging spectroscopy, flowing afterglow-photoelectron spectroscopy and the flowing afterglow-selected ion flow tube technique, and electronic structure calculations at the B3LYP/6-311++G(d,p) level of density functional theory (DFT) have been employed to study the mechanism of the reaction of the hydroxide ion (HO-) with 1H-1,2,3-triazole. Four different product ion species have been identified experimentally, and the DFT calculations suggest that deprotonation by HO- at all sites of the triazole takes place to yield these products. Deprotonation of 1H-1,2,3-triazole at the N1-H site gives the major product ion, the 1,2,3-triazolide ion. The 335 nm photoelectron-imaging spectrum of the ion has been measured. The electron affinity (EA) of the 1,2,3-triazolyl radical has been determined to be 3.447 +/- 0.004 eV. This EA and the gas-phase acidity of 2H-1,2,3-triazole are combined in a negative ion thermochemical cycle to determine the N-H bond dissociation energy of 2H-1,2,3-triazole to be 112.2 +/- 0.6 kcal mol-1. The 363.8 nm photoelectron spectroscopic measurements have identified the other three product ions. Deprotonation of 1H-1,2,3-triazole at the C5 position initiates fragmentation of the ring structure to yield a minor product, the ketenimine anion. Another minor product, the iminodiazomethyl anion, is generated by deprotonation of 1H-1,2,3-triazole at the C4 position, followed by N1-N2 bond fission. Formation of the other minor product, the 2H-1,2,3-triazol-4-ide ion, can be rationalized by initial deprotonation of 1H-1,2,3-triazole at the N1-H site and subsequent proton exchanges within the ion-molecule complex. The EA of the 2H-1,2,3-triazol-4-yl radical is 1.865 +/- 0.004 eV.

  3. Production of inositol trisphosphates upon α-adrenergic stimulation in BC3H-1 muscle cells

    International Nuclear Information System (INIS)

    Ambler, S.K.; Thompson, B.; Brown, J.H.; Taylor, P.

    1986-01-01

    Activation of α 1 -adrenergic receptors in BC3H-1 muscle cells rapidly mobilizes intracellular and results in a paradoxically slower accumulation of inositol trisphosphate. A possible explanation for this discrepancy may be provided by the recent findings of Irvine et al. of additional Ins P3 isomers besides the Ca ++ -mobilizing isomer, Ins 1,4,5-P3. They have eluted and separated the inositol phosphates of BC3H-1 cells with an NH 4 + x HCO 2 - /H 3 PO 4 gradient on a Whatman Partisil 10SAX column using Hewlett-Packard HPLC. Commercial [ 3 H]Ins 1,4,5-P3 and [ 3 H]inositol phosphates from carbachol-stimulated parotid glands were used as standards. Little or no Ins 1,3,4-P3 could be detected in control or phenylephrine-treated BC3H-1 cells. Ins 1,4,5-P3 followed the pattern of agonist stimulation observed previously. As a positive control, Ins P3 isomers were also measured in 1321N1 astrocytoma cells. Muscarinic stimulation of 1321N1 cells results in both the rapid accumulation of Ins P3 and Ca ++ mobilization. There is no detectable basal Ins 1,3,4-P3, but carbachol stimulates a rapid production of this compound in 1321N1 cells. Agonist activation also results in a rapid increase in Ins 1,4,5-P3 above basal values. These studies indicate that Ins 1,3,4-P3 does not contribute to the InsP3 signal in BC3H-1 cells and multiple mechanisms may exist for the coupling of receptors to PI turnover

  4. Histamine release inhibitory activity of Piper nigrum leaf.

    Science.gov (United States)

    Hirata, Noriko; Naruto, Shunsuke; Inaba, Kazunori; Itoh, Kimihisa; Tokunaga, Masashi; Iinuma, Munekazu; Matsuda, Hideaki

    2008-10-01

    Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.

  5. H1N1, globalization and the epidemiology of inequality.

    Science.gov (United States)

    Sparke, Matthew; Anguelov, Dimitar

    2012-07-01

    This paper examines the lessons learned from the 2009 H1N1 pandemic in relation to wider work on globalization and the epidemiology of inequality. The media attention and economic resources diverted to the threats posed by H1N1 were significant inequalities themselves when contrasted with weaker responses to more lethal threats posed by other diseases associated with global inequality. However, the multiple inequalities revealed by H1N1 itself in 2009 still provide important insights into the future of global health in the context of market-led globalization. These lessons relate to at least four main forms of inequality: (1) inequalities in blame for the outbreak in the media; (2) inequalities in risk management; (3) inequalities in access to medicines; and (4) inequalities encoded in the actual emergence of new flu viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Genetic characterization of the influenza A pandemic (H1N1 2009 virus isolates from India.

    Directory of Open Access Journals (Sweden)

    Varsha A Potdar

    Full Text Available BACKGROUND: The Influenza A pandemic H1N1 2009 (H1N1pdm virus appeared in India in May 2009 and thereafter outbreaks with considerable morbidity and mortality have been reported from many parts of the country. Continuous monitoring of the genetic makeup of the virus is essential to understand its evolution within the country in relation to global diversification and to track the mutations that may affect the behavior of the virus. METHODS: H1N1pdm viruses were isolated from both recovered and fatal cases representing major cities and sequenced. Phylogenetic analyses of six concatenated whole genomes and the hemagglutinin (HA gene of seven more isolates from May-September 2009 was performed with reference to 685 whole genomes of global isolates available as of November 24, 2009. Molecular characterization of all the 8 segments was carried out for known pathogenic markers. RESULTS: The first isolate of May 2009 belonged to clade 5. Although clade 7 was the dominant H1N1pdm lineage in India, both clades 6 and 7 were found to be co-circulating. The neuraminidase of all the Indian isolates possessed H275, the marker for sensitivity to the neuraminidase inhibitor Oseltamivir. Some of the mutations in HA are at or in the vicinity of antigenic sites and may therefore be of possible antigenic significance. Among these a D222G mutation in the HA receptor binding domain was found in two of the eight Indian isolates obtained from fatal cases. CONCLUSIONS: The majority of the 13 Indian isolates grouped in the globally most widely circulating H1N1pdm clade 7. Further, correlations of the mutations specific to clade 7 Indian isolates to viral fitness and adaptability in the country remains to be understood. The D222G mutation in HA from isolates of fatal cases needs to be studied for pathogenicity.

  7. Structural Characterization of H-1 Parvovirus: Comparison of Infectious Virions to Empty Capsids

    Science.gov (United States)

    Halder, Sujata; Nam, Hyun-Joo; Govindasamy, Lakshmanan; Vogel, Michèle; Dinsart, Christiane; Salomé, Nathalie; McKenna, Robert

    2013-01-01

    The structure of single-stranded DNA (ssDNA) packaging H-1 parvovirus (H-1PV), which is being developed as an antitumor gene delivery vector, has been determined for wild-type (wt) virions and noninfectious (empty) capsids to 2.7- and 3.2-Å resolution, respectively, using X-ray crystallography. The capsid viral protein (VP) structure consists of an α-helix and an eight-stranded anti-parallel β-barrel with large loop regions between the strands. The β-barrel and loops form the capsid core and surface, respectively. In the wt structure, 600 nucleotides are ordered in an interior DNA binding pocket of the capsid. This accounts for ∼12% of the H-1PV genome. The wt structure is identical to the empty capsid structure, except for side chain conformation variations at the nucleotide binding pocket. Comparison of the H-1PV nucleotides to those observed in canine parvovirus and minute virus of mice, two members of the genus Parvovirus, showed both similarity in structure and analogous interactions. This observation suggests a functional role, such as in capsid stability and/or ssDNA genome recognition for encapsulation. The VP structure differs from those of other parvoviruses in surface loop regions that control receptor binding, tissue tropism, pathogenicity, and antibody recognition, including VP sequences reported to determine tumor cell tropism for oncotropic rodent parvoviruses. These structures of H-1PV provide insight into structural features that dictate capsid stabilization following genome packaging and three-dimensional information applicable for rational design of tumor-targeted recombinant gene delivery vectors. PMID:23449783

  8. Treatment and Prevention of Pandemic H1N1 Influenza.

    Science.gov (United States)

    Rewar, Suresh; Mirdha, Dashrath; Rewar, Prahlad

    2015-01-01

    Swine influenza is a respiratory infection common to pigs worldwide caused by type A influenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness in humans and affect persons of all age groups. People in close contact with swine are at especially high risk. Until recently, epidemiological study of influenza was limited to resource-rich countries. The World Health Organization declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported 30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine influenza were reported with 774 deaths. The Centers for Disease Control and Prevention recommend real-time polymerase chain reaction as the method of choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical treatment of swine influenza and can make the illness milder and enable the patient to feel better faster. Antiviral drugs are most effective when they are started within the first 48 hours after the clinical signs begin, although they also may be used in severe or high-risk cases first seen after this time. The Centers for Disease Control and Prevention recommends use of oseltamivir (Tamiflu, Genentech) or zanamivir (Relenza, GlaxoSmithKline). Prevention of swine influenza has 3 components: prevention in swine, prevention of transmission to humans, and prevention of its spread among humans. Because of limited treatment options, high risk for secondary infection, and frequent need for intensive care of individuals with H1N1 pneumonia, environmental control, including vaccination of high-risk populations and public education are critical to control of swine influenza out breaks. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Lower and upper chromatic numbers for BSTSs(2h - 1

    Directory of Open Access Journals (Sweden)

    Marco Buratti

    2001-08-01

    Full Text Available In [Discrete Math. 174, (1997 247-259] an infinite class of STSs(2h - 1 was found with the upper chromatic number not(χ=h. We prove that in this class, for all STSs(2h - 1 with h<10, the lower chromatic number coincides with the upper chromatic number, i.e. χ=not(χ=h and moreover, there exists a infinite sub-class of STSs with χ=not(χ=h for any value of h.

  10. Narcolepsy: Association with H1N1 Infection and Vaccination

    Directory of Open Access Journals (Sweden)

    Ji Hyun Song

    2016-12-01

    Full Text Available Epidemiological studies have demonstrated an association between H1N1 influenza infection and vaccinations. This article reviews the various studies, and suggests the biological mechanisms explaining why and how H1N1 influenza infection or vaccine stimulates the autoimmune response, thereby resulting in narcolepsy. Among the vaccines, the effect of Pandemrix was scrutinized more than other vaccines, due to its higher association with an increase of narcolepsy onset. The consequences of using other vaccines which contain same or different adjuvants as Pandemrix, were also analyzed.

  11. FT-Raman and QM/MM study of the interaction between histamine and DNA

    International Nuclear Information System (INIS)

    Ruiz-Chica, A.J.; Soriano, A.; Tunon, I.; Sanchez-Jimenez, F.M.; Silla, E.; Ramirez, F.J.

    2006-01-01

    The interaction between histamine and highly polymerized calf-thymus DNA has been investigated using FT-Raman spectroscopy and the hybrid QM/MM (quantum mechanics/molecular mechanics) methodology. Raman spectra of solutions containing histamine and calf-thymus DNA, at different molar ratios, were recorded. Solutions were prepared at physiological settings of pH and ionic strength, using both natural and heavy water as the solvent. The analysis of the spectral changes on the DNA Raman spectra when adding different concentrations of histamine allowed us to identify the reactive sites of DNA and histamine, which were used to built two minor groove and one intercalated binding models. They were further used as starting points of the QM/MM theoretical study. However, minimal energy points were only reached for the two minor groove models. For each optimized structure, we calculated analytical force constants of histamine molecule in order to perform the vibrational dynamics. Normal mode descriptions allowed us to compare calculated wavenumbers for DNA-interacting histamine to those measured in the Raman spectra of DNA-histamine solutions

  12. Targeting of histamine producing cells by EGCG: a green dart against inflammation?

    Science.gov (United States)

    Melgarejo, Esther; Medina, Miguel Angel; Sánchez-Jiménez, Francisca; Urdiales, José Luis

    2010-09-01

    The human body is made of some 250 different cell types. From them, only a small subset of cell types is able to produce histamine. They include some neurons, enterochromaffin-like cells, gastrin-containing cells, mast cells, basophils, and monocytes/macrophages, among others. In spite of the reduced number of these histamine-producing cell types, they are involved in very different physiological processes. Their deregulation is related with many highly prevalent, as well as emergent and rare diseases, mainly those described as inflammation-dependent pathologies, including mastocytosis, basophilic leukemia, gastric ulcer, Crohn disease, and other inflammatory bowel diseases. Furthermore, oncogenic transformation switches some non-histamine-producing cells to a histamine producing phenotype. This is the case of melanoma, small cell lung carcinoma, and several types of neuroendocrine tumors. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target histamine-producing cells producing great alterations in their behavior, with relevant effects on their proliferative potential, as well as their adhesion, migration, and invasion potentials. In fact, EGCG has been shown to have potent anti-inflammatory, anti-tumoral, and anti-angiogenic effects and to be a potent inhibitor of the histamine-producing enzyme, histidine decarboxylase. Herein, we review the many specific effects of EGCG on concrete molecular targets of histamine-producing cells and discuss the relevance of these data to support the potential therapeutic interest of this compound to treat inflammation-dependent diseases.

  13. Positive Selection on Hemagglutinin and Neuraminidase Genes of H1N1 Influenza Viruses

    LENUS (Irish Health Repository)

    Li, Wenfu

    2011-04-21

    Abstract Background Since its emergence in March 2009, the pandemic 2009 H1N1 influenza A virus has posed a serious threat to public health. To trace the evolutionary path of these new pathogens, we performed a selection-pressure analysis of a large number of hemagglutinin (HA) and neuraminidase (NA) gene sequences of H1N1 influenza viruses from different hosts. Results Phylogenetic analysis revealed that both HA and NA genes have evolved into five distinct clusters, with further analyses indicating that the pandemic 2009 strains have experienced the strongest positive selection. We also found evidence of strong selection acting on the seasonal human H1N1 isolates. However, swine viruses from North America and Eurasia were under weak positive selection, while there was no significant evidence of positive selection acting on the avian isolates. A site-by-site analysis revealed that the positively selected sites were located in both of the cleaved products of HA (HA1 and HA2), as well as NA. In addition, the pandemic 2009 strains were subject to differential selection pressures compared to seasonal human, North American swine and Eurasian swine H1N1 viruses. Conclusions Most of these positively and\\/or differentially selected sites were situated in the B-cell and\\/or T-cell antigenic regions, suggesting that selection at these sites might be responsible for the antigenic variation of the viruses. Moreover, some sites were also associated with glycosylation and receptor-binding ability. Thus, selection at these positions might have helped the pandemic 2009 H1N1 viruses to adapt to the new hosts after they were introduced from pigs to humans. Positive selection on position 274 of NA protein, associated with drug resistance, might account for the prevalence of drug-resistant variants of seasonal human H1N1 influenza viruses, but there was no evidence that positive selection was responsible for the spread of the drug resistance of the pandemic H1N1 strains.

  14. The data acquisition system for the HERA H1 experiment

    International Nuclear Information System (INIS)

    Haynes, W.J.

    1990-06-01

    The HERA ep collider will set new challenges for the acquisition of data from large particle physics experiments. Short bunch-crossing times combined with high data rates imply sophisticated designs based on current technology. This paper describes how a multi-microprocessor system is being used at the H1 experiment. (author)

  15. The H^{-1}-norm of tubular neighbourhoods of curves

    NARCIS (Netherlands)

    Gennip, van Y.; Peletier, M.A.

    2011-01-01

    We study the H^{-1}-norm of the function 1 on tubular neighbourhoods of curves in R^2. We take the limit of small thickness epsilon, and we prove two different asymptotic results. The first is an asymptotic development for a fixed curve in the limit epsilon to 0, containing contributions from the

  16. Spread of H1N1 within Households

    Centers for Disease Control (CDC) Podcasts

    This podcast describes an investigation into how H1N1 was spreading within households during the initial days of the pandemic in Texas. CDC's Dr. Oliver Morgan discusses what investigators learned about the role that children played in introducing the virus into households and spreading flu.

  17. Influenza A (H1N1) pneumonia: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Amorim, Viviane Brandao; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Zanetti, Glaucia [Escola de Medicina de Petropolis, RJ (Brazil); Hochhegger, Bruno [Santa Casa de Misericordia de Porto Alegre, RS (Brazil)

    2013-11-01

    Objective: to describe aspects found on HRCT scans of the chest in patients infected with the influenza A (H1N1) virus. Methods: we retrospectively analyzed the HRCT scans of 71 patients (38 females and 33 males) with H1N1 infection, confirmed through laboratory tests, between July and September of 2009. The HRCT scans were interpreted by two thoracic radiologists independently, and in case of disagreement, the decisions were made by consensus. Results: the most common HRCT findings were ground-glass opacities (85%), consolidation (64%), or a combination of ground-glass opacities and consolidation (58%). Other findings were airspace nodules (25%), bronchial wall thickening (25%), interlobular septal thickening (21%), crazy-paving pattern (15%), perilobular pattern (3%), and air trapping (3%). The findings were frequently bilateral (89%), with a random distribution (68%). Pleural effusion, when observed, was typically minimal. No lymphadenopathy was identified. Conclusions: the most common findings were ground-glass opacities and consolidations, or a combination of both. Involvement was commonly bilateral with no axial or cranio caudal predominance in the distribution. Although the major tomographic findings in H1N1 infection are nonspecific, it is important to recognize such findings in order to include infection with the H1N1 virus in the differential diagnosis of respiratory symptoms. (author)

  18. Charge transfer in H2+-H(1s) collisions

    International Nuclear Information System (INIS)

    Errea, L.F.; Macias, A.; Mendez, L.; Rabadan, I.; Riera, A.

    2005-01-01

    We present an ab initio study of H 2 + +H(1s) collisions at H 2 + impact energies between 0.4 and 50keV. Cross sections are obtained within the sudden approximation for rotation and vibration of the diatomic molecule. We have found that anisotropy effects are crucial to correctly describe this system in this energy range

  19. H1N1 Influenza A hos mennesker og svin

    DEFF Research Database (Denmark)

    Larsen, Lars Erik

    2009-01-01

    Den nye pandemiske influenza A stamme H1N1 er hovedsagelig et nyt virus, som spredes mellem mennesker, men virusset er formodentlig opstået ved blanding af to svineinfluenza-virus og har derfor bibeholdt evnen til at kunne smitte fra mennesker til svin og fra svin til svin. Det er derfor vigtigt...

  20. Pneumococcal Pneumonia and Pandemic H1N1

    Centers for Disease Control (CDC) Podcasts

    2012-06-06

    Dr. George Nelson, a CDC medical officer, discusses the relationship between pneumococcal pneumonia and Pandemic H1N1.  Created: 6/6/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 6/6/2012.

  1. Development of the H1 backward silicon strip detector

    International Nuclear Information System (INIS)

    Eick, W.; Hansen, K.; Lange, W.; Prell, S.; Zimmermann, W.; Bullough, M.A.; Greenwood, N.M.; Lucas, A.D.; Newton, A.M.; Wilburn, C.D.; Horisberger, R.; Pitzl, D.; Haynes, W.J.; Noyes, G.

    1996-10-01

    The development and first results are described of a silicon strip detector telescope for the HERA experiment H1 designed to measure the polar angle of deep inelastic scattered electrons at small Bjorken x and low momentum transfers Q 2 . (orig.)

  2. Development of the H1 backward silicon strip detector

    International Nuclear Information System (INIS)

    Eick, W.; Hansen, K.; Lange, W.; Prell, S.; Zimmermann, W.; Bullough, M.A.; Greenwood, N.M.; Lucas, A.D.; Newton, A.M.; Wilburn, C.D.; Horisberger, R.; Pitzl, D.; Haynes, W.J.; Noyes, G.

    1997-01-01

    The development and first results are described of a silicon strip detector telescope for the HERA experiment H1 designed to measure the polar angle of deep inelastic scattered electrons at small Bjorken x and low momentum transfers Q 2 . (orig.)

  3. HISTAMINE IN CANNED SARDINES HISTAMINA EM CONSERVAS DE SARDINHA

    Directory of Open Access Journals (Sweden)

    Fancislene Bernardes Tebalti do Carmo

    2010-04-01

    Full Text Available In this study, the presence of histamine in 122 samples of canned sardines produced with three different species by three industries located in the municipalities of Sao Goncalo and Niteroi was evaluated. The samples were divided into five lots with copies of sardines from Venezuela (Sardinella aurita, Morocco (S. pilchardus and Brazil (S. brasiliensis. The initial quality of raw material was evaluated by sensorial parameters and by the histamine level using a semi-quantitative method of thin-layer chromatography. The results of the samples from Venezuela and Morocco showed values below 5 mg/100g, and the national samples showed values similar or greater than 10 mg/100g. It follows that there is need for greater control and monitoring of temperature from capture to processing, to guarantee good quality to the final product, and to avoid risk of poisoning to the consumer.

    KEY WORDS: Canned fish, histamine, quality, sardines.

    O presente estudo avaliou a presença de histamina em 122 amostras de sardinha em conserva, produzidas com três diferentes espécies, por três indústrias, localizadas nos municípios de São Gonçalo e Niterói. As amostras foram divididas em cinco lotes com exemplares de sardinhas provenientes da Venezuela (Sardinella aurita, Marrocos (S. pilchardus e do Brasil (S. brasiliensis. Avaliou-se a qualidade inicial da matéria-prima por meio de parâmetros sensoriais e pelo teor de histamina utilizando-se o método de cromatografia em camada delgada. As amostras oriundas da Venezuela e Marrocos apresentaram valores abaixo de 5 mg/100 g e as nacionais, valores semelhantes ou superiores a 10 mg/100g. Conclui-se que há necessidade de um maior controle e monitorização da temperatura da sardinha desde a captura até o processamento, para que o produto final apresente boa qualidade e não represente perigo de intoxicação ao consumidor.

    PALAVRAS-CHAVES: Conserva, histamina, qualidade, sardinha.

  4. PCR detection and identification of histamine-forming bacteria in filleted tuna fish samples.

    Science.gov (United States)

    Ferrario, Chiara; Pegollo, Chiara; Ricci, Giovanni; Borgo, Francesca; Fortina, M Grazia

    2012-02-01

    Total of 14 filleted yellowfin tuna fish (Thunnus albacares) sold in wholesale fish market and supermarkets in Milan, Italy, were purchased and tested to determine microbial count, histamine level, histamine-forming bacteria, and their ability to produce histamine in culture broth. Although histamine level was less than 10 ppm, many samples showed high total viable bacterial and enterobacterial counts that reached dangerous levels after temperature abuse for short periods of time. A PCR assay targeting a 709-bp fragment of the histidine decarboxylase gene (hdc) revealed that 30.5% of the 141 enteric bacteria isolated from samples were positive and potentially able to produce histamine. The hdc positive strains were mainly isolated from fish bought at wholesale fish market, where we observed several possible risk factors, such as handling in poor and non-refrigerated conditions during fillet preparation. These positive strains were identified as Citrobacter koseri/Enterobacter spp. and Morganella morganii, by 16S/23S rRNA internal transcribed spacer amplification and 16S rRNA sequence analysis. The strains showed a variable ability of histamine production, with Morganella morganii being the most active histamine-producing species. A direct DNA extraction from fish and a PCR targeting the hdc gene showed a high degree of concordance with the results obtained through microbiological and chemical analyses, and could aid in the prompt detection of potentially contaminated fish products, before histamine accumulates. The use of methods for the early and rapid detection of bacteria producing biogenic amines is important for preventing accumulation of these toxic substances in food products. In this study, we used a molecular approach for the detection of histamine-forming bacteria in fish. PCR-based methods require expensive equipment and a high degree of training for the user, but are fast (marketing and can be used in the investigation of risk reduction strategies.

  5. Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

    Science.gov (United States)

    Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

    2012-07-06

    In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Molecular treatment of the ion-pair formation reaction in H(1s) + H(1s) collisions

    Energy Technology Data Exchange (ETDEWEB)

    Borondo, F.; Martin, F.; Yaez, M.

    1987-01-01

    All the available theoretical calculations of the cross section for the ion-pair formation reaction H(1s)+H(1s)..-->..H/sup +/H/sup -/(1s/sup 2/) have been performed using methods that are only valid at high collision energies. They get good agreement with the experiments for impact energies greater than 25 keV, but fail completely at smaller energies. In this work we report the cross section for this reaction at impact energies less than 10 keV, calculated in the framework of the impact-parameter approximation and using the molecular method with a common translation factor.

  7. Imaging MOSS tomographic system for H-1NF

    International Nuclear Information System (INIS)

    Glass, F.; Howard, J.

    1999-01-01

    A tomographic diagnostic utilising the Modulated Optical Solid-State spectrometer (MOSS) is planned for the H-1NF stellarator at the ANU. It is designed to create two-dimensional temperature or velocity maps of a poloidal cross-section of the high temperature plasma of H-1NF. The introduction of the MOSS spectrometers has enabled the development of several diagnostics to be used on the H-1NF stellerator. The MOSS spectrometer allows calculations of the plasma temperature and bulk velocity based on a line-integrated measurement of light emitted from electronic transitions within the plasma. A tomographic system utilising a rotatable multi-view ring apparatus and spatial multiplexing through a MOSS spectrometer is currently being developed. The ring apparatus is placed inside the H-1NF vessel and encircles the plasma. Multiple line-of-sight views collect light through a poloidal cross-section of the plasma and the emitted light is coupled into large core optical fibres. The transmitted light, via the optical fibre bundle, is then imaged through a large aperture MOSS spectrometer and onto another optical fibre array. Each fibre is then fed into a photomultiplier tube for signal detection. Characterisation of the properties of the lithium niobate (LiNbO 3 ) crystal used for modulation in the MOSS spectrometer is being undertaken to account for ray divergence in the imaging system. Tomographic techniques enable the construction of a temperature or velocity map of the poloidal cross-section. Rotating the ring apparatus to a new viewing position for the next pulse of plasma should allow an accurate picture to be built up based on the reproducibility of the plasma pulses. It is expected that initial testing of the system will begin in May when H-1NF begins operations at 0.5 Telsa field strength

  8. Liberation of plasma histamine after application of non-ionic contrast media

    International Nuclear Information System (INIS)

    Weiss, H.D.; Jansen, O.; Schallock, J.

    1989-01-01

    In 94 patients the levels of plasmahistamine have been measured after application of three non-ionic contrast media (Iopromid, Iopamidol, Iohexol) and after application of blood-isotonic saline solution. A significant liberation of histamine could be observed after administration of contrast media and also after administration of saline solution. Neither between the three nonionic contrast media nor between the contrast media and the saline solution significant differences could be measured. Administering contrast media after subsequently saline solution the levels of histamine were lower than in case of pure contrast media application. A psychogen induced histamine liberation is discussed. (orig.) [de

  9. Influence of iodinated contrast media on the activities of histamine inactivating enzymes diamine oxidase and histamine N-methyltransferase in vitro.

    Science.gov (United States)

    Kuefner, M A; Feurle, J; Petersen, J; Uder, M; Schwelberger, H G

    2014-01-01

    Iodinated contrast media can cause pseudoallergic reactions associated with histamine release in significant numbers of patients. To clarify whether these adverse reactions may be aggravated by a compromised histamine catabolism we asked if radiographic contrast agents in vitro inhibit the histamine inactivating enzymes diamine oxidase (DAO) and histamine N-methyltransferase (HMT). Nine iodinated contrast agents were tested in vitro. Following pre-incubation of purified porcine kidney DAO and recombinant human HMT with 0.1-10mM of the respective contrast medium (H2O and specific inhibitors of DAO and HMT as controls) enzyme activities were determined by using radiometric micro assays. None of the contrast media irrespective of their structure showed significant inhibition of the activities of DAO and HMT. Pre-incubation of the enzymes with specific inhibitors led to complete inhibition of the respective enzymatic activity. The iodinated contrast media tested in vitro did not exhibit inhibition of histamine converting enzymes at physiologically relevant concentrations. However due to the in vitro character of this study these results do not directly reflect the in vivo situation. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.

  10. Adaptation of Pandemic H1N1 Influenza Viruses in Mice▿

    Science.gov (United States)

    Ilyushina, Natalia A.; Khalenkov, Alexey M.; Seiler, Jon P.; Forrest, Heather L.; Bovin, Nicolai V.; Marjuki, Henju; Barman, Subrata; Webster, Robert G.; Webby, Richard J.

    2010-01-01

    The molecular mechanism by which pandemic 2009 influenza A viruses were able to sufficiently adapt to humans is largely unknown. Subsequent human infections with novel H1N1 influenza viruses prompted an investigation of the molecular determinants of the host range and pathogenicity of pandemic influenza viruses in mammals. To address this problem, we assessed the genetic basis for increased virulence of A/CA/04/09 (H1N1) and A/TN/1-560/09 (H1N1) isolates, which are not lethal for mice, in a new mammalian host by promoting their mouse adaptation. The resulting mouse lung-adapted variants showed significantly enhanced growth characteristics in eggs, extended extrapulmonary tissue tropism, and pathogenicity in mice. All mouse-adapted viruses except A/TN/1-560/09-MA2 grew faster and to higher titers in cells than the original strains. We found that 10 amino acid changes in the ribonucleoprotein (RNP) complex (PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and hemagglutinin (HA) glycoprotein (K119N, G155E, S183P, R221K, and D222G) controlled enhanced mouse virulence of pandemic isolates. HA mutations acquired during adaptation affected viral receptor specificity by enhancing binding to α2,3 together with decreasing binding to α2,6 sialyl receptors. PB2 E158G/A and PA L295P amino acid substitutions were responsible for the significant enhancement of transcription and replication activity of the mouse-adapted H1N1 variants. Taken together, our findings suggest that changes optimizing receptor specificity and interaction of viral polymerase components with host cellular factors are the major mechanisms that contribute to the optimal competitive advantage of pandemic influenza viruses in mice. These modulators of virulence, therefore, may have been the driving components of early evolution, which paved the way for novel 2009 viruses in mammals. PMID:20592084

  11. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    Energy Technology Data Exchange (ETDEWEB)

    Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

    2013-02-08

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

  12. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    International Nuclear Information System (INIS)

    Takaoka, Yuki; Kawamoto, Seiji; Katayama, Akiko; Nakano, Toshiaki; Yamanaka, Yasushi; Takahashi, Miki; Shimada, Yayoi; Chiang, Kuei-Chen; Ohmori, Naoya; Aki, Tsunehiro; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Chen, Chao-Long; Ono, Kazuhisa

    2013-01-01

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4 + Foxp3 + Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

  13. Differential regulation of histamine- and bradykinin-stimulated phospholipase C in adrenal chromaffin cells: evidence for involvement of different protein kinase C isoforms.

    Science.gov (United States)

    Sena, C M; Rosário, L M; Parker, P J; Patel, V; Boarder, M R

    1996-03-01

    In this report we investigate the isoforms of protein kinase C (PKC) present in cultured adrenal chromaffin cells with respect to their modulation by treatment with phorbol ester and their possible differential involvement in the regulation of responses to histamine and bradykinin. The presence of individual isoforms of PKC was investigated by using eight isoform specific antisera, as a result of which PKC-alpha, epsilon, and zeta were identified. To characterize down-regulation of these enzymes, cells were incubated for 6-48 h with 1 microM phorbol myristate acetate (PMA). PKC-epsilon down-regulated more rapidly than PKC-alpha. At 12 h, PMA pretreatment, for example, PKC-epsilon was maximally down-regulated (23 +/- 4% of controls), whereas PKC-alpha was unchanged. PKC-alpha showed partial down-regulation by 24 h of PMA pretreatment. PKC-zeta did not down-regulate at any of the times tested. Translocation from cytosol to membrane in response to PMA was also more rapid for PKC-epsilon than for PKC-alpha. The accumulation of total 3H-inositol (poly) phosphates in response to bradykinin or histamine was essentially abolished by prior treatment with 10-min PMA treatment (1 microM). However, with 12-h exposure to PMA, the bradykinin response was restored to the level seen with no prior PMA exposure. The histamine response showed no recovery by 12 h of PMA, but showed partial recovery by 24 h of PMA pretreatment. These observations showed that the restoration of the response to bradykinin corresponds to the loss of PKC-epsilon, whereas the restoration of the histamine response corresponds to the loss of PKC-alpha. This picture was confirmed with further studies on cytosolic Ca2+. The results show that chromaffin cells exhibit an unusual pattern of down-regulation of PKC isoforms on prolonged exposure to PMA, and that there is a differential effect of exposure to PMA on the histamine and bradykinin responses, suggesting that different PLC-linked receptors in chromafin

  14. Citrullination regulates pluripotency and histone H1 binding to chromatin

    DEFF Research Database (Denmark)

    Christophorou, Maria A; Castelo-Branco, Gonçalo; Halley-Stott, Richard P

    2014-01-01

    citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune...... and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel...... PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic...

  15. Data storage and data access at H1

    International Nuclear Information System (INIS)

    Gerhards, R.; Kleinwort, C.; Kruener-Marquis, U.; Niebergall, F.

    1996-01-01

    The electron proton collider HERA at the DESY laboratory in Hamburg and the H1 experiment are now in successful operation for more than three years. The H1 experiment is logging data at an average rate of 500KB/s which results in a yearly raw data volume of several Terabytes. The data are reconstructed with a delay of only a few hours, also yielding several Terabytes of reconstructed data after physics oriented event classification. Physics analysis is performed on a SGI Challenge computer, equipped with about 500 GB of disk and, since a couple of months, direct access to a Storage Tek ACS 4400 silo. The disk space is mainly devoted to store the reconstructed data in very compressed format (typically 5 to 10 KB per event). This allows for very efficient and fast physics analysis. Monte Carlo data, on the other hand, are kept in the ACS silo and staged to disk on demand. (author)

  16. The readout system of the new H1 silicon detectors

    International Nuclear Information System (INIS)

    Buerger, J.; Hansen, K.; Lange, W.; Prell, S.; Zimmermann, W.; Henschel, H.; Haynes, W.J.; Noyes, G.W.; Joensson, L.; Gabathuler, K.; Horisberger, R.; Wagener, M.; Eichler, R.; Erdmann, W.; Niggli, H.; Pitzl, D.

    1995-03-01

    The H1 detector at HERA at DESY undergoes presently a major upgrade. In this context silicon strip detectors have been installed at beginning of 1995. The high bunch crossing frequency of HERA (10.4 MHz) demands a novel readout architecture which includes pipelining, signal processing and data reduction at a very early stage. The front end readout is hierarchically organized. The detector elements are read out by the APC chip which contains an analog pipeline and performs first background subtraction. Up to five readout chips are controlled by a Decoder Chip. The readout processor module (OnSiRoC) operates the detectors, controls the Decoder Chips and performs a first level data reduction. The paper describes the readout architecture of the H1 Silicon Detectors and performance data of the complete readout chain. (orig.)

  17. Ten years of Object-Oriented analysis on H1

    International Nuclear Information System (INIS)

    Laycock, Paul

    2012-01-01

    Over a decade ago, the H1 Collaboration decided to embrace the object-oriented paradigm and completely redesign its data analysis model and data storage format. The event data model, based on the ROOT framework, consists of three layers - tracks and calorimeter clusters, identified particles and finally event summary data - with a singleton class providing unified access. This original solution was then augmented with a fourth layer containing user-defined objects. This contribution will summarise the history of the solutions used, from modifications to the original design, to the evolution of the high-level end-user analysis object framework which is used by H1 today. Several important issues are addressed - the portability of expert knowledge to increase the efficiency of data analysis, the flexibility of the framework to incorporate new analyses, the performance and ease of use, and lessons learned for future projects.

  18. Results from the H1 experiment at HERA

    International Nuclear Information System (INIS)

    Krasny, M.W.

    1993-01-01

    Results obtained by the H1 collaboration at HERA from the analysis of the data collected in 1992 - the first year of HERA operation are presented. Measurements of the total photoproduction cross-section and the inclusive jet cross-section in γp scattering, the structure function F 2 (x,Q 2 ) and the jet rates in deep inelastic ep scattering, and results of direct searches for leptoquarks are discussed. (author) 37 refs., 6 figs

  19. Underreporting of 2009 H1N1 Influenza Cases

    Centers for Disease Control (CDC) Podcasts

    Influenza cases are difficult to track because many people don't go to the doctor or get tested for flu when they're sick. The first months of the 2009 H1N1 influenza pandemic were no different. In this podcast, CDC's Dr. Carrie Reed discusses a study in the December issue of Emerging Infectious Diseases that looked at the actual number of cases reported and estimated the true number of cases when correcting for underreporting.

  20. Spread of H1N1 within Households

    Centers for Disease Control (CDC) Podcasts

    2010-03-29

    This podcast describes an investigation into how H1N1 was spreading within households during the initial days of the pandemic in Texas. CDC's Dr. Oliver Morgan discusses what investigators learned about the role that children played in introducing the virus into households and spreading flu.  Created: 3/29/2010 by Emerging Infectious Diseases.   Date Released: 3/29/2010.

  1. Contextualizing ethics: ventilators, H1N1 and marginalized populations.

    Science.gov (United States)

    Silva, Diego S; Nie, Jason X; Rossiter, Kate; Sahni, Sachin; Upshur, Ross E G

    2010-01-01

    If the H1N1 pandemic worsens, there may not be enough ventilated beds to care for all persons with respiratory failure. To date, researchers who explicitly discuss the ethics of intensive care unit admission and the allocation of ventilators during an influenza pandemic have based criteria predominantly on the principles of utility and efficiency, that is, promoting actions that maximize the greatest good for the greatest number of people. However, haphazardly applying utility and efficiency potentially disadvantages marginalized populations who might be at increased risk of severe reactions to H1N1. In Canada, Aboriginals represent 3% of Canadians, yet 11% of H1N1 cases requiring hospitalization involve Aboriginal persons. Aboriginal persons suffer from high rates of obesity due to socio-economic inequalities. Obesity is also a risk factor for severe H1N1 reactions. Yet, since obesity is found to increase the duration of stay in ventilated beds and a long stay is not considered an optimal use of ventilators, applying the principles of utility and efficiency may magnify existing social inequalities. Although promoting utility and efficiency is important, other ethical principles, such as equity and need, require thoughtful consideration and implementation. Furthermore, since public resources are being used to address a public health hazard, the viewpoints of the public, and specifically stakeholders who will be disproportionately affected, should inform decision-makers. Finally, giving attention to the needs and rights of marginalized populations means that ventilators should not be allocated based on criteria that exacerbate the social injustices faced by these groups of people.

  2. The H1 calorimetry: Performance and upgrade program

    International Nuclear Information System (INIS)

    Borras, K.

    1995-04-01

    The energies of particles are measured in the H1 detector with four different calorimeters. Their designs, which are optimized for their particular requirements, are briefly described. Their performance is characterized in terms of their operational stability, the precision of their energy scale and their trigger functionality. The most important among the four calorimeters is the large liquid argon calorimeter and therefore most emphasis is given to the description of this component. (orig.)

  3. The H1 SPACAL time-to-digital converter system

    International Nuclear Information System (INIS)

    Eisenhandler, E.; Landon, M.; Thompson, G.

    1995-01-01

    This paper describes a pipelined 1,400-channel Time-to-Digital Converter (TDC) system for the H1 Scintillating Fiber Calorimeter, which will soon be installed in the H1 experiment at DESY. The main task of the TDC system is to determine the time of arrival of energy depositions, and send this information from bunch crossings that satisfy the event trigger into the H1 data acquisition system. In addition, the TDC system must monitor the timing trigger, which vetoes bunch crossings that contain too much background energy. Products of the interaction are separated from background on the basis of their different times of arrival with respect to the bunch crossing clock. For this monitoring the TDC system uses automatic on-board histogramming hardware that produces a family of histograms for each of 1,400 channels. The TDC function is performed by the TMC1004 ASIC. The system digitizes over a range of 32ns per bunch crossing with 1ns bins and a precision of 1ns. Because of the way the TMC1004 is designed, it is possible to vary the size of the bins between 0.6ns and 3ns by trading off measurement range for bin size. The system occupies two 9U VME crates

  4. Brain Histamine -Methyltransferase as a Possible Target of Treatment for Methamphetamine Overdose

    Directory of Open Access Journals (Sweden)

    Junichi Kitanaka

    2016-01-01

    Full Text Available Stereotypical behaviors induced by methamphetamine (METH overdose are one of the overt symptoms of METH abuse, which can be easily assessed in animal models. Currently, there is no successful treatment for METH overdose. There is increasing evidence that elevated levels of brain histamine can attenuate METH-induced behavioral abnormalities, which might therefore constitute a novel therapeutic treatment for METH abuse and METH overdose. In mammals, histamine N -methyltransferase (HMT is the sole enzyme responsible for degrading histamine in the brain. Metoprine, one of the most potent HMT inhibitors, can cross the blood-brain barrier and increase brain histamine levels by inhibiting HMT. Consequently, this compound can be a candidate for a prototype of drugs for the treatment of METH overdose.

  5. The effect of tartrazine on histamine release from rat peritoneal mast cells.

    Science.gov (United States)

    Safford, R J; Goodwin, B F

    1984-01-01

    The release of histamine from purified rat peritoneal mast cells induced by specific antigen (egg albumin), compound 48/80 and calcium ionophore A23187 was modified by tartrazine. Histamine release induced by 48/80 and antigen was inhibited by the presence of 10(-5) to 10(-2)M tartrazine. The inhibitory effect on egg albumin induced histamine release was maximal when the tartrazine was added simultaneously with egg albumin, and was reduced by increased preincubation of the cells with tartrazine. Tartrazine had a small inhibitory effect on ionophore induced release at high concentrations, but augmented histamine release at tartrazine concentrations of 10(-3) and 10(-4)M. Augmentation of ionophore induced release was maximal at between 0-5 min preincubation of the cells with tartrazine.

  6. Liquid chromatography with luminol-based electrochemiluminescence detection determination of histamine

    NARCIS (Netherlands)

    Steijger, O.M.; Kamminga, D.A.; Brummelhuis, A.; Lingeman, H.

    1998-01-01

    The liquid chromatographic determination of histamine was achieved by precolumn derivatization with N-(4-aminobutyl)-N-ethylisoluminol isothiocyanate and electrochemiluminescence detection. Detection was carried out using postcolumn on-line electrochemical reagent generation and oxidation of the

  7. Inhibition of basophil histamine release by gangliosides. Further studies on the significance of cell membrane sialic acid in the histamine release process

    DEFF Research Database (Denmark)

    Jensen, C; Norn, S; Thastrup, Ole

    1987-01-01

    with the glucolipid mixture increased the sialic acid content of the cells, and this increase was attributed to an insertion of gangliosides into the cell membrane. The inhibition of histamine release was abolished by increasing the calcium concentration, which substantiates our previous findings that cell membrane......Histamine release from human basophils was inhibited by preincubation of the cells with a glucolipid mixture containing sialic acid-containing gangliosides. This was true for histamine release induced by anti-IgE, Concanavalin A and the calcium ionophore A23187, whereas the release induced by S....... aureus Wood 46 was not affected. It was demonstrated that the inhibitory capacity of the glucolipid mixture could be attributed to the content of gangliosides, since no inhibition was obtained with cerebrosides or with gangliosides from which sialic acid was removed. Preincubation of the cells...

  8. Determination of histamine in milkfish stick implicated in food-borne poisoning

    Directory of Open Access Journals (Sweden)

    Yi-Chen Lee

    2016-01-01

    Full Text Available An incident of food-borne poisoning causing illness in 37 victims due to ingestion of fried fish sticks occurred in September 2014, in Tainan city, southern Taiwan. Leftovers of the victims' fried fish sticks and 16 other raw fish stick samples from retail stores were collected and tested to determine the occurrence of histamine and histamine-forming bacteria. Two suspected fried fish samples contained 86.6 mg/100 g and 235.0 mg/100 g histamine; levels that are greater than the potential hazard action level (50 mg/100 g in most illness cases. Given the allergy-like symptoms of the victims and the high histamine content in the suspected fried fish samples, this food-borne poisoning was strongly suspected to be caused by histamine intoxication. Moreover, the fish species of suspected samples was identified as milkfish (Chanos chanos, using polymerase chain reaction direct sequence analysis. In addition, four of the 16 commercial raw milkfish stick samples (25% had histamine levels greater than the US Food & Drug Administration guideline of 5.0 mg/100 g for scombroid fish and/or products. Ten histamine-producing bacterial strains, capable of producing 373–1261 ppm of histamine in trypticase soy broth supplemented with 1.0% L-histidine, were identified as Enterobacter aerogenes (4 strains, Enterobacter cloacae (1 strain, Morganella morganii (2 strains, Serratia marcescens (1 strain, Hafnia alvei (1 strain, and Raoultella orithinolytica (1 strain, by 16S ribosomal DNA sequencing with polymerase chain reaction amplification.

  9. Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Xudong Sun

    2017-06-01

    Full Text Available Background/Aims: Subacute ruminal acidosis (SARA is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Methods: Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor cultured in different pH medium (pH 7.2 or 5.5. qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. Results: The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2 and acidic (pH=5.5 medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6 and interleukin 1 beta (IL-1β, thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. Conclusion: The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway.

  10. Early and late histamine release induced by albumin, hetastarch and polygeline: some unexpected findings.

    Science.gov (United States)

    Celik, I; Duda, D; Stinner, B; Kimura, K; Gajek, H; Lorenz, W

    2003-10-01

    The perioperative use of colloidal plasma substitutes is still under discussion. We therefore conducted a prospective randomised study with three commonly used plasma substitutes to examine their histamine releasing effects in 21 volunteers. MATERIAL OR SUBJETS: 21 male volunteers were enrolled in this prospective, randomised, controlled clinical study. Endpoints were the incidence of early and late histamine release and the time course of the release kinetics. Normovolemic hemodilution technique was used with hydroxyethyl starch (n = 6), human albumin (n = 6) and polygeline (n = 9). Measurement and observation period was 240 min after the start of the plasma substitute infusion. Heart rate, blood pressure, SaO(2), clinical symptoms/signs and plasma histamine were measured during the observation period. The incidence of histamine release over the whole observation period in all three groups was 100%. Histamine release occurred frequently in all three groups until 30 min (50%-78%) and up to 240 min (late release reaction: 67%-83%) after the start of infusion. Surprisingly even hydroxyethyl starch, which is regarded as a generally safe and effective plasma substitute, caused high incidences of late histamine release (67%). Histamine release is a well known side effect of polygeline and - to a lesser extent - also of albumin, but was a novel finding for hydroxyethyl starch. We demonstrated for the first time histamine releasing effects of hydroxyethyl starch over a long period of time after administration. This perioperatively and for intensive care possibly relevant finding should make clinicians aware of late side effects not yet connected with the clinical use of these colloidal plasma substitutes.

  11. Precooking as a Control for Histamine Formation during the Processing of Tuna: An Industrial Process Validation.

    Science.gov (United States)

    Adams, Farzana; Nolte, Fred; Colton, James; De Beer, John; Weddig, Lisa

    2018-02-23

    An experiment to validate the precooking of tuna as a control for histamine formation was carried out at a commercial tuna factory in Fiji. Albacore tuna ( Thunnus alalunga) were brought on board long-line catcher vessels alive, immediately chilled but never frozen, and delivered to an on-shore facility within 3 to 13 days. These fish were then allowed to spoil at 25 to 30°C for 21 to 25 h to induce high levels of histamine (>50 ppm), as a simulation of "worst-case" postharvest conditions, and subsequently frozen. These spoiled fish later were thawed normally and then precooked at a commercial tuna processing facility to a target maximum core temperature of 60°C. These tuna were then held at ambient temperatures of 19 to 37°C for up to 30 h, and samples were collected every 6 h for histamine analysis. After precooking, no further histamine formation was observed for 12 to 18 h, indicating that a conservative minimum core temperature of 60°C pauses subsequent histamine formation for 12 to 18 h. Using the maximum core temperature of 60°C provided a challenge study to validate a recommended minimum core temperature of 60°C, and 12 to 18 h was sufficient to convert precooked tuna into frozen loins or canned tuna. This industrial-scale process validation study provides support at a high confidence level for the preventive histamine control associated with precooking. This study was conducted with tuna deliberately allowed to spoil to induce high concentrations of histamine and histamine-forming capacity and to fail standard organoleptic evaluations, and the critical limits for precooking were validated. Thus, these limits can be used in a hazard analysis critical control point plan in which precooking is identified as a critical control point.

  12. Complexity of the influence of gangliosides on histamine release from human basophils and rat mast cells

    DEFF Research Database (Denmark)

    Jensen, C; Svendsen, U G; Thastrup, Ole

    1987-01-01

    The influence of exogenous addition of gangliosides on histamine release from human basophils and rat mast cells was examined in vitro. Gangliosides dose-dependently inhibited histamine release, and this inhibition was dependent on the ganglioside sialic acid content, since GT1b, having 3 sialic...... was reflected in the sensitivity of the cells to extracellular calcium, since inhibition of the release could be counteracted by increasing the extracellular concentration of calcium....

  13. Endophytic Fungi Associated With Turmeric (Curcuma longa L. Can Inhibit Histamine-Forming Bacteria in Fish

    Directory of Open Access Journals (Sweden)

    Eris Septiana

    2017-01-01

    Full Text Available Turmeric (Curcuma longa L. is a medicinal plant that is commonly used as spice and preservative. Many types of endophytic fungi have been reported as being associated with medicinal plants and able to synthesize secondary metabolites. In this study, endophytic fungi were isolated from all plant parts of turmeric plants. Identification of the endophytic fungi was done using morphological characteristics and sequencing of the internal transcribed spacer (ITS region of ribosomal DNA. The dual culture method was used for screening antibacterial activity of the endophytic fungi against Morganella morganii, a common histamine-producing bacteria. The disc diffusion method was used to test the ability of water fractions of selected endophytic fungi to inhibit M. morganii growth. Two-dimensional thin layer chromatography was used to determine the fungal extract inhibition activity on histamine formation. In total, 11 endophytic fungi were successfully isolated and identified as Arthrobotrys foliicola, Cochliobolus kusanoi, Daldinia eschscholzii, Fusarium oxysporum, Fusarium proliferatum, Fusarium solani, Fusarium verticillioides, Phanerochaete chrysosporium, and Phaeosphaeria ammophilae. Five isolates showed inhibition activity against M. morganii in the dual culture tests. Based on the disc diffusion assay, A. foliicola and F. verticillioides inhibited the growth of M. morganii as a histamine-producing bacteria, and inhibiting histamine formation in fish. The best effects in inhibiting growth of the histamine-producing bacteria and histamine formation inhibition in fish were produced with F. verticillioides water fraction at 0°C incubation.

  14. Skin reactions to histamine of healthy subjects after hypnotically induced emotions of sadness, anger, and happiness.

    Science.gov (United States)

    Zachariae, R; Jørgensen, M M; Egekvist, H; Bjerring, P

    2001-08-01

    The severity of symptoms in asthma and other hypersensitivity-related disorders has been associated with changes in mood but little is known about the mechanisms possibly mediating such a relationship. The purpose of this study was to examine the influence of mood on skin reactivity to histamine by comparing the effects of hypnotically induced emotions on flare and wheal reactions to cutaneous histamine prick tests. Fifteen highly hypnotically susceptible volunteers had their cutaneous reactivity to histamine measured before hypnosis at 1, 2, 3, 4, 5, 10, and 15 min after the histamine prick. These measurements were repeated under three hypnotically induced emotions of sadness, anger, and happiness presented in a counterbalanced order. Skin reactions were measured as change in histamine flare and wheal area in mm2 per minute. The increase in flare reaction in the time interval from 1 to 3 min during happiness and anger was significantly smaller than flare reactions during sadness (P<0.05). No effect of emotion was found for wheal reactions. Hypnotic susceptibility scores were associated with increased flare reactions at baseline (r=0.56; P<0.05) and during the condition of happiness (r=0.56; P<0.05). Our results agree with previous studies showing mood to be a predictor of cutaneous immediate-type hypersensitivity and histamine skin reactions. The results are also in concordance with earlier findings of an association between hypnotic susceptibility and increased reactivity to an allergen.

  15. Pulmonary function in patients with pandemic H1N1

    Directory of Open Access Journals (Sweden)

    Soraia Koppe

    Full Text Available Abstract Introduction: The influenza A (H1N1 was responsible for the 2009 pandemic, especially with severe pulmonary complications. Objective: To describe characteristics of patients in a university hospital in Curitiba - PR with laboratory diagnosis of influenza A (H1N1 and its post hospital discharge in the 2009 lung function pandemic. Methodology: A retrospective observational study. It was used as a data source the institution Epidemiology Service (SEPIH and spirometry tests of patients who were admitted in 2009, 18 years without lung disease associated and non-pregnant. Descriptive statistics were used and applied Fisher's exact test for relationship between comorbidity and spirometry tests. Results: There were 84 confirmed cases, of these 11 were eligible for the study with a mean age of 44.27 years (± 9.63 and 63.63% males. 54.54% of the 11 patients had comorbidities associated with systemic arterial hypertension (54.54%, diabetes (18.18% and late postoperative period of kidney transplantation (18.18% were the most frequent. Most patients (81.81% had BMI ≥ 25kg / m². The Spirometry test was performed approximately 40.09 (± 15.27 days after discharge, of these, 5 had restrictive pattern and all had abnormal chest radiograph results. There was no statistically significant difference between the results of Spirometry and comorbidities (p=0.24. Conclusions: The group evaluated in this research did not show a direct relationship between Spirometry and comorbidities, but changes in Spirometry in some patients after hospital discharge stood out, suggesting changes in lung function due to influenza A (H1N1.

  16. The H1 forward proton spectrometer at HERA

    International Nuclear Information System (INIS)

    Esch, P. van; Kapichine, M.; Morozov, A.; Spaskov, V.; Bartel, W.; List, B.; Mahlke-Krueger, H.; Schroeder, V.; Wilksen, T.; Buesser, F.W.; Geske, K.; Karschnik, O.; Niebergall, F.; Riege, H.; Schuett, J.; Staa, R. van; Wittek, C.; Dau, D.; Newton, D.; Kotelnikov, S.K.; Lebedev, A.; Rusakov, S.; Astvatsatourov, A.; Baehr, J.; Harder, U.; Hiller, K.; Hoffmann, B.; Luedecke, H.; Nahnhauer, R.

    2000-01-01

    The forward proton spectrometer is part of the H1 detector at the HERA collider. Protons with energies above 500 GeV and polar angles below 1 mrad can be detected by this spectrometer. The main detector components are scintillating fiber detectors read out by position-sensitive photo-multipliers. These detectors are housed in the so-called Roman Pots which allow them to be moved close to the circulating proton beam. Four Roman Pot stations are located at distances between 60 and 90 m from the interaction point

  17. The H1 forward proton spectrometer at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Esch, P. van; Kapichine, M.; Morozov, A.; Spaskov, V.; Bartel, W.; List, B.; Mahlke-Krueger, H.; Schroeder, V.; Wilksen, T.; Buesser, F.W.; Geske, K.; Karschnik, O.; Niebergall, F.; Riege, H.; Schuett, J.; Staa, R. van; Wittek, C.; Dau, D.; Newton, D.; Kotelnikov, S.K.; Lebedev, A.; Rusakov, S.; Astvatsatourov, A.; Baehr, J.; Harder, U.; Hiller, K. E-mail: hiller@ifh.de; Hoffmann, B.; Luedecke, H.; Nahnhauer, R

    2000-05-21

    The forward proton spectrometer is part of the H1 detector at the HERA collider. Protons with energies above 500 GeV and polar angles below 1 mrad can be detected by this spectrometer. The main detector components are scintillating fiber detectors read out by position-sensitive photo-multipliers. These detectors are housed in the so-called Roman Pots which allow them to be moved close to the circulating proton beam. Four Roman Pot stations are located at distances between 60 and 90 m from the interaction point.

  18. Underreporting of 2009 H1N1 Influenza Cases

    Centers for Disease Control (CDC) Podcasts

    2009-12-08

    Influenza cases are difficult to track because many people don't go to the doctor or get tested for flu when they're sick. The first months of the 2009 H1N1 influenza pandemic were no different. In this podcast, CDC's Dr. Carrie Reed discusses a study in the December issue of Emerging Infectious Diseases that looked at the actual number of cases reported and estimated the true number of cases when correcting for underreporting.  Created: 12/8/2009 by Emerging Infectious Diseases.   Date Released: 12/8/2009.

  19. Histamine protects bone marrow against cellular damage induced by Ionizing radiation

    International Nuclear Information System (INIS)

    Medina, Vanina; Sambuco, Lorena; Massari, Noelia; Cricco, Graciela; Martin, Gabriela; Bergoc, Rosa; Rivera, Elena S.

    2008-01-01

    After surgery, radiotherapy is arguably one of the most important treatments for cancer, especially for localized disease that has not spread. However, ionizing radiation is toxic not only to tumor cells but also to healthy tissues causing serious adverse effects to patients. We have recently reported that histamine prevents ionizing radiation-induced toxicity on mouse small intestine. The aim of the present work was to determine whether histamine is able to protect bone marrow cells against ionizing radiation damage. For that purpose 56 mice were divided into 4 groups. Histamine and Histamine-10Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 20 hours before irradiation and continued till the end of experimental period; untreated group received saline. Histamine-10Gy and untreated-10Gy groups were irradiated with a single dose on whole-body using Cesium-137 source (7 Gy/min) and were sacrificed 3 days after irradiation. Bone marrow was removed, fixed and stained with hematoxylin and eosin. The number of megacariocytes per 40x field, bone marrow tropism, edema, vascular damage, and other histological characteristics of bone marrow cells were evaluated. We further determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA) and cells in the S phase of the cell cycle were identified by immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Results indicate that histamine treatment substantially reduced the grade of aplasia, the edema and the vascular damage induced by ionizing radiation on bone marrow. Additionally, histamine preserved medullar components increasing significantly the number of megacariocytes per field (5.4 ± 0.4 vs. 2.8 ± 0.4 in Control-10 Gy, P<0.01). This effect was associated with an increased proliferation rate determined by the augmented PCNA expression and BrdU incorporation of bone marrow cells. On the basis of these results, we conclude that histamine

  20. Glucagon effects on 3H-histamine uptake by the isolated guinea-pig heart during anaphylaxis.

    Science.gov (United States)

    Rosic, Mirko; Parodi, Oberdan; Jakovljevic, Vladimir; Colic, Maja; Zivkovic, Vladimir; Jokovic, Vuk; Pantovic, Suzana

    2014-01-01

    We estimated the influence of acute glucagon applications on (3)H-histamine uptake by the isolated guinea-pig heart, during a single (3)H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2 (-), and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change (3)H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, (3)H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of (3)H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9-7.38 × 10(-8) μM) is significantly lower than the histamine level in the absence of glucagon (10.35-10.45 × 10(-8) μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, O2 (-) level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.

  1. The H1 lead/scintillating-fibre calorimeter

    International Nuclear Information System (INIS)

    Appuhn, R.D.; Arndt, C.; Barrelet, E.

    1996-08-01

    The backward region of the H1 detector has been upgraded in order to provide improved measurement of the scattered electron in deep inelastic scattering events. The centerpiece of the upgrade is a high-resolution lead/scintillating-fibre calorimeter. The main design goals of the calorimeter are: good coverage of the region close to the beam pipe, high angular resolution and energy resolution of better than 2% for 30 GeV electrons. The calorimeter should be capable of providing coarse hadronic energy measurement and precise time information to suppress out-of-time background events at the first trigger level. It must be compact due to space restrictions. These requirements were fulfilled by constructing two separate calorimeter sections. The inner electromagnetic section is made of 0.5 mm scintillating plastic fibres embedded in a lead matrix. Its lead-to-fibre ratio is 2.3:1 by volume. The outer hadronic section consists of 1.0 mm diameter fibres with a lead-to-fibre ratio of 3.4:1. The mechanical construction of the new calorimeter and its assembly in the H1 detector are described. (orig.)

  2. The H1 lead/scintillating-fibre calorimeter

    International Nuclear Information System (INIS)

    Appuhn, R.-D.; Arndt, C.; Barrelet, E.

    1997-01-01

    The backward region of the H1 detector has been upgraded in order to provide improved measurement of the scattered electron in deep inelastic scattering events. The centerpiece of the upgrade is a high-resolution lead/scintillating-fibre calorimeter. The main design goals of the calorimeter are: good coverage of the region close to the beam pipe, high angular resolution and energy resolution of better than 2% for 30 GeV electrons. The calorimeter should be capable of providing coarse hadronic energy measurement and precise time information to suppress out-of-time background events at the first trigger level. It must be compact due to space restrictions. These requirements were fulfilled by constructing two separate calorimeter sections. The inner electromagnetic section is made of 0.5 mm scintillating plastic fibres embedded in a lead matrix. Its lead-to-fibre ratio is 2.3:1 by volume. The outer hadronic section consists of 1.0 mm diameter fibres with a lead-to-fibre ratio of 3.4:1. The mechanical construction of the new calorimeter and its assembly in the H1 detector are described. (orig.)

  3. Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses

    OpenAIRE

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

    2014-01-01

    Background The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. Findings The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decrease...

  4. Safety and efficacy of bilastine: a new H(1)-antihistamine for the treatment of allergic rhinoconjunctivitis and urticaria.

    Science.gov (United States)

    Church, Martin K

    2011-09-01

    New H(1)-antihistamines should be effective in relieving the symptoms of allergic disease, should have a rapid onset and long duration of action and should neither cause sedation nor interact with cytochrome P450. A review of bilastine was undertaken to determine whether this newer H(1)-antihistamine meets these requirements. A Medline search was conducted to identify preclinical and clinical studies of bilastine. This was supplemented with additional articles or abstracts cited in reference lists and/or obtained from online sources and internal reports supplied by Faes Farma. Review of these data indicated that bilastine has high selectivity for H(1)-receptors, is rapidly and effectively absorbed, undergoes negligible metabolism and is a substrate for P-glycoprotein, which limits its passage across the blood-brain barrier. At the recommended dose of 20 mg, bilastine is non-sedative, does not enhance the effects of alcohol or CNS sedatives, does not impair actual driving tests, shows no cardiotoxicity and has a similar efficacy to other second-generation H(1)-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria. In view of its favorable pharmacological and clinical characteristics, bilastine is likely to have particular benefit in urticaria for which guidelines recommend increasing the dosage of H(1)-antihistamines up to fourfold if standard dosing is ineffective.

  5. In vitro histamine release from basophils of asthmatic and atopic individuals in D2O

    International Nuclear Information System (INIS)

    Tung, R.; Lichtenstein, L.M.

    1982-01-01

    It was found that spontaneous histamine release from human basophils in H 2 O-based buffers is negligible; in D 2 O-based buffers, however, release is observed with the cells of some donors. Analysis of this phenomenon revealed release from the basophils of 1 of 22 control individuals (5%), 15 of 47 patients with allergic rhinitis (32%), and 14 of 20 asthmatic patients (70%). The difference between both patient groups and controls and between atopics and asthmatics was highly significant. That D 2 O release was not cytotoxic is suggested by the finding that 37 0 was optimal, with inhibition at 4 0 C or 46 0 C as well as by EDTA, 2-deoxyglucose, and dibromoacetophenone, an inhibitor of phospholipase A 2 . The release mechanism was unusual in that dibutyryl cAMP and agonists that cause an increase in cAMP lead to no inhibition. No correlation was noted between the total serum IgE level (and thus the number of IgE receptors on the basophil surface) and the magnitude of D 2 O release. No increase in D 2 O release was observed in 17 ragweed-sensitive patients through a ragweed season. A unique property of D 2 O release was the loss of reactivity by preincubating cells at 37 0 C for 30 min before adding D 2 O. Non-D 2 O-reactive cells could be ''converted'' to D 2 O-reactive cells by incubation with antigen in the whole blood phase during leukocyte isolation; these cells showed the same loss of releaseability at 37 0 C and an inhibitor profile similar to D 2 O-responsive cells from ragweed allergic or asthmatic patients. We suggest that D 2 O-based buffers reveal, in atopic and asthmatic patients, in vivo basophil activation; whether this is due to IgE cross-links, to C split products, or to other stimuli is not yet clear

  6. About a significance of the avian linker histone (H1) polymorphic ...

    Indian Academy of Sciences (India)

    60

    structural disorder may specify histone H1 interaction with both DNA and partnering proteins through ... from the studies conducted on mammalian model, including the human H1 variants. However ..... Thus, the disparate layout of histone H1.

  7. Non-Imidazole Histamine H₃ Ligands. Part VII. Synthesis, In Vitro and In Vivo Characterization of 5-Substituted-2-thiazol-4-n-propylpiperazines.

    Science.gov (United States)

    Guryn, Roman; Staszewski, Marek; Stasiak, Anna; McNaught Flores, Daniel; Fogel, Wiesława Agnieszka; Leurs, Rob; Walczyński, Krzysztof

    2018-02-03

    H₃ receptors present on histaminergic and non-histaminergic neurons, act as autoreceptors or heteroreceptors controlling neurotransmitter release and synthesis. Previous, studies have found that the compound N -methyl- N -3-phenylalkyl-2-[2-(4-n-propylpiperazin-1-yl)-1,3-thiazol-5-yl]ethan-1-amine ( ADS-531, 2c ) exhibits high in vitro potency toward H₃ guinea pig jejunal receptors, with pA₂ = 8.27. To optimize the structure of the lead compound ADS-531 , a series of 5-substituted-2-thiazol-4- n -propylpiperazines 3 were synthesized and subjected to in vitro pharmacological characterization; the alkyl chain between position 2 of the thiazole ring and the terminal secondary N -methylamino function was elongated from three to four methylene groups and the N -methylamino functionality was substituted by benzyl-, 2-phenylethyl-, and 3-phenyl-propyl- moieties. SAR studies on novel non-imidazole, 5-substituted-2-thiazol-4- n -propyl-piperazines 3 showed that the most active compound 3a (pA₂ = 8.38), additionally possessed a weak competitive H₁-antagonistic activity. Therefore, compound ADS-531 , which did not exhibit any H₁-antagonistic activity, was chosen for further evaluation for its affinity to the recombinant rat and human histamine H₃ receptors (rH₃R and hH₃R, respectively). ADS-531 exhibited nanomolar affinity for both rH₃R and hH₃R receptors. It was also shown that, ADS-531 given subchronically to rats (s.c. 3 mg/kg, 5 days) penetrated the brain, where it affected dopamine, noradrenaline and serotonin concentration; however, it did not affect histamine concentration nor feeding behavior.

  8. Experiences at HERA with the H1 data acquisition system

    International Nuclear Information System (INIS)

    Haynes, W.J.

    1992-09-01

    The recently commissioned HERA collider provides a significant pointer to the problems that have to be surmounted in data acquisition systems at the next generation of hadron machines. With bunch crossings, between 30 GeV electrons and 820 GeV protons, 96 nanoseconds apart, the H1 experiment illustrates the application of sophisticated pipelining solutions in the readout of several hundred thousand electronic channels. A modular, multiprocessor design structure emphasis the architectural concepts necessary to cope with large data throughput and yet remain flexible enough to exploit ongoing technological advances in both hardware and software. The range of techniques implemented will be surveyed, covering various digitisation solutions at the front-end through to embedded microprocessor arrays in standard busses controlled by graphics-based stations executing object- orientated code. The experiences gained in developing such a system are also discussed. (orig.)

  9. H1N1 pandemic preparedness and business continuity plan

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    SaskPower's H1N1 pandemic preparedness and business continuity plan was designed to prepare SaskPower employees for elevated levels of absenteeism during a potential pandemic. Emergency management and business continuity will be facilitated if critical duties and essential services are maintained without interruption. A layered approach was used to develop a range of response measures designed to meet a range of possible pandemic threats. The plan identified essential activities, tasks and functions and outlined methods of mitigating supply disruptions and possible shortages. Methods of minimizing illness in employees were discussed, as well as methods of maintaining a safe and secure work environment. The measures were developed in accordance with the World Health Organization (WHO) 6 phases of pandemic alert. The plan was also designed to be read by SaskPower's key suppliers in order to ensure their pandemic readiness. 5 tabs.

  10. Results from the H1 experiment at HERA

    International Nuclear Information System (INIS)

    Roeck, A. de

    1994-01-01

    New results from the H1 experiment at HERA on photoproduction, deep inelastic scattering and search for exotic particles are presented. Clear evidence is found for hard scattering in photoproduction interactions. Jets have been observed and used to examine the x γ distribution, indicating the need for a gluonic component in the photon. Hadronic final states and jet cross sections have been measured in deep inelastic scattering. A class of deep inelastic events with diffractive characteristics has been observed. The proton structure function F 2 (x, Q 2 ) has been measured in the new Bjorken-x region 10 -4 -2 and is found to rise with decreasing x. New limits for leptoquarks, squarks and excited electrons have been deduced. (orig.)

  11. Technicon H*1 Hematology System: Optical Design Considerations

    Science.gov (United States)

    Colella, G. M.; Tycko, D. H.; Groner, W.

    1988-06-01

    The Technicon H*1 systemTM is a clinical laboratory flow cytometer which performs a complete hematology profile, providing quantitative information on the various types of cells in a blood sample. A light-scattering method, using a HeNe laser, determines in a single flow channel the red cell count, platelet count, and the distributions of red cell volume, red cell hemoglobin concentration, and platelet volume. To accomplish this the scattered light from each red cell in the sample is measured in real time at two angular intervals. The cell volume and the hemoglobin concentration within the cell are derived from these two measurements. Severe accuracy and precision specifications are placed on the medically important red cell count (RBC) and the mean red cell volume (MCV). From the point of view of optical system design, the dominant factor is the requirement that RBC and MCV have precision and accuracy of the order of 2%. Signal-to-noise and scattering-angle definition requirements dictated the choice of a HeNe laser light source. The optics includes an illumination system for producing a sharply defined, uniformly illuminated scattering region and a detection system which must accurately define the accepted scattering angles. In previous cytometric methods for determining MCV only a single quantity was measured for each cell. Such methods cannot disentangle the independent effects of cell size and hemoglobin concentration on the measurement, thus compromising MCV accuracy. The present double-angle scattering method overcomes this accuracy problem. The H*1 red cell method, the supporting optical design and data demonstrating that the use of this technique eliminates interference between the observed red cell indices are presented.

  12. Noxious heat and scratching decrease histamine-induced itch and skin blood flow.

    Science.gov (United States)

    Yosipovitch, Gil; Fast, Katharine; Bernhard, Jeffrey D

    2005-12-01

    The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.

  13. Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response

    Directory of Open Access Journals (Sweden)

    D. Remirez

    2002-01-01

    Full Text Available It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300 mg/kg post-orally (p.o. was administered 1 h before the challenge with 1 μg of ovalbumin (OA in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o. also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phyco-cyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells.

  14. Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

    Science.gov (United States)

    Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

    2015-04-01

    An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

  15. The Itch-Producing Agents Histamine and Cowhage Activate Separate Populations of Primate Spinothalamic Tract Neurons

    Science.gov (United States)

    Davidson, Steve; Zhang, Xijing; Yoon, Chul H.; Khasabov, Sergey G.; Simone, Donald A.; Giesler, Glenn J.

    2010-01-01

    Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage. PMID:17855615

  16. Detection and Characterization of Histamine-Producing Strains of Photobacterium damselae subsp. damselae Isolated from Mullets

    Directory of Open Access Journals (Sweden)

    Marcello Trevisani

    2017-06-01

    Full Text Available Photobacterium damselae subsp. damselae (Pdd is considered to be an emerging pathogen of marine fish and has also been implicated in cases of histamine food poisoning. In this study, eight strains isolated from mullets of the genera Mugil and Liza captured in the Ligurian Sea were characterized, and a method to detect histamine-producing Pdd from fish samples was developed. The histamine-producing potential of the strains was evaluated in culture media (TSB+ using a histamine biosensor. Subsequently, two strains were used to contaminate mackerel fillets (4 or 40 CFU/g, simulating a cross-contamination on the selling fish stalls. Sample homogenates were enriched in TSB+. The cultures were then inoculated on thiosulfate-citrate-bile salts-sucrose agar (TCBS and the dark green colonies were cultured on Niven agar. The violet isolates were characterized using specific biochemical and PCR based tests. All Pdd strains were histamine producers, yielding concentration varying from 167 and 8977 µg/mL in TSB+ cultures incubated at 30 °C for 24 h. Pdd colonies were detected from the inoculated mackerel samples and their histidine decarboxylase gene was amplified using species-specific primer pairs designed for this study. The results indicate that mullets can be source of Pdd and the fish retailers needs to evaluate the risk posed by cross-contamination on the selling fish stalls.

  17. Enhanced Indirect Photochemical Transformation of Histidine and Histamine through Association with Chromophoric Dissolved Organic Matter.

    Science.gov (United States)

    Chu, Chiheng; Lundeen, Rachel A; Remucal, Christina K; Sander, Michael; McNeill, Kristopher

    2015-05-05

    Photochemical transformations greatly affect the stability and fate of amino acids (AAs) in sunlit aquatic ecosystems. Whereas the direct phototransformation of dissolved AAs is well investigated, their indirect photolysis in the presence of chromophoric dissolved organic matter (CDOM) is poorly understood. In aquatic systems, CDOM may act both as sorbent for AAs and as photosensitizer, creating microenvironments with high concentrations of photochemically produced reactive intermediates, such as singlet oxygen (1O2). This study provides a systematic investigation of the indirect photochemical transformation of histidine (His) and histamine by 1O2 in solutions containing CDOM as a function of solution pH. Both His and histamine showed pH-dependent enhanced phototransformation in the CDOM systems as compared to systems in which model, low-molecular-weight 1O2 sensitizers were used. Enhanced reactivity resulted from sorption of His and histamine to CDOM and thus exposure to elevated 1O2 concentrations in the CDOM microenvironment. The extent of reactivity enhancement depended on solution pH via its effects on the protonation state of His, histamine, and CDOM. Sorption-enhanced reactivity was independently supported by depressed rate enhancements in the presence of a cosorbate that competitively displaced His and histamine from CDOM. Incorporating sorption and photochemical transformation processes into a reaction rate prediction model improved the description of the abiotic photochemical transformation rates of His in the presence of CDOM.

  18. Increased release of histamine in patients with respiratory symptoms related to perfume.

    Science.gov (United States)

    Elberling, J; Skov, P S; Mosbech, H; Holst, H; Dirksen, A; Johansen, J D

    2007-11-01

    Environmental perfume exposure may cause respiratory symptoms. Individuals with asthma and perfume contact allergy report such symptoms more frequently than others. However, immunologic mechanisms have not been demonstrated and the symptoms are not associated with IgE-mediated allergy. The study aimed to investigate whether basophils from patients with respiratory symptoms related to perfume released more histamine in the presence of perfume as compared with healthy volunteers. Histamine release was measured by the glass fibre method. Blood was obtained from healthy volunteers (n=20) and patients with respiratory symptoms related to perfume (n=17) attending a dermatological outpatient clinic for patch testing. The effect of an international brand perfume was investigated using the basophil histamine release test with perfume. Furthermore, basophils from a healthy non-atopic donor were incubated with participant's sera and histamine release induced by perfume was measured. In both groups incremental perfume concentrations showed a positive and significant (Pperfume concentration, the basophils released significantly (PPerfume induces a dose-dependent non-IgE-mediated release of histamine from human peripheral blood basophils. Increased basophil reactivity to perfume was found in patients with respiratory symptoms related to perfume.

  19. The effect of vacuum packaging on histamine changes of milkfish sticks at various storage temperatures.

    Science.gov (United States)

    Kung, Hsien-Feng; Lee, Yi-Chen; Lin, Chiang-Wei; Huang, Yu-Ru; Cheng, Chao-An; Lin, Chia-Min; Tsai, Yung-Hsiang

    2017-10-01

    The effects of polyethylene packaging (PEP) (in air) and vacuum packaging (VP) on the histamine related quality of milkfish sticks stored at different temperatures (-20°C, 4°C, 15°C, and 25°C) were studied. The results showed that the aerobic plate count (APC), pH, total volatile basic nitrogen (TVBN), and histamine contents increased as storage time increased when the PEP and VP samples were stored at 25°C. At below 15°C, the APC, TVBN, pH, and histamine levels in PEP and VP samples were retarded, but the VP samples had considerably lower levels of APC, TVBN, and histamine than PEP samples. Once the frozen fish samples stored at -20°C for 2 months were thawed and stored at 25°C, VP retarded the increase of histamine in milkfish sticks as compared to PEP. In summary, this result suggested the milkfish sticks packed with VP and stored below 4°C could prevent deterioration of product quality and extend shelf-life. Copyright © 2017. Published by Elsevier B.V.

  20. Comparison of analytical methods for the determination of histamine in reference canned fish samples

    Science.gov (United States)

    Jakšić, S.; Baloš, M. Ž.; Mihaljev, Ž.; Prodanov Radulović, J.; Nešić, K.

    2017-09-01

    Two screening methods for histamine in canned fish, an enzymatic test and a competitive direct enzyme-linked immunosorbent assay (CD-ELISA), were compared with the reversed-phase liquid chromatography (RP-HPLC) standard method. For enzymatic and CD-ELISA methods, determination was conducted according to producers’ manuals. For RP-HPLC, histamine was derivatized with dansyl-chloride, followed by RP-HPLC and diode array detection. Results of analysis of canned fish, supplied as reference samples for proficiency testing, showed good agreement when histamine was present at higher concentrations (above 100 mg kg-1). At a lower level (16.95 mg kg-1), the enzymatic test produced some higher results. Generally, analysis of four reference samples according to CD-ELISA and RP-HPLC showed good agreement for histamine determination (r=0.977 in concentration range 16.95-216 mg kg-1) The results show that the applied enzymatic test and CD-ELISA appeared to be suitable screening methods for the determination of histamine in canned fish.

  1. La influenza A (H1N1: estado actual del conocimiento Influenza A (H1N1 virus: current information

    Directory of Open Access Journals (Sweden)

    Laura Margarita González Valdés

    2010-03-01

    Full Text Available Se revisó la bibliografía actualizada sobre el tema a partir de los principales buscadores, y reuniones internacionales realizadas sobre la pandemia de la influenza A (H1N1. Se tratan los aspectos relacionados con la historia, la aparición de la pandemia, la biología de la enfermedad, la epidemiología, el cuadro clínico, el tratamiento y el pronóstico y la prevención. La gripe A (H1N1 es una pandemia causada por una variante nueva del virus de la Influenza A que ha sufrido cambios antigénicos en la hemaglutinina y la neuraminidasa. Esto hace que la población sea altamente vulnerable a la infección y produce una sobrecarga temporal enorme a los servicios de salud. El virus se trasmite como otros virus Influenza. Su letalidad es similar a la de la influenza estacional, pero puede incrementarse en personas con factores de riesgo y en adultos jóvenes sanos. El asma y el embarazo parecen ser condiciones de base importantes para incrementar la severidad de la infección. Puede existir cierta protección por inmunidad cruzada con cepas que circularon en el pasado. El espectro clínico va desde personas asintomáticas hasta las formas graves que requieren internación en cuidados intensivos, con rápido deterioro hasta llegar a la insuficiencia respiratoria en un plazo de 24 horas. La vacunación durante la pandemia no parece ser suficientemente efectiva. Son necesarios antivirales (oseltamivir y zanamivir, y las medidas preventivas higiénico-sanitarias son muy eficaces.An updated review using the main search motors and international meetings already celebrated related to Influenza A H1N1 pandemics. Items related to the history, the appearance of the pandemics, the biology of the disease, its epidemiology, clinics, treatment, prognosis and prevention. Grippe A H1N1 is a pandemic caused by a new variant of the Influenza A virus that has suffered antigenic changes in haemaglutinin and neuraminidase. This turns populations more susceptible to

  2. Development of an analytical method for the determination of histamine in fish by liquid chromatography of high performance in reverse phase

    International Nuclear Information System (INIS)

    Valverde Chavarria, Juan Carlos; Barquero Quiros, Mirian

    2004-01-01

    The histamine is a biogenic amine able to promote allergic intoxications in sensitive persons. For this reason is necessary to have a method of analysis with sensitivity, precision and accuracy able to quantify lower amounts than actual FDA Normative sets. A reverse phase chromatographic method was developed. To identify and quantify histamine through automatic generation of histamine derivative of OPA, using an ultraviolet detector, performance parameters of developed method were adequate to quantification of histamine amount lower than FDA Normative. (Author) [es

  3. Identification of Human H1N2 and Human-Swine Reassortant H1N2 and H1N1 Influenza A Viruses among Pigs in Ontario, Canada (2003 to 2005)†

    OpenAIRE

    Karasin, Alexander I.; Carman, Suzanne; Olsen, Christopher W.

    2006-01-01

    Since 2003, three novel genotypes of H1 influenza viruses have been recovered from Canadian pigs, including a wholly human H1N2 virus and human-swine reassortants. These isolates demonstrate that human-lineage H1N2 viruses are infectious for pigs and that viruses with a human PB1/swine PA/swine PB2 polymerase complex can replicate in pigs.

  4. Utilization of Diamine Oxidase Enzyme from Mung Bean Sprouts (Vigna radiata L) for Histamine biosensors

    Science.gov (United States)

    Karim, Abdul; Wahab, A. W.; Raya, I.; Natsir, H.; Arif, A. R.

    2018-03-01

    This research is aimed to utilize the diamine oxidase enzyme (DAO) which isolated from mung bean sprouts (Vigna radiata L) to develop histamine biosensors based on electode enzyme with the amperometric method (cyclic voltammetry).The DAO enzyme is trapped inside the membrane of chitin-cellulose acetate 2:1 and glutaraldehyde which super imposed on a Pt electrode. Histamine will be oxidized by DAO enzyme to produce aldehydes and H2O2 that acting as electron transfer mediators.The performance of biosensors will be measured at various concentrations of glutaraldehyde, temperature changes and different range of pH. Recently, it has been found that the optimal conditions obtained from the paramaters as follows; at 25% of glutaraldehyde, temperature of 37°C and pH of 7.4. Eventually, the results provided an expectation for applying histamine biosensors in determining the freshness and safety of fish specifically skombroidae families.

  5. Increased release of histamine in patients with respiratory symptoms related to perfume

    DEFF Research Database (Denmark)

    Elberling, J; Skov, P S; Mosbech, H

    2007-01-01

    BACKGROUND: Environmental perfume exposure may cause respiratory symptoms. Individuals with asthma and perfume contact allergy report such symptoms more frequently than others. However, immunologic mechanisms have not been demonstrated and the symptoms are not associated with IgE-mediated allergy....... The study aimed to investigate whether basophils from patients with respiratory symptoms related to perfume released more histamine in the presence of perfume as compared with healthy volunteers. METHODS: Histamine release was measured by the glass fibre method. Blood was obtained from healthy volunteers (n......=20) and patients with respiratory symptoms related to perfume (n=17) attending a dermatological outpatient clinic for patch testing. The effect of an international brand perfume was investigated using the basophil histamine release test with perfume. Furthermore, basophils from a healthy non...

  6. Carvacrol attenuates serum levels of total protein, phospholipase A2 and histamine in asthmatic guinea pig

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Boskabady

    2016-11-01

    Full Text Available Objective: Pharmacological effects of carvacrol such as its anti-inflammatory activities have been shows. In this study the effects of carvacrol on serum levels of total protein (TP, phospholipase A2 (PLA2 and histamine in sensitized guinea pigs was evaluated. Materials and Methods: Sensitized guinea pigs were given drinking water alone (group S, drinking water containing three concentrations of carvacrol (40, 80 and 160 µg/ml or dexamethasone. Serum levels of TP, PLA2 and histamine were examined I all sensitized groups as well as a non-sensitized control group (n=6 for each group. Results: In sensitized animals, serum levels of TP, PLA2 and histamine were significantly increased compared to control animals (p