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Sample records for h1 receptor occupancy

  1. Bilastine vs. hydroxyzine: occupation of brain histamine H1 -receptors evaluated by positron emission tomography in healthy volunteers.

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    Farré, Magí; Pérez-Mañá, Clara; Papaseit, Esther; Menoyo, Esther; Pérez, Marta; Martin, Soraya; Bullich, Santiago; Rojas, Santiago; Herance, José-Raúl; Trampal, Carlos; Labeaga, Luis; Valiente, Román

    2014-11-01

    A close correlation exists between positron emission tomography (PET)-determined histamine H1 -receptor occupancy (H1 RO) and the incidence of sedation. Antihistamines with H1 RO bilastine, a second generation antihistamine, with that of hydroxyzine. This randomized, double-blind, crossover study used PET imaging with [(11) C]-doxepin to evaluate H1 RO in 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and H1 ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated. The mean binding potential of all five regions of interest (total binding potential) was significantly greater with bilastine than hydroxyzine (mean value 0.26 vs. 0.13, P bilastine and placebo. Overall H1 RO by bilastine was significantly lower than that by hydroxyzine (mean value -3.92% vs. 53.95%, P bilastine plasma concentrations and total binding potential values. No significant between-treatment differences were observed for sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine. A single oral dose of bilastine 20 mg had minimal H1 RO, was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective and PET criteria as a non-sedating antihistamine. © 2014 The British Pharmacological Society.

  2. Structural Analysis of the Histamine H1 Receptor.

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    Shiroishi, Mitsunori; Kobayashi, Takuya

    2017-01-01

    The crystal structure of the human histamine H1 receptor (H1R) has been determined in complex with its inverse agonist doxepin, a first-generation antihistamine. The crystal structure showed that doxepin sits deeply inside the ligand-binding pocket and predominantly interacts with residues highly conserved among other aminergic receptors. This binding mode is considered to result in the low selectivity of the first-generation antihistamines for H1R. The crystal structure also revealed the mechanism of receptor inactivation by the inverse agonist doxepin. On the other hand, the crystal structure elucidated the anion-binding site near the extracellular portion of the receptor. This site consists of residues not conserved among other aminergic receptors, which are specific for H1R. Docking simulation and biochemical experimentation demonstrated that a carboxyl group on the second-generation antihistamines interacts with the anion-binding site. These results imply that the anion-binding site is a key site for the development of highly selective antihistamine drugs.

  3. Ophthalmic antihistamines and H1-H4 receptors.

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    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.

  4. The use of New Generation H1 Receptor Blockers and Advantages in Terms of Reliability

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    Muhammed Yayla

    2013-10-01

    Full Text Available H1 receptor blockers are one of the most commonly prescribed medications in the treatment of allergic disorders. These disease have reduced life quality of people and prevalent in the world. H1 receptor blockers has been used since 1940 and lead to some adverse effects such as sedation because of their chemical and pharmacological properties. Therefore new generations have been studied for reduced their adverse effect. The aims of this review are to exhibit advantages of new produced H1 receptor blockers compared to classical antihistamines and demonstrate efficacies of clinical uses of new produced H1 antihistamines. New generation H1 receptor blockers which have been developed after 1980s has less lipophilic properties and their sedative effects are minimized compared to classical antihistamines. Also, their specificity, affinity for H1 receptors and antihistaminergic effects are higher than classical H1 receptor blockers. Although new generation H1 receptor blockers are better tolerated than classical H1 receptor blockers, some of them lead to potential cardio toxicity. Consequently new generation H1 receptor blockers are reliable and efficient drugs, they provide convenience in the treatment of allergic disorders and prevent development of phobia against drugs.

  5. Functional pharmacology of H1 histamine receptors expressed in mouse preoptic/anterior hypothalamic neurons

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    Tabarean, I V

    2013-01-01

    BACKGROUND AND PURPOSE Histamine H1 receptors are highly expressed in hypothalamic neurons and mediate histaminergic modulation of several brain-controlled physiological functions, such as sleep, feeding and thermoregulation. In spite of the fact that the mouse is used as an experimental model for studying histaminergic signalling, the pharmacological characteristics of mouse H1 receptors have not been studied. In particular, selective and potent H1 receptor agonists have not been identified. EXPERIMENTAL APPROACH Ca2+ imaging using fura-2 fluorescence signals and whole-cell patch-clamp recordings were carried out in mouse preoptic/anterior hypothalamic neurons in culture. KEY RESULTS The H1 receptor antagonists mepyramine and trans-triprolidine potently antagonized the activation by histamine of these receptors with IC50 values of 0.02 and 0.2 μM respectively. All H1 receptor agonists studied had relatively low potency at the H1 receptors expressed by these neurons. Methylhistaprodifen and 2-(3-trifluoromethylphenyl)histamine had full-agonist activity with potencies similar to that of histamine. In contrast, 2-pyridylethylamine and betahistine showed only partial agonist activity and lower potency than histamine. The histamine receptor agonist, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptanecarboxamide (HTMT) had no agonist activity at the H1 receptors H1 receptors expressed by mouse preoptic/anterior hypothalamic neurons but displayed antagonist activity. CONCLUSIONS AND IMPLICATIONS Methylhistaprodifen and 2-(3-trifluoromethylphenyl)histamine were identified as full agonists of mouse H1 receptors. These results also indicated that histamine H1 receptors in mice exhibited a pharmacological profile in terms of agonism, significantly different from those of H1 receptors expressed in other species. PMID:23808378

  6. 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

  7. Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity.

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    Corcóstegui, Reyes; Labeaga, Luis; Innerárity, Ana; Berisa, Agustin; Orjales, Aurelio

    2005-01-01

    This study aimed to establish the receptor selectivity and antihistaminic activity of bilastine, a new selective antihistamine receptor antagonist. In vitro experiments were conducted using a receptor binding screening panel and guinea-pig and rat tissues. Antihistaminic activity was determined using H1 receptor binding studies and in vitro H1 antagonism studies conducted in guinea-pig tissues and human cell lines. Receptor selectivity was established using a receptor binding screening panel and a receptor antagonism screening conducted in guinea-pig, rat and rabbit tissues. Inhibition of inflammatory mediators was determined through the Schultz-Dale reaction in sensitised guinea-pig ileum. Bilastine binds to histamine H1-receptors as indicated by its displacement of [3H]-pyrilamine from H1-receptors expressed in guinea-pig cerebellum and human embryonic kidney (HEK) cell lines. The studies conducted on guinea-pig smooth muscle demonstrated the capability of bilastine to antagonise H1-receptors. Bilastine is selective for histamine H1-receptors as shown in receptor-binding screening conducted to determine the binding capacity of bilastine to 30 different receptors. The specificity of its H1-receptor antagonistic activity was also demonstrated in a series of in vitro experiments conducted on guinea-pig and rat tissues. The results of these studies confirmed the lack of significant antagonism against serotonin, bradykinin, leukotriene D4, calcium, muscarinic M3-receptors, alpha1-adrenoceptors, beta2-adrenoceptors, and H2- and H3-receptors. The results of the in vitro Schultz-Dale reaction demonstrated that bilastine also has anti-inflammatory activity. These preclinical studies provide evidence that bilastine has H1- antihistamine activity, with high specificity for H1-receptors, and poor or no affinity for other receptors. Bilastine has also been shown to have anti-inflammatory properties.

  8. Histamine H1 Receptor Gene Expression and Drug Action of Antihistamines.

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    Fukui, Hiroyuki; Mizuguchi, Hiroyuki; Nemoto, Hisao; Kitamura, Yoshiaki; Kashiwada, Yoshiki; Takeda, Noriaki

    2017-01-01

    The upregulation mechanism of histamine H1 receptor through the activation of protein kinase C-δ (PKCδ) and the receptor gene expression was discovered. Levels of histamine H1 receptor mRNA and IL-4 mRNA in nasal mucosa were elevated by the provocation of nasal hypersensitivity model rats. Pretreatment with antihistamines suppressed the elevation of mRNA levels. Scores of nasal symptoms were correlatively alleviated to the suppression level of mRNAs above. A correlation between scores of nasal symptoms and levels of histamine H1 receptor mRNA in the nasal mucosa was observed in patients with pollinosis. Both scores of nasal symptoms and the level of histamine H1 receptor mRNA were improved by prophylactic treatment of antihistamines. Similar to the antihistamines, pretreatment with antiallergic natural medicines showed alleviation of nasal symptoms with correlative suppression of gene expression in nasal hypersensitivity model rats through the suppression of PKCδ. Similar effects of antihistamines and antiallergic natural medicines support that histamine H1 receptor-mediated activation of histamine H1 receptor gene expression is an important signaling pathway for the symptoms of allergic diseases. Antihistamines with inverse agonist activity showed the suppression of constitutive histamine H1 receptor gene expression, suggesting the advantage of therapeutic effect.

  9. Effects of simvastatin and 6-hydroxydopamine on histaminergic H1 receptor binding density in rat brains.

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    Hu, Chang-Hua; Deng, Chao; Mackovski, Nikolce; Long, Ling; Zhu, Cansheng; Yang, Yu; Wang, Yuge; Chen, Jiezhong; Huang, Xu-Feng; Wang, Qing

    2010-12-01

    Statins have been widely used for the treatment of a variety of medical conditions including psychoneurological disorders beyond their original use in lowering cholesterol. Histamine receptors play an important role in the regulation of neural activity, however, it is unknown whether statins act on histamine receptors, particularly for their neural regulatory effects. This study examined the effects of simvastatin and 6-hydroxydopamine (6-OHDA) lesions on histamine H1 receptors using [(3)H] pyrilamine binding autoradiography. Compared to the saline group, simvastatin (1 mg/kg/day) significantly decreased H1 receptor bindings in the primary motor cortex (M1), ventromedial hypothalamic nucleus (VMH), caudate putamen (CPu), accumbens core (AcbC) and prefrontal cortex (PfC) (all p<0.05); however 10 mg/kg/day simvastatin increased H1 receptor density only in the medial amygdaloid nucleus (Mep) (p<0.05), but had no significant effect in other regions examined. The 6-OHDA lesion did not alter H1 receptor binding density in most brain areas, except a trend decrease in the hippocampus (p=0.07) and a trend increase in the cingulate cortex (p=0.06). These results suggested that simvastatin has different effects on the H1 receptors in different rat brain regions depending on the doses. Therefore, simvastatin can modulate histaminergic neurotransmission in the brain, and support the role of H1 receptors in psychoneurological disorders. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Inverse agonistic activity of antihistamines and suppression of histamine H1 receptor gene expression.

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    Mizuguchi, Hiroyuki; Ono, Shohei; Hattori, Masashi; Fukui, Hiroyuki

    2012-01-01

    Histamine H(1) receptor (H1R) expression influences the severity of allergy symptoms. We examined the effect of inverse agonists on H1R gene expression. Two inverse agonists (carebastine and mepyramine), but not the neutral antagonist oxatomide, decreased inositol phosphate accumulation. The inverse agonists also decreased H1R gene expression and down-regulated H1R mRNA below basal expression, while basal H1R mRNA expression was maintained after oxatomide treatment. These results suggest that inverse agonists more potently alleviate allergy symptoms by not only inhibiting stimulus-induced up-regulation of H1R gene expression but also by suppressing basal histamine signaling through their inverse agonistic activity.

  11. Structure of the human histamine H1 receptor complex with doxepin.

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    Shimamura, Tatsuro; Shiroishi, Mitsunori; Weyand, Simone; Tsujimoto, Hirokazu; Winter, Graeme; Katritch, Vsevolod; Abagyan, Ruben; Cherezov, Vadim; Liu, Wei; Han, Gye Won; Kobayashi, Takuya; Stevens, Raymond C; Iwata, So

    2011-06-22

    The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H(1) receptor (H(1)R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H(1)R complex with doxepin, a first-generation H(1)R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp 428(6.48), a highly conserved key residue in G-protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H(1)R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys 191(5.39) and/or Lys 179(ECL2), both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H(1)R antagonist specificity against H(1)R. ©2011 Macmillan Publishers Limited. All rights reserved

  12. Pharmacological properties of cardiovascular histamine H1 receptor binding sites: characterisation with 2-phenylhistamines.

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    Carman-Krzan, M; Krzan, M; Schunack, W

    1997-04-01

    We determined and compared the molecular properties of histamine H1 receptor binding sites in bovine thoracic aorta smooth muscle and guinea pig myocardial membranes from ventricles with saturation and inhibition binding assay, using 3H-mepyramine to label the receptor and specific and selective H1 receptor agonists of the 2-phenylhistamine group as displacers of specific 3H-mepyramine binding. 3H-mepyramine binds in a saturable manner to a homogenous population of binding sites with a K(D) of 5.6 nM and a Bmax of 57 fmol/mg of protein in bovine aorta vascular smooth muscle membranes, whereas in the guinea pig myocardium high and low affinity 3H-mepyramine binding sites exist having the following molecular characteristics: a K(D) of 1.6 nM and a Bmax of 99 fmol/mg of protein (high affinity site) and a K(D) 15.0 nM and a Bmax of 466 fmol/mg of protein (low affinity site). Halogenated 2-phenylhistamines: 2-(3-fluoro-) (2-FPH), 2-(3-trifluoromethyl-) (2-triFMPH), 2-(3-chloro-) (2-CPH), 2-(3-bromo-) (2-BPH) and 2-(3-iodophenyl)histamine (2-IPH), which showed high selectivity and potency for H1 receptors in the functional pharmacological studies, were potent inhibitors of specific radioligand binding in comparison with histamine and parent nonhalogenated 2-phenylhistamine (2-PH). Their rank order of potencies and affinities differ significantly for the vascular and cardiac H1 receptor binding sites: Specific 3H-mepyramine binding to H1 receptors in bovine vascular smooth muscle membranes was displaced in a biphasic manner by 2-(3-fluoro-), 2-(3-trifluoromethyl-), 2-(3-chloro-), 2-(3-bromo-), 2-(3-iodophenyl)histamine and histamine. In guinea pig ventricular myocardium the rank order was 2-(3-iodo-), 2-(3-bromo-), histamine, 2-(3-chloro-), and 2-(3-fluorophenyl)histamine showing better correlation with the lipophilicity of the derivatives than in vascular tissue (order of lipophilicity: 2-triFMPH >2-IPH >2-BPH >2-CPH >2-FPH >2-PH). Displacement of the radioligand binding

  13. Effects of Olopatadine Hydrochloride, a Histamine H 1 Receptor Antagonist, on Histamine-Induced Skin Responses

    OpenAIRE

    Takashi Hashimoto; Norito Ishii; Takahiro Hamada; Teruki Dainichi; Tadashi Karashima; Takekuni Nakama; Shinichiro Yasumoto

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H1 receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. Th...

  14. Effects of olopatadine hydrochloride, a histamine h(1) receptor antagonist, on histamine-induced skin responses.

    Science.gov (United States)

    Hashimoto, Takashi; Ishii, Norito; Hamada, Takahiro; Dainichi, Teruki; Karashima, Tadashi; Nakama, Takekuni; Yasumoto, Shinichiro

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H(1) receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration.

  15. Effects of Olopatadine Hydrochloride, a Histamine H1 Receptor Antagonist, on Histamine-Induced Skin Responses

    Science.gov (United States)

    Hashimoto, Takashi; Ishii, Norito; Hamada, Takahiro; Dainichi, Teruki; Karashima, Tadashi; Nakama, Takekuni; Yasumoto, Shinichiro

    2010-01-01

    Effects of olopatadine hydrochloride, a histamine H1 receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration. PMID:20886023

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

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    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. Differences in histamine H1 and H2 receptor responses in several rabbit arteries

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    Robinson, C.P.; Maxson, S.

    1982-06-01

    Responses of helically cut segments from six different rabbit arteries to the selective histamine H1 receptor agonist 2-pyridylethylamine (PEA) and, in strips contracted by 10-4 M phenylephrine, to the selective histamine H2 agonist dimaprit have been determined. 10-3 M PEA contracted the renal artery, 96 +/- 2%; mesenteric artery, 92 +/- 2%; coeliac artery, 88 +/- 11% aorta 75 +/- 4%' ear artery 64 +/- 10% and pulmonary artery 48 +/- 5% of the maximal contraction to norepinephrine. 10-3 M dimaprit relaxed the phenylephrine contracted ear artery 48 +/- 8%; renal artery, 43 +/- 8%; coeliac artery 41 +/- 8%; mesenteric artery 36 +/- 5%; aorta 16 +/- 3%; and pulmonary artery 11 +/- 1% of the initial contractile tension. Strips in which histamine H1 receptors are blocked by 7 X 10-6 M mepyramine which are contracted by phenylephrine are partially relaxed by histamine. Cooling these strips markedly enhanced relaxations of the mesenteric and coeliac arteries but not those of the other four vessels. Exposure of the strips to dibenamine potentiated relaxations of all of the arteries except the ear artery and pulmonary artery. Thus there is heterogeneity among the arteries in their responses to histamine H1 and H2 receptor activation.

  18. 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

  19. Ca2+-dependent down-regulation of human histamine H1receptors in Chinese hamster ovary cells.

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    Hishinuma, Shigeru; Komazaki, Hiroshi; Tsukamoto, Hayato; Hatahara, Hirokazu; Fukui, Hiroyuki; Shoji, Masaru

    2018-01-01

    G q/11 protein-coupled human histamine H 1 receptors in Chinese hamster ovary cells stimulated with histamine undergo clathrin-dependent endocytosis followed by proteasome/lysosome-mediated down-regulation. In this study, we evaluated the effects of a sustained increase in intracellular Ca 2+ concentrations induced by a receptor-bypassed stimulation with ionomycin, a Ca 2+ ionophore, on the endocytosis and down-regulation of H 1 receptors in Chinese hamster ovary cells. All cellular and cell-surface H 1 receptors were detected by the binding of [ 3 H]mepyramine to intact cells sensitive to the hydrophobic and hydrophilic H 1 receptor ligands, mepyramine and pirdonium, respectively. The pretreatment of cells with ionomycin markedly reduced the mepyramine- and pirdonium-sensitive binding sites of [ 3 H]mepyramine, which were completely abrogated by the deprivation of extracellular Ca 2+ and partially by a ubiquitin-activating enzyme inhibitor (UBEI-41), but were not affected by inhibitors of calmodulin (W-7 or calmidazolium) and protein kinase C (chelerythrine or GF109203X). These ionomycin-induced changes were also not affected by inhibitors of receptor endocytosis via clathrin (hypertonic sucrose) and caveolae/lipid rafts (filipin or nystatin) or by inhibitors of lysosomes (E-64, leupeptin, chloroquine, or NH 4 Cl), proteasomes (lactacystin or MG-132), and a Ca 2+ -dependent non-lysosomal cysteine protease (calpain) (MDL28170). Since H 1 receptors were normally detected by confocal immunofluorescence microscopy with an antibody against H 1 receptors, even after the ionomycin treatment, H 1 receptors appeared to exist in a form to which [ 3 H]mepyramine was unable to bind. These results suggest that H 1 receptors are apparently down-regulated by a sustained increase in intracellular Ca 2+ concentrations with no process of endocytosis and lysosomal/proteasomal degradation of receptors. © 2017 International Society for Neurochemistry.

  20. Interactions between histamine H1 receptor and its antagonists by using cell membrane chromatography method.

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    Ma, Weina; Zhang, Dongdong; Li, Jing; Che, Delu; Liu, Rui; Zhang, Jie; Zhang, Yanmin

    2015-11-01

    A high histamine H1 receptor (H1 R) expression cell membrane chromatography (CMC) method was developed to investigate the affinity of ligands for H1 R. The affinity of ligands for H1 R was evaluated by frontal analysis. Competition studies and molecular docking study were utilized to study the interactions that occurred at specific binding sites on H1 R. The KD values measured by frontal analysis were (8.72 ± 0.21) × 10(-7)  M for azelastine, (9.12 ± 0.26) × 10(-7)  M for cyproheptadine, (9.90 ± 0.18) × 10(-7)  M for doxepin, (1.42 ± 0.13) × 10(-6)  M for astemizole, (2.25 ± 0.36) × 10(-6)  M for chlorpheniramine and (3.10 ± 0.27) × 10(-6)  M for diphenhydramine. The results had a positive correlation with those from radioligand binding assay. The ability of displacement order measured on the binding sites occupied by doxepin was doxepin (KD , (2.95 ± 0.21) × 10(-8)  M) > astemizole (KD , (5.03 ± 0.18) × 10(-7)  M) > chlorpheniramine (KD , (1.27 ± 0.16) × 10(-6)  M) > cyproheptadine (KD , (1.61 ± 0.27) × 10(-6)  M), whose order met with the scores by molecular docking study. The studies showed CMC could be applied to investigate drug-receptor interactions. © 2015 Royal Pharmaceutical Society.

  1. 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 (H1) 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 H1 receptor, the similar studies on non-human pet H1 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 H1 receptors were built based on the crystal structure of human H1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H1 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 H1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H1 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. All rights

  2. Expression and localization of histamine H1, H2, and H3 receptors in rat olfactory epithelium.

    Science.gov (United States)

    Yu, Chao; Li, Li; Xia, Qingjie; Tang, Yuedi

    2017-10-01

    Histamine is an important chemical mediator in the development of allergic rhinitis and plays a key role in eliciting the nasal symptoms of the disorder. Histamine may also affect smell as a neurotransmitter. However, whether histamine receptors are present in the mammalian olfactory epithelium has not yet been examined. The aim of this study was to investigate the expression and distribution of histamine H1, H2, and H3 receptors in rat olfactory epithelium. Real-time quantitative PCR and immunohistochemical staining were performed to examine the mRNA level and protein expression and localization of histamine receptors (H1, H2, and H3) in rat olfactory epithelium. We demonstrated that mRNAs encoding histamine H1, H2, and H3 receptors were detected in rat olfactory epithelium. Immunohistochemistry also showed strong positive staining for these receptors. Co-localization of histamine H1, H2, and H3 receptors with olfactory mature protein revealed that these three histamine receptors were mainly localized in olfactory receptor neurons. These findings indicate that histamine H1, H2, and H3 receptors are present in rat olfactory epithelium and may play a physiological role in olfactory transmission. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 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

  4. In silico analysis of the histaprodifen induced activation pathway of the guinea-pig histamine H1-receptor

    Science.gov (United States)

    Straßer, Andrea; Wittmann, Hans-Joachim

    2010-09-01

    The binding of (partial) agonists in the binding pocket of biogenic amine receptors induces a conformational change from the inactive to the active state of the receptors. There is only little knowledge about the binding pathways of ligands into binding pocket on molecular level. So far, it was not possible with molecular dynamic simulations to observe the ligand binding and receptor activation. Furthermore, there is nearly nothing known, in which state of ligand binding, the receptor gets activated. The aim of this study was to get more detailed insight into the process of ligand binding and receptor activation. With the recently developed LigPath algorithm, we scanned the potential energy surface of the binding process of dimeric histaprodifen, a partial agonist at the histamine H1-receptor, into the guinea pig histamine H1-receptor, taking also into account the receptor activation. The calculations exhibited large conformational changes of Trp6.48 and Phe6.55 during ligand binding and receptor activation. Additionally, conformational changes were also observed for Phe6.52, Tyr6.51 and Phe6.44. Conformational changes of Trp6.48 and Phe6.52 are discussed in literature as rotamer toggle switch in context with receptor activation. Additionally, the calculations indicate that the binding of dimeric histaprodifen, accompanied by receptor activation is energetically preferred. In general, this study gives new, theoretical insights onto ligand binding and receptor activation on molecular level.

  5. The Target Residence Time of Antihistamines Determines Their Antagonism of the G Protein-Coupled Histamine H1 Receptor.

    Science.gov (United States)

    Bosma, Reggie; Witt, Gesa; Vaas, Lea A I; Josimovic, Ivana; Gribbon, Philip; Vischer, Henry F; Gul, Sheraz; Leurs, Rob

    2017-01-01

    The pharmacodynamics of drug-candidates is often optimized by metrics that describe target binding (Kd or Ki value) or target modulation (IC50). However, these metrics are determined at equilibrium conditions, and consequently information regarding the onset and offset of target engagement and modulation is lost. Drug-target residence time is a measure for the lifetime of the drug-target complex, which has recently been receiving considerable interest, as target residence time is shown to have prognostic value for the in vivo efficacy of several drugs. In this study, we have investigated the relation between the increased residence time of antihistamines at the histamine H1 receptor (H1R) and the duration of effective target-inhibition by these antagonists. Hela cells, endogenously expressing low levels of the H1R, were incubated with a series of antihistamines and dissociation was initiated by washing away the unbound antihistamines. Using a calcium-sensitive fluorescent dye and a label free, dynamic mass redistribution based assay, functional recovery of the H1R responsiveness was measured by stimulating the cells with histamine over time, and the recovery was quantified as the receptor recovery time. Using these assays, we determined that the receptor recovery time for a set of antihistamines differed more than 40-fold and was highly correlated to their H1R residence times, as determined with competitive radioligand binding experiments to the H1R in a cell homogenate. Thus, the receptor recovery time is proposed as a cell-based and physiologically relevant metric for the lead optimization of G protein-coupled receptor antagonists, like the H1R antagonists. Both, label-free or real-time, classical signaling assays allow an efficient and physiologically relevant determination of kinetic properties of drug molecules.

  6. Estrogenic regulation of histamine receptor subtype H1 expression in the ventromedial nucleus of the hypothalamus in female rats.

    Directory of Open Access Journals (Sweden)

    Hiroko Mori

    Full Text Available Female sexual behavior is controlled by central estrogenic action in the ventromedial nucleus of the hypothalamus (VMN. This region plays a pivotal role in facilitating sex-related behavior in response to estrogen stimulation via neural activation by several neurotransmitters, including histamine, which participates in this mechanism through its strong neural potentiating action. However, the mechanism through which estrogen signaling is linked to the histamine system in the VMN is unclear. This study was undertaken to investigate the relationship between estrogen and histamine receptor subtype H1 (H1R, which is a potent subtype among histamine receptors in the brain. We show localization of H1R exclusively in the ventrolateral subregion of the female VMN (vl VMN, and not in the dorsomedial subregion. In the vl VMN, abundantly expressed H1R were mostly colocalized with estrogen receptor α. Intriguingly, H1R mRNA levels in the vl VMN were significantly elevated in ovariectomized female rats treated with estrogen benzoate. These data suggest that estrogen can amplify histamine signaling by enhancing H1R expression in the vl VMN. This enhancement of histamine signaling might be functionally important for allowing neural excitation in response to estrogen stimulation of the neural circuit and may serve as an accelerator of female sexual arousal.

  7. In vivo pharmacological characterisation of bilastine, a potent and selective histamine H1 receptor antagonist.

    Science.gov (United States)

    Corcóstegui, Reyes; Labeaga, Luis; Innerárity, Ana; Berisa, Agustín; Orjales, Aurelio

    2006-01-01

    We set out to establish the in vivo histamine H(1) receptor antagonistic (antihistaminic) and antiallergic properties of bilastine. In vivo antihistaminic activity experiments consisted of measurement of: inhibition of increase in capillary permeability and reduction in microvascular extravasation and bronchospasm in rats and guinea pigs induced by histamine and other inflammatory mediators; and protection against lethality induced by histamine and other inflammatory mediators in rats. In vivo antiallergic activity experiments consisted of measurement of passive and active cutaneous anaphylactic reactions as well as type III and type IV allergic reactions in sensitised rodents. In the in vivo antihistaminic activity experiments, bilastine was shown to have a positive effect, similar to that of cetirizine and more potent than that of fexofenadine. The results of the in vivo antiallergic activity experiments showed that the properties of bilastine in this setting are similar to those observed for cetirizine and superior to fexofenadine in the model of passive cutaneous anaphylactic reaction. When active cutaneous anaphylactic reaction experiments were conducted, bilastine showed significant activity, less potent than that observed with cetirizine but superior to that of fexofenadine. Evaluation of the type III allergic reaction showed that of the antihistamines only bilastine was able to inhibit oedema in sensitised mice, although its effect in this respect was much less potent than that observed with dexamethasone. In terms of the type IV allergic reaction, neither bilastine, cetirizine nor fexofenadine significantly modified the effect caused by oxazolone. The results of our in vivo preclinical studies corroborate those obtained from previously conducted in vitro experiments of bilastine, and provide evidence that bilastine possesses antihistaminic as well as antiallergic properties, with similar potency to cetirizine and superior potency to fexofenadine.

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

    Energy Technology Data Exchange (ETDEWEB)

    Notcovich, Cintia [Laboratorio de Patologia y Farmacologia Molecular, Instituto de Biologia y Medicina Experimental (Argentina); Laboratorio de Farmacologia de Receptores, Catedra de Quimica Medicinal, Departamento de Farmacologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires (Argentina); Diez, Federico [Laboratorio de Farmacologia de Receptores, Catedra de Quimica Medicinal, Departamento de Farmacologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires (Argentina); Tubio, Maria Rosario [Laboratorio de Patologia y Farmacologia Molecular, Instituto de Biologia y Medicina Experimental (Argentina); Laboratorio de Farmacologia de Receptores, Catedra de Quimica Medicinal, Departamento de Farmacologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires (Argentina); Baldi, Alberto [Laboratorio de Patologia y Farmacologia Molecular, Instituto de Biologia y Medicina Experimental (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires (Argentina); Kazanietz, Marcelo G. [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Davio, Carlos [Laboratorio de Farmacologia de Receptores, Catedra de Quimica Medicinal, Departamento de Farmacologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires (Argentina); Shayo, Carina, E-mail: cshayo@dna.uba.ar [Laboratorio de Patologia y Farmacologia Molecular, Instituto de Biologia y Medicina Experimental (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires (Argentina)

    2010-02-01

    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{sub 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 {beta}2-chimaerin. On the other hand, H1R-induced ERK1/2 activation was inhibited by U73122 but not affected by C3 or {beta}2-chimaerin, suggesting that ERK1/2 activation was dependent on PLC and independent of RhoA or Rac. [{sup 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.

  9. Evolution of human receptor binding affinity of H1N1 hemagglutinins from 1918 to 2009 pandemic influenza A virus.

    Science.gov (United States)

    Nunthaboot, Nadtanet; Rungrotmongkol, Thanyada; Malaisree, Maturos; Kaiyawet, Nopporn; Decha, Panita; Sompornpisut, Pornthep; Poovorawan, Yong; Hannongbua, Supot

    2010-08-23

    The recent outbreak of the novel 2009 H1N1 influenza in humans has focused global attention on this virus, which could potentially have introduced a more dangerous pandemic of influenza flu. In the initial step of the viral attachment, hemagglutinin (HA), a viral glycoprotein surface, is responsible for the binding to the human SIA alpha2,6-linked sialopentasaccharide host cell receptor (hHAR). Dynamical and structural properties, based on molecular dynamics simulations of the four different HAs of Spanish 1918 (H1-1918), swine 1930 (H1-1930), seasonal 2005 (H1-2005), and a novel 2009 (H1-2009) H1N1 bound to the hHAR were compared. In all four HA-hHAR complexes, major interactions with the receptor binding were gained from HA residue Y95 and the conserved HA residues of the 130-loop, 190-helix, and 220-loop. However, introduction of the charged HA residues K145 and E227 in the 2009 HA binding pocket was found to increase the HA-hHAR binding efficiency in comparison to the three previously recognized H1N1 strains. Changing of the noncharged HA G225 residue to a negatively charged D225 provides a larger number of hydrogen-bonding interactions. The increase in hydrophilicity of the receptor binding region is apparently an evolution of the current pandemic flu from the 1918 Spanish, 1930 swine, and 2005 seasonal strains. Detailed analysis could help the understanding of how different HAs effectively attach and bind with the hHAR.

  10. Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases.

    Science.gov (United States)

    Pujol, J; Godoy, P; Soldevila, N; Castilla, J; González-Candelas, F; Mayoral, J M; Astray, J; Garcia, S; Martin, V; Tamames, S; Delgado, M; Domínguez, A

    2016-03-01

    This study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009-2010 and 2010-2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0·97, 95% confidence interval (CI) 0·74-1·27], but an association (aOR 1·53, 95% CI 1·01-2·31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0·41, 95% CI 0·23-0·73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza.

  11. Comparison of levocabastine, a new selective H1-receptor antagonist, and disodium cromoglycate, in a nasal provocation test with allergen.

    OpenAIRE

    Kolly, M; Pécoud, A

    1986-01-01

    The effect of intranasal administration of levocabastine, a new selective H1-receptor antagonist, was investigated in a nasal provocation test (NPT) performed with allergens. The NPT allowed a quantitative estimation of the nasal allergic threshold (concentration of allergen necessary to trigger the reaction). In addition, the intensity of the three major rhinitis symptoms (obstruction, rhinorrhea and sneezing) was determined. Twelve adult patients, allergic to grass pollen, underwent a first...

  12. H1-Receptor activation triggers the endogenous nitric oxide signalling system in the rat submandibular gland

    Directory of Open Access Journals (Sweden)

    Enri Borda

    2002-01-01

    Full Text Available Background: Histamine is released from mast cells by immunologic and non-immunologic stimuli during salivary gland inflammation, regulating salivary secretion. The receptor-secretory mechanism has not been studied in detail.

  13. Implication of prostaglandins and histamine h1 and h2 receptors in radiation-induced temperature responses of rats

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

    Exposure of rats to 1-15 Gy cobalt 60 gamma radiation 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 cyclooxgenase 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 H(1) and H(2) receptors may be involved in radiation-induced hypothermia since both the H(1) receptor antagonist, mepyramine, and H(2) receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggested 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-04-01

    Exposure of rats to 1-15 Gy gamma radiation (/sup 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.

  15. 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

  16. Effect of receptor binding specificity on the immunogenicity and protective efficacy of influenza virus A H1 vaccines.

    Science.gov (United States)

    Sun, Xiangjie; Cao, Weiping; Pappas, Claudia; Liu, Feng; Katz, Jacqueline M; Tumpey, Terrence M

    2014-09-01

    The biological basis for the poor immunogenicity of unadjuvanted avian influenza A virus vaccines in mammals is not well understood. Here, we mutated the hemagglutinin (HA) of two H1N1 virus vaccines to determine whether virus receptor binding specificity contributes to the low immunogenicity of avian influenza virus vaccines. Mutations were introduced into the HA of an avian influenza virus, A/Duck/New York/15024-21/96 (Dk/96) which switched the binding preference from α2,3- to α2,6-linked sialic acid (SA). A switch in receptor specificity of the human A/South Carolina/1/18 (SC/18) virus generated a mutant virus with α2,3 SA (avian) binding preference. Inactivated vaccines were generated and administered to mice and ferrets intramuscularly. We found that the vaccines with human receptor binding preference induced slightly higher antibody titers and cell-mediated immune responses compared to their isogenic viruses with avian receptor binding specificity. Upon challenge with DK/96 or SC18 virus, differences in lung virus titers between the vaccine groups with different receptor-binding specificities were minimal. Overall, our data suggest that receptor binding specificity contributes only marginally to the immunogenicity of avian influenza vaccines and that other factors may also be involved. Published by Elsevier Inc.

  17. Asp73-dependent and -independent regulation of the affinity of ligands for human histamine H1 receptors by Na().

    Science.gov (United States)

    Hishinuma, Shigeru; Kosaka, Kiyoe; Akatsu, Chizuru; Uesawa, Yoshihiro; Fukui, Hiroyuki; Shoji, Masaru

    2017-03-15

    The affinity of ligands for G-protein-coupled receptors (GPCRs) is allosterically regulated by Na(+) via a highly conserved aspartate residue (Asp(2.50)) in the second transmembrane domain of GPCRs. In the present study, we examined the Na(+)-mediated regulation of the affinity of ligands for Gq/11-protein-coupled human histamine H1 receptors in Chinese hamster ovary cells. The affinities of 3 agonists and 20 antihistamines were evaluated by their displacement curves against the binding of [(3)H]-mepyramine to membrane preparations in the presence or absence of 100mM NaCl. The affinities of most drugs including histamine, an agonist, and d-chlorpheniramine, a first-generation antihistamine, were reduced by NaCl, with the extent of NaCl-mediated changes varying widely between drugs. In contrast, the affinities of some second-generation antihistamines such as fexofenadine were increased by NaCl. These changes were retained in intact cells. The mutation of Asp(2.50) (Asp73) to asparagine abrogated NaCl-induced reductions in affinities for histamine and d-chlorpheniramine, but not NaCl-induced increases in the affinity for fexofenadine. Quantitative structure-activity relationship (QSAR) analyses showed that these Na(+)-mediated changes were explained and predicted by a combination of the molecular energies and implicit solvation energies of the compounds. These results suggest that Na(+) diversely regulates the affinity of ligands for H1 receptors from the extracellular sites of receptors via Asp73-dependent and -independent mechanisms in a manner that depends on the physicochemical properties of ligands. These results may contribute to a deeper understanding of the fundamental mechanisms by which the affinity of ligands for their receptors is allosterically regulated by Na(+). Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Histamine induces the production of matrix metalloproteinase-9 in human astrocytic cultures via H1-receptor subtype.

    Science.gov (United States)

    Patel, Aarti; Vasanthan, Vishnu; Fu, Wen; Fahlman, Richard P; MacTavish, David; Jhamandas, Jack H

    2016-05-01

    Accumulation of β-amyloid (Aβ) protein within the brain is a neuropathological hallmark of Alzheimer's disease (AD). One strategy to facilitate Aβ clearance from the brain is to promote Aβ catabolism. Matrix metalloproteinase-9 (MMP-9), a member of the family of Zn(+2)-containing endoproteases, known to be expressed and secreted by astrocytes, is capable of degrading Aβ. Histamine, a major aminergic brain neurotransmitter, stimulates the production of MMP-9 in keratinocytes through the histamine H1 receptor (H1R). In the present study, we show that histamine evokes a concentration- and calcium-dependent release of MMP-9 from human astrocytic U373 cells and primary cultures of human and rat astrocytes through the H1R subtype. Activation of H1R on astrocytes elevated intracellular levels of Ca(2+) that was accompanied by time-dependent increases in MAP kinase p44/p42 and PKC. In-cell western blots revealed dose-dependent increases in both enzymes, confirming involvement of these signal transduction pathways. We next investigated the extent of recombinant human MMP-9 (rhMMP-9) proteolytic activity on soluble oligomeric Aβ (soAβ). Mass spectrometry demonstrated time-dependent cleavage of soAβ (20 μM), but not another amyloidogenic protein amylin, upon incubation with rhMMP-9 (100 nM) at 1, 4 and 17 h. Furthermore, Western blots showed a shift in soAβ equilibrium toward lower order, less toxic monomeric species. In conclusion, both MAPK p44/p42 and PKC pathways appear to be involved in histamine-upregulated MMP-9 release via H1Rs in astrocytes. Furthermore, MMP-9 appears to cleave soAβ into less toxic monomeric species. Given the key role of histamine in MMP-9 release, this neurotransmitter may serve as a potential therapeutic target for AD.

  19. Relative Efficacy of Seven Common H1 Receptor Antagonist Antihistamines in Chronic Idiopathic Urticaria

    Directory of Open Access Journals (Sweden)

    Mohan Singh

    1987-01-01

    Full Text Available The order of clinical potency of seven Hi receptor antagonist antihistamines in usual therapeutic doses was evaluated in 30 patients of chronic idiopathic urticaria by a double blind, placebo controlled trial utilizing a self-assessment method. The analysis of mean whealing and, itching scores established a potency sequence in the -decreasing order of cyproheptidine, hydroxyzine, chlorpheniramine, embramine, promethazine, dimeth′mdene and dexchlorpheniramme. The differences between the first five antihistamines were not statistically significant, though these were superior to ddxchlorpheniralmine and placebo. Dexchlorpheniramine was statistically better than placebo.

  20. Effect of a new selective H1 receptor antagonist (levocabastine) in a nasal and conjunctival provocation test.

    Science.gov (United States)

    Pécoud, A; Zuber, P; Kolly, M

    1987-01-01

    Levocabastine is a new selective H1 receptor antagonist. The effect of the drug administered locally was compared to placebo in a quantified nasal and conjunctival provocation test with allergens performed in patients allergic to grass pollen. In the nasal provocation test, levocabastine was able to increase the 'reaction threshold' (dose of allergen necessary to trigger allergic symptoms) in 9 out of 12 patients; the drug inhibited rhinorrhea and sneezing, but not nasal obstruction. In the conjunctival provocation test, the 'reaction threshold' clearly increased in 10 out of 11 patients. The local administration of levocabastine might be useful in allergic rhinitis and conjunctivitis.

  1. 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

    We have studied the effect of histamine and H1- or H2-receptor antagonists on cutaneous blood flow and catecholamine release in man. Histamine was infused alone or in combination with mepyramine, an H1-antagonist or cimetidine, an H2-antagonist for 2 h. Cutaneous blood flow was measured continuou......We have studied the effect of histamine and H1- or H2-receptor antagonists on cutaneous blood flow and catecholamine release in man. Histamine was infused alone or in combination with mepyramine, an H1-antagonist or cimetidine, an H2-antagonist for 2 h. Cutaneous blood flow was measured...... that histamine causes an immediate cutaneous vasodilatation through H1-receptors and a more sustained response through H2-receptors. The vasodilatation is accompanied by an increase in plasma catecholamine concentrations. Despite the continuous infusion of histamine, blood flow decreased during the last hour...

  2. Role of H1 receptors and P-selectin in histamine-induced leukocyte rolling and adhesion in postcapillary venules.

    Science.gov (United States)

    Asako, H; Kurose, I; Wolf, R; DeFrees, S; Zheng, Z L; Phillips, M L; Paulson, J C; Granger, D N

    1994-04-01

    The objective of this study was to define the nature, magnitude, and mechanisms of histamine-induced leukocyte-endothelial cell interactions in postcapillary venules of the rat mesentery using intravital microscopic techniques. Superfusion of the mesentery with histamine (10(-7)-10(-5) M) resulted in a dose-related increase in the number of rolling leukocytes, a reduction in rolling velocity, and an increased clearance of FITC-labeled rat albumin from blood to superfusate. The histamine-induced recruitment of rolling leukocytes and increased albumin clearance were prevented by histamine H1 (hydroxyzine, diphenhydramine) but not H2 (cimetidine) receptor antagonists. Because histamine induces expression of the adhesion molecule P-selectin in cultured endothelial cells, a monoclonal antibody directed against rat P-selectin and soluble sialyl-LewisX oligosaccharide (the carbohydrate ligand to P-selectin) were also tested as inhibitors. Both were effective in preventing the histamine-induced recruitment of rolling leukocytes, but neither agent attenuated the increased albumin clearance. These observations suggest that (a) histamine recruits rolling leukocytes and increases albumin leakage in postcapillary venules via H1 receptor activation, (b) histamine-induced recruitment of rolling leukocytes is mediated in part by P-selectin expressed on the endothelial cell surface, and (c) the histamine-induced vascular albumin leakage is unrelated to leukocyte-endothelial cell adhesion. Our results are consistent with the view that histamine may act as a mediator of acute inflammatory reactions.

  3. Histamine Stimulates Hydrogen Peroxide Production by Bronchial Epithelial Cells via Histamine H1 Receptor and Dual Oxidase

    Science.gov (United States)

    Rada, Balázs; Boudreau, Howard E.; Park, Jonathan J.

    2014-01-01

    Oxidative stress has been implicated in the pathogenesis of bronchial asthma. Besides granulocytes, the airway epithelium can produce large amounts of reactive oxygen species and can contribute to asthma-related oxidative stress. Histamine is a major inflammatory mediator present in large quantities in asthmatic airways. Whether histamine triggers epithelium-derived oxidative stress is unknown. We therefore aimed at characterizing human airway epithelial H2O2 production stimulated by histamine. We found that air–liquid interface cultures of primary human bronchial epithelial cells (BECs) and an immortalized BEC model (Cdk4/hTERT HBEC) produce H2O2 in response to histamine. The main source of airway epithelial H2O2 is an NADPH dual oxidase, Duox1. Out of the four histamine receptors (H1R–H4R), H1R has the highest expression in BECs and mediates the H2O2–producing effects of histamine. IL-4 induces Duox1 gene and protein expression levels and enhances histamine-induced H2O2 production by epithelial cells. Using HEK-293 cells expressing Duox1 or Duox2 and endogenous H1R, histamine triggers an immediate intracellular calcium signal and H2O2 release. Overexpression of H1R further increases the oxidative output of Duox-expressing HEK-293 cells. Our observations show that BECs respond to histamine with Duox-mediated H2O2 production. These findings reveal a mechanism that could be an important contributor to oxidative stress characteristic of asthmatic airways, suggesting novel therapeutic targets for treating asthmatic airway disease. PMID:23962049

  4. Histamine induces KCNQ channel-dependent gamma oscillations in rat hippocampus via activation of the H1 receptor.

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    Andersson, Richard; Galter, Dagmar; Papadia, Daniela; Fisahn, André

    2017-05-15

    Histamine is an aminergic neurotransmitter, which regulates wakefulness, arousal and attention in the central nervous system. Histamine receptors have been the target of efforts to develop pro-cognitive drugs to treat disorders such as Alzheimer's disease and schizophrenia. Cognitive functions including attention are closely associated with gamma oscillations, a rhythmical electrical activity pattern in the 30-80 Hz range, which depends on the synchronized activity of excitatory pyramidal cells and inhibitory fast-spiking interneurons. We set out to explore whether histamine has a role in promoting gamma oscillations in the hippocampus. Using in-situ hybridization we demonstrate that histamine receptor subtypes 1, 2 and 3 are expressed in stratum pyramidale of area CA3 in rats. We show that both pyramidal cells and fast-spiking interneurons depolarize and increase action potential firing in response to histamine in vitro. The activation of histamine receptors generates dose-dependent, transient gamma oscillations in area CA3 of the hippocampus - the locus of the gamma rhythm generator. We also demonstrate that this histamine effect is independent of muscarinic receptors. Using specific antagonists we provide evidence that histamine gamma rhythmogenesis specifically depends on the H1 receptor. Histamine also depolarized both pyramidal cells and fast-spiking interneurons and increased membrane resistance in pyramidal cells. The increased membrane resistance is potentially mediated by the inhibition of potassium channels because application of the KCNQ channel opener ICA110381 abolished the oscillations. Taken together our data demonstrate a novel and physiological mechanism for generating gamma oscillations in hippocampus and suggest a role for KCNQ channels in this cognition-relevant brain activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Up-regulation of airway smooth muscle histamine H1 receptor mRNA, protein and function by ß2-adrenoceptor activation

    NARCIS (Netherlands)

    Mak, J.CW; Roffel, A.F; Katsunuma, T; Elzinga, C.R S; Zaagsma, Hans; Barnes, P.J

    Histamine, released from activated mast cells, causes bronchoconstriction mediated by H-1 receptors, whereas beta(2)-agonists are widely used for the relief of bronchoconstriction. In this study, we examined the effects of the beta(2)-adrenoceptor agonist, fenoterol, on the expression of H-1

  6. Changes in Histamine Receptors (H1, H2, and H3 Expression in Rat Medial Vestibular Nucleus and Flocculus after Unilateral Labyrinthectomy: Histamine Receptors in Vestibular Compensation.

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    Liuqing Zhou

    Full Text Available Vestibular compensation is the process of behavioral recovery following peripheral vestibular lesion. In clinics, the histaminergic medicine is the most widely prescribed for the treatment of vertigo and motion sickness, however, the molecular mechanisms by which histamine modulates vestibular function remain unclear. During recovery from the lesion, the modulation of histamine receptors in the medial vestibular nucleus (MVN and the flocculus may play an important role. Here with the means of quantitative real-time PCR, western blotting and immunohistochemistry, we studied the expression of histamine receptors (H1, H2, and H3 in the bilateral MVN and the flocculus of rats on the 1st, 3rd, and 7th day following unilateral labyrinthectomy (UL. Our results have shown that on the ipsi-lesional flocculus the H1, H2 and H3 receptors mRNA and the protein increased significantly on the 1st and 3rd day, with compare of sham controls and as well the contralateral side of UL. However, on the 7th day after UL, this expression returned to basal levels. Furthermore, elevated mRNA and protein levels of H1, H2 and H3 receptors were observed in the ipsi-lesional MVN on the 1st day after UL compared with sham controls and as well the contralateral side of UL. However, this asymmetric expression was absent by the 3rd post-UL. Our findings suggest that the upregulation of histamine receptors in the MVN and the flocculus may contribute to rebalancing the spontaneous discharge in bilateral MVN neurons during vestibular compensation.

  7. 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

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    Hazem Adel Ashmawi

    2009-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Os receptores de histamina mediam vias nociceptivas principalmente no sistema nervoso central. Alguns estudos mostraram efeito analgésico de antagonistas de receptor de histamina no sistema nervoso periférico. Não está claro se o efeito analgésico local é classe específico ou droga específico. MÉTODO: Para responder a essa questão, utilizamos três diferentes antagonistas do receptor H1 (pirilamina, prometazina e cetirizina administrados diretamente na pata do rato, pela via intraperitoneal ou por bloqueio de nervo periférico em modelo de dor induzida por formalina. Observamos o efeito das drogas no comportamento do número de elevações da pata. RESULTADOS: Na fase I, a pirilamina local diminuiu o número de elevações da pata de forma dose-dependente. Na dose mais alta, a diminuição foi de 97,8%. Para a prometazina, a diminuição foi de 92% e para cetizirina, 23,9%. Na fase II, a pirilamina diminuiu o número de elevações da pata em 93,5%, a prometazina em 78,2% e a cetirizina em 80,1%. A administração dos fármacos por via intraperitoneal não alterou o comportamento doloroso. Quando utilizadas para bloqueio de nervo periférico, na fase I, a pirilamina diminuiu o número de elevações da pata em 96,7%, a prometazina em 73,3% e a cetirizina em 23,9%. Na fase II, a pirilamina levou à diminuição de 86,6%, a prometazina de 64,4% e a cetirizina de 19,9%. CONCLUSÕES: Os resultados mostraram que os antagonistas de receptor da histamina H1 apresentam efeitos analgésicos locais, diferentes do efeito sistêmico, sendo um deles anti-inflamatório e classe específico e o outro específico para prometazina e pirilamina, semelhante a efeito clínico anestésico local.JUSTIFICATIVA Y OBJETIVOS: Los receptores de histamina intermedian las vías nociceptivas, principalmente en el sistema nervioso central. Algunos estudios arrojaron un efecto analgésico de antagonistas de receptor de histamina en el

  8. 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.

  9. 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.

  10. 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.

  11. Design, synthesis and histamine H1-receptor antagonistic activity of some novel 4-amino-2-(substituted)-5-(substituted) aryl-6-[(substituted aryl) amino] pyrimidines.

    Science.gov (United States)

    Chhabria, Mahesh T; Patel, Vimal T; Rajan, Kombu S; Brahmkshatriya, Pathik S

    2009-01-01

    A series of 4-amino-2-(substituted)-5-(substituted)aryl-6-[(substituted)aryl)-amino]pyrimidines was designed based on the triangular pharmacophoric requirements for histamine H1-receptor antagonists. The designed molecules were synthesized by condensation of arylacetonitriles with respective arylisothiocyanates to form corresponding acrylonitriles followed by cyclocondensation with carboxamidines to afford substituted pyrimidines. All compounds were screened for their histamine H1-receptor antagonistic activity using the model "Inhibition of the isotonic contraction induced by histamine on isolated guinea pig ileum". Target compounds were also evaluated for their sedative potential as well as their anticholinergic activities as these two are known to be the common adverse effects of histamine H1-receptor antagonists. Compounds 2h, 2i, 2j and 2k exhibited potent histamine H1-receptor antagonistic activity, which was found to be comparable with the standard drug, cetirizine (CAS 83881-51-0) and more potent than the conventional drug mepyramine (CAS 91-84-9). Some of the compounds have displayed very low sedative potential compared to diphenhydramine (CAS 58-73-1), but was found higher than cetirizine. None of them showed anticholinergic activity indicating potentialities of this series to be developed as second-generation histamine H1-receptor antagonists.

  12. Role of the thalamic submedius nucleus histamine H1 and H 2 and opioid receptors in modulation of formalin-induced orofacial pain in rats.

    Science.gov (United States)

    Erfanparast, Amir; Tamaddonfard, Esmaeal; Taati, Mina; Dabaghi, Milad

    2015-10-01

    Histamine and opioid systems are involved in supraspinal modulation of pain. In this study, we investigated the effects of separate and combined microinjections of agonists and antagonists of histamine H1 and H2 and opioid receptors into the thalamic submedius (Sm) nucleus on the formalin-induced orofacial pain. Two guide cannulas were implanted into the right and left sides of the Sm in ketamine- and xylazine-anesthetized rats. Orofacial formalin pain was induced by subcutaneous injection of a diluted formalin solution (50 μl, 1.5%) into the vibrissa pad. Face rubbing durations were recorded at 3-min blocks for 45 min. Formalin produced a biphasic pain response (first phase: 0-3 min and second phase: 15-33 min). Separate and combined microinjections of histamine H1 and H2 receptor agonists, 2-pyridylethylamine (2-PEA) and dimaprit, respectively, and opioid receptor agonist, morphine, attenuated the second phase of pain. The analgesic effects induced by 2-PEA, dimaprit, and morphine were blocked by prior microinjections of fexofenadine (a histamine H1 receptor antagonist), famotidine (a histamine H2 receptor antagonist), and naloxone (an opioid receptor antagonist), respectively. Naloxone also prevented 2-PEA- and dimaprit-induced antinociception, and the analgesic effect induced by morphine was inhibited by fexofenadine and famotidine. These results showed the involvement of histamine H1 and H2 and opioid receptors in the Sm modulation of orofacial pain. Opioid receptor might be involved in analgesia induced by activation of histamine H1 and H2 receptors and vice versa.

  13. Comparison of levocabastine, a new selective H1-receptor antagonist, and disodium cromoglycate, in a nasal provocation test with allergen.

    Science.gov (United States)

    Kolly, M; Pécoud, A

    1986-10-01

    The effect of intranasal administration of levocabastine, a new selective H1-receptor antagonist, was investigated in a nasal provocation test (NPT) performed with allergens. The NPT allowed a quantitative estimation of the nasal allergic threshold (concentration of allergen necessary to trigger the reaction). In addition, the intensity of the three major rhinitis symptoms (obstruction, rhinorrhea and sneezing) was determined. Twelve adult patients, allergic to grass pollen, underwent a first NPT without pretreatment ('initial NPT'); the NPT was then repeated after the single intranasal administration of either placebo, 8 mg disodium cromoglycate (DSCG) or 0.2 mg levocabastine in a double-blind random order. The NPTs gave reproducible results since both the threshold and symptom intensities were similar in the initial NPT and in the NPT performed after placebo. The reaction threshold increased in 8/12 patients after DSCG (0.05 less than P less than 0.1) and in 9/12 patients after levocabastine (P less than 0.05). Levocabastine clearly inhibited rhinorrhea (P less than 0.001) and sneezing (P less than 0.02) but did not influence the nasal obstruction. DSCG inhibited rhinorrhea only (P less than 0.01). The intranasal administration of levocabastine might be useful in the treatment of allergic rhinitis.

  14. HPLC method development, validation and its application to investigate in vitro effect of pioglitazone on the availability of H1 receptor antagonists

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    Agha Zeeshan Mirza

    2017-02-01

    Full Text Available The method has been developed and validated for the simultaneous determination of pioglitazone and H1-receptor antagonists (fexofenadine, cetirizine and levocetirizine in formulations and human serum. Utilizing HPLC techniques, an assay was designed to determine the in vitro effects of pioglitazone on H1-receptor antagonists. Obtained results were verified using the UV spectrophotometric technique. First-derivative values versus concentrations were used to plot calibration curves of these drugs and were found to similar with the HPLC data. The availability of pioglitazone remained unchanged in absence or presence of fexofenadine, cetirizine and levocetirizine. This in vitro analysis confirms the harmless co-administration of pioglitazone and H1-receptor antagonists, and can serve as the foundation for designing further in vivo studies.

  15. Selective potentiation of histamine H1-receptor stimulated calcium responses by 1,4-dithiothreitol in DDT1MF-2 cells.

    Science.gov (United States)

    Dickenson, J M; Hill, S J

    1994-11-01

    The effect of 1,4-dithiothreitol (DTT) on agonist-stimulated increases in intracellular free calcium concentration ([Ca2+]i) has been investigated in the smooth muscle cell line, DDT1MF-2, derived from hamster vas deferens. Pretreatment with DTT (1 mM) produced a large leftward parallel shift in concentration-response curve for histamine H1-receptor mediated increases in [Ca2+]i. The EC50 values for H1-receptor stimulated increases in [Ca2+]i in the absence and presence of DTT were 11.3 +/- 1.5 microM (N = 6) and 0.52 +/- 0.15 microM (N = 6), respectively. DTT had no significant effect on the maximum Ca2+ response elicited by histamine (100 microM). In the presence of DTT the partial H1-receptor agonist 2-pyridylethylamine (100 microM) increased [Ca2+]i from 112 +/- 14 nM to 237 +/- 24 nM (N = 10). In control cells 2-pyridylethylamine (100 microM) did not elicit a Ca2+ response. DTT had no significant effect on the maximum Ca2+ response elicited by 1 mM 2-pyridylethylamine. The enhancement of histamine H1-receptor Ca2+ responses by DTT was reversed by the sulphydryl oxidizing agent dithiobis-(2-nitrobenzoic acid). DTT had no significant effect on adenosine A1-, bradykinin and ATP-receptor stimulated increases in [Ca2+]i. [3H]mepyramine binding experiments confirmed that DTT increased agonist affinity. DTT produced a small, but significant, leftward shift in concentration-response curve for histamine displacement of [3H]mepyramine binding. These data suggest that DTT potentiates H1-receptor mediated Ca2+ responses by increasing agonist affinity.

  16. Effects of administration of histamine and its H1, H2, and H3 receptor antagonists into the primary somatosensory cortex on inflammatory pain in rats

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    Esmaeal Tamaddonfard

    2014-01-01

    These results indicate that at PSC levels, histamine through post-synaptic H1, H2, and pre-synaptic H3 receptors might be involved in pain modulation. The endogenous opioid system may be involved in histamine- and thioperamide-induced antinociception.

  17. Rupatadine effectively prevents the histamine-induced up regulation of histamine H1R and bradykinin B2R receptor gene expression in the rat paw.

    Science.gov (United States)

    Molyva, Dimitra; Kalokasidis, Konstantinos; Poulios, Christos; Dedi, Hara; Karkavelas, George; Mirtsou, Vassiliki; Goulas, Antonis

    2014-12-01

    Activation of histamine H1 receptor (H1R) is a well-known hallmark of allergic and inflammatory pathology. Both types of bradykinin receptors (B1R and B2R) are also known to contribute significantly to the latter and some sort of functional interaction between them and H1R has been alluded to in the past. Here we use an experimental model of rat paw oedema formation to examine the effect of exogenously added histamine on the gene expression of H1R and bradykinin receptors B1R and B2R, alone or in combination to rupatadine, a second generation antihistamine agent. Histamine-induced oedema formation was monitored with a plethysmometer. The gene expression of H1R, B1R and B2R was analyzed with both conventional and real-time PCR. Rupatadine fumarate was used in pure form and administered intraperitoneally, prior to histamine injection into the paw. Microscopy of haematoxylin and eosin-stained sections of paw tissue was used to examine effects on tissue architecture. Histamine injection into the paw resulted in significant up regulation of H1R and B2R without inducing significant cellular infiltration, but appears to affect less the expression of B1R. Rupatadine was, under the conditions used in this study, very effective in preventing this effect and in suppressing oedema formation through its antihistamine action. Rupatadine has a suppressing effect on H1R and B2R gene expression which could add to its efficacy towards allergy and allergy-like conditions. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. 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.

  19. Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication.

    Science.gov (United States)

    Vehof, Jelle; Risselada, Arne J; Al Hadithy, Asmar F Y; Burger, Huibert; Snieder, Harold; Wilffert, Bob; Arends, Johan; Wunderink, Lex; Knegtering, Henrikus; Wiersma, Durk; Cohen, Dan; Mulder, Hans; Bruggeman, Richard

    2011-07-01

    Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c). We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor. A significant association of interaction between haplotype rs346074-rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants. This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics.

  20. Histamine H1 and H4 receptor expression on the ocular surface of patients with chronic allergic conjunctival diseases.

    Science.gov (United States)

    Inada, Noriko; Shoji, Jun; Shiraki, Yukiko; Aso, Hiroshi; Yamagami, Satoru

    2017-10-01

    This study investigated the histamine H1 and H4 receptors mRNA (H1R and H4R, respectively) expression on the ocular surface of patients with chronic forms of allergic conjunctival diseases to determine whether they can serve as biomarkers for allergic inflammation in the conjunctiva. We examined 19 patients with vernal or atopic keratoconjunctivitis (AKC/VKC group) and 15 healthy volunteers (control group). The AKC/VKC group was divided into active and stable stage subgroups. Specimens were obtained from the upper tarsal conjunctiva of each participant using a modified impression cytology method. H1R, H4R, and eotaxin-1, -2, and -3 mRNA (eotaxin-1, eotaxin-2, eotaxin-3, respectively) expression was determined by real-time RT-PCR. Immunohistochemical analysis for eosinophil cationic protein (ECP), eosinophil major basic protein (MBP), eotaxin-2, and histamine H4 receptor (H4R) were performed using conjunctival smears. The number of H4R-positive patients was higher in the active than the stable stage subgroup and control group, whereas no difference was observed for H1R. H1R levels were higher in the active than in the stable stage subgroup, while those of H4R were higher in the active stage subgroup than in the control group. H1R and H4R levels were correlated with eotaxin-2 level. In immunohistochemical analysis, H4R revealed their expression on eosinophils in conjunctival smears of patients with AKC/VKC. H4R is useful as biomarkers of allergic inflammation on ocular surfaces. Most notably, H4R expressed on eosinophils is useful as a biomarker of eosinophilic inflammation of the ocular surface. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  1. Endogenous expression of histamine H1 receptors functionally coupled to phosphoinositide hydrolysis in C6 glioma cells: regulation by cyclic AMP.

    OpenAIRE

    Peakman, M C; Hill, S. J.

    1994-01-01

    1. The effects of histamine receptor agonists and antagonists on phospholipid hydrolysis in rat-derived C6 glioma cells have been investigated. 2. Histamine H1 receptor-stimulation caused a concentration-dependent increase in the accumulation of total [3H]-inositol phosphates in cells prelabelled with [3H]-myo-inositol. The rank order of agonist potencies was histamine (EC50 = 24 microM) > N alpha-methylhistamine (EC50 = 31 microM) > 2-thiazolylethylamine (EC50 = 91 microM). 3. The response t...

  2. Endogenous expression of histamine H1 receptors functionally coupled to phosphoinositide hydrolysis in C6 glioma cells: regulation by cyclic AMP.

    Science.gov (United States)

    Peakman, M C; Hill, S J

    1994-12-01

    1. The effects of histamine receptor agonists and antagonists on phospholipid hydrolysis in rat-derived C6 glioma cells have been investigated. 2. Histamine H1 receptor-stimulation caused a concentration-dependent increase in the accumulation of total [3H]-inositol phosphates in cells prelabelled with [3H]-myo-inositol. The rank order of agonist potencies was histamine (EC50 = 24 microM) > N alpha-methylhistamine (EC50 = 31 microM) > 2-thiazolylethylamine (EC50 = 91 microM). 3. The response to 0.1 mM histamine was antagonized in a concentration-dependent manner by the H1-antagonists, mepyramine (apparent Kd = 1 nM) and (+)-chlorpheniramine (apparent Kd = 4 nM). In addition, (-)-chlorpheniramine was more than two orders of magnitude less potent than its (+)-stereoisomer. 4. Elevation of intracellular cyclic AMP accumulation with forskolin (10 microM, EC50 = 0.3 microM), isoprenaline (1 microM, EC50 = 4 nM) or rolipram (0.5 mM), significantly reduced the histamine-mediated (0.1 mM) inositol phosphate response by 37%, 43% and 26% respectively. In contrast, 1,9-dideoxyforskolin did not increase cyclic AMP accumulation and had no effect on the phosphoinositide response to histamine. 5. These data indicate the presence of functionally coupled, endogenous histamine H1 receptors in C6 glioma cells. Furthermore, the results also indicate that H1 receptor-mediated phospholipid hydrolysis is inhibited by the elevation of cyclic AMP levels in these cells.

  3. Differential thermodynamic driving force of first- and second-generation antihistamines to determine their binding affinity for human H1 receptors.

    Science.gov (United States)

    Hishinuma, Shigeru; Sugawara, Kenta; Uesawa, Yoshihiro; Fukui, Hiroyuki; Shoji, Masaru

    2014-09-15

    Differential binding sites for first- and second-generation antihistamines were indicated on the basis of the crystal structure of human histamine H1 receptors. In this study, we evaluated differences between the thermodynamic driving forces of first- and second-generation antihistamines for human H1 receptors and their structural determinants. The binding enthalpy and entropy of 20 antihistamines were estimated with the van't Hoff equation using their dissociation constants obtained from their displacement curves against the binding of [(3)H]mepyramine to membrane preparations of Chinese hamster ovary cells expressing human H1 receptors at various temperatures from 4°C to 37°C. Structural determinants of antihistamines for their thermodynamic binding properties were assessed by quantitative structure-activity relationship (QSAR) analyses. We found that entropy-dependent binding was more evident in second- than first-generation antihistamines, resulting in enthalpy-entropy compensation between the binding forces of first- and second-generation antihistamines. QSAR analyses indicated that enthalpy-entropy compensation was determined by the sum of degrees, maximal electrostatic potentials, water-accessible surface area and hydrogen binding acceptor count of antihistamines to regulate their affinity for receptors. In conclusion, it was revealed that entropy-dependent hydrophobic interaction was more important in the binding of second-generation antihistamines, even though the hydrophilicity of second-generation antihistamines is generally increased. Furthermore, their structural determinants responsible for enthalpy-entropy compensation were explored by QSAR analyses. These findings may contribute to understanding the fundamental mechanisms of how the affinity of ligands for their receptors is regulated. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

    Directory of Open Access Journals (Sweden)

    K.R. Serafim

    2013-05-01

    Full Text Available This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2 protocol in an elevated plus-maze (EPM. Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL, 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist, or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist. After 40 min, they were subjected to the EPM test. In T2 (24 h later, each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE and open arm time (%OAT. However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

  5. Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia

    NARCIS (Netherlands)

    Lavalaye, J.; Linszen, D. H.; Booij, J.; Reneman, L.; Gersons, B. P.; van Royen, E. A.

    1999-01-01

    A crucial characteristic of antipsychotic medication is the occupancy of the dopamine (DA) D2 receptor. We assessed striatal DA D2 receptor occupancy by olanzapine and risperidone in 36 young patients [31 males, 5 females; mean age 21.1 years (16-28)] with first episode schizophrenia, using

  6. 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.

  7. Rupatadine: a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. A review of pharmacological profile and clinical management of allergic rhinitis.

    Science.gov (United States)

    Izquierdo, Iñaki; Merlos, Manuel; García-Rafanell, Julián

    2003-06-01

    Rupatadine is a new agent for the management of diseases with allergic inflammatory conditions, such as seasonal and perennial rhinitis. The pharmacological profile of rupatadine offers particular benefits in terms of a strong antagonist activity towards both histamine H1 receptors and platelet-activating factor (PAF) receptors. Rupatadine has a rapid onset of action, and its long-lasting effect (>24 h) permits once-daily dosing. Rupatadine should not be used in combination with the cytochrome P450 inhibitors, such as erythromycin or ketoconazole, due to an increase in AUC and Cmax for rupatadine, although no clinically relevant adverse events have been reported. In addition, rupatadine, at the recommended dose of 10 mg, has been shown to be free of sedative effects and not to cause significant changes in the corrected QT interval in special populations, including the elderly, nor when coadministered with erythromycin or ketoconazole. Preclinical data have also shown that rupatadine and its main active metabolites did not interfere with cloned human HERG channel and did not affect in vitro isolated dog Purkinje fibers at concentrations at least 2000 times greater than those obtained with therapeutic doses in humans. Rupatadine is clinically effective in relieving symptoms in patients with seasonal and perennial allergic rhinitis. Newly published data on its efficacy and safety suggest that this compound may improve the nasal and non-nasal symptoms in comparison to other currently available second generation H1 receptor antihistamines. 2003 Prous Science. All rights reserved.

  8. 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 (H1 , H2 , and H3 ). 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 EC50 of 1.3 µM, but failed to significantly alter sIPSC amplitude. HA-induced increases in sIPSC frequency were sensitive to tetrodotoxin (TTX), required extracellular Ca2+ , 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 H1 and H2 receptors were involved in HA-induced increases in sIPSCs and interneuron excitability. Immunohistochemical staining showed that both H1 and H2 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.

  9. Proton pump inhibitor use and fracture risk - effect modification by histamine H1 receptor blockade. Observational case-control study using National Prescription Data.

    Science.gov (United States)

    Abrahamsen, Bo; Vestergaard, Peter

    2013-11-01

    It remains unknown why proton pump inhibitor (PPI) use may be associated with risk of osteoporotic fractures; evidence of direct effects on calcium absorption or on the osteoclast in humans is weak or absent. However, the ensuing increased gastrin levels may cause histamine production through hypertrophy of gastric enterochromaffin like cells, which could lead to bone loss. We speculated that H1 receptor antagonists (H1RA) used for allergies would then reduce the effect of PPI on bone. We therefore conducted a register-based case-control study comprising 124,655 patients with hospital treated fractures, who were matched 3:1 with non fracture control subjects of the same age and gender. Use of prescription medications was retrieved from the National Prescription Database and data was analyzed using conditional logistic regression analysis. We observed a significant interaction between PPI and H1RA use on fracture risk in general (adjusted OR 0.92, 95% CI 0.87-0.98) though not on hip fracture risk (adjusted OR 0.99, 95% CI 0.85-1.16). There was a significant modification of the interaction by age (pfracture categories). As previously shown, fracture risk was higher in PPI users both for fractures in general and for hip fractures. Irrespective of PPI use, H1RA users had lower risk of hip fractures than non-users (adjusted OR 0.86, 95% CI 0.79-0.93). This short report suggests that the effects of PPI on bone could be driven by in part by increased histamine release as the increased fracture risk can be modified by H1RA. © 2013.

  10. Synergistic Roles for Receptor Occupancy and Aggregation in Integrin Transmembrane Function

    Science.gov (United States)

    Miyamoto, Shingo; Akiyama, Steven K.; Yamada, Kenneth M.

    1995-02-01

    Integrin receptors mediate cell adhesion, signal transduction, and cytoskeletal organization. How a single transmembrane receptor can fulfill multiple functions was clarified by comparing roles of receptor occupancy and aggregation. Integrin occupancy by monovalent ligand induced receptor redistribution, but minimal tyrosine phosphorylation signaling or cytoskeletal protein redistribution. Aggregation of integrins by noninhibitory monoclonal antibodies on beads induced intracellular accumulations of pp125FAK and tensin, as well as phosphorylation, but no accumulation of other cytoskeletal proteins such as talin. Combining antibody-mediated clustering with monovalent ligand occupancy induced accumulation of seven cytoskeletal proteins, including α-actinin, talin, and F-actin, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides. Integrins therefore mediate a complex repertoire of functions through the distinct effects of receptor aggregation, receptor occupancy, or both together.

  11. In Silico Biology of H1N1: Molecular Modelling of Novel Receptors and Docking Studies of Inhibitors to Reveal New Insight in Flu Treatment

    Directory of Open Access Journals (Sweden)

    Deepak Kumar Behera

    2012-01-01

    Full Text Available Influenza is an infectious disease caused by RNA viruses of the family Orthomyxoviridae. The new influenza H1N1 viral stain has emerged by the genetic combination of genes from human, pig, and bird’s H1N1 virus. The influenza virus is roughly spherical and is enveloped by a lipid membrane. There are two glycoproteins in this lipid membrane; namely, hemagglutinin (HA which helps in attachment of the viral strain on the host cell surface and neuraminidase (NA that is responsible for initiation of viral infection. We have developed homology models of both Hemagglutinin and Neuraminidase receptors from H1N1 strains in eastern India. The docking studies of B-Sialic acid and O-Sialic acid in the optimized and energy-minimized homology models show important H-bonding interactions with ALA142, ASP230, GLN231, GLU232, and THR141. This information can be used for structure-based and pharmacophore-based new drug design. We have also calculated ADME properties (Human Oral Absorption (HOA and % HOA for Oseltamivir which have been subject of debate for long.

  12. Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI

    DEFF Research Database (Denmark)

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian

    2013-01-01

    This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3...... responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide...... a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system...

  13. Correlation of receptor occupancy of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse brain with in vivo activity of allosteric mGluR1 antagonists.

    Science.gov (United States)

    Suzuki, Gentaroh; Kawagoe-Takaki, Hiroko; Inoue, Takao; Kimura, Toshifumi; Hikichi, Hirohiko; Murai, Takashi; Satow, Akio; Hata, Mikiko; Maehara, Shunsuke; Ito, Satoru; Kawamoto, Hiroshi; Ozaki, Satoshi; Ohta, Hisashi

    2009-07-01

    The aim of this study was to clarify the relationship between receptor occupancy and in vivo pharmacological activity of mGluR1 antagonists. The tritiated mGluR1-selective allosteric antagonist [(3)H]FTIDC (4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide) was identified as a radioligand having high affinity for mGluR1-expressing CHO cells (K(D) = 2.1 nM) and mouse cerebellum (K(D) = 3.7 nM). [(3)H]FTIDC bound to mGluR1 was displaced by structurally unrelated allosteric antagonists, suggesting there is a mutual binding pocket shared with different allosteric antagonists. The binding specificity of [(3)H]FTIDC for mGluR1 in brain sections was demonstrated by the lack of significant binding to brain sections prepared from mGluR1-knockout mice. Ex vivo receptor occupancy with [(3)H]FTIDC revealed that the receptor occupancy level by FTIDC correlated well with FTIDC dosage and plasma concentration. Intracerebroventricular administration of (S)-3,5-dihydroxyphenylglycine is known to elicit face washing behavior that is mainly mediated by mGluR1. Inhibition of this behavioral change by FTIDC correlated with the receptor occupancy level of mGluR1 in the brain. A linear relationship between the receptor occupancy and in vivo activity was also demonstrated using structurally diverse mGluR1 antagonists. The receptor occupancy assays could help provide guidelines for selecting appropriate doses of allosteric mGluR1 antagonist for examining the function of mGluR1 in vivo.

  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.

    Science.gov (United States)

    Mizuguchi, Hiroyuki; Das, Asish K; Maeyama, Kazutaka; Dev, Shrabanti; Shahriar, Masum; Kitamura, Yoshiaki; Takeda, Noriaki; Fukui, Hiroyuki

    2016-04-01

    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. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  15. Impact of protein binding on receptor occupancy: A two-compartment model

    OpenAIRE

    Peletier, Lambertus A.; Benson, Neil; Van Der Graaf, Piet H.

    2010-01-01

    Abstract In this paper we analyse the impact of protein- and lipid- and receptor-binding on receptor occupancy in a two-compartment system, with proteins in both compartments and lipids and receptors in the peripheral compartment only. We do this for two manners of drug administration: a bolus administration and a constant rate infusion, both into the central compartment. We derive explicit approximations for the time-curves of the different compounds valid for a wide range of real...

  16. [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.

  17. Role of receptor occupancy assays by flow cytometry in drug development.

    Science.gov (United States)

    Stewart, Jennifer J; Green, Cherie L; Jones, Nicholas; Liang, Meina; Xu, Yuanxin; Wilkins, Danice E C; Moulard, Maxime; Czechowska, Kamila; Lanham, David; McCloskey, Thomas W; Ferbas, John; van der Strate, Barry W A; Högerkorp, Carl-Magnus; Wyant, Timothy; Lackey, Alan; Litwin, Virginia

    2016-03-01

    The measurement of the binding of a biotherapeutic to its cellular target, receptor occupancy (RO), is increasingly important in development of biologically-based therapeutic agents. Receptor occupancy (RO) assays by flow cytometry describe the qualitative and/or quantitative assessment of the binding of a therapeutic agent to its cell surface target. Such RO assays can be as simple as measuring the number of cell surface receptors bound by an antireceptor therapeutic agent or can be designed to address more complicated scenarios such as internalization or shedding events once a receptor engages the administered therapeutic agent. Data generated from RO assays can also be used to model whether given doses of an experimental therapeutic agent and their administration schedules lead to predicted levels of receptor occupancy and whether the receptor is modulated (up or down) on cells engaged by the therapeutic agent. There are a variety of approaches that can be used when undertaking RO assays and with the ability to measure distinct subsets in heterogeneous populations, flow cytometry is ideally suited to RO measurements. This article highlights the importance of RO assays on the flow cytometric platform in the development of biotherapeutic agents. © 2016 The Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc.

  18. Predicting dopamine D2 receptor occupancy in humans using a physiology-based approach

    NARCIS (Netherlands)

    Johnson, Martin; Kozielska, Magdalena; Pilla Reddy, Venkatesh; Vermeulen, An; Barton, Hugh A.; Grimwood, Sarah; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

    2011-01-01

    Objectives: A hybrid physiology-based pharmacokinetic and pharmacodynamic model (PBPKPD) was used to predict the time course of dopamine receptor occupancy (D2RO) in human striatum following the administration of antipsychotic (AP) drugs, using in vitro and in silico information. Methods: A hybrid

  19. Determination of receptor occupancy in the presence of mass dose: [(11)C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746.

    Science.gov (United States)

    Gallezot, Jean-Dominique; Planeta, Beata; Nabulsi, Nabeel; Palumbo, Donna; Li, Xiaoxi; Liu, Jing; Rowinski, Carolyn; Chidsey, Kristin; Labaree, David; Ropchan, Jim; Lin, Shu-Fei; Sawant-Basak, Aarti; McCarthy, Timothy J; Schmidt, Anne W; Huang, Yiyun; Carson, Richard E

    2017-03-01

    Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds "tracer" levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [(11)C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [(11)C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%-97% and 30%-93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%-15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

  20. Recent Methods for Measuring Dopamine D3 receptor Occupancy In Vivo: Importance for Drug Development

    Directory of Open Access Journals (Sweden)

    Bernard eLe Foll

    2014-07-01

    Full Text Available There is considerable interest in developing highly selective dopamine D3 receptor ligands for a variety of mental health disorders. Dopamine D3 receptors have been implicated in Parkinson’s Disease, schizophrenia, anxiety, depression, and substance use disorders. The most concrete evidence suggests a role for the D3 receptor in drug-seeking behaviors. D3 receptors are a subtype of D2 receptors, and traditionally the functional role of these two receptors has been difficult to differentiate. Over the past 10-15 years a number of compounds selective for D3 over D2 receptors have been developed. However, translating these findings into clinical research has been difficult as many of these compounds cannot be used in humans. Therefore, the functional data involving the D3 receptor in drug addiction mostly comes from preclinical studies. Recently, with the advent of [11C]-(+-PHNO, it has become possible to image D3 receptors in the human brain with increased selectivity and sensitivity. This is a significant innovation over traditional methods such as [11C]-raclopride that cannot differentiate between D2 and D3 receptors. The use of [11C]-(+-PHNO will allow for further delineation of the role of D3 receptors. Here, we review recent evidence that the role of the D3 receptor has functional importance and is distinct from the role of the D2 receptor. We then introduce the utility of analyzing [11C]-(+-PHNO binding by region of interest. This novel methodology can be used in preclinical and clinical approaches for the measurement of occupancy of both D3 and D2 receptors. Evidence that [11C]-(+-PHNO can provide insights into the function of D3 receptors in addiction is also presented.

  1. Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats.

    Science.gov (United States)

    Mizuguchi, Hiroyuki; Hatano, Masaya; Matsushita, Chiyo; Umehara, Hayato; Kuroda, Wakana; Kitamura, Yoshiyuki; Takeda, Noriaki; Fukui, Hiroyuki

    2008-12-01

    Antihistamines are effective for treatment of seasonal nasal allergy. Recently, prophylactic treatment with antihistamines in patients with pollinosis was reported to be more effective when started before the pollen season. The administration with antihistamines from 2 to 6 weeks before onset of the pollen season is recommended for management of allergic rhinitis in Japan. To determine the reason for the effectiveness of prophylactic treatment with antihistamines, the effects of repeated pre-treatment with antihistamines before provocation with toluene 2,4-diisocyanate (TDI) on their nasal allergy-like behavior and up-regulations of histamine H(1) receptors (H1R) and interleukin (IL)-4 mRNAs in their nasal mucosa were examined. Provocation with TDI induced sneezing and up-regulations of H1R and IL-4 mRNAs in the nasal mucosa of TDI-sensitized rats. Repeated pre-treatments with antihistamines including epinastine, olopatadine, or d-chlorpheniramine for 1 to 5 weeks before provocation with TDI suppressed TDI-induced sneezing and the up-regulations of H1R and IL-4 mRNAs in the nasal mucosa more than their administrations once or for 3 days before TDI provocation. Our data indicate that repeated pre-treatment with antihistamines before provocation with TDI is more effective than their single treatment in reducing nasal allergy-like behavior by causing additional suppression of up-regulations of H1R and IL-4 mRNAs in the nasal mucosa.

  2. Therapeutic window of dopamine D2/3 receptor occupancy to treat psychosis in Alzheimer's disease.

    Science.gov (United States)

    Reeves, Suzanne; McLachlan, Emma; Bertrand, Julie; Antonio, Fabrizia D; Brownings, Stuart; Nair, Akshay; Greaves, Suki; Smith, Alan; Taylor, David; Dunn, Joel; Marsden, Paul; Kessler, Robert; Howard, Robert

    2017-04-01

    See Caravaggio and Graff-Guerrero (doi:10.1093/awx023) for a scientific commentary on this article.Antipsychotic drugs, originally developed to treat schizophrenia, are used to treat psychosis, agitation and aggression in Alzheimer's disease. In the absence of dopamine D2/3 receptor occupancy data to inform antipsychotic prescribing for psychosis in Alzheimer's disease, the mechanisms underpinning antipsychotic efficacy and side effects are poorly understood. This study used a population approach to investigate the relationship between amisulpride blood concentration and central D2/3 occupancy in older people with Alzheimer's disease by combining: (i) pharmacokinetic data (280 venous samples) from a phase I single (50 mg) dose study in healthy older people (n = 20, 65-79 years); (ii) pharmacokinetic, 18F-fallypride D2/3 receptor imaging and clinical outcome data on patients with Alzheimer's disease who were prescribed amisulpride (25-75 mg daily) to treat psychosis as part of an open study (n = 28; 69-92 years; 41 blood samples, five pretreatment scans, 19 post-treatment scans); and (iii) 18F-fallypride imaging of an antipsychotic free Alzheimer's disease control group (n = 10, 78-92 years), to provide additional pretreatment data. Non-linear mixed effects modelling was used to describe pharmacokinetic-occupancy curves in caudate, putamen and thalamus. Model outputs were used to estimate threshold steady state blood concentration and occupancy required to elicit a clinically relevant response (>25% reduction in scores on delusions, hallucinations and agitation domains of the Neuropsychiatric Inventory) and extrapyramidal side effects (Simpson Angus Scale scores > 3). Average steady state blood levels were low (71 ± 30 ng/ml), and associated with high D2/3 occupancies (65 ± 8%, caudate; 67 ± 11%, thalamus; 52 ± 11%, putamen). Antipsychotic clinical response occurred at a threshold concentration of 20 ng/ml and D2/3 occupancies of 43% (caudate), 25% (putamen), 43

  3. Occupancy of pramipexole (Sifrol at cerebral dopamine D2/3 receptors in Parkinson's disease patients

    Directory of Open Access Journals (Sweden)

    Angela Deutschländer

    2016-01-01

    Full Text Available Whereas positron emission tomography (PET with the antagonist ligand [18F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [18F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0.7 mg p.d., and again at a later date, after withholding pramipexole 48–72 h (OFF-Sifrol; in that condition the serum pramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ˂ 0.01 occupancy at [18F]fallypride binding sites in globus pallidus (8% thalamus (9% and substantia nigra (19%, as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum.

  4. Novel fused pyrrole heterocyclic ring systems as structure analogs of LE 300: Synthesis and pharmacological evaluation as serotonin 5-HT(2A), dopamine and histamine H(1) receptor ligands.

    Science.gov (United States)

    Rostom, Sherif A F

    2010-02-01

    LE 300 represents a structurally novel type of antagonists acting preferentially at the dopamine D(1)/D(5 )receptors and the serotonin 5-HT(2A )receptor. This compound consists of a ten-membered central azecine ring fused to an indole ring on one side and a benzene moiety on the other side. To estimate the importance of the indole and / or phenyl moieties in this highly active benz-indolo-azecine, both rings were removed and replaced with a 1H-pyrrole counterpart. Accordingly, some new analogs of LE 300 namely, pyrrolo[2,3-g]indolizine, pyrrolo[3,2-a]quinolizine rings and their corresponding dimethylpyrrolo[2,3-d]azonine, and dimethylpyrrolo[2,3-d]azecine were synthesized to be evaluated for their activity at the 5-HT(2A) and dopamine D(1), D(2L), D(4), D(5) receptors in relation to LE 300. In addition, their activity at the H(1)-histamine receptors was also determined. The results suggested that the rigid pyrrolo[2,3-g]indolizine 7 and pyrrolo[3,2-a]quinolizine 8 analogs lacked biological activity in the adopted three bioassays. However, their corresponding flexible pyrrolo[2,3-d]azonine 11 and pyrrolo[2,3-d]azecine 12 derivatives revealed weak partial agonistic activity and weak antagonistic potency at the serotonin 5-HT(2A )and histamine H(1 )receptors, respectively. Meanwhile, they showed no affinity to any of the four utilized dopamine receptors. Variation in ring size did not contribute to a significant influence on the three tested bioactivities. Removal of the hydrophobic moiety (phenyl ring) and replacement of the indole moiety with a 1H-pyrrole counterpart led to a dramatic alteration in the profile of activity of such azecine-type compounds.

  5. 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......(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....... This is the first benzothiadiazine dioxide AMPApam to reach the nanomolar range....

  6. Threshold of Dopamine D2/3 Receptor Occupancy for Hyperprolactinemia in Older Patients With Schizophrenia.

    Science.gov (United States)

    Iwata, Yusuke; Nakajima, Shinichiro; Caravaggio, Fernando; Suzuki, Takefumi; Uchida, Hiroyuki; Plitman, Eric; Chung, Jun Ku; Mar, Wanna; Gerretsen, Philip; Pollock, Bruce G; Mulsant, Benoit H; Rajji, Tarek K; Mamo, David C; Graff-Guerrero, Ariel

    2016-12-01

    Although hyperprolactinemia carries a long-term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean ± SD age = 60.2 ± 6.7 years) taking olanzapine or risperidone. Subjects underwent [¹¹C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels. The relationship between prolactin levels and D2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests. Prolactin levels decreased following dose reduction (mean ± SD = 24.1 ± 30.2 ng/mL to 17.2 ± 15.1 ng/mL; P < .001). Prolactin levels were associated with female gender (β = .32, P = .006, vs male), antipsychotics (β = .23, P = .02, risperidone vs olanzapine), and D2/3R occupancy (β = .23, P = .04). Those with D2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers. Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects. ClinicalTrials.gov identifier: NCT00716755.

  7. Effect of zolpidem on miniature IPSCs and occupancy of postsynaptic GABAA receptors in central synapses.

    Science.gov (United States)

    Perrais, D; Ropert, N

    1999-01-15

    GABAA-mediated miniature IPSCs (mIPSCs) were recorded from layer V pyramidal neurons of the visual cortex using whole-cell patch-clamp recording in rat brain slices. At room temperature, the benzodiazepine site agonist zolpidem enhanced both the amplitude (to 138 +/- 26% of control value at 10 microM) and the duration (163 +/- 14%) of mIPSCs. The enhancement of mIPSC amplitude was not caused by an increase of the single-channel conductance of the postsynaptic receptors, as determined by peak-scaled non-stationary fluctuation analysis of mIPSCs. The effect of zolpidem on fast, synaptic-like (1 msec duration) applications of GABA to outside-out patches was also investigated. The EC50 for fast GABA applications was 310 microM. In patches, zolpidem enhanced the amplitude of currents elicited by subsaturating GABA applications (100-300 microM) but not by saturating applications (10 mM). The increase of mIPSC amplitude by zolpidem provides evidence that the GABAA receptors are not saturated during miniature synaptic transmission in the recorded cells. By comparing the facilitation induced by 1 microM zolpidem on outside-out patches and mIPSCs, we estimated the concentration of GABA seen by the postsynaptic GABAA receptors to be approximately 300 microM after single vesicle release. We have estimated a similar degree of receptor occupancy at room and physiological temperature. However, at 35 degreesC, zolpidem did not enhance the amplitude of mIPSCs or of subsaturating GABA applications on patches, implying that, in these neurons, zolpidem cannot be used to probe the degree of receptor occupancy at physiological temperature.

  8. Effect of Secondhand Smoke on Occupancy of Nicotinic Acetylcholine Receptors in Brain

    Science.gov (United States)

    Brody, Arthur L.; Mandelkern, Mark A.; London, Edythe D.; Khan, Aliyah; Kozman, Daniel; Costello, Matthew R.; Vellios, Evan E.; Archie, Meena M.; Bascom, Rebecca; Mukhin, Alexey G.

    2012-01-01

    Context Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. Objective To determine whether moderate SHS exposure results in brain α4β2* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and Participants Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (also known as 2-[18F]fluoro-A-85380, or 2-FA) were used to determine α4β2* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger’s seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure Changes induced by SHS in 2-FA specific binding volume of distribution as a measure of α4β2* nAChR occupancy. Results An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F1,22=42.5, P cars and other enclosed spaces. PMID:21536968

  9. Influence of combined thrombin stimulation, surface activation, and receptor occupancy on organization of GPIb/IX receptors on human platelets.

    Science.gov (United States)

    White, J G; Krumwiede, M; Cocking-Johnson, D; Escolar, G

    1994-09-01

    Down-regulation and clearance of as many as 60-80% of GPIb/IX receptors from exposed surfaces on thrombin-activated platelets to channels of the open canalicular system (OCS) is considered to be a fundamental mechanism regulating platelet adhesivity in vitro and in vivo. The present study has combined thrombin stimulation in suspension, surface activation on formvar grids, receptor occupancy by von Willebrand factor (vWF) and exposure to anti-vWF antibody in an effort to demonstrate the removal of GPIb/IX receptors from activated cells. Individually the stimuli failed to cause any change in the frequency of GPIb/IX receptors. Combined, the stimuli were no more effective than when each was used alone. The only way to cause GPIb/IX to move was to add anti-vWF to thrombin-activated platelets allowed to spread on formvar grids and covered with multimers of ristocetin-activated human or bovine vWF. Translocation of GPIb/IX-vWF-anti-vWF complexes from peripheral margins into caps over cell centres, however, did not clear the peripheral zone of vWF binding capacity. Exposure of capped platelets after fixation to a second incubation with vWF demonstrated as many multimers extending from the central cap to the peripheral margins as were seen on platelets exposed a single time to vWF. Antibodies to GPIb, but not to GPIIb/IIIA, prevented the second labelling by vWF. Down-regulation or clearance of GPIb/IX, in light of this study, does not appear to be a fundamental mechanism modulating platelet adhesivity.

  10. Human formyl peptide receptor ligand binding domain(s). Studies using an improved mutagenesis/expression vector reveal a novel mechanism for the regulation of receptor occupancy.

    Science.gov (United States)

    Perez, H D; Vilander, L; Andrews, W H; Holmes, R

    1994-09-09

    Recently, we reported the domain requirements for the binding of formyl peptide to its specific receptor. Based on experiments using receptor chimeras, we also postulated an importance for the amino-terminal domain of the receptor in ligand binding (Perez, H. D., Holmes, R., Vilander, L., Adams, R., Manzana, W., Jolley, D., and Andrews, W. H. (1993) J. Biol. Chem. 268, 2292-2295). We have begun to perform a detailed analysis of the regions within the formyl peptide receptor involved in ligand binding. To address the importance of the receptor amino-terminal domain, we substituted (or inserted) hydrophilic sequences within the amino-terminal domain, expressed the receptors, and determined their ability to bind ligand. A stretch of nine amino acids next to the initial methionine was identified as crucial for receptor occupancy. A peptide containing such a sequence specifically completed binding of the ligand to the receptor. Alanine screen mutagenesis of the second extracellular domain also identified amino acids involved in ligand binding as well as a disulfide bond (Cys98 to Cys176) crucial for maintaining the binding pocket. These studies provide evidence for a novel mechanism involved in regulation of receptor occupancy. Binding of the ligand induces conformational changes in the receptor that result in the apposition of the amino-terminal domain over the ligand, providing a lid to the binding pocket.

  11. Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine and diphenhydramine, measured by PET with 11C-doxepin

    National Research Council Canada - National Science Library

    Tashiro, Manabu; Duan, Xudong; Kato, Motohisa; Miyake, Masayasu; Watanuki, Shoichi; Ishikawa, Yoichi; Funaki, Yoshihito; Iwata, Ren; Itoh, Masatoshi; Yanai, Kazuhiko

    2008-01-01

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • `Bepotastine besilate' is a novel second-generation antihistamine developed in Japan and its antiallergic effects have already been demonstrated by various studies...

  12. Small mouse cholangiocytes proliferate in response to H1 histamine receptor stimulation by activation of the IP3/CaMK I/CREB pathway.

    Science.gov (United States)

    Francis, Heather; Glaser, Shannon; Demorrow, Sharon; Gaudio, Eugenio; Ueno, Yoshiyuki; Venter, Julie; Dostal, David; Onori, Paolo; Franchitto, Antonio; Marzioni, Marco; Vaculin, Shelley; Vaculin, Bradley; Katki, Khurshed; Stutes, Monique; Savage, Jennifer; Alpini, Gianfranco

    2008-08-01

    Cholangiopathies are characterized by the heterogeneous proliferation of different-sized cholangiocytes. Large cholangiocytes proliferate by a cAMP-dependent mechanism. The function of small cholangiocytes may depend on the activation of inositol trisphosphate (IP(3))/Ca(2+)-dependent signaling pathways; however, data supporting this speculation are lacking. Four histamine receptors exist (HRH1, HRH2, HRH3, and HRH4). In several cells: 1) activation of HRH1 increases intracellular Ca(2+) concentration levels; and 2) increased [Ca(2+)](i) levels are coupled with calmodulin-dependent stimulation of calmodulin-dependent protein kinase (CaMK) and activation of cAMP-response element binding protein (CREB). HRH1 agonists modulate small cholangiocyte proliferation by activation of IP(3)/Ca(2+)-dependent CaMK/CREB. We evaluated HRH1 expression in cholangiocytes. Small and large cholangiocytes were stimulated with histamine trifluoromethyl toluidide (HTMT dimaleate; HRH1 agonist) for 24-48 h with/without terfenadine, BAPTA/AM, or W7 before measuring proliferation. Expression of CaMK I, II, and IV was evaluated in small and large cholangiocytes. We measured IP(3), Ca(2+) and cAMP levels, phosphorylation of CaMK I, and activation of CREB (in the absence/presence of W7) in small cholangiocytes treated with HTMT dimaleate. CaMK I knockdown was performed in small cholangiocytes stimulated with HTMT dimaleate before measurement of proliferation and CREB activity. Small and large cholangiocytes express HRH1, CaMK I, and CaMK II. Small (but not large) cholangiocytes proliferate in response to HTMT dimaleate and are blocked by terfenadine (HRH1 antagonist), BAPTA/AM, and W7. In small cholangiocytes, HTMT dimaleate increased IP(3)/Ca(2+) levels, CaMK I phosphorylation, and CREB activity. Gene knockdown of CaMK I ablated the effects of HTMT dimaleate on small cholangiocyte proliferation and CREB activation. The IP(3)/Ca(2+)/CaMK I/CREB pathway is important in the regulation of small

  13. 20 CFR 655.700 - What statutory provisions govern the employment of H-1B, H-1B1, and E-3 nonimmigrants and how do...

    Science.gov (United States)

    2010-04-01

    ... issued H-1B visas— (i) 195,000 in fiscal year 2001; (ii) 195,000 in fiscal year 2002; (iii) 195,000 in... employment of H-1B, H-1B1, and E-3 nonimmigrants and how do employers apply for H-1B, H-1B1, and E-3 visas... Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as...

  14. Label-free Protein Detection Based on the Heat-Transfer Method--A Case Study with the Peanut Allergen Ara h 1 and Aptamer-Based Synthetic Receptors.

    Science.gov (United States)

    Peeters, Marloes; van Grinsven, Bart; Cleij, Thomas J; Jiménez-Monroy, Kathia Lorena; Cornelis, Peter; Pérez-Ruiz, Elena; Wackers, Gideon; Thoelen, Ronald; De Ceuninck, Ward; Lammertyn, Jeroen; Wagner, Patrick

    2015-05-20

    Aptamers are an emerging class of molecules that, because of the development of the systematic evolution of ligands by exponential enrichment (SELEX) process, can recognize virtually every target ranging from ions, to proteins, and even whole cells. Although there are many techniques capable of detecting template molecules with aptamer-based systems with high specificity and selectivity, they lack the possibility of integrating them into a compact and portable biosensor setup. Therefore, we will present the heat-transfer method (HTM) as an interesting alternative because this offers detection in a fast and low-cost manner and has the possibility of performing experiments with a fully integrated device. This concept has been demonstrated for a variety of applications including DNA mutation analysis and screening of cancer cells. To the best our knowledge, this is the first report on HTM-based detection of proteins, in this case specifically with aptamer-type receptors. For proof-of-principle purposes, measurements will be performed with the peanut allergen Ara h 1 and results indicate detection limits in the lower nanomolar regime in buffer liquid. As a first proof-of-application, spiked Ara h 1 solutions will be studied in a food matrix of dissolved peanut butter. Reference experiments with the quartz-crystal microbalance will allow for an estimate of the areal density of aptamer molecules on the sensor-chip surface.

  15. Dopamine D2 Receptor Occupancy as a Predictor of Catalepsy in Rats : A Pharmacokinetic-Pharmacodynamic Modeling Approach

    NARCIS (Netherlands)

    Johnson, Martin; Kozielska, Magdalena; Reddy, Venkatesh Pilla; Vermeulen, An; Barton, Hugh A.; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    2014-01-01

    Objectives Dopamine D-2 receptor occupancy (D2RO) is the major determinant of efficacy and safety in schizophrenia drug therapy. Excessive D2RO (>80%) is known to cause catalepsy (CAT) in rats and extrapyramidal side effects (EPS) in human. The objective of this study was to use pharmacokinetic and

  16. Nonsteroidal selective glucocorticoid modulators: the effect of C-10 substitution on receptor selectivity and functional potency of 5-allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines.

    Science.gov (United States)

    Kym, Philip R; Kort, Michael E; Coghlan, Michael J; Moore, Jimmie L; Tang, Rui; Ratajczyk, James D; Larson, Daniel P; Elmore, Steven W; Pratt, John K; Stashko, Michael A; Falls, H Douglass; Lin, Chun W; Nakane, Masake; Miller, Loan; Tyree, Curtis M; Miner, Jeffery N; Jacobson, Peer B; Wilcox, Denise M; Nguyen, Phong; Lane, Benjamin C

    2003-03-13

    The preparation and characterization of a series of C-10 substituted 5-allyl-2,5-dihydro-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines as a novel class of selective ligands for the glucocorticoid receptor is described. Substitution at the C-10 position of the tetracyclic core with linear, two-atom appendages (OCH(3), OCF(2)H, NHMe, SMe, CH=CH(2), Ctbd1;CH, CH(2)OH) provided molecules of high affinity (K(i) = 2-8 nM) for the human glucocorticoid receptor (hGR) with limited cross-reactivity with other steroid receptors (PR, MR, AR, ER). Optimal analogues showed slightly less potent but highly efficacious E-selectin repression with reduced levels of GRE activation efficacy in reporter gene assays relative to prednisolone. Preliminary SAR of analogues containing substitution at the C-9 and C-10 positions identified the 9-OH, 10-OMe analogue 50 and the 9-OH, 10-Cl analogue 58 as compounds that demonstrated potent, GR-mediated inhibition in a conconavalin A stimulated T-cell proliferation assay in both rodent and human whole blood monocytes. When evaluated for their in vivo effects in carrageenan-induced paw edema in rats, 50, 58, and 10-OCF(2)H analogue 35 showed dose-dependent anti-inflammatory effects (50, ED(50) = 16 mg/kg; 58, ED(50) = 15 mg/kg; 35, ED(50) = 21 mg/kg vs ED(50) = 15 mg/kg for 18 and ED(50) = 4 mg/kg for prednisolone).

  17. Transient receptor potential genes, smoking, occupational exposures and cough in adults

    Directory of Open Access Journals (Sweden)

    Smit Lidwien AM

    2012-03-01

    Full Text Available Abstract Background Transient receptor potential (TRP vanilloid and ankyrin cation channels are activated by various noxious chemicals and may play an important role in the pathogenesis of cough. The aim was to study the influence of single nucleotide polymorphisms (SNPs in TRP genes and irritant exposures on cough. Methods Nocturnal, usual, and chronic cough, smoking, and job history were obtained by questionnaire in 844 asthmatic and 2046 non-asthmatic adults from the Epidemiological study on the Genetics and Environment of Asthma (EGEA and the European Community Respiratory Health Survey (ECRHS. Occupational exposures to vapors, gases, dusts, and/or fumes were assessed by a job-exposure matrix. Fifty-eight tagging SNPs in TRPV1, TRPV4, and TRPA1 were tested under an additive model. Results Statistically significant associations of 6 TRPV1 SNPs with cough symptoms were found in non-asthmatics after correction for multiple comparisons. Results were consistent across the eight countries examined. Haplotype-based association analysis confirmed the single SNP analyses for nocturnal cough (7-SNP haplotype: p-global = 4.8 × 10-6 and usual cough (9-SNP haplotype: p-global = 4.5 × 10-6. Cough symptoms were associated with exposure to irritants such as cigarette smoke and occupational exposures (p TRPV1 further increased the risk of cough symptoms from irritant exposures in asthmatics and non-asthmatics (interaction p Conclusions TRPV1 SNPs were associated with cough among subjects without asthma from two independent studies in eight European countries. TRPV1 SNPs may enhance susceptibility to cough in current smokers and in subjects with a history of workplace exposures.

  18. Changes in gene expression induced by histamine, fexofenadine and osthole: Expression of histamine H1 receptor, COX-2, NF-κB, CCR1, chemokine CCL5/RANTES and interleukin-1β in PBMC allergic and non-allergic patients.

    Science.gov (United States)

    Kordulewska, Natalia Karolina; Kostyra, Elżbieta; Cieślińska, Anna; Matysiewicz, Michał; Fiedorowicz, Ewa; Sienkiewicz-Szłapka, Edyta

    2017-03-01

    Fexofenadine (FXF) is a third-generation antihistamine drug and osthole is assumed as a natural antihistamine alternative. This paper compares results of histamine, FXF and osthole impact on HRH-1, COX-2, NF-κB-p50, CCR1 mRNA expression. We also measured mRNA expression of IL-1β and CCL5/RANTES in incubated peripheral blood mononuclear cells (PBMC) to compared how histamine, FXF and osthole had influence on expression level and interacts on product secretion. The purpose was to investigate expression pattern in asthma PBMC. The cultures were treated 72h with FXF and osthole. We measured mRNA expression of histamine HRH-1, COX-2, NF-κB-p50, CCR1, IL-1β and CCL5/RANTES with Real-Time PCR (RT-PCR). The present study suggest that osthole may be a potential inhibitor of histamine H1 receptor activity. We also demonstrated that cells cultured with histamine increase COX-2 mRNA expression and osthole reduce it. Allergy remains one of the most common chronic diseases in Europe and it is rapidly approaching epidemic proportions; with current predictions estimating that the number of allergy-afflicted will equal the healthy population by 2020. It is therefore paramount to find new pharmaceuticals which successfully combat allergic disease. Copyright © 2016 Elsevier GmbH. All rights reserved.

  19. H-1 Upgrades (4BW/4BN) (H-1 Upgrades)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-101 H-1 Upgrades (4BW/4BN) (H-1 Upgrades) As of FY 2017 President’s Budget Defense...5 Mission and Description 6 Executive Summary 7 Threshold Breaches 8 Schedule 9 Performance 11 Track to Budget 16 Cost and...Funding 17 Low Rate Initial Production 26 Foreign Military Sales 27 Nuclear Costs 27 Unit Cost 28 Cost Variance 31 Contracts

  20. Activation of A1-adenosine receptors promotes leukocyte recruitment to the lung and attenuates acute lung injury in mice infected with influenza A/WSN/33 (H1N1) virus.

    Science.gov (United States)

    Aeffner, Famke; Woods, Parker S; Davis, Ian C

    2014-09-01

    We have shown that bronchoalveolar epithelial A1-adenosine receptors (A1-AdoR) are activated in influenza A virus-infected mice. Alveolar macrophages and neutrophils also express A1-AdoRs, and we hypothesized that activation of A1-AdoRs on these cells will promote macrophage and neutrophil chemotaxis and activation and thereby play a role in the pathogenesis of influenza virus-induced acute lung injury. Wild-type (WT) C57BL/6 mice, congenic A1-AdoR knockout (A1-KO) mice, and mice that had undergone reciprocal bone marrow transfer were inoculated intranasally with 10,000 PFU/mouse influenza A/WSN/33 (H1N1) virus. Alternatively, WT mice underwent daily treatment with the A1-AdoR antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) from 1 day prior to inoculation. Infection increased bronchoalveolar lining fluid (BALF) adenosine comparably in WT and A1-KO mice. Infection of WT mice resulted in reduced carotid arterial O2 saturation (hypoxemia), lung pathology, pulmonary edema, reduced lung compliance, increased basal airway resistance, and hyperresponsiveness to methacholine. These effects were absent or significantly attenuated in A1-KO mice. Levels of BALF leukocytes, gamma interferon (IFN-γ), and interleukin 10 (IL-10) were significantly reduced in infected A1-KO mice, but levels of KC, IP-10, and MCP-1 were increased. Reciprocal bone marrow transfer resulted in WT-like lung injury severity, but BALF leukocyte levels increased only in WT and A1-KO mice with WT bone barrow. Hypoxemia, pulmonary edema, and levels of BALF alveolar macrophages, neutrophils, IFN-γ, and IL-10 were reduced in DPCPX-treated WT mice. Levels of viral replication did not differ between mouse strains or treatment groups. These findings indicate that adenosine activation of leukocyte A1-AdoRs plays a significant role in their recruitment to the infected lung and contributes to influenza pathogenesis. A1-AdoR inhibitor therapy may therefore be beneficial in patients with influenza virus

  1. Recent methods for measuring dopamine D3 receptor occupancy in vivo: importance for drug development

    National Research Council Canada - National Science Library

    Le Foll, Bernard; Wilson, Alan A; Graff, Ariel; Boileau, Isabelle; Di Ciano, Patricia

    2014-01-01

    .... The most concrete evidence suggests a role for the D3 receptor in drug-seeking behaviors. D3 receptors are a subtype of D2 receptors, and traditionally the functional role of these two receptors has been difficult to differentiate...

  2. Relationship between Dose, Drug Levels, and D2 Receptor Occupancy for the Atypical Antipsychotics Risperidone and Paliperidone

    Science.gov (United States)

    Votaw, J. R.; Ritchie, J.; Howell, L. L.

    2012-01-01

    Blockade of D2 family dopamine receptors (D2Rs) is a fundamental property of antipsychotics, and the degree of striatal D2R occupancy has been related to antipsychotic and motor effects of these drugs. Recent studies suggest the D2R occupancy of antipsychotics may differ in extrastriatal regions compared with the dorsal striatum. We studied this issue in macaque monkeys by using a within-subjects design. [18F]fallypride positron emission tomography scans were obtained on four different doses of risperidone and paliperidone (the 9-OH metabolite of risperidone) and compared with multiple off-drug scans in each animal. The half-life of the two drugs in these monkeys was determined to be between 3 and 4 h, and drug was administered by a constant infusion through an intragastric catheter. The D2R occupancy of antipsychotic was determined in the caudate, putamen, ventral striatum, and four prefrontal and temporal cortical regions and was related to serum and cerebrospinal fluid drug levels. Repeated 2-week treatment with risperidone or paliperidone did not produce lasting changes in D2R binding potential in any region examined. As expected, D2R binding potential was highest in the caudate and putamen and was approximately one-third that level in the ventral striatum and 2% of that level in the cortical regions. We found dose-dependent D2R occupancy for both risperidone and paliperidone in both basal ganglia and cortical regions of interest. We could not find evidence of regional variation in D2R occupancy of either drug. Comparison of D2R occupancy and serum drug levels supports a target of 40 to 80 ng/ml active drug for these two atypical antipsychotics. PMID:22214649

  3. ITI-007 demonstrates brain occupancy at serotonin 5-HT₂A and dopamine D₂ receptors and serotonin transporters using positron emission tomography in healthy volunteers.

    Science.gov (United States)

    Davis, Robert E; Vanover, Kimberly E; Zhou, Yun; Brašić, James R; Guevara, Maria; Bisuna, Blanca; Ye, Weiguo; Raymont, Vanessa; Willis, William; Kumar, Anil; Gapasin, Lorena; Goldwater, D Ronald; Mates, Sharon; Wong, Dean F

    2015-08-01

    Central modulation of serotonin and dopamine underlies efficacy for a variety of psychiatric therapeutics. ITI-007 is an investigational new drug in development for treatment of schizophrenia, mood disorders, and other neuropsychiatric disorders. The purpose of this study was to determine brain occupancy of ITI-007 at serotonin 5-HT2A receptors, dopamine D2 receptors, and serotonin transporters using positron emission tomography (PET) in 16 healthy volunteers. Carbon-11-MDL100907, carbon-11-raclopride, and carbon-11-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) (carbon-11-DASB) were used as the radiotracers for imaging 5-HT2A receptors, D2 receptors, and serotonin transporters, respectively. Brain regions of interest were outlined using magnetic resonance tomography (MRT) with cerebellum as the reference region. Binding potentials were estimated by fitting a simplified reference tissue model to the measured tissue-time activity curves. Target occupancy was expressed as percent change in the binding potentials before and after ITI-007 administration. Oral ITI-007 (10-40 mg) was safe and well tolerated. ITI-007 rapidly entered the brain with long-lasting and dose-related occupancy. ITI-007 (10 mg) demonstrated high occupancy (>80 %) of cortical 5-HT2A receptors and low occupancy of striatal D2 receptors (~12 %). D2 receptor occupancy increased with dose and significantly correlated with plasma concentrations (r (2) = 0.68, p = 0.002). ITI-007 (40 mg) resulted in peak occupancy up to 39 % of striatal D2 receptors and 33 % of striatal serotonin transporters. The results provide evidence for a central mechanism of action via dopaminergic and serotonergic pathways for ITI-007 in living human brain and valuable information to aid dose selection for future clinical trials.

  4. A computation of H1(Γ, H1(Σ))

    DEFF Research Database (Denmark)

    Villemoes, Rasmus

    Let Σ = Σg,1 be a compact surface of genus g at least 3 with one boundary component, Γ its mapping class group and M = H1(Σ, ℤ) the first integral homology of Σ. Using that Γ is generated by the Dehn twists in a collection of 2g+1 simple closed curves (Humphries' generators) and simple relations ...

  5. Insight into illness and its relationship to illness severity, cognition and estimated antipsychotic dopamine receptor occupancy in schizophrenia: An antipsychotic dose reduction study.

    Science.gov (United States)

    Gerretsen, Philip; Takeuchi, Hiroyoshi; Ozzoude, Miracle; Graff-Guerrero, Ariel; Uchida, Hiroyuki

    2017-05-01

    Little is known about the influence of D 2 receptor occupancy on impaired insight into illness (III)-a core feature of schizophrenia. III is associated with illness severity and cognitive dysfunction. Comparably, supratherapeutic D 2 receptor occupancy can impair cognition. However, it is unclear how illness severity, cognition, and D 2 receptor occupancy interact to influence III in schizophrenia. The aim of this study was to explore the influence of antipsychotic dose reduction on the relationships of illness severity and cognition to III. III was assessed at baseline and 28 weeks post-antipsychotic dose reduction in 16 participants with schizophrenia and plasma antipsychotic concentrations. III was assessed primarily with the Schedule for the Assessment of Insight-Japanese version, and secondarily with the Positive and Negative Syndrome Scale item G12. Correlation and regression analyses were performed to explore III's relationship to illness severity, cognition, and estimated D 2 receptor occupancy (Est.D 2 ). Cognition and Est.D 2 predicted III at baseline. At 28 weeks post-reduction, illness severity and Est.D 2 predicted III. Our findings suggest a complex relationship may exist among III, illness severity, cognition and Est.D 2 . At higher D 2 receptor occupancies, III is influenced by cognitive dysfunction, whereas, at lower occupancies, illness severity has a stronger effect on III. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. 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.

  7. Development of a population pharmacokinetic model to predict brain distribution and dopamine D2 receptor occupancy of raclopride in nonanesthetized rat

    NARCIS (Netherlands)

    Wong, Y.C.; Ilz, aut ikkova T.I.; Wijk, van R.C.; Hartman, R.J.; Lange, de E.C.M.

    2018-01-01

    BACKGROUND: Raclopride is a selective antagonist of the dopamine D2 receptor. It is one of the most frequently used in vivo D2 tracers (at low doses) for assessing drug-induced receptor occupancy (RO) in animals and humans. It is also commonly used as a pharmacological blocker (at high doses) to

  8. 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.

  9. 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.

    Science.gov (United States)

    Kitamura, Yoshiaki; Nakagawa, Hideyuki; Fujii, Tatsuya; Sakoda, Takema; Enomoto, Tadao; Mizuguchi, Hiroyuki; Fukui, Hiroyuki; Takeda, Noriaki

    2015-11-01

    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. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  10. Positive Allosteric Modulators of 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors Belonging to 4-Cyclopropyl-3,4-dihydro-2H-1,2,4-pyridothiadiazine Dioxides and Diversely Chloro-Substituted 4-Cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides

    DEFF Research Database (Denmark)

    Francotte, Pierre; Nørholm, Ann-Beth; Deva, Taru

    2014-01-01

    Two 4-ethyl-substituted pyridothiadiazine dioxides belonging to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulators were cocrystallized with the GluA2 ligand binding domain in order to decipher the impact of the position of the nitrogen atom...... on their binding mode at the AMPA receptors. The latter was found to be very similar to that of previously described benzothiadiazine-type AMPA receptor modulators. The affinity of the two compounds for the receptor was determined by isothermal titration calorimetry. Accordingly, the synthesis and biological...... evaluation of novel 4-cyclopropyl-substituted pyridothiadiazine dioxides was performed and completed with the synthesis of the corresponding chloro-substituted 4-cyclopropyl-3,4-dihydro-2H-benzothiadiazine 1,1-dioxides. The "8-aza" compound 32 was found to be the most potent pyridothiadiazine-type AMPA...

  11. Screening of allergic components mediated by H(1)R in homoharringtonine injection through H(1)R/CMC-HPLC/MS.

    Science.gov (United States)

    Guo, Ying; Han, Shengli; Cao, Jingjing; Liu, Qi; Zhang, Tao

    2014-12-01

    It has been reported that the histamine H1 receptor (H(1)R) gene is up-regulated in patients with allergic rhinitis and H(1)R expression level strongly correlates with the severity of allergy symptoms. Drugs for therapy should avoid allergy symptoms, especially for patients with over-expressed H(1)R. Therefore, screening of the components which could induce H(1)R activation is urgently needed for drug safety evaluation. Homoharringtonine injection is a preparation for acute nonlymphocytic leukemia, which is approved by China Food and Drug Administration (CFDA) and US Food and Drug Administration. However, severely adverse reactions often occur with intravenous injection of the preparation. In present study, an H(1)R/CMC model was applied for capturing membrane retained components which could induce H(1)R activation. Retention components were enriched and analyzed by H(1)R/CMC-HPLC/MS. Homoharringtonine was recognized, separated and identified in homoharringtonine injection. Ca(2+) flux assay and p-IP3R expression founded that homoharringtonine retained by the H1 R/CMC model increased phosphorylation of IP3R and promoted cytosolic free Ca(2+) elevation in a dose-dependent manner which further verified the activity of homoharringtonine in activating the H1 R. In conclusion, homoharringtonine was screened and identified as a potential allergic factor. This provides an indication that a patient with over-expressed H1 R should be aware of possible allergic reaction when applying homoharringtonine injection. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Evaluation of Antipsychotic Dose Reduction in Late-Life Schizophrenia: A Prospective Dopamine D2/3 Receptor Occupancy Study.

    Science.gov (United States)

    Graff-Guerrero, Ariel; Rajji, Tarek K; Mulsant, Benoit H; Nakajima, Shinichiro; Caravaggio, Fernando; Suzuki, Takefumi; Uchida, Hiroyuki; Gerretsen, Philip; Mar, Wanna; Pollock, Bruce G; Mamo, David C

    2015-09-01

    Patients with late-life schizophrenia (LLS) are highly susceptible to antipsychotic adverse effects. Treatment guidelines endorse lower antipsychotic doses. However, the optimal dose of antipsychotics and associated dopamine D2/3 receptor (D2/3R) occupancies remain largely unexplored in patients with LLS. To evaluate effects of antipsychotic dose reduction on striatal dopamine D2/3R occupancies, clinical variables, and blood pharmacokinetic measures in patients with LLS. An open-label, single-arm prospective study with a 3- to 6-month follow-up period (January 10, 2007, to October 21, 2013) was conducted at an academic tertiary care center with practice for ambulatory care. Participants included 35 outpatients with clinically stable LLS (patients aged ≥ 50 years receiving olanzapine or risperidone monotherapy at the same dose for 6 to 12 months). Follow-up was completed on October 21, 2013, and analysis was conducted from October 22, 2014, to February 2, 2015. Carbon 11-labeled raclopride positron emission tomography, clinical measures, and blood pharmacokinetic measures performed before and after gradual dose reduction by up to 40% from the baseline dose and at least 3 months after dose reduction. Striatal dopamine D2/3R occupancies with antipsychotics, clinical measures (Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Targeted Inventory on Problems in Schizophrenia, Simpson-Angus Scale, Barnes Rating Scale for Drug-Induced Akathisia, Udvalg for Kliniske Undersøgelser Side Effect Rating Scale), and blood pharmacokinetic measures (prolactin and antipsychotic blood levels). Dopamine D2/3R occupancy of the entire sample decreased by a mean (SD) of 6.2% (8.2%) following dose reduction (from 70% [12%] to 64% [12%]; P < .001). The lowest D2/3R occupancy associated with clinical stability was 50%. Extrapyramidal symptoms (EPSs) were more likely to occur with D2/3R occupancies higher than 60%: 90.5% (19 of 21) of the participants with

  13. Transient receptor potential genes, smoking, occupational exposures and cough in adults

    NARCIS (Netherlands)

    Smit, L.A.|info:eu-repo/dai/nl/311470882; Kogevinas, M.; Antó, J.; Bouzigon, E.; González, J.R.; Le Moual, N.; Kromhout, J.|info:eu-repo/dai/nl/074385224; Carsin, A.; Pin, I.; Jarvis, D.; Vermeulen, R.C.H.|info:eu-repo/dai/nl/216532620; Janson, C.; Heinrich, J.; Gut, I.; Lathrop, M.; Valverde, M.A.; Demenais, F.; Kauffmann, F.

    2012-01-01

    BACKGROUND: Transient receptor potential (TRP) vanilloid and ankyrin cation channels are activated by various noxious chemicals and may play an important role in the pathogenesis of cough. The aim was to study the influence of single nucleotide polymorphisms (SNPs) in TRP genes and irritant

  14. 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.

  15. Evaluation of [11C]Me-NB1 as a potential PET radioligand for measuring GluN2B-containing NMDA receptors, drug occupancy and receptor crosstalk.

    Science.gov (United States)

    Krämer, Stefanie D; Betzel, Thomas; Mu, Linjing; Haider, Ahmed; Herde Müller, Adrienne; Boninsegni, Anna K; Keller, Claudia; Szermerski, Marina; Schibli, Roger; Wünsch, Bernhard; Ametamey, Simon M

    2017-11-30

    Clinical and preclinical research with modulators binding to the NMDA receptor GluN2B N-terminal domain (NTD) aim for the treatment of various neurological diseases. However, the interpretation of the results is hampered by the lack of a suitable NMDA PET tracer for assessing the receptor occupancy of candidate drugs. We have developed [11C]Me-NB1 as a PET tracer for imaging GluN1/GluN2B-containing NMDA receptors and used it to investigate in rats the dose-dependent receptor occupancy of eliprodil, a GluN2B NTD modulator. Methods: [11C]Me-NB1 was synthesized and characterized by in vitro displacement binding experiments with rat brain membranes, in vitro autoradiography, blocking and displacement experiments by PET and PET kinetic modeling with an arterial input function. Receptor occupancy by eliprodil was studied in vivo by PET with [11C]Me-NB1. Results: [11C]Me-NB1 was synthesized at 290±90 GBq/µmol specific activity, 7.4±1.9 GBq total activity at the end of synthesis and >99% radiochemical purity. [11C]Me-NB1 binding in rat brain was blocked in vitro and in vivo by the NTD modulators Ro-25-6981 and eliprodil. In vivo, half maximal receptor occupancy by eliprodil occurred at 1.5 μg/kg. At 1 mg/kg eliprodil, a dose with reported neuroprotective effects, >99.5% binding sites were occupied. In vitro, [11C]Me‑NB1 binding was independent of sigma 1 receptor (Sigma1R) and the Sigma1R agonist (+)‑pentazocine did not compete for high affinity binding. In vivo, 2.5 mg/kg (+)‑pentazocine abolished [11C]Me-NB1 specific binding, indicating an indirect effect of Sigma1R on [11C]Me-NB1 binding. Conclusion: [11C]Me-NB1 is suitable for the in vivo imaging of NMDA GluN1/GluN2B receptors and the assessment of the receptor occupancy by NTD modulators. GluN1/GluN2B NMDA receptors are fully occupied at neuroprotective doses of eliprodil. Furthermore, [11C]Me-NB1 enables imaging of GluN1/GluN2B NMDA receptor crosstalk. Copyright © 2017 by the Society of Nuclear Medicine

  16. H1-antihistamines induce vacuolation in astrocytes through macroautophagy.

    Science.gov (United States)

    Hu, Wei-Wei; Yang, Ying; Wang, Zhe; Shen, Zhe; Zhang, Xiang-Nan; Wang, Guang-Hui; Chen, Zhong

    2012-04-15

    H1-antihistamines induce vacuolation in vascular smooth muscle cells, which may contribute to their cardiovascular toxicity. The CNS toxicity of H1-antihistamines may also be related to their non-receptor-mediated activity. The aim of this study was to investigate whether H1-antihistamines induce vacuolation in astrocytes and the mechanism involved. The H1-antihistamines induced large numbers of giant vacuoles in astrocytes. Such vacuoles were marked with both the lysosome marker Lysotracker Red and the alkalescent fluorescence dye monodansylcadaverine, which indicated that these vacuoles were lysosome-like acidic vesicles. Quantitative analysis of monodansylcadaverine fluorescence showed that the effect of H1-antihistamines on vacuolation in astrocytes was dose-dependent, and was alleviated by extracellular acidification, but aggravated by extracellular alkalization. The order of potency to induce vacuolation at high concentrations of H1-antihistamines (diphenhydramine>pyrilamine>astemizole>triprolidine) corresponded to their pKa ranking. Co-treatment with histamine and the histamine receptor-1 agonist trifluoromethyl toluidide did not inhibit the vacuolation. Bafilomycin A1, a vacuolar (V)-ATPase inhibitor, which inhibits intracellular vacuole or vesicle acidification, clearly reversed the vacuolation and intracellular accumulation of diphenhydramine. The macroautophagy inhibitor 3-methyladenine largely reversed the percentage of LC3-positive astrocytes induced by diphenhydramine, while only partly reversing the number of monodansylcadaverine-labeled vesicles. In Atg5⁻/⁻ mouse embryonic fibroblasts, which cannot form autophagosomes, the number of vacuoles induced by diphenhydramine was less than that in wild-type cells. These results indicated that H1-antihistamines induce V-ATPase-dependent acidic vacuole formation in astrocytes, and this is partly mediated by macroautophagy. The pKa and alkalescent characteristic of H1-antihistamines may be the major

  17. 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 ...

  18. H1-antihistamines induce vacuolation in astrocytes through macroautophagy

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Wei-Wei; Yang, Ying; Wang, Zhe; Shen, Zhe; Zhang, Xiang-Nan [Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058 (China); Wang, Guang-Hui [College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123 (China); Chen, Zhong, E-mail: chenzhong@zju.edu.cn [Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058 (China)

    2012-04-15

    H1-antihistamines induce vacuolation in vascular smooth muscle cells, which may contribute to their cardiovascular toxicity. The CNS toxicity of H1-antihistamines may also be related to their non-receptor-mediated activity. The aim of this study was to investigate whether H1-antihistamines induce vacuolation in astrocytes and the mechanism involved. The H1-antihistamines induced large numbers of giant vacuoles in astrocytes. Such vacuoles were marked with both the lysosome marker Lysotracker Red and the alkalescent fluorescence dye monodansylcadaverine, which indicated that these vacuoles were lysosome-like acidic vesicles. Quantitative analysis of monodansylcadaverine fluorescence showed that the effect of H1-antihistamines on vacuolation in astrocytes was dose-dependent, and was alleviated by extracellular acidification, but aggravated by extracellular alkalization. The order of potency to induce vacuolation at high concentrations of H1-antihistamines (diphenhydramine > pyrilamine > astemizole > triprolidine) corresponded to their pKa ranking. Co-treatment with histamine and the histamine receptor-1 agonist trifluoromethyl toluidide did not inhibit the vacuolation. Bafilomycin A1, a vacuolar (V)-ATPase inhibitor, which inhibits intracellular vacuole or vesicle acidification, clearly reversed the vacuolation and intracellular accumulation of diphenhydramine. The macroautophagy inhibitor 3-methyladenine largely reversed the percentage of LC3-positive astrocytes induced by diphenhydramine, while only partly reversing the number of monodansylcadaverine-labeled vesicles. In Atg5{sup −/−} mouse embryonic fibroblasts, which cannot form autophagosomes, the number of vacuoles induced by diphenhydramine was less than that in wild-type cells. These results indicated that H1-antihistamines induce V-ATPase-dependent acidic vacuole formation in astrocytes, and this is partly mediated by macroautophagy. The pKa and alkalescent characteristic of H1-antihistamines may be the

  19. Intracoronary eptifibatide bolus administration during percutaneous coronary revascularization for acute coronary syndromes with evaluation of platelet glycoprotein IIb/IIIa receptor occupancy and platelet function: the Intracoronary Eptifibatide (ICE) Trial.

    Science.gov (United States)

    Deibele, Albert J; Jennings, Lisa K; Tcheng, James E; Neva, Cathy; Earhart, Angela D; Gibson, C Michael

    2010-02-16

    Eptifibatide reduces major adverse cardiac events in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). Intracoronary bolus administration of eptifibatide may result in higher levels of platelet glycoprotein IIb/IIIa receptor occupancy in the local coronary bed, disaggregate thrombus in the epicardial artery and microvasculature, and thereby improve coronary flow. Patients undergoing PCI for an acute coronary syndrome were randomized to either intracoronary or intravenous bolus administration of eptifibatide. The primary end point was the local glycoprotein IIb/IIIa receptor occupancy measured in the coronary sinus. There were no angiographic, electrophysiological, or other adverse findings attributable to intracoronary eptifibatide. Platelet glycoprotein IIb/IIIa receptor occupancy was significantly greater with intracoronary versus intravenous administration: first bolus, 94+/-9% versus 51+/-15% (Peptifibatide during PCI in patients with acute coronary syndromes results in higher local platelet glycoprotein IIb/IIIa receptor occupancy, which is associated with improved microvascular perfusion demonstrated by an improved cTFC.

  20. Myastenia gravis following H1N1 infection

    OpenAIRE

    Silva, Horta e; Nascimento, A.; Zwolinski, N.; André, A.

    2016-01-01

    Introduction: Myasthenia gravis is an auto-immune disease, resulting from the production of anti-Ach receptor antibodies at the neuromuscular junction. In spite of its unknown etiology, there seems to exist some factors which withstand its arise and/or the worsening of the patient's clinical condition.The mainstay of medical treatment relies on anticholinesterase drugs and immunosuppression. Thymectomy is considered the treatment of choice in selected cases.Influenza A (H1N1) viral infection ...

  1. EBNA2 binds to genomic intervals associated with multiple sclerosis and overlaps with vitamin D receptor occupancy.

    Directory of Open Access Journals (Sweden)

    Vito A G Ricigliano

    Full Text Available Epstein-Barr virus (EBV is a non-heritable factor that associates with multiple sclerosis (MS. However its causal relationship with the disease is still unclear. The virus establishes a complex co-existence with the host that includes regulatory influences on gene expression. Hence, if EBV contributes to the pathogenesis of MS it may do so by interacting with disease predisposing genes. To verify this hypothesis we evaluated EBV nuclear antigen 2 (EBNA2, a protein that recent works by our and other groups have implicated in disease development binding inside MS associated genomic intervals. We found that EBNA2 binding occurs within MS susceptibility sites more than expected by chance (factor of observed vs expected overlap [O/E] = 5.392-fold, p < 2.0e-05. This remains significant after controlling for multiple genomic confounders. We then asked whether this observation is significant per se or should also be viewed in the context of other disease relevant gene-environment interactions, such as those attributable to vitamin D. We therefore verified the overlap between EBNA2 genomic occupancy and vitamin D receptor (VDR binding sites. EBNA2 shows a striking overlap with VDR binding sites (O/E = 96.16-fold, p < 2.0e-05, even after controlling for the chromatin accessibility state of shared regions (p <0.001. Furthermore, MS susceptibility regions are preferentially targeted by both EBNA2 and VDR than by EBNA2 alone (enrichment difference = 1.722-fold, p = 0.0267. Taken together, these findings demonstrate that EBV participates in the gene-environment interactions that predispose to MS.

  2. H1N1 update review.

    Science.gov (United States)

    Alenzi, Faris Q

    2010-03-01

    There is worldwide concern on the spreading pandemic wave of the new swine influenza virus (S-OIV). The WHO has placed the pandemic threat alert to level 6. World leaders and scientists importantly stress that regulations and pandemic preparedness may lower the morbidity and mortality. This review describes the background, origin, epidemiology, signs and symptoms, methods of detecting H1N1, the risk of H1N1 pandemic control plans, immunity to H1N1, vaccination against H1N1, hospital management, patient management, and treatment of symptoms. It also describes in considerable detail the responsibilities of health professionals in navigating the complex areas of laboratory diagnosis, patient isolation procedures, and how to minimize and manage any accompanying staff infections, all of which are vital processes to help mitigate and minimize the seriousness of local and national de-novo outbreaks of emerging H1N1 infection.

  3. Relationship between Occupational Stress, 5-HT2A Receptor Polymorphisms and Mental Health in Petroleum Workers in the Xinjiang Arid Desert: A Cross-Sectional Study.

    Science.gov (United States)

    Jiang, Ting; Ge, Hua; Sun, Jian; Li, Rong; Han, Rui; Liu, Jiwen

    2017-04-10

    At present, there is growing interest in research examining the relationship between occupational stress and mental health. Owing to the socioeconomic impact of occupational stress and the unique environment of petroleum workers in Xinjiang, a cross-sectional study was carried out between April and December 2015 to investigate the relationship between occupational stress, 5-hydroxytryptamine receptor (5-HTR2A) genotype, and mental health. A total of 1485 workers were selected. The Symptom Checklist 90 was used to assess nine classes of psychological symptoms. Work-related stressors were evaluated using the Occupational Stress Inventory-Revised Edition. Levels of 5-HTR2A (the Tl02C and A-1438G single nucleotide polymorphism in the 5-HTR2A gene) were measured by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The findings of the present study revealed a high prevalence rate of mental health problems (40.29%) in petroleum workers stationed in the arid desert, and suggested a strong correlation between occupational stress and mental health. The TC and CC genotype of Tl02C were found to be protective factors against mental health problems (odds ratio (OR) = 0.455, 95% confidence interval (CI): = 0.269-0.771, odds ratio (OR) = 0.340, 95% confidence interval (CI): 0.162-0.716). AG and GG genotype of A-1438G [odds ratio (OR) 1 = 2.729, 95% confidence interval (CI): 1.433-5.195; odds ratio (OR) 2 = 2.480, 95% confidence interval (CI): 1.221-5.037] were revealed as risk factors. These data provide evidence that occupational stress and 5-HTR2A gene polymorphism contributes to the incidence of mental health problems.

  4. Relationship between Occupational Stress, 5-HT2A Receptor Polymorphisms and Mental Health in Petroleum Workers in the Xinjiang Arid Desert: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Ting Jiang

    2017-04-01

    Full Text Available At present, there is growing interest in research examining the relationship between occupational stress and mental health. Owing to the socioeconomic impact of occupational stress and the unique environment of petroleum workers in Xinjiang, a cross-sectional study was carried out between April and December 2015 to investigate the relationship between occupational stress, 5-hydroxytryptamine receptor (5-HTR2A genotype, and mental health. A total of 1485 workers were selected. The Symptom Checklist 90 was used to assess nine classes of psychological symptoms. Work-related stressors were evaluated using the Occupational Stress Inventory-Revised Edition. Levels of 5-HTR2A (the Tl02C and A-1438G single nucleotide polymorphism in the 5-HTR2A gene were measured by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP. The findings of the present study revealed a high prevalence rate of mental health problems (40.29% in petroleum workers stationed in the arid desert, and suggested a strong correlation between occupational stress and mental health. The TC and CC genotype of Tl02C were found to be protective factors against mental health problems (odds ratio (OR = 0.455, 95% confidence interval (CI: = 0.269–0.771, odds ratio (OR = 0.340, 95% confidence interval (CI: 0.162–0.716. AG and GG genotype of A-1438G [odds ratio (OR 1 = 2.729, 95% confidence interval (CI: 1.433–5.195; odds ratio (OR 2 = 2.480, 95% confidence interval (CI: 1.221–5.037] were revealed as risk factors. These data provide evidence that occupational stress and 5-HTR2A gene polymorphism contributes to the incidence of mental health problems.

  5. Molecular dynamics of histone H1

    National Research Council Canada - National Science Library

    Raghuram, Nikhil; Carrero, Gustavo; Thng, John; Hendzel, Michael J

    2009-01-01

    .... In this review, we focus on the wealth of information gathered on the molecular kinetics of histone H1 molecules using novel imaging techniques, such as fluorescence recovery after photobleaching...

  6. Dopamine D2/3 Receptor Occupancy Following Dose Reduction Is Predictable With Minimal Plasma Antipsychotic Concentrations: An Open-Label Clinical Trial.

    Science.gov (United States)

    Nakajima, Shinichiro; Uchida, Hiroyuki; Bies, Robert R; Caravaggio, Fernando; Suzuki, Takefumi; Plitman, Eric; Mar, Wanna; Gerretsen, Philip; Pollock, Bruce G; Mulsant, Benoit H; Mamo, David C; Graff-Guerrero, Ariel

    2016-01-01

    Population pharmacokinetics can predict antipsychotic blood concentrations at a given time point prior to a dosage change. Those predicted blood concentrations could be used to estimate the corresponding dopamine D2/3 receptors (D2/3R) occupancy by antipsychotics based on the tight relationship between blood and brain pharmacokinetics. However, this 2-step prediction has never been tested. Two blood samples were collected at separate time points from 32 clinically stable outpatients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; mean ± SD age: 60.1 ± 7.3 years) to measure plasma concentrations of olanzapine or risperidone at baseline. Then, subjects underwent a dose reduction of olanzapine or risperidone and completed a [(11)C]-raclopride positron emission tomography scan to measure D2/3R occupancy in the putamen. The plasma concentration at the time of the scan was predicted with the 2 samples based on population pharmacokinetic model, using NONMEM. D2/3R occupancy was then estimated by incorporating the predicted plasma concentration in a hyperbole saturation model. The predicted occupancy was compared to the observed value. The mean (95% CI) prediction errors for the prediction of D2/3R occupancy were -1.76% (-5.11 to 1.58) for olanzapine and 0.64% (-6.18 to 7.46) for risperidone. The observed and predicted D2/3R occupancy levels were highly correlated (r = 0.67, P = .001 for olanzapine; r = 0.67, P = .02 for risperidone). D2/3R occupancy levels can be predicted from blood drug concentrations collected prior to dosage change. Although this 2-step model is subject to a small degree of error, it could be used to select oral doses aimed at achieving optimal D2/3R occupancy on an individual basis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Estimation of drug receptor occupancy when non-displaceable binding differs between brain regions – extending the simplified reference tissue model.

    Science.gov (United States)

    Kågedal, Matts; Varnäs, Katarina; Hooker, Andrew C; Karlsson, Mats O

    2015-07-01

    The simplified reference tissue model (SRTM) is used for estimation of receptor occupancy assuming that the non-displaceable binding in the reference region is identical to the brain regions of interest. The aim of this work was to extend the SRTM to also account for inter-regional differences in non-displaceable concentrations, and to investigate if this model allowed estimation of receptor occupancy using white matter as reference. It was also investigated if an apparent higher affinity in caudate compared with other brain regions, could be better explained by a difference in the extent of non-displaceable binding. The analysis was based on a PET study in six healthy volunteers using the 5-HT1B receptor radioligand [(11)C]-AZ10419369. The radioligand was given intravenously as a tracer dose alone and following different oral doses of the 5-HT1B receptor antagonist AZD3783. Non-linear mixed effects models were developed where differences between regions in non-specific concentrations were accounted for. The properties of the models were also evaluated by means of simulation studies. The estimate (95% CI) of Ki(PL) was 10.2 ng ml(-1) (5.4, 15) and 10.4 ng ml(-1) (8.1, 13.6) based on the extended SRTM with white matter as reference and based on the SRTM using cerebellum as reference, respectively. The estimate (95% CI) of Ki(PL) for caudate relative to other brain regions was 55% (48, 62%). The extended SRTM allows consideration of white matter as reference region when no suitable grey matter region exists. AZD3783 affinity appears to be higher in the caudate compared with other brain regions. © 2014 The British Pharmacological Society.

  8. 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.

  9. H1N1 and influenza viruses

    Science.gov (United States)

    Mirdamadi, Kamelia; Einarson, Adrienne

    2011-01-01

    Abstract Question I have been encouraging pregnant women to receive both the H1N1 and influenza vaccines since I became aware of Health Canada’s guidelines. However, some of the women in my practice have heard conflicting information, often from media sources, and they are hesitant to be vaccinated. What is the evidence behind these guidelines, and should I really be convincing these women to be vaccinated? Answer Pregnant women and growing fetuses are considered a population vulnerable to H1N1 and influenza viruses. Health Canada published a report in late 2010 estimating that this population was at increased risk of hospitalization and severe outcomes of H1N1 infection. Recommendations included pregnant women as a priority group to receive the H1N1 vaccine as well as the influenza vaccine. This information should be explained unambiguously to pregnant women, and they should be made aware of the sensationalism of media reports, which are often based on opinion and not evidence. PMID:21918141

  10. Lack of association between dopaminergic antagonism and negative symptoms in schizophrenia: a positron emission tomography dopamine D2/3 receptor occupancy study.

    Science.gov (United States)

    Fervaha, Gagan; Caravaggio, Fernando; Mamo, David C; Mulsant, Benoit H; Pollock, Bruce G; Nakajima, Shinichiro; Gerretsen, Philip; Rajji, Tarek K; Mar, Wanna; Iwata, Yusuke; Plitman, Eric; Chung, Jun Ku; Remington, Gary; Graff-Guerrero, Ariel

    2016-10-01

    Several pre-clinical studies suggest that antipsychotic medications cause secondary negative symptoms. However, direct evidence for a relationship among antipsychotic medications, their direct effects on neurotransmitter systems, and negative symptoms in schizophrenia remains controversial. The objective of this study was to examine the relationship between antipsychotic-related dopamine D2/3 receptor occupancy and negative symptoms in patients with schizophrenia. Forty-one clinically stable outpatients with schizophrenia participated in this prospective dose reduction positron emission tomography (PET) study. Clinical assessments and [11C]-raclopride PET scans were performed before and after participants underwent gradual dose reduction of their antipsychotic medication by up to 40 % from the baseline dose. No significant relationship was found between antipsychotic-related dopamine D2/3 receptor occupancy and negative symptom severity at baseline or follow-up. Similar null findings were found for subdomains of negative symptoms (amotivation and diminished expression). Occupancy was significantly lower following dose reduction; however, negative symptom severity did not change significantly, though a trend toward reduction was noted. Examination of change scores between these two variables revealed no systematic relationship. Our cross-sectional and longitudinal results failed to find a significant dose-dependent relationship between severity of negative symptoms and antipsychotic-related dopaminergic antagonism in schizophrenia. These findings argue against the notion that antipsychotics necessarily cause secondary negative symptoms. Our results are also in contrast with the behavioral effects of dopaminergic antagonism routinely reported in pre-clinical investigations, suggesting that the role of this variable in the context of chronic treatment and schizophrenia needs to be re-examined.

  11. Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with (11)C-SA4503 and microPET.

    Science.gov (United States)

    Ramakrishnan, Nisha K; Visser, Anniek K D; Schepers, Marianne; Luurtsema, Gert; Nyakas, Csaba J; Elsinga, Philip H; Ishiwata, Kiichi; Dierckx, Rudi A J O; van Waarde, Aren

    2014-10-01

    Sigma-1 receptor agonists are under investigation as potential disease-modifying agents for several CNS disorders. Donepezil, an acetylcholinesterase inhibitor used for the symptomatic treatment of Alzheimer's disease, is also a high-affinity sigma-1 agonist. The objectives of the present study were to investigate if the sigma-1 agonist tracer (11)C-SA4503 and microPET can be used to determine sigma-1 receptor occupancy (RO) of donepezil in the rat brain; to establish RO of donepezil at doses commonly used in rodent behavioural studies; and to determine the effective plasma concentration of donepezil required for 50 % of max-min occupancy (EC50). Male Wistar rats were pre-treated with donepezil (0.1 to 10 mg/kg) for about 1 h before microPET scans using (11)C-SA4503. The total distribution volume (V T) of the tracer was determined by Logan graphical analysis using time activity curves from arterial plasma and regions of interest drawn around the entire brain and individual brain regions. RO by donepezil was calculated from a modified Lassen plot, and ED50 was estimated from the sigmoidal dose-response curves obtained when the RO was plotted against log donepezil dose. A dose-dependent reduction was observed for V T in the whole brain as well as individual brain regions. RO increased dose-dependently and was 93 % at 10 mg/kg. ED50 was 1.29 mg/kg. Donepezil, in the common dose range, was found to dose-dependently occupy a significant fraction of the sigma-1 receptor population. The data indicate that it is possible to determine sigma-1 RO by an agonist drug in rat brain, using (11)C-SA4503 and microPET.

  12. Safety profile of bilastine: 2nd generation H1-antihistamines.

    Science.gov (United States)

    Scaglione, F

    2012-12-01

    Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

  13. Evaluation of Efficacy and Sedative Profiles of H1 Antihistamines by Large-Scale Surveillance Using the Visual Analogue Scale (VAS

    Directory of Open Access Journals (Sweden)

    Norimasa Izumi

    2008-01-01

    Conclusions: The sedative properties of the H1 antihistamines obtained from VAS analysis were very similar to those of H1R occupancy from positron emission tomography (PET studies and PIR from meta-analysis. Our results indicate that large-scale surveillance using VAS might be useful to evaluate the profiles of H1 antihistamines.

  14. Evaluation of the Agonist PET Radioligand [11C]GR103545 to Image Kappa Opioid Receptor in Humans: Kinetic Model Selection, Test-Retest Reproducibility and Receptor Occupancy by the Antagonist PF-04455242

    Science.gov (United States)

    Naganawa, Mika; Jacobsen, Leslie K.; Zheng, Ming-Qiang; Lin, Shu-Fei; Banerjee, Anindita; Byon, Wonkyung; Weinzimmer, David; Tomasi, Giampaolo; Nabulsi, Nabeel; Grimwood, Sarah; Badura, Lori L.; Carson, Richard E.; McCarthy, Timothy J.; Huang, Yiyun

    2014-01-01

    Introduction Kappa opioid receptors (KOR) are implicated in several brain disorders. In this report, a first-in-human Positron Emission Tomography (PET) study was conducted with the potent and selective KOR agonist tracer, [11C]GR103545, to determine an appropriate kinetic model for analysis of PET imaging data and assess the test-retest reproducibility of model-derived binding parameters. The non-displaceable distribution volume (VND) was estimated from a blocking study with naltrexone. In addition, KOR occupancy of PF-04455242, a selective KOR antagonist that is active in preclinical models of depression, was also investigated. Methods For determination of a kinetic model and evaluation of test-retest reproducibility, 11 subjects were scanned twice with [11C]GR103545. Seven subjects were scanned before and 75 min after oral administration of naltrexone (150 mg). For the KOR occupancy study, six subjects were scanned at baseline and 1.5 h and 8 h after an oral dose of PF-04455242 (15 mg, n = 1 and 30 mg, n = 5). Metabolite-corrected arterial input functions were measured and all scans were 150 min in duration. Regional time-activity curves (TACs) were analyzed with 1- and 2-tissue compartment models (1TC and 2TC) and the multilinear analysis (MA1) method to derive regional volume of distribution (VT). Relative test-retest variability (TRV), absolute test-retest variability (aTRV) and intra-class coefficient (ICC) were calculated to assess test-retest reproducibility of regional VT. Occupancy plots were computed for blocking studies to estimate occupancy and VND. The half maximal inhibitory concentration (IC50) of PF-04455242 was determined from occupancies and drug concentrations in plasma. [11C]GR103545 in vivo KD was also estimated. Results Regional TACs were well described by the 2TC model and MA1. However, 2TC VT was sometimes estimated with high standard error. Thus MA1 was the model of choice. Test-retest variability was ~15%, depending on the outcome

  15. Development of a population pharmacokinetic model to predict brain distribution and dopamine D2 receptor occupancy of raclopride in non-anesthetized rat.

    Science.gov (United States)

    Wong, Yin Cheong; Ilkova, Trayana; van Wijk, Rob C; Hartman, Robin; de Lange, Elizabeth C M

    2018-01-01

    Raclopride is a selective antagonist of the dopamine D2 receptor. It is one of the most frequently used in vivo D2 tracers (at low doses) for assessing drug-induced receptor occupancy (RO) in animals and humans. It is also commonly used as a pharmacological blocker (at high doses) to occupy the available D2 receptors and antagonize the action of dopamine or drugs on D2 in preclinical studies. The aims of this study were to comprehensively evaluate its pharmacokinetic (PK) profiles in different brain compartments and to establish a PK-RO model that could predict the brain distribution and RO of raclopride in the freely moving rat using a LC-MS based approach. Rats (n=24) received a 10-min IV infusion of non-radiolabeled raclopride (1.61μmol/kg, i.e. 0.56mg/kg). Plasma and the brain tissues of striatum (with high density of D2 receptors) and cerebellum (with negligible amount of D2 receptors) were collected. Additional microdialysis experiments were performed in some rats (n=7) to measure the free drug concentration in the extracellular fluid of the striatum and cerebellum. Raclopride concentrations in all samples were analyzed by LC-MS. A population PK-RO model was constructed in NONMEM to describe the concentration-time profiles in the unbound plasma, brain extracellular fluid and brain tissue compartments and to estimate the RO based on raclopride-D2 receptor binding kinetics. In plasma raclopride showed a rapid distribution phase followed by a slower elimination phase. The striatum tissue concentrations were consistently higher than that of cerebellum tissue throughout the whole experimental period (10-h) due to higher non-specific tissue binding and D2 receptor binding in the striatum. Model-based simulations accurately predicted the literature data on rat plasma PK, brain tissue PK and D2 RO at different time points after intravenous or subcutaneous administration of raclopride at tracer dose (RO 30%). For the first time a predictive model that could describe

  16. Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia.

    Science.gov (United States)

    Tateno, Amane; Arakawa, Ryosuke; Okumura, Masaki; Fukuta, Hajime; Honjo, Kazuyoshi; Ishihara, Keiichi; Nakamura, Hiroshi; Kumita, Shin-ichiro; Okubo, Yoshiro

    2013-04-01

    Blonanserin is a novel antipsychotic with high affinities for dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D(2) receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]raclopride for the striatum and 1 with [(11)C]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D(2) receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D(2) receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

  17. Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines.

    Science.gov (United States)

    Stahl, Stephen M

    2008-12-01

    Numerous "antihistamines" as well as various psychotropic medications with antihistamine properties are widely utilized to treat insomnia. Over-the-counter sleep aids usually contain an antihistamine and various antidepressants and antipsychotics with antihistamine properties have sedative-hypnotic actions. Although widely used for the treatment of insomnia, many agents that block the histamine H1 receptor are also widely considered to have therapeutic limitations, including the development of next-day carryover sedation, as well as problems with chronic use, such as the development of tolerance to sedative-hypnotic actions and weight gain. Although these clinical actions are classically attributed to blockade of the H1 receptor, recent findings with H1 selective agents and H1 selective dosing of older agents are challenging these notions and suggest that some of the clinical limitations of current H1-blocking agents at their currently utilized doses could be attributable to other properties of these drugs, especially to their simultaneous actions on muscarinic, cholinergic, and adrenergic receptors. Selective H1 antagonism is emerging as a novel approach to the treatment of insomnia, without tolerance, weight gain, or the need for the restrictive prescription scheduling required of other hypnotics.

  18. Panblok-H1+advax H1N1/2009pdm vaccine: Insights into rapid development of a delta inulin adjuvanted recombinant pandemic influenza vaccine.

    Science.gov (United States)

    Honda-Okubo, Yoshikazu; Rajapaksha, Harinda; Sajkov, Dimitar; Gordon, David; Cox, Manon M J; Petrovsky, Nikolai

    2017-06-03

    Timely vaccine supply is critical during influenza pandemics but is impeded by current virus-based manufacturing methods. The 2009 H1N1/2009pdm 'swine flu' pandemic reinforced the need for innovation in pandemic vaccine design. We report on insights gained during rapid development of a pandemic vaccine based on recombinant haemagglutinin (rHA) formulated with Advax™ delta inulin adjuvant (Panblok-H1/Advax). Panblok-H1/Advax was designed and manufactured within 1 month of the pandemic declaration by WHO and successfully entered human clinical testing in under 3 months from first isolation and sequencing of the novel pandemic virus, requiring several major challenges to be overcome. Panblok-H1/Advax successfully induced neutralising antibodies against the pandemic strain, but also induced cross-neutralising antibodies in a subset of subjects against an H1N1 strain (A/Puerto Rico/8/34) derived from the 1918 Spanish flu, highlighting the possibility to use Advax to induce more broadly cross-protective antibody responses. Interestingly, the rHA from H1N1/2009pdm exhibited variants in the receptor binding domain that had a major impact on receptor binding and hemagglutination ability. We used an in silico structural modeling approach to better understand the unusual behavior of the novel hemagglutinin, thereby demonstrating the power of computational modeling approaches for rapid characterization of new pandemic viruses. While challenges remain in ensuring ultrafast vaccine access for the entire population in response to future pandemics, the adjuvanted recombinant Panblok-H1/Advax vaccine proved its utility during a real-life pandemic situation.

  19. H1-antihistamines for chronic spontaneous urticaria.

    Science.gov (United States)

    Sharma, Maulina; Bennett, Cathy; Cohen, Stuart N; Carter, Ben

    2014-11-14

    Background Chronic spontaneous urticaria (CSU) is characterised by the development of crops of red, itchy, raised weals or hives with no identifiable external cause.Objectives To assess the effects of H1-antihistamines for CSU.Search methods We searched the following databases up to June 2014: Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 5), MEDLINE(from 1946), EMBASE (from 1974) and PsycINFO (from 1806). We searched five trials registers and checked articles for references to relevant randomised controlled trials.Selection criteria We included randomised controlled trials of H1-antihistamines for CSU. Interventions included single therapy or a combination of H1-antihistamines compared with no treatment (placebo) or another active pharmacological compound at any dose.Data collection and analysis We used standard methodological procedures as expected by The Cochrane Collaboration.Our primary outcome measures were proportion of participants with complete suppression of urticaria: 'good or excellent' response,50% or greater improvement in quality of life measures, and adverse events.We present risk ratios (RR) with 95% confidence intervals(CIs). Main results We identified 73 studies (9759 participants); 34 studies provided data for 23 comparisons. The duration of the intervention was up to two weeks (short-term) or longer than two weeks and up to three months (intermediate-term).Cetirizine 10mg once daily in the short term and in the intermediate term led to complete suppression of urticaria by more participants than was seen with placebo (RR 2.72, 95% CI 1.51 to 4.91). For this same outcome, comparison of desloratadine versus placebo in the intermediate term (5 mg) (RR 37.00, 95% CI 2.31 to 593.70) and in the short term (20 mg) (RR 15.97, 95% CI 1.04 to 245.04)favoured desloratadine, but no differences were seen between 5 mg and 10 mg for short-term treatment.Levocetirizine 20 mg per day (short-term) was more effective for complete suppression of

  20. Comparative assessment of platelet GpIIb/IIIa receptor occupancy ratio with Eptifibatide/Tirofiban in patients presenting with ACS and undergoing PCI

    Science.gov (United States)

    Puri, Aniket; Bansal, A.; Narain, V.S.; Sethi, R.; Dwivedi, S.K.; Puri, V.K.; Saran, R.K.

    2013-01-01

    Background The level of platelet inhibition by a Glycoprotein IIb/IIIa (GpIIb/IIIa) antagonist therapy necessary to minimize thrombotic complications in patients undergoing percutaneous coronary intervention (PCI) is a subject of debate. The degree of platelet inhibition obtained 10 min after start of GpIIb/IIIa antagonist therapy predicts adverse events after PCI. The aim of this study was to look at platelet inhibition and to compare platelet GpIIb/IIIa receptors occupancy ratio (GpRO) with Eptifibatide and Tirofiban using various dose regimens and correlate with 30-day clinical outcomes in patients presenting with high-risk acute coronary syndromes (ACS) and undergoing PCI. Methods The patients were divided into four sub groups: (1) Eptifibatide two intracoronary bolus (180 μg/kg) alone (EB); or (2) two intravenous bolus (180 μg/kg) followed by infusion at 2 μg/kg/min for 24 h (EB + Inf); and (3) Tirofiban standard bolus dose (0.4 μg/kg) over 30 min followed by infusion at 0.1 μg/kg/min (TStd); or (4) at ADVANCE dose bolus (25 μg/kg) over 3 min, followed by infusion at 0.1 μg/kg/min (TAdv). Number of GpIIb/IIIa receptors was assessed by flow cytometry at baseline and 10 min after the bolus and percentage of free receptors was determined to calculate the GpRO. Patients were followed for 30 days for any major adverse cardiac events (MACE). Results 200 consecutive patients (including 74% with ST-elevation ACS) were enrolled. GpRO in groups EB (n = 48) and EB + Inf (n = 44) were 62.7% ± 27.2% and 61.4% ± 6.1% respectively while in the groups TStd (n = 96) and TAdv (n = 12) groups were 35.1% ± 17.74% and 68.8% ± 27.3% respectively. The GpRO was similar in EB, EB + Inf and TAdv groups and was significantly higher than TStd group (p < 0.0001). The 30-day MACE rates in EB (4.2%), EB + Inf (4.5%) and TAdv (4.2%) were significantly lower than TStd group (12.5%) (p < 0.01). Conclusions Standard dose Tirofiban results in

  1. 76 FR 11686 - Registration Requirement for Petitioners Seeking to File H-1B Petitions on Behalf of Aliens...

    Science.gov (United States)

    2011-03-03

    ... (LCA) in the occupational specialty in which the alien will be employed. See 8 CFR 214.2(h)(4)(i)(B)(1) and 8 CFR 214.2(h)(1)(ii)(B)(3). Upon certification of the LCA, the employer may then file an H-1B... three years and may not exceed the validity period of the LCA. See 8 CFR 214.2(h)(9)(iii)(A)(1). Prior...

  2. Analysis list: Suv39h1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Suv39h1 Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Suv...39h1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Suv39h1.5.tsv http://dbarchive.bi...osciencedbc.jp/kyushu-u/mm9/target/Suv39h1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Suv39h

  3. 2009 H1N1 Flu Vaccine Facts

    Science.gov (United States)

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

  4. Occupancy of dopamine D{sub 2} receptors in the mouse brain measured using ultra-high-resolution single-photon emission tomography and [{sup 123}I]IBF

    Energy Technology Data Exchange (ETDEWEB)

    Acton, Paul D.; Hou, Catherine; Kung, Mei-Ping; Ploessl, Karl; Keeney, Cindy L. [Department of Radiology, University of Pennsylvania, 3700 Market Street, Room 305, Philadelphia, PA 19104 (United States); Kung, Hank F. [Department of Radiology, University of Pennsylvania, 3700 Market Street, Room 305, Philadelphia, PA 19104 (United States); Department of Pharmacology, University of Pennsylvania, Philadelphia (United States)

    2002-11-01

    Functional imaging of small animals, such as mice and rats, using ultra-high-resolution positron emission tomography (PET) and single-photon emission tomography (SPET) should be a valuable tool in studies of drug occupancy of cerebral binding sites. In this study we aimed to demonstrate the feasibility of using ultra-high-resolution SPET to measure the occupancy of dopamine D{sub 2} receptors by a competing drug, using the dopamine D{sub 2} receptor-specific radioligand iodine-123 5-iodo-7-N-[(1-ethyl-2-pyrrolidinyl) methyl] carboxamido-2,3-dihydrobenzofuran ([{sup 123}I]IBF). Fourteen normal male mice (CD-1) were jugular vein-cannulated and a bolus infusion protocol was used to deliver 360 MBq [{sup 123}I]IBF into the mouse (bolus-to-infusion ratio 1.8:1). The mice were scanned using an ultra-high-resolution triple-headed SPET system equipped with pinhole collimators. After sustained equilibrium had been achieved, varying doses of raclopride, a potent dopamine D{sub 2} receptor antagonist, were injected through the tail vein and the tracer was allowed to regain equilibrium. A simple equilibrium ratio of striatum to cerebellum provided a measure of D{sub 2} receptor binding both before and after injection of raclopride. Following raclopride administration, the system returned to equilibrium with lower specific binding in the striatum, while the counts in the cerebellum were unaffected. Receptor occupancy was 5.2%{+-}2.9% (control), 52.1%{+-}11.1% (0.3 mg/kg), 79.3%{+-}4.8% (1.0 mg/kg), and 94.7%{+-}2.2% (3.0 mg/kg), which gave an ED{sub 50}=0.26{+-}0.03 mg/kg using a single receptor site saturation model. This study has demonstrated clearly that ultra-high-resolution SPET of small animals is capable of measuring displacement and occupancy of dopamine D{sub 2} receptors by competing ligands. (orig.)

  5. Comparison of dopamine D3 and D2 receptor occupancies by a single dose of blonanserin in healthy subjects: A positron emission tomography study with [11C]-(+)-PHNO.

    Science.gov (United States)

    Tateno, Amane; Sakayori, Takeshi; Kim, Woo-Chan; Honjo, Kazuyoshi; Nakayama, Haruo; Arakawa, Ryosuke; Okubo, Yoshiro

    2018-01-13

    Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Six healthy males (mean 35.7±7.6 years) received two positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3-81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4-84.3%; mean±SD, 73.3±8.2%), ventral striatum (range 40.1-88.2%; mean±SD, 60.8±17.1%), globus pallidus (range 65.8-87.6%; mean±SD, 75.7±8.6%), and substantia nigra (range 56.0-88.7%; mean±SD, 72.4±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79). A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism.

  6. 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)

  7. Occupational dermatosis

    National Research Council Canada - National Science Library

    Alchorne, Alice de Oliveira de Avelar; Alchorne, Maurício Mota de Avelar; Silva, Marzia Macedo

    2010-01-01

    Occupational Dermatosis is described as any alteration in the skin, mucosa or annexes that is directly or indirectly caused, conditioned, maintained or aggravated by agents present in the occupational...

  8. Health costs from hospitalization with H1N1 infection during the 2009–2010 influenza pandemic compared with non-H1N1 respiratory infections

    Directory of Open Access Journals (Sweden)

    Courcoutsakis N

    2012-03-01

    Full Text Available Paul Zarogoulidis1, Dimitrios Glaros2,3, Theodoros Kontakiotis1, Marios Froudarakis4, loannis Kioumis1, loannis Kouroumichakis3, Anastasios Tsiotsios1, Anastasios Kallianos5, Paschalis Steiropoulos4, Konstantinos Porpodis1, Evagelia Nena6, Despoina Papakosta1, Aggeliki Rapti5, Theodoros C Constantinidis6, Theodora Kerenidi7, Maria Panopoulou8, Georgia Trakada9, Nikolaos Courcoutsakis10, Evangelia Fouka11, Konstantinos Zarogoulidis1, Efstratios Maltezos2,31Aristotle University of Thessaloniki, Pulmonary Department, "G Papanikolaou" Hospital, Exochi, Thessaloniki, 2Unit of Infectious Diseases, General University Hospital of Alexandroupolis, 3Second Department of Internal Medicine, 4Pulmonary Department, General University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 52nd Pulmonology Clinic, Hospital of Chest Diseases "SOTIRIA," Athens, 6Laboratory of Hygiene and Environmental Protection, Occupational Medicine Section, Teaching Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Greece, Alexandroupolis, 7Pulmonary Department, University of Larissa, Larissa, 8Microbiology Department, General University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 9Pulmonary Department, University of Athens, Athens, 10Radiology Department, General University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 111st Pulmonary Department, "G Papanikolaou" Hospital, Exochi, Thessaloniki, GreeceBackground: The first positive patient with influenza A (H1N1 was recorded in March 2009 and the pandemic continued with new outbreaks throughout 2010. This study's objective was to quantify the total cost of inpatient care and identify factors associated with the increased cost of the 2009–2010 influenza A pandemic in comparison with nonviral respiratory infection.Methods: In total, 133 positive and 103 negative H1N1 patients were included from three tertiary

  9. H1N1: pandemia e perspectiva atual H1N1: overview and perspectives

    Directory of Open Access Journals (Sweden)

    Nancy Bellei

    2011-12-01

    Full Text Available O vírus influenza de origem suína, A/California/04/2009 (H1N1, foi inicialmente detectado no México e determinou a pandemia de influenza de 2009. Em agosto de 2010, a Organização Mundial da Saúde (OMS declarou o início da fase pós-pandêmica. As características dessa última pandemia foram marcadamente diferentes das anteriores. O vírus emergiu de rearranjos genéticos originários em hospedeiro mamífero não humano, demonstrou transmissibilidade interespécies e afetou a população humana de forma diferente dos vírus pandêmicos anteriores (1918, 1957 e 1968 com maior morbidade e mortalidade em crianças e adultos jovens. Atualmente, o vírus apresenta padrão sazonal da mesma forma que o influenza A H3N2 e o influenza B, mantendo, até o momento, o mesmo perfil de patogenicidade, espectro clínico e sensibilidade a antivirais. A cepa foi incluída na vacina sazonal trivalente anual recomendada, principalmente para proteção dos grupos de risco mais vulneráveis a complicações pelas diferentes cepas de influenza.The swine origin influenza virus A/CALIFORNIA/04/2009 (H1N1 was first detected in Mexico and determined the 2009 influenza pandemic. In August 2010, World Health Organization (WHO declared the beginning of the post-pandemic period. This last pandemic was distinctly different from previous ones. The virus emerged from genetic rearrangement in non-human mammalian host. Moreover, its inter-species transmission is fully reported. However, it affected human population differently from previous pandemic viruses (1918, 1957, 1968, with increased morbidity and mortality among children and young adults. Currently, the virus has a seasonal pattern in the same way as influenza A H3N2 and influenza B, maintaining the same pathogenicity profile, clinical spectrum and sensitivity to antiviral agents. The strain was included in the annual trivalent seasonal vaccine formulation, mainly for risk groups, which are more vulnerable to

  10. 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”.

  11. Measuring receptor occupancy with PET

    NARCIS (Netherlands)

    van Waarde, A

    2000-01-01

    Many physiological and biochemical measurements can be performed noninvasively in humans with modern imaging techniques like magnetic resonance imaging (MRI), positron emission tomography (PET) or single-photon emission computed tomography (SPECT). This review focuses on the monitoring of

  12. Bilastine: A New Nonsedating Oral H1 Antihistamine for Treatment of Allergic Rhinoconjunctivitis and Urticaria

    OpenAIRE

    Wolthers, Ole D.

    2013-01-01

    Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis a...

  13. Risk Factors for Pandemic (H1N1) 2009 Virus Seroconversion among Hospital Staff, Singapore

    Science.gov (United States)

    Lee, Vernon J.M.; Barr, Ian; Lin, Cui; Goh, Rachelle; Lee, Caroline; Singh, Baldev; Tan, Jessie; Lim, Wei-Yen; Cook, Alex R.; Ang, Brenda; Chow, Angela; Tan, Boon Huan; Loh, Jimmy; Shaw, Robert; Chia, Kee Seng; Lin, Raymond T.P.; Leo, Yee Sin

    2010-01-01

    We describe incidence and risk factors for pandemic (H1N1) 2009 virus infection in healthcare personnel during the June–September 2009 epidemic in Singapore. Personnel contributed 3 serologic samples during June–October 2009, with seroconversion defined as a >4-fold increase in hemagglutination inhibition titers to pandemic (H1N1) 2009. Of 531 participants, 35 showed evidence of seroconversion. Seroconversion rates were highest in nurses (28/290) and lowest in allied health staff (2/116). Significant risk factors on multivariate analysis were being a nurse (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 1.0–19.6) and working in pandemic (H1N1) 2009 isolation wards (aOR 4.5, 95% CI 1.3–15.6). Contact with pandemic (H1N1) 2009–infected colleagues (aOR 2.5, 95% CI 0.9–6.6) and larger household size (aOR 1.2, 95% CI 1.0–1.4) were of borderline significance. Our study suggests that seroconversion was associated with occupational and nonoccupational risk factors. PMID:20875280

  14. Quantitative projection of human brain penetration of the H3antagonist PF-03654746 by integrating rat-derived brain partitioning and PET receptor occupancy.

    Science.gov (United States)

    Sawant-Basak, Aarti; Chen, Laigao; Shaffer, Christopher L; Palumbo, Donna; Schmidt, Anne; Tseng, Elaine; Spracklin, Douglas K; Gallezot, Jean-Dominique; Labaree, David; Nabulsi, Nabeel; Huang, Yiyun; Carson, Richard E; McCarthy, Timothy

    2017-02-01

    1. Unbound brain drug concentration (C b,u ), a valid surrogate of interstitial fluid drug concentration (C ISF ), cannot be directly determined in humans, which limits accurately defining the human C b,u :C p,u of investigational molecules. 2. For the H 3 R antagonist (1R,3R)-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-lmethyl)phenyl]cyclobutane-1-carboxamide (PF-03654746), we interrogated C b,u :C p,u in humans and nonhuman primate (NHP). 3. In rat, PF-03654746 achieved net blood-brain barrier (BBB) equilibrium (C b,u :C p,u of 2.11). 4. In NHP and humans, the PET receptor occupancy-based C p,u IC 50 of PF-03654746 was 0.99 nM and 0.31 nM, respectively, which were 2.1- and 7.4-fold lower than its in vitro human H 3 K i (2.3 nM). 5. In an attempt to understand this higher-than-expected potency in humans and NHP, rat-derived C b,u :C p,u of PF-03654746 was integrated with C p,u IC 50 to identify unbound (neuro) potency of PF-03654746, nIC 50 . 6. The nIC 50 of PF-03654746 was 2.1 nM in NHP and 0.66 nM in human which better correlated (1.1- and 3.49-fold lower) with in vitro human H 3 K i (2.3 nM). 7. This correlation of the nIC 50 and in vitro hH 3 K i suggested the translation of net BBB equilibrium of PF-03654746 from rat to NHP and humans, and confirmed the use of C p,u as a reliable surrogate of C b,u . 8. Thus, nIC 50 quantitatively informed the human C b,u :C p,u of PF-03654746.

  15. 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 ...

  16. Second-generation H1-antihistamines in chronic urticaria: an evidence-based review.

    Science.gov (United States)

    Kavosh, Eric R; Khan, David A

    2011-12-01

    The effects of urticaria are predominantly mediated by histamine release; therefore, H1-antihistamines are the mainstay of treatment. Second-generation H1-antihistamines, compared with their first-generation counterparts, have demonstrated improved peripheral H1-receptor selectivity and decreased lipophilicity (which minimizes CNS adverse effects), and antiallergic properties in addition to being histamine inverse agonists. Evidence of clinical efficacy and tolerability of second-generation H1-antihistamines available in the US for the treatment of chronic urticaria (CU) was analyzed using the GRADE system to develop the strength of recommendations for particular therapies. The evidence for the safety and efficacy of the majority of second-generation H1-antihistamines available in the US is of high quality and leads to a strong recommendation for their use in CU. There is a limited amount of data of variable quality comparing the efficacy between various second-generation H1-antihistamines in CU leading to weak recommendations for using cetirizine over fexofenadine and levocetirizine over desloratadine. Limited data of variable quality exist for the efficacy of higher doses of second-generation H1-antihistamines in CU patients not responsive to standard doses. These limited data lead to a strong recommendation that higher than recommended doses of fexofenadine do not offer greater efficacy in control of CU and a weak recommendation that higher doses of levocetirizine and desloratadine are more effective in CU unresponsive to standard doses. More studies of higher quality are required to make any firm recommendations regarding second-generation H1-antihistamines in the treatment of physical urticarias. All second-generation H1-antihistamines appear to be very well tolerated in CU patients, with rare reports of adverse effects. Due to the relatively large gaps in the quantity and quality of evidence, particularly for choice of H1-antihistamines, use of higher doses

  17. 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.

  18. Histamine and H1-antihistamines: celebrating a century of progress.

    Science.gov (United States)

    Simons, F Estelle R; Simons, Keith J

    2011-12-01

    In this review we celebrate a century of progress since the initial description of the physiologic and pathologic roles of histamine and 70 years of progress since the introduction of H(1)-antihistamines for clinical use. We discuss histamine and clinically relevant information about the molecular mechanisms of action of H(1)-antihistamines as inverse agonists (not antagonists or blockers) with immunoregulatory effects. Unlike first (old)-generation H(1)-antihistamines introduced from 1942 to the mid-1980s, most of the second (new)-generation H(1)-antihistamines introduced subsequently have been investigated extensively with regard to clinical pharmacology, efficacy, and safety; moreover, they are relatively free from adverse effects and not causally linked with fatalities after overdose. Important advances include improved nasal and ophthalmic H(1)-antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis treatment, respectively, and effective and safe use of high (up to 4-fold) doses of oral second-generation H(1)-antihistamines for chronic urticaria treatment. New H(1)-antihistamines introduced for clinical use include oral formulations (bilastine and rupatadine), and ophthalmic formulations (alcaftadine and bepotastine). Clinical studies of H(3)-antihistamines with enhanced decongestant effects have been conducted in patients with allergic rhinitis. Additional novel compounds being studied include H(4)-antihistamines with anti-inflammatory effects in allergic rhinitis, atopic dermatitis, and other diseases. Antihistamines have a storied past and a promising future. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  19. 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.

  20. Synthesis and Pharmacology of Mono-, Di-, and Trialkyl-Substituted 7-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides Combined with X-ray Structure Analysis to Understand the Unexpected Structure-Activity Relationship at AMPA Receptors

    DEFF Research Database (Denmark)

    Larsen, Anja Probst; Francotte, Pierre; Frydenvang, Karla

    2016-01-01

    of a series of mono-, di-, or trialkyl-substituted 7-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides, comprising in total 16 new modulators. The trisubstituted compounds 7b, 7d, and 7e revealed potent activity (EC2× = 2.7-4.3 μM; concentration of compound responsible for a 2-fold increase...... the cyclopropyl group constitutes the best choice of substituent. 7b was subjected to X-ray structural analysis in complex with the GluA2 ligand-binding domain. We propose an explanation of the unexpected structure-activity relationship of this new series of mono-, di-, and trialkyl-substituted 1......, whereas introduction of a 4-cyclopropyl group does not enhance potency of 2,3,4-alkyl-substituted BTDs. A hydrogen bond donor in the 2-position of the BTD is not necessary for modulator potency....

  1. Nationwide molecular surveillance of pandemic H1N1 influenza A virus genomes: Canada, 2009.

    Directory of Open Access Journals (Sweden)

    Morag Graham

    Full Text Available BACKGROUND: In April 2009, a novel triple-reassortant swine influenza A H1N1 virus ("A/H1N1pdm"; also known as SOIV was detected and spread globally as the first influenza pandemic of the 21(st century. Sequencing has since been conducted at an unprecedented rate globally in order to monitor the diversification of this emergent virus and to track mutations that may affect virus behavior. METHODOLOGY/PRINCIPAL FINDINGS: By Sanger sequencing, we determined consensus whole-genome sequences for A/H1N1pdm viruses sampled nationwide in Canada over 33 weeks during the 2009 first and second pandemic waves. A total of 235 virus genomes sampled from unique subjects were analyzed, providing insight into the temporal and spatial trajectory of A/H1N1pdm lineages within Canada. Three clades (2, 3, and 7 were identifiable within the first two weeks of A/H1N1pdm appearance, with clades 5 and 6 appearing thereafter; further diversification was not apparent. Only two viral sites displayed evidence of adaptive evolution, located in hemagglutinin (HA corresponding to D222 in the HA receptor-binding site, and to E374 at HA2-subunit position 47. Among the Canadian sampled viruses, we observed notable genetic diversity (1.47 x 10⁻³ amino acid substitutions per site in the gene encoding PB1, particularly within the viral genomic RNA (vRNA-binding domain (residues 493-757. This genome data set supports the conclusion that A/H1N1pdm is evolving but not excessively relative to other H1N1 influenza A viruses. Entropy analysis was used to investigate whether any mutated A/H1N1pdm protein residues were associated with infection severity; however no virus genotypes were observed to trend with infection severity. One virus that harboured heterozygote coding mutations, including PB2 D567D/G, was attributed to a severe and potentially mixed infection; yet the functional significance of this PB2 mutation remains unknown. CONCLUSIONS/SIGNIFICANCE: These findings contribute to

  2. 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.

  3. Evidence that the coactivator CBP/p300 is important for phenobarbital-induced but not basal expression of the CYP2H1 gene

    National Research Council Canada - National Science Library

    Dogra, Satish C; Tremethick, David; May, Brian K

    2003-01-01

    We have previously identified an upstream 556-bp enhancer domain for the chicken CYP2H1 gene that responds to phenobarbital and binds several transcription factors, including the orphan chicken xenobiotic receptor (CXR...

  4. 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.

  5. Synthesis and structure-activity relationships of novel histamine H1 antagonists: indolylpiperidinyl benzoic acid derivatives.

    Science.gov (United States)

    Fonquerna, Silvia; Miralpeix, Montse; Pagès, Lluís; Puig, Carles; Cardús, Arantxa; Antón, Francisca; Cárdenas, Alvaro; Vilella, Dolors; Aparici, Mónica; Calaf, Elena; Prieto, José; Gras, Jordi; Huerta, Josep M; Warrellow, Graham; Beleta, Jorge; Ryder, Hamish

    2004-12-02

    A series of indolylpiperidinyl derivatives were prepared and evaluated for their activity as histamine H(1) antagonists. Structure-activity relationship studies were directed toward improving in vivo activity and pharmacokinetic profile of our first lead (1). Substitution of fluorine in position 6 on the indolyl ring led to higher in vivo activity in the inhibition of histamine-induced cutaneous vascular permeability assay but lower selectivity toward 5HT(2) receptor. Extensive optimization was carried out within this series and a number of histamine H(1) antagonists showing potency and long duration of action in vivo and low brain penetration or cardiotoxic potential were identified. Within this novel series, indolylpiperidines 15, 20, 48,51 and 52 exhibited a long half-life in rat and have been selected for further preclinical evaluation.

  6. Formal kinetics of H1N1 epidemic

    Directory of Open Access Journals (Sweden)

    Gurevich Konstantin G

    2009-09-01

    Full Text Available Abstract Background The formal kinetics of the H1N1 epidemic seems to take the form of an exponential curve. There is a good correlation between this theoretical model and epidemiological data on the number of H1N1-infected people. But this formal model leads to paradoxes about the dates when everyone becomes infected: in Mexico this will happen after one year, then in the rest of the world. Further implications of the formal model The general limitations of this formal kinetics model are discussed. More detailed modeling is examined and the implications are examined in the light of currently available data. The evidence indicates that not more than 10% of the population is initially resistant to the H1N1 virus. Conclusion We are probably only at the initial stage of development of the H1N1 epidemic. Increasing the number of H1N1-resistant people in future (e.g. due to vaccination may influence the dynamics of epidemic development. At present, the development of the epidemic depends only on the number of people in the population who are initially resistant to the virus.

  7. Occupational health

    CERN Document Server

    Fingret, Dr Ann

    2013-01-01

    Offers a comprehensive view of health and safety issues at work. An invaluable resource for managers, personnel professionals and occupational health practitioners. Recommended by the Institute of Personnel Management.

  8. Occupational Therapists

    Science.gov (United States)

    ... bachelor’s degree and specific coursework, including biology and physiology. Many programs also require applicants to have volunteered ... of many conditions and ailments commonly associated with aging, such as arthritis and stroke. Occupational therapists also ...

  9. Occupational Health

    Science.gov (United States)

    Occupational health problems occur at work or because of the kind of work you do. These problems can include ... by exposure to radiation Exposure to germs in health care settings Good job safety and prevention practices ...

  10. Occupational Asthma

    Science.gov (United States)

    ... the enzymes of the bacteria Bacillus subtilis, while bakers may develop an allergy and occupational asthma symptoms ... counts Continuing education center Find an allergist / immunologist Journals Login / My membership Search your symptoms Shop the ...

  11. H1N1 in dialysis units: Prevention and management

    Directory of Open Access Journals (Sweden)

    Karkar Ayman

    2010-01-01

    Full Text Available Dialysis patients are at increased risk of contracting influenza A H1N1 and deve-loping serious illness. Increasing the awareness of dialysis patients and continuous education and training of medical staff on early recognition and management of influenza A H1N1 can help in saving the life of patients. Antiviral drugs and influenza vaccines are effective in providing ade-quate immunity in dialysis patients with strict implementation of infection control policies and procedures can help in preventing and controlling the dissemination of influenza A H1N1 in dia-lysis units. We report a case of a patient who presented with HINI influenza and developed acute kidney injury during his hospitalization and his course with disease.

  12. 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.

  13. NM23-H1: a Metastasis-Associated Gene

    Directory of Open Access Journals (Sweden)

    Yi-Torng Tee

    2006-06-01

    Full Text Available The protein product of nm23-H1 gene has activity of nucleoside diphosphate (NDP kinase, which catalyzes the phosphorylation of nucleoside diphosphates to the corresponding nucleoside triphosphates. Reductions in nm23 expression have been significantly associated with aggressive behavior in melanoma, breast, colon, and gastric carcinomas. On the contrary, high levels of nm23 gene expression are noted in the advanced stage of thyroid carcinomas and associated with significant reductions in survival for neuroblastoma and osteosarcoma patients. Although expression of nm23/NDP kinase is divergent in various malignant tumors, its reduced expression seems to be related to increased metastatic potential in most carcinoma types. However, it is hypothesized that nm23 may play a tissue-specific role, and that different regulatory mechanisms may act in different tumors. In ovarian carcinoma, nm23-H1/NDP kinase may be correlated with some clinicopathologic characteristics. In cervical cancer, nm23-H1 is probably involved in cervical carcinogenesis and correlated with some aggressive parameters. Overexpression of nm23-H1 protein may indicate poor survival for cervical cancer patients. Other than histidine 118 residue (amino acid sequence 118: histidine concerned with NDP kinase activity of nm23-H1, serine 120 (amino acid sequence 120: serine related activity of histidine-dependent protein phosphotransfer was recently reported to be responsible for its biological suppressive effects. To inhibit metastatic potential, nm23-H1 is also demonstrated to co-immunoprecipitate the kinase suppressor of Ras and phosphorylate it, and therefore reduce activation of the extracellular signal-regulated kinase mitogen-activated protein kinase pathway in response to signaling.

  14. 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.

  15. 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.

  16. 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.

  17. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

    Influenza vaccines with the ability to induce immune responses cross-reacting with drifted virus variants would be of great advantage for vaccine development against seasonal and emerging new strains. We demonstrate that gene gun administrated DNA vaccine encoding HA and NA and/or NP and M proteins...... 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....... These results suggest not only a unique ability of the DNA vaccines, but perhaps also natural infection, to induce cross-protective responses against even extremely drifted virus variants....

  18. Influenza A (H1N1) 2009: a pandemic alarm

    Indian Academy of Sciences (India)

    Prakash

    The most recent updates given by WHO confirm a total of 2,67,105 reported cases of .... Diagnosis of the new reassortant virus needs to be updated accordingly. In response to the rise in H1N1 swine flu ..... Biological and epidemiological aspects of influenza virus H5N1 in context of India; Indian J. Exp. Biol. 44 265–278.

  19. 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.

  20. 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...

  1. Influenza A (H1N1) 2009: a pandemic alarm

    Indian Academy of Sciences (India)

    At this critical juncture when the world has not yet recovered from the threat of avian influenza, the virus has returned in the disguise of swine influenza, a lesser known illness common in pigs. It has reached pandemic proportions in a short time span with health personnel still devising ways to identify the novel H1N1 virus ...

  2. 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)

  3. Narcolepsy and H1N1 Influenza Vaccination

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-07-01

    Full Text Available The incidence of narcolepsy between January 2000 and December 2010 in children in western Sweden and its relation to the Pandemrix H1N1 influenza vaccination were assessed by collection of data from hospital and clinic medical records and by parent telephone interviews.

  4. PTEN Interacts with Histone H1 and Controls Chromatin Condensation

    Science.gov (United States)

    Chen, Zhu Hong; Zhu, Minglu; Yang, Jingyi; Liang, Hui; He, Jinxue; He, Shiming; Wang, Pan; Kang, Xi; McNutt, Michael A.; Yin, Yuxin; Shen, Wen H.

    2014-01-01

    SUMMARY Chromatin organization and dynamics are integral to global gene transcription. Histone modification influences chromatin status and gene expression. PTEN plays multiple roles in tumor suppression, development and metabolism. Here we report on the interplay of PTEN, histone H1 and chromatin. We show that loss of PTEN leads to dissociation of histone H1 from chromatin and decondensation of chromatin. PTEN deletion also results in elevation of histone H4 acetylation at lysine 16, an epigenetic marker for chromatin activation. We found that PTEN and histone H1 physically interact through their C-terminal domains. Disruption of the PTEN C-terminus promotes the chromatin association of MOF acetyltransferase and induces H4K16 acetylation. Hyperacetylation of H4K16 impairs the association of PTEN with histone H1, which constitutes regulatory feedback that may deteriorate chromatin stability. Our results demonstrate that PTEN controls chromatin condensation, thus influencing gene expression. We propose that PTEN regulates global gene transcription profiling through histones and chromatin remodeling. PMID:25199838

  5. 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.

  6. Occupational mortality

    DEFF Research Database (Denmark)

    Lynge, Elsebeth

    2011-01-01

    INTRODUCTION: This paper aims to present the methods and main results from the Danish occupational mortality studies, and to set the Danish studies into the international context of occupational mortality studies. RESEARCH TOPICS: The first Danish occupational mortality study from 1970......-1975 revealed a considerable social class gradient in male mortality where university teachers and farmers had a 40% lower mortality and waiters and seamen had an about 100% higher mortality than the average for economically active men. The social class gradient was less steep for women. A similar pattern...... was found in 1996- 2005. CONCLUSION: In view of the considerable societal changes which have taken place from the beginning of the 1970s to the turn of the century, surprisingly small changes have taken place in the mortality pattern across social groups....

  7. Prediction of biological functions on glycosylation site migrations in human influenza H1N1 viruses.

    Science.gov (United States)

    Sun, Shisheng; Wang, Qinzhe; Zhao, Fei; Chen, Wentian; Li, Zheng

    2012-01-01

    Protein glycosylation alteration is typically employed by various viruses for escaping immune pressures from their hosts. Our previous work had shown that not only the increase of glycosylation sites (glycosites) numbers, but also glycosite migration might be involved in the evolution of human seasonal influenza H1N1 viruses. More importantly, glycosite migration was likely a more effectively alteration way for the host adaption of human influenza H1N1 viruses. In this study, we provided more bioinformatics and statistic evidences for further predicting the significant biological functions of glycosite migration in the host adaptation of human influenza H1N1 viruses, by employing homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites of HA and NA. The results showed that glycosite migrations in human influenza viruses have at least five possible functions: to more effectively mask the antigenic sites, to more effectively protect the enzymatic cleavage sites of neuraminidase (NA), to stabilize the polymeric structures, to regulate the receptor binding and catalytic activities and to balance the binding activity of hemagglutinin (HA) with the release activity of NA. The information here can provide some constructive suggestions for the function research related to protein glycosylation of influenza viruses, although these predictions still need to be supported by experimental data.

  8. Evidence of cross-reactive immunity to 2009 pandemic influenza A virus in workers seropositive to swine H1N1 influenza viruses circulating in Italy.

    Science.gov (United States)

    De Marco, Maria A; Porru, Stefano; Cordioli, Paolo; Cesana, Bruno M; Moreno, Ana; Calzoletti, Laura; Bonfanti, Lebana; Boni, Arianna; Di Carlo, Antonio Scotto; Arici, Cecilia; Carta, Angela; Castrucci, Maria R; Donatelli, Isabella; Tomao, Paola; Peri, Vittoria M; Di Trani, Livia; Vonesch, Nicoletta

    2013-01-01

    Pigs play a key epidemiologic role in the ecology of influenza A viruses (IAVs) emerging from animal hosts and transmitted to humans. Between 2008 and 2010, we investigated the health risk of occupational exposure to swine influenza viruses (SIVs) in Italy, during the emergence and spread of the 2009 H1N1 pandemic (H1N1pdm) virus. Serum samples from 123 swine workers (SWs) and 379 control subjects (Cs), not exposed to pig herds, were tested by haemagglutination inhibition (HI) assay against selected SIVs belonging to H1N1 (swH1N1), H1N2 (swH1N2) and H3N2 (swH3N2) subtypes circulating in the study area. Potential cross-reactivity between swine and human IAVs was evaluated by testing sera against recent, pandemic and seasonal, human influenza viruses (H1N1 and H3N2 antigenic subtypes). Samples tested against swH1N1 and H1N1pdm viruses were categorized into sera collected before (n. 84 SWs; n. 234 Cs) and after (n. 39 SWs; n. 145 Cs) the pandemic peak. HI-antibody titers ≥10 were considered positive. In both pre-pandemic and post-pandemic peak subperiods, SWs showed significantly higher swH1N1 seroprevalences when compared with Cs (52.4% vs. 4.7% and 59% vs. 9.7%, respectively). Comparable HI results were obtained against H1N1pdm antigen (58.3% vs. 7.7% and 59% vs. 31.7%, respectively). No differences were found between HI seroreactivity detected in SWs and Cs against swH1N2 (33.3% vs. 40.4%) and swH3N2 (51.2 vs. 55.4%) viruses. These findings indicate the occurrence of swH1N1 transmission from pigs to Italian SWs. A significant increase of H1N1pdm seroprevalences occurred in the post-pandemic peak subperiod in the Cs (pimmunity related to previous swH1N1 infections. These data underline the importance of risk assessment and occupational health surveillance activities aimed at early detection and control of SIVs with pandemic potential in humans.

  9. Evolutionary genomics of the pandemic 2009 H1N1 influenza viruses (pH1N 1v

    Directory of Open Access Journals (Sweden)

    Song Gang

    2011-05-01

    Full Text Available Abstract Background A new strain of human H1N1 influenza A viruses was broken out in the April 2009 and caused worldwide pandemic emergency. The present study is trying to estimate a temporal reassortment history of 2009 H1N1 viruses by phylogenetic analysis based on a total 394 sequences of H1N1viruses isolated from swine, human and avian. Results Phylogenetic trees of eight gene segments showed that viruses sampled from human formed a well-supported clade, whereas swine and avian lineages were intermixed together. A new divergence swine sublineage containing gene segments of 2009 H1N1 viruses was characterized, which were closely related with swine viruses collected from USA and South Korea during 2004 to 2007 in six segments (PB2, PB1, PA, HA, NP and NS, and to swine viruses isolated from Thailand during 2004 to 2005 in NA and M. Substitution rates were varied drastically among eight segments and the average substitution rate was generally higher in 2009 H1N1 than in swine and human viruses (F2,23 = 5.972, P dN/dS substitution ratios were identified in 2009 H1N1 than in swine and human viruses except M2 gene (F2, 25 = 3.779, P Conclusion Our results implied that at least four reassortments or transmissions probably occurred before 2009 H1N1 viruses. Initial reassortment arose in 1976 and avian-like Eurasian swine viruses emerged. The second transmission happened in Asia and North America between 1988 and 1992, and mostly influenced six segments (PB2, PB1, PA, HA, NP and NS. The third reassortment occurred between North American swine and avian viruses during 1998 to 2000, which involved PB2 and PA segments. Recent reassortments occurred among avian-to-swine reassortant, Eurasian and classical swine viruses during 2004 to 2005. South Korea, Thailand and USA, were identified as locations where reassortments most likely happened. The co-circulation of multiple swine sublineages and special lifestyle in Asia might have facilitated mixing of

  10. 20 CFR 655.735 - What are the special provisions for short-term placement of H-1B nonimmigrants at place(s) of...

    Science.gov (United States)

    2010-04-01

    ... Applications and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty... E-3 Visas in Specialty Occupations § 655.735 What are the special provisions for short-term... 31) or the employer's fiscal year, whichever the employer chooses. (e) The employer may not make...

  11. Genetic Characterization and Evolution of H1N1pdm09 after Circulation in a Swine Farm

    Directory of Open Access Journals (Sweden)

    Arianna Boni

    2014-01-01

    Full Text Available Following the emergence of the A(H1N1pdm09 in humans, this novel influenza virus was reverse transmitted from infected people to swine population worldwide. In this study we investigated the molecular evolution of A(H1N1pdm09 virus identified in pigs reared in a single herd. Nasal swabs taken from pigs showing respiratory distress were tested for influenza type A and A(H1N1pdm09 by real-time RT-PCR assays. Virus isolation from positive samples was attempted by inoculation of nasal swabs samples into specific pathogen free embryonated chicken eggs (ECE and complete genome sequencing was performed on virus strains after replication on ECE or from original swab sample. The molecular analysis of hemagglutinin (HA showed, in four of the swine influenza viruses under study, a unique significant amino acid change, represented by a two-amino acid insertion at the HA receptor binding site. Phylogenetic analysis of HA, neuraminidase, and concatenated internal genes revealed a very similar topology, with viruses under study forming a separate cluster, branching outside the A(H1N1pdm09 isolates recognized until 2014. The emergence of this new cluster of A(H1N1pdm09 in swine raises further concerns about whether A(H1N1pdm09 with new molecular characteristics will become established in pigs and potentially transmitted to humans.

  12. 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.

  13. Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with (11)C-SA4503 and microPET

    NARCIS (Netherlands)

    Kuzhuppilly Ramakrishnan, Nisha; Visser, Anniek K. D.; Schepers, Marianne; Luurtsema, Gert; Nyakas, Csaba J.; Elsinga, Philip H.; Ishiwata, Kiichi; Dierckx, Rudi A. J. O.; van Waarde, Aren

    2014-01-01

    RATIONALE: Sigma-1 receptor agonists are under investigation as potential disease-modifying agents for several CNS disorders. Donepezil, an acetylcholinesterase inhibitor used for the symptomatic treatment of Alzheimer's disease, is also a high-affinity sigma-1 agonist. OBJECTIVES: The objectives of

  14. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements

    DEFF Research Database (Denmark)

    Ettrup, Anders; Mikkelsen, Jens D; Lehel, Szabolcs

    2011-01-01

    Small-molecule a(7) nicotinic acetylcholine receptor (a(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled a(7)nAChR PET tracer would be important for in vivo quantification of a(7)n...

  15. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements

    DEFF Research Database (Denmark)

    Ettrup, Anders; Mikkelsen, Jens D; Lehel, Szabolcs

    2011-01-01

    Small-molecule α(7) nicotinic acetylcholine receptor (α(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled α(7)nAChR PET tracer would be important for in vivo quantification of α(7)n...

  16. 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.

  17. Crystal structure of bis(1-benzyl-1H-1,2,4-triazole perchloric acid monosolvate

    Directory of Open Access Journals (Sweden)

    Yong-Qi Qin

    2014-12-01

    Full Text Available The title compound, 2C9H9N3·HClO4, was prepared by reaction of 1-benzyl-1H-1,2,4-triazole and HClO4 in ethanol at room temperature. The asymmetric unit consists of two molecules of 1-benzyl-1H-1,2,4-triazole and one of HClO4 molecule. The benzene and triazole rings make dihedral angles of 85.45 (8 and 84.76 (8° in the two molecules. The H-atom position of the perchloric acid molecule is split over two O atoms (real peaks on difference map, with site-occupation factors of 0.5. These H atoms form two classical hydrogen bonds [2.546 (5 and 2.620 (4 Å] with the same N atoms in both molecules. Five intermolecular non-classical C—H...O interactions, with C...O distances in the range 3.147 (5–3.483 (5 Å, are found in the crystal structure.

  18. Crystal structure of bis-(1-benzyl-1H-1,2,4-triazole) perchloric acid monosolvate.

    Science.gov (United States)

    Qin, Yong-Qi; Xue, Jin-Hui; Qiao, Yuan-Biao; Zhang, Zi-Feng

    2014-12-01

    The title compound, 2C9H9N3·HClO4, was prepared by reaction of 1-benzyl-1H-1,2,4-triazole and HClO4 in ethanol at room temperature. The asymmetric unit consists of two mol-ecules of 1-benzyl-1H-1,2,4-triazole and one of HClO4 mol-ecule. The benzene and triazole rings make dihedral angles of 85.45 (8) and 84.76 (8)° in the two mol-ecules. The H-atom position of the perchloric acid mol-ecule is split over two O atoms (real peaks on difference map), with site-occupation factors of 0.5. These H atoms form two classical hydrogen bonds [2.546 (5) and 2.620 (4) Å] with the same N atoms in both mol-ecules. Five inter-molecular non-classical C-H⋯O inter-actions, with C⋯O distances in the range 3.147 (5)-3.483 (5) Å, are found in the crystal structure.

  19. Alterations of Histone H1 Phosphorylation During Bladder Carcinogenesis

    Science.gov (United States)

    Telu, Kelly H.; Abbaoui, Besma; Thomas-Ahner, Jennifer M.; Zynger, Debra L.; Clinton, Steven K.

    2013-01-01

    There is a crucial need for development of prognostic and predictive biomarkers in human bladder carcinogenesis in order to personalize preventive and therapeutic strategies and improve outcomes. Epigenetic alterations, such as histone modifications, are implicated in the genetic dysregulation that is fundamental to carcinogenesis. Here we focus on profiling the histone modifications during the progression of bladder cancer. Histones were extracted from normal human bladder epithelial cells, an immortalized human bladder epithelial cell line (hTERT), and four human bladder cancer cell lines (RT4, J82, T24, and UMUC3) ranging from superficial low-grade to invasive high-grade cancers. Liquid Chromatography-Mass Spectrometry (LC-MS) profiling revealed a statistically significant increase in phosphorylation of H1 linker histones from normal human bladder epithelial cells to low-grade superficial to high-grade invasive bladder cancer cells. This finding was further validated by immunohistochemical staining of the normal epithelium and transitional cell cancer from human bladders. Cell cycle analysis of histone H1 phosphorylation by western blotting showed an increase of phosphorylation from G0/G1 phase to M phase, again supporting this as a proliferative marker. Changes in histone H1 phosphorylation status may further clarify epigenetic changes during bladder carcinogenesis and provide diagnostic and prognostic biomarkers or targets for future therapeutic interventions. PMID:23675690

  20. 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

  1. Designing inhibitors of M2 proton channel against H1N1 swine influenza virus.

    Directory of Open Access Journals (Sweden)

    Qi-Shi Du

    2010-02-01

    Full Text Available M2 proton channel of H1N1 influenza A virus is the target protein of anti-flu drugs amantadine and rimantadine. However, the two once powerful adamantane-based drugs lost their 90% bioactivity because of mutations of virus in recent twenty years. The NMR structure of the M2 channel protein determined by Schnell and Chou (Nature, 2008, 451, 591-595 may help people to solve the drug-resistant problem and develop more powerful new drugs against H1N1 influenza virus.Docking calculation is performed to build the complex structure between receptor M2 proton channel and ligands, including existing drugs amantadine and rimantadine, and two newly designed inhibitors. The computer-aided drug design methods are used to calculate the binding free energies, with the computational biology techniques to analyze the interactions between M2 proton channel and adamantine-based inhibitors.1 The NMR structure of M2 proton channel provides a reliable structural basis for rational drug design against influenza virus. 2 The channel gating mechanism and the inhibiting mechanism of M2 proton channel, revealed by the NMR structure of M2 proton channel, provides the new ideas for channel inhibitor design. 3 The newly designed adamantane-based inhibitors based on the modeled structure of H1N1-M2 proton channel have two pharmacophore groups, which act like a "barrel hoop", holding two adjacent helices of the H1N1-M2 tetramer through the two pharmacophore groups outside the channel. 4 The inhibitors with such binding mechanism may overcome the drug resistance problem of influenza A virus to the adamantane-based drugs.

  2. About Occupational Therapy

    Science.gov (United States)

    ... if}} {{{tweet}}} About Occupational Therapy What Is Occupational Therapy? Occupational therapy practitioners ask, "What matters to you?" not, " ... about our science-driven and evidence-based profession. Occupational Therapy: Improving Function While Controlling Costs 4 4 The ...

  3. The Genomic Landscape of the Somatic Linker Histone Subtypes H1.1 to H1.5 in Human Cells

    Directory of Open Access Journals (Sweden)

    Annalisa Izzo

    2013-06-01

    Full Text Available Human cells contain five canonical, replication-dependent somatic histone H1 subtypes (H1.1, H1.2, H1.3, H1.4, and H1.5. Although they are key chromatin components, the genomic distribution of the H1 subtypes is still unknown, and their role in chromatin processes has thus far remained elusive. Here, we map the genomic localization of all somatic replication-dependent H1 subtypes in human lung fibroblasts using an integrative DNA adenine methyltransferase identification (DamID analysis. We find in general that H1.2 to H1.5 are depleted from CpG-dense regions and active regulatory regions. H1.1 shows a DamID binding profile distinct from the other subtypes, suggesting a unique function. H1 subtypes can mark specific domains and repressive regions, pointing toward a role for H1 in three-dimensional genome organization. Our work integrates H1 subtypes into the epigenome maps of human cells and provides a valuable resource to refine our understanding of the significance of H1 and its heterogeneity in the control of genome function.

  4. The electronics of the H1 lead/scintillating-fibre calorimeters-H1 SpaCal Group

    Energy Technology Data Exchange (ETDEWEB)

    Appuhn, R.-D. E-mail: cozzika@hep.saclay.cea.fr; Arndt, C.; Barrelet, E.; Barschke, R.; Bassler, U.; Blouzon, F.; Boudry, V.; Brasse, F.; Bruel, Ph.; Bruncko, D.; Buchholz, R.; Cahan, B.; Chechelnitski, S.; Claxton, B.; Cozzika, G.; Cvach, J.; Dagoret-Campagne, S.; Dau, W.D.; Deckers, H.; Deckers, T.; Descamps, F.; Dirkmann, M.; Dowdell, J.; Drancourt, C.; Durant, O.; Efremenko, V.; Eisenhandler, E.; Eliseev, A.N.; Falley, G.; Ferencei, J.; Fleischer, M.; Fominykh, B.; Gadow, K.; Goerlach, U.; Gorbov, L.A.; Gorelov, I.; Grewe, M.; Hajduk, L.; Herynek, I.; Hladky, J.; Huette, M.; Hutter, H.; Janata, M.; Janczur, W.; Janoth, J.; Joensson, L.; Kacl, I.; Kolanoski, H.; Korbel, V.; Krivan, F.; Lacour, D.; Laforge, B.; Lamarche, F.; Landon, M.P.J.; Laporte, J.-F.; Lebollo, H.; Coguie, A. Le; Lehner, F.; Maracek, R.; Matricon, P.; Meier, K.; Meyer, A.; Migliori, A.; Moreau, F.; Mueller, G.; Murin, P.; Nagovizin, V.; Nicholls, T.C.; Ozerov, D.; Passerieux, J.-P.; Perez, E.; Pharabod, J.P.; Poeschl, R.; Renard, Ch.; Rostovtsev, A.; Royon, C.; Rybicki, K.; Schlief, S.; Schmitt, K.; Schuhmacher, A.; Semenov, A.; Shekelyan, V.; Sirois, Y.; Smirnov, P.A.; Solochenko, V.; Spalek, J.; Spielmann, S.; Steiner, H.; Stellberger, A.; Stiewe, J.; Tasevsky, M.; Tchernyshov, V.; Thiele, K.; Tzamariudaki, E.; Valkar, S.; Vallee, C.; Vallereau, A.; VanDenPlas, D.; Villet, G.; Wacker, K.; Walther, A.; Weber, M.; Wegener, D.; Wenk, T.; Zacek, J.; Zhokin, A.; Zini, P.; Zuber, K

    1999-05-01

    The electronic system developed for the SpaCal lead/scintillating-fibre calorimeters of the H1 detector in operation at the HERA ep collider is described in detail and the performance achieved during H1 data taking is presented. The 10 MHz bunch crossing rate of HERA puts severe constraints on the requirements of the electronics. The energy and time readout are performed, respectively, with a 14-bit dynamic range and with a resolution of {approx}0.4 ns. The trigger branch consists of a nanosecond-resolution calorimetric time of flight for background rejection and an electron trigger based on analog 'sliding windows'. The on-line background rejection currently achieved is {approx}10{sup 6}. The electron trigger allows a low-energy trigger threshold to be set at {approx}0.50{+-}0.08 (RMS) GeV with an efficiency {>=}99.9%. The energy and time performance of the readout and trigger electronics is based on a newly developed low noise ({sigma}{sub noise}{approx}0.4 MeV) wideband (f{<=}200 mHz) preamplifier located at the output of the photomultipliers which are used for the fibre light readout in the {approx}1 T magnetic field of H1.

  5. Post-translational modifications of linker histone H1 variants in mammals

    Science.gov (United States)

    Starkova, T. Yu; Polyanichko, A. M.; Artamonova, T. O.; Khodorkovskii, M. A.; Kostyleva, E. I.; Chikhirzhina, E. V.; Tomilin, A. N.

    2017-02-01

    The covalent modifications of the linker histone H1 and the core histones are thought to play an important role in the control of chromatin functioning. Histone H1 variants from K562 cell line (hH1), mouse (mH1) and calf (cH1) thymi were studied by matrix-activated laser desorption/ionization fourier transform ion cyclotron resonance mass-spectroscopy (MALDI-FT-ICR-MS). The proteomics analysis revealed novel post-translational modifications of the histone H1, such as meK34-mH1.4, meK35-cH1.1, meK35-mH1.1, meK75-hH1.2, meK75-hH1.3, acK26-hH1.4, acK26-hH1.3 and acK17-hH1.1. The comparison of the hH1, mH1 and cH1 proteins has demonstrated that the types and positions of the post-translational modifications of the globular domains of the H1.2-H1.4 variants are very conservative. However, the post-translational modifications of the N- and C-terminal tails of H1.2, H1.3 and H1.4 are different. The differences of post-translational modifications in the N- and C-terminal tails of H1.2, H1.3 and H1.4 likely lead to the differences in DNA-H1 and H1-protein interactions.

  6. Post-translational modifications of linker histone H1 variants in mammals.

    Science.gov (United States)

    Starkova, T Yu; Polyanichko, A M; Artamonova, T O; Khodorkovskii, M A; Kostyleva, E I; Chikhirzhina, E V; Tomilin, A N

    2017-02-16

    The covalent modifications of the linker histone H1 and the core histones are thought to play an important role in the control of chromatin functioning. Histone H1 variants from K562 cell line (hH1), mouse (mH1) and calf (cH1) thymi were studied by matrix-activated laser desorption/ionization fourier transform ion cyclotron resonance mass-spectroscopy (MALDI-FT-ICR-MS). The proteomics analysis revealed novel post-translational modifications of the histone H1, such as meK34-mH1.4, meK35-cH1.1, meK35-mH1.1, meK75-hH1.2, meK75-hH1.3, acK26-hH1.4, acK26-hH1.3 and acK17-hH1.1. The comparison of the hH1, mH1 and cH1 proteins has demonstrated that the types and positions of the post-translational modifications of the globular domains of the H1.2-H1.4 variants are very conservative. However, the post-translational modifications of the N- and C-terminal tails of H1.2, H1.3 and H1.4 are different. The differences of post-translational modifications in the N- and C-terminal tails of H1.2, H1.3 and H1.4 likely lead to the differences in DNA-H1 and H1-protein interactions.

  7. H1-Antihistamine Premedication in NSAID-Associated Urticaria.

    Science.gov (United States)

    Trautmann, Axel; Anders, Diana; Stoevesandt, Johanna

    Therapeutic options for pain management are restricted in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced or NSAID-exacerbated urticaria because strong cyclooxygenase (COX)-I inhibiting NSAID cannot be used. Alternative NSAID such as weak COX-I inhibitors or selective COX-II inhibitors are sometimes not sufficiently effective or have potentially troublesome adverse effects. To date, prophylactic premedication with H1-antihistamines is rarely practiced in patients concurrently suffering from recurrent pain and NSAID-associated urticaria. Our data analysis aims to clarify whether prophylactic premedication before the intake of NSAID is effective, safe, and practicable. Data of 21 patients with NSAID-induced or NSAID-exacerbated urticaria who underwent single dose NSAID provocation 30 minutes after premedication with 5 mg desloratadine were retrospectively evaluated. After H1-antihistamine premedication, 17 patients tolerated 16 single dose provocation tests with strong COX-I inhibitors and 2 tests with weak COX-I inhibitors. Despite H1-antihistamine premedication, 2 patients developed acute urticaria after intake of 400 mg ibuprofen. Another 2 patients with acute urticaria after intake of 800 mg ibuprofen tolerated 400 mg ibuprofen and 1000 mg paracetamol, respectively. In the majority of patients with NSAID-induced or NSAID-exacerbated urticaria concurrently suffering from intermittent pain, a premedication regimen with 5 mg desloratadine 30 minutes before intake of a strong COX-I inhibitor seems to be effective, safe, and practicable. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Occupational epidemiology.

    Science.gov (United States)

    Guidotti, T L

    2000-02-01

    The epidemiological literature for assessing risk in many, if not most, modern occupations has now become sufficiently obsolete that it can no longer be depended upon to guide either prevention or adjudication of compensation. This obsolescence must be dealt with by developing new sources of information pertinent to occupational hazards and the risks associated with most occupations. Ideally, a comprehensive surveillance mechanism that would be automatically updated for the changing risk in a changing economy would be ideal and may be attainable with further developments in health information technology. The characteristics of such a system are described. However, there are many obstacles to such a system which appear insurmountable in the short term. A more eclectic plan for cooperation and data-sharing would help in the short term and would establish a pattern of collaboration that could both place adjudication on a more solid foundation and avoid allegations of collusion in business. The general outline for a practical programme of collaboration along these lines is presented.

  10. Characterization in vitro and in vivo of a pandemic H1N1 influenza virus from a fatal case.

    Science.gov (United States)

    Rodriguez, Ariel; Falcon, Ana; Cuevas, Maria Teresa; Pozo, Francisco; Guerra, Susana; García-Barreno, Blanca; Martinez-Orellana, Pamela; Pérez-Breña, Pilar; Montoya, Maria; Melero, Jose Antonio; Pizarro, Manuel; Ortin, Juan; Casas, Inmaculada; Nieto, Amelia

    2013-01-01

    Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32).

  11. Characterization in vitro and in vivo of a pandemic H1N1 influenza virus from a fatal case.

    Directory of Open Access Journals (Sweden)

    Ariel Rodriguez

    Full Text Available Pandemic 2009 H1N1 (pH1N1 influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M or from a fatal case (F, both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5 genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32.

  12. 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.

  13. Occupation: nurse; occupational hazard: radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nickson, K.

    1984-03-01

    The work of the occupational health nurses at the Pickering Generating Station is described. A staff of two nurses teach first aid and safety, practice an emergency plan, and monitor personnel for minimum health standards for radiation workers. Special attention is paid to problems which might be aggravated by radiation, such as skin complaints, respiratory diseases, emotional stability, or phobias regarding heights, plastic suits, or radiation itself. Procedures used in treating contaminated personnel are outlined.

  14. Sensitization of the histamine H1 receptor by increased ligand affinity.

    NARCIS (Netherlands)

    Bloemers, S.M.; Verheule, S.; Peppelenbosch, M.P.; Smit, M.J.; Tertoolen, L.G.J.; de Laat, S.

    1998-01-01

    Histamine regulates a variety of physiological processes including inflammation, gastric acid secretion, and neurotransmission. The cellular response to histamine is subject to dynamic control, and exaggerated histamine reactivity in response to cysteinyl leukotrienes and other stimuli is important

  15. Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH(1)R, but low affinity to hH(4)R.

    Science.gov (United States)

    Wagner, Eva; Wittmann, Hans-Joachim; Elz, Sigurd; Strasser, Andrea

    2011-11-01

    In literature, a synergism between histamine H(1) and H(4) receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H(1) antagonist and JNJ7777120, a H(4) receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H(1) and one H(4) pharmacophor, connected by an appropriate spacer, in order to address both, H(1)R and H(4)R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH(1)R and hH(4)R. The new compounds revealed (high) affinity to hH(1)R, but showed only low affinity to hH(4)R. Additionally, we performed molecular dynamic studies for some selected compounds at hH(1)R, in order to obtain information about the binding mode of these compounds on molecular level. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Occupational physiology

    CERN Document Server

    Toomingas, Allan; Tornqvist, Ewa Wigaeus

    2011-01-01

    In a clear and accessible presentation, Occupational Physiology focuses on important issues in the modern working world. Exploring major public health problems-such as musculoskeletal disorders and stress-this book explains connections between work, well-being, and health based on up-to-date research in the field. It provides useful methods for risk assessment and guidelines on arranging a good working life from the perspective of the working individual, the company, and society as a whole.The book focuses on common, stressful situations in different professions. Reviewing bodily demands and r

  17. Citrullination regulates pluripotency and histone H1 binding to chromatin

    Science.gov (United States)

    Christophorou, Maria A.; Castelo-Branco, Gonçalo; Halley-Stott, Richard P.; Oliveira, Clara Slade; Loos, Remco; Radzisheuskaya, Aliaksandra; Mowen, Kerri A.; Bertone, Paul; Silva, José C. R.; Zernicka-Goetz, Magdalena; Nielsen, Michael L.; Gurdon, John B.; Kouzarides, Tony

    2014-03-01

    Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although 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 response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes 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 insights into how citrullination regulates chromatin compaction.

  18. 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.

  19. Pandemic H1N1 influenza virus in Chilean commercial turkeys with genetic and serologic comparisons to U.S. H1N1 avian influenza vaccine isolates

    Science.gov (United States)

    Beginning in April 2009, a novel H1N1 influenza virus has caused acute respiratory disease in humans, first in Mexico and then spreading around the world. The resulting pandemic influenza A H1N1 2009 (pH1N1) virus was isolated in swine in Canada in June, 2009, and later in turkey breeders in Chile, ...

  20. Immunity to pre-1950 H1N1 influenza viruses confers cross-protection against the pandemic swine-origin 2009 A (H1N1) influenza virus.

    Science.gov (United States)

    Skountzou, Ioanna; Koutsonanos, Dimitrios G; Kim, Jin Hyang; Powers, Ryan; Satyabhama, Lakshmipriyadarshini; Masseoud, Feda; Weldon, William C; Martin, Maria Del Pilar; Mittler, Robert S; Compans, Richard; Jacob, Joshy

    2010-08-01

    The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, 60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that influenza strains that circulated 50-60 y ago might provide cross-protection against the swine-origin 2009 H1N1 influenza virus. To test this, we determined the ability of representative H1N1 influenza viruses that circulated in the human population from 1930 to 2000, to induce cross-reactivity to and cross-protection against the pandemic swine-origin H1N1 virus, A/California/04/09. We show that exposure of mice to the 1947 virus, A/FM/1/47, or the 1934 virus, A/PR/8/34, induced robust cross-protective immune responses and these mice were protected against a lethal challenge with mouse-adapted A/California/04/09 H1N1 virus. Conversely, we observed that mice exposed to the 2009 H1N1 virus were protected against a lethal challenge with mouse-adapted 1947 or 1934 H1N1 viruses. In addition, exposure to the 2009 H1N1 virus induced broad cross-reactivity against H1N1 as well as H3N2 influenza viruses. Finally, we show that vaccination with the older H1N1 viruses, particularly A/FM/1/47, confers protective immunity against the 2009 pandemic H1N1 virus. Taken together, our data provide an explanation for the decreased susceptibility of the elderly to the 2009 H1N1 outbreak and demonstrate that vaccination with the pre-1950 influenza strains can cross-protect against the pandemic swine-origin 2009 H1N1 influenza virus.

  1. Narcolepsy and H1N1 vaccination: a link?

    Science.gov (United States)

    Thebault, Simon; Vincent, Angela; Gringras, Paul

    2013-11-01

    A number of European countries have reported a dramatic increase in the rates of childhood narcolepsy with cataplexy in children immunized with a split-virion adjuvanted swine flu vaccine. Here, we review the strengths and weaknesses of these epidemiological studies and possible neuroimmunological mechanisms. Initial concerns of a 13-fold increased relative risk of narcolepsy were raised by the Scandinavian health protection agencies in 2010. Subsequent retrospective studies support these findings in Canada, France, Ireland, England and Denmark. The cases are predominantly young children who present with severe and rapid onset of cataplexy as well as narcolepsy often within a few weeks of vaccination. The proposed mechanism for postvaccination narcolepsy is one in which an environmental trigger causes or enhances an antibody-mediated autoimmune response in patients with a preexisting genetic susceptibility. However, there have not yet been any reports of specific autoimmunity, either antibody or T-cell-mediated. There is a strong association between narcolepsy and H1N1 vaccination. However, whether this reflects a true increase in affected individuals or a hastening of disease onset in individuals who would otherwise have developed narcolepsy later will become clear in the coming years. The pathological explanation of this association and narcolepsy is likely to be autoimmune, although supportive evidence is lacking.Video abstract available: See the Video Supplementary Digital Content 1 (http://links.lww.com/COPM/A9).

  2. Physics from the first year of H1 at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Kiesling, C. [Max-Planck-Institut fuer Physik, Muenchen (Germany)

    1994-12-01

    In this report the author summarizes the results from the H1 experiment at HERA, using the data from the first year of running, 1992, when an integrated luminosity of 25 nb{sup {minus}1} has been recorded. These results include photoproduction, the measurement of the deep inelastic scattering, both for neutral current reactions and the search for physics beyond the Standard Model. Apart from the measurement of a moderate rise in the total photoproduction cross section, clear evidence is seen for hard interactions in single particle spectra and jet production, requiring a {open_quotes}resolved{close_quotes} photon as expected in QCD. The investigation of the global properties of hadronic final states in deep inelastic scattering demonstrates the need for further improvement of present QCD models. Evidence is found for a class of events with diffractive characteristics, exhibiting a large gap of hadronic energy flow about the proton direction. The proton structure function F{sub 2}{sup p}(x, Q{sup 2}) has been measured for neutral current events for Bjorken x in the range 10{sup {minus}4} - 10{sup {minus}2} and Q{sup 2} > 5 GeV{sup 2}, showing a steep rise towards small x. Furthermore, using 1993 data, a measurement of the cross section for charged current events is presented, clearly demonstrating, for the first time, the propagator effect of the W boson. Finally, new limits on leptoquarks, leptogluons, and excited electrons have been determined.

  3. Constrained H1-regularization schemes for diffeomorphic image registration

    Science.gov (United States)

    Mang, Andreas; Biros, George

    2017-01-01

    We propose regularization schemes for deformable registration and efficient algorithms for their numerical approximation. We treat image registration as a variational optimal control problem. The deformation map is parametrized by its velocity. Tikhonov regularization ensures well-posedness. Our scheme augments standard smoothness regularization operators based on H1- and H2-seminorms with a constraint on the divergence of the velocity field, which resembles variational formulations for Stokes incompressible flows. In our formulation, we invert for a stationary velocity field and a mass source map. This allows us to explicitly control the compressibility of the deformation map and by that the determinant of the deformation gradient. We also introduce a new regularization scheme that allows us to control shear. We use a globalized, preconditioned, matrix-free, reduced space (Gauss–)Newton–Krylov scheme for numerical optimization. We exploit variable elimination techniques to reduce the number of unknowns of our system; we only iterate on the reduced space of the velocity field. Our current implementation is limited to the two-dimensional case. The numerical experiments demonstrate that we can control the determinant of the deformation gradient without compromising registration quality. This additional control allows us to avoid oversmoothing of the deformation map. We also demonstrate that we can promote or penalize shear whilst controlling the determinant of the deformation gradient. PMID:29075361

  4. Occupational Therapy (For Parents)

    Science.gov (United States)

    ... Late for the Flu Vaccine? Eating Disorders Arrhythmias Occupational Therapy KidsHealth > For Parents > Occupational Therapy Print A A ... for some kids. continue Kids Who Might Need Occupational Therapy According to the AOTA, kids with these medical ...

  5. Antigenic drift of the pandemic 2009 A(H1N1 influenza virus in A ferret model.

    Directory of Open Access Journals (Sweden)

    Teagan Guarnaccia

    Full Text Available Surveillance data indicate that most circulating A(H1N1pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1pdm09 influenza

  6. Image processing occupancy sensor

    Science.gov (United States)

    Brackney, Larry J.

    2016-09-27

    A system and method of detecting occupants in a building automation system environment using image based occupancy detection and position determinations. In one example, the system includes an image processing occupancy sensor that detects the number and position of occupants within a space that has controllable building elements such as lighting and ventilation diffusers. Based on the position and location of the occupants, the system can finely control the elements to optimize conditions for the occupants, optimize energy usage, among other advantages.

  7. Occupational therapy students' perceptions of occupational therapy.

    Science.gov (United States)

    Turpin, Merrill June; Rodger, Sylvia; Hall, Anna R

    2012-10-01

    An understanding of students' perceptions of occupational therapy on entry is required to recognise how professional socialisation occurs through curriculum. Findings pertain to a qualitative study investigating students' perceptions of occupational therapy upon entry to two occupational therapy programmes in Australia. Students commencing Bachelor of Occupational Therapy and Masters of Occupational Therapy Studies programmes participated in the study (n = 462). A purpose-designed questionnaire was distributed to students in the first lecture of each programme. Preliminary analysis comprised identification of keywords/phrases and coding categories were generated from patterns of keywords. Frequency counts and percentages of keywords/phrases within categories were completed. Students' responses were categorised as 'what' occupational therapists do; 'how' they do it; 'why' they do it; and 'who' they work with. In 'what' occupational therapists do students frequently described 'helping' people. Both undergraduate and graduate entry masters students used the term 'rehabilitation' to describe how occupational therapy is done, with graduate entry students occasionally responding with 'through occupation' and 'modifying the environment'. Students perceived the 'why' of occupational therapy as getting back to 'everyday activities', with some students emphasising returning to 'normal' activities or life. Regarding the 'who' category, students also thought occupational therapists worked with people with an 'injury' or 'disability'. Students entered their occupational therapy programmes with perceptions consistent with the general public's views of occupational therapy. However, graduate entry students exposed to a pre-reading package prior to entry had more advanced occupational therapy concepts than undergraduate students. © 2011 The Authors. Australian Occupational Therapy Journal © 2011 Occupational Therapy Australia.

  8. A surveillance system to reduce transmission of pandemic H1N1 (2009 influenza in a 2600-bed medical center.

    Directory of Open Access Journals (Sweden)

    Tsui-Ping Chu

    Full Text Available BACKGROUND: Concerns have been raised about how the transmission of emerging infectious diseases from patients to healthcare workers (HCWs and vice versa could be recognized and prevented in a timely manner. An effective strategy to block transmission of pandemic H1N1 (2009 influenza in HCWs is important. METHODOLOGY/PRINCIPAL FINDINGS: An infection control program was implemented to survey and prevent nosocomial outbreaks of H1N1 (2009 influenza at a 2,600-bed, tertiary-care academic hospital. In total, 4,963 employees at Kaohsiung Chang Gung Memorial Hospital recorded their temperature and received online education on control practices for influenza infections. Administration records provided vaccination records and occupational characteristics of all HCWs. Early recognition of a pandemic H1N1 (2009 influenza case was followed by a semi-structured questionnaire to analyze possible routes of patient contact, household contact, or unspecified contact. Surveillance spanned August 1, 2009 to January 31, 2010; 51 HCWs were confirmed to have novel H1N1 (2009 influenza by quantitative real-time reverse transcription polymerase chain reaction. Prevalence of patient contact, household contact, or unspecified contact infection was 13.7% (7/51, 13.7% (7/51, and 72.5% (37/51, respectively. The prevalence of the novel H1N1 infection was significantly lower among vaccinated HCWs than among unvaccinated HCWs (p<0.001. Higher viral loads in throat swabs were found in HCWs with patient and household contact infection than in those with unspecified contact infection (4.15 vs. 3.53 copies/mL, log(10, p = 0.035. CONCLUSION: A surveillance system with daily temperature recordings and online education for HCWs is important for a low attack rate of H1N1 (2009 influenza transmission before H1N1 (2009 influenza vaccination is available, and the attack rate is further decreased after mass vaccination. Unspecified contact infection rates were significantly higher than

  9. Sequence analysis of haemagglutinin and neuraminidase of H1N1 strain from a patient coinfected with Mycobacterium tuberculosis.

    Science.gov (United States)

    Alghamdi, Ahmed N; Mahfouz, Mohammad E; Hamdi, Fahd A; Al Aboud, Daifullah; Al-Laylah, Tawfiq Z; Alotaibi, Mohammed I; Al-Thomali, Khalid W A; Abdel-Moneim, Ahmed S

    2017-08-01

    The 2009 H1N1 pandemic (H1N1pdm09) was associated with a considerable influenza-related morbidity and mortality. Among the complications, Mycobacterial tuberculosis was recorded as a coinfection with influenza in rare cases. The full-length sequences of the viral haemagglutinin and neuraminidase of H1N1pdm09 influenza A virus were analyzed from a recently infected patient. The patient was chronically infected with Mycobacterium tuberculosis. Molecular modelling and in-silico docking of the virus, and other selected strains with the drug oseltamivir were conducted and compared. Sequence analysis of the viral haemagglutinin revealed it to be closely related to the 6B.1 clade, with high identity to the circulating H1N1pdm09 strains, and confirmed that the virus still harbouring high affinity to the α-2,6-sialic acid human receptor. The viral neuraminidase showed high identity to the neuraminidase of the recently circulating strains of the virus with no evidence of the development of oseltamivir-resistant mutants. Regular monitoring of the circulating strains is recommended to screen for a possible emergence of drug-resistant strains. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Inelastic neutron scattering in Zr2NiH1.9 and Zr2NiH4.6

    Indian Academy of Sciences (India)

    meV (table 1) may be associated to d site occupancy of hydrogen atom in Zr2NiH4.6. 4. Conclusions. The inelastic neutron scattering measurements have been reported for both. Zr2NiH1.9 and Zr2NiH4.6. The observed vibrational frequencies in the range of. 35–180 meV are assigned to the vibration of hydrogen atoms in ...

  11. Caracterització funcional de dBigH1: la variant germinal i embrionària d'histona H1 a Drosophila

    OpenAIRE

    Pérez Montero, Salvador

    2015-01-01

    Durant el desenvolupament d’aquesta tesi doctoral hem identificat i caracteritzat la variant d’histona H1 present a la línia germinal i l’embrió primerenc de Drosophila melanogaster. Els metazous contenen múltiples variants d’histona H1. Particularment, la majoria d’espècies estudiades contenen diverses variants d’histona H1 que reemplacen les H1 somàtiques a la línia germinal i als primers estadis del desenvolupament embrionari. Drosophila era l’excepció ja que, fins ara tan sols es con...

  12. Aptamers that bind to the hemagglutinin of the recent pandemic influenza virus H1N1 and efficiently inhibit agglutination.

    Science.gov (United States)

    Gopinath, Subash C B; Kumar, Penmetcha K R

    2013-11-01

    Influenza virus hemagglutinin (HA) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for typing influenza A viruses. In this study we have selected RNA aptamers (D-12 and D-26) that specifically target the HA protein of the recent pandemic influenza virus pdmH1N1 (A/California/07/2009). Among the selected aptamers the D-26 aptamer showed higher affinity for the HA of pdmH1N1 and was able to distinguish HA derived from other sub-types of influenza A viruses. The affinity of the D-26 aptamer was further improved upon incorporation of 2'-fluoropyrimidines to a level of 67 fM. Furthermore, the high affinity D-12 and D-26 aptamers were tested for their ability to interfere with HA-glycan interactions using a chicken red blood cell (RBC) agglutination assay. At a concentration of 200 nM the D-26 aptamer completely abolished the agglutination of RBCs, whereas D-12 only did so at 400 nM. These studies suggest that the selected aptamer D-26 not only has a higher affinity and specificity for the HA of pdmH1N1 but also has a better ability to efficiently interfere with HA-glycan interactions compared with the D-12 aptamer. The D-26 aptamer warrants further study regarding its application in developing topical virucidal products against the pdmH1N1 virus and also in surveillance of the pdmH1N1 influenza virus. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Dicarbonyl Induced Structural Perturbations Make Histone H1 Highly Immunogenic and Generate an Auto-Immune Response in Cancer.

    Directory of Open Access Journals (Sweden)

    Abdul Rouf Mir

    Full Text Available Increased oxidative stress under hyperglycemic conditions, through the interaction of AGEs with RAGE receptors and via activation of interleukin mediated transcription signalling, has been reported in cancer. Proteins modifications are being explored for their roles in the development and progression of cancer and autoantibody response against them is gaining interest as a probe for early detection of the disease. This study has analysed the changes in histone H1 upon modification by methylglyoxal (MG and its implications in auto-immunopathogenesis of cancer. Modified histone showed modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs. It showed masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence. MG aggressively oxidized histone H1 leading to the accumulation of reactive carbonyls. Far UV CD measurements showed di-carbonyl induced enhancement of the alpha structure and the induction of beta sheet conformation; and thermal denaturation (Tm studies confirmed the thermal stability of the modified histone. FTIR analysis showed amide I band shift, generation of a carboxyethyl group and N-Cα vibrations in the modified histone. LCMS analysis confirmed the formation of Nε-(carboxyethyllysine and electron microscopic studies revealed the amorphous aggregate formation. The modified histone showed altered cooperative binding with DNA. Modified H1 induced high titre antibodies in rabbits and the IgG isolated form sera of rabbits immunized with modified H1 exhibited specific binding with its immunogen in Western Blot analysis. IgG isolated from the sera of patients with lung cancer, prostate cancer, breast cancer and cancer of head and neck region showed better recognition for neo-epitopes on the modified histone, reflecting the presence of circulating autoantibodies in cancer. Since reports suggest a link between AGE-RAGE axis and

  14. 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

    ... training, including incumbent worker training, and placement into high- growth industries and occupations... control group members. This qualitative information will enable the evaluation to describe the program...

  15. 20 CFR 655.705 - What Federal agencies are involved in the H-1B and H-1B1 programs, and what are the...

    Science.gov (United States)

    2010-04-01

    ... offer a position filled by an H-1B nonimmigrant to an equally or better qualified United States worker....S. workers, to offer the job to U.S. applicants who are equally or better qualified than the H-1B... EMPLOYMENT OF FOREIGN WORKERS IN THE UNITED STATES Labor Condition Applications and Requirements for...

  16. H1DS: A new web-based data access system

    Energy Technology Data Exchange (ETDEWEB)

    Pretty, D.G., E-mail: david.pretty@anu.edu.au; Blackwell, B.D.

    2014-05-15

    Highlights: • We present H1DS, a new RESTful web service for accessing fusion data. • We examine the scalability and extensibility of H1DS. • We present a fast and user friendly web browser client for the H1DS web service. • A summary relational database is presented as an application of the H1DS API. - Abstract: A new data access system, H1DS, has been developed and deployed for the H-1 Heliac at the Australian Plasma Fusion Research Facility. The data system provides access to fusion data via a RESTful web service. With the URL acting as the API to the data system, H1DS provides a scalable and extensible framework which is intuitive to new users, and allows access from any internet connected device. The H1DS framework, originally designed to work with MDSplus, has a modular design which can be extended to provide access to alternative data storage systems.

  17. Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata

    DEFF Research Database (Denmark)

    Dao, Trong Tuan; Nguyen, Phi Hung; Lee, Hong Sik

    2011-01-01

    -8) chalcones were isolated as active principles from the acetone extract of Glycyrrhiza inflata. Compounds 3 and 6 without prenyl group showed strong inhibitory effects on various neuraminidases from influenza viral strains, H1N1, H9N2, novel H1N1 (WT), and oseltamivir-resistant novel H1N1 (H274Y) expressed...

  18. File list: Oth.ALL.20.H1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.20.H1.AllCell dm3 TFs and others H1 All cell types SRX287934,SRX287933,SRX2...87755,SRX287756 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.ALL.20.H1.AllCell.bed ...

  19. Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines.

    Directory of Open Access Journals (Sweden)

    Balaji Manicassamy

    2010-01-01

    Full Text Available The recent 2009 pandemic H1N1 virus infection in humans has resulted in nearly 5,000 deaths worldwide. Early epidemiological findings indicated a low level of infection in the older population (>65 years with the pandemic virus, and a greater susceptibility in people younger than 35 years of age, a phenomenon correlated with the presence of cross-reactive immunity in the older population. It is unclear what virus(es might be responsible for this apparent cross-protection against the 2009 pandemic H1N1 virus. We describe a mouse lethal challenge model for the 2009 pandemic H1N1 strain, used together with a panel of inactivated H1N1 virus vaccines and hemagglutinin (HA monoclonal antibodies to dissect the possible humoral antigenic determinants of pre-existing immunity against this virus in the human population. By hemagglutinination inhibition (HI assays and vaccination/challenge studies, we demonstrate that the 2009 pandemic H1N1 virus is antigenically similar to human H1N1 viruses that circulated from 1918-1943 and to classical swine H1N1 viruses. Antibodies elicited against 1918-like or classical swine H1N1 vaccines completely protect C57B/6 mice from lethal challenge with the influenza A/Netherlands/602/2009 virus isolate. In contrast, contemporary H1N1 vaccines afforded only partial protection. Passive immunization with cross-reactive monoclonal antibodies (mAbs raised against either 1918 or A/California/04/2009 HA proteins offered full protection from death. Analysis of mAb antibody escape mutants, generated by selection of 2009 H1N1 virus with these mAbs, indicate that antigenic site Sa is one of the conserved cross-protective epitopes. Our findings in mice agree with serological data showing high prevalence of 2009 H1N1 cross-reactive antibodies only in the older population, indicating that prior infection with 1918-like viruses or vaccination against the 1976 swine H1N1 virus in the USA are likely to provide protection against the 2009

  20. Bilastine: a new nonsedating oral H1 antihistamine for treatment of allergic rhinoconjunctivitis and urticaria.

    Science.gov (United States)

    Wolthers, Ole D

    2013-01-01

    Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

  1. Bilastine: A New Nonsedating Oral H1 Antihistamine for Treatment of Allergic Rhinoconjunctivitis and Urticaria

    Directory of Open Access Journals (Sweden)

    Ole D. Wolthers

    2013-01-01

    Full Text Available Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

  2. Pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effect of bilastine.

    Science.gov (United States)

    Jauregizar, Nerea; de la Fuente, Leire; Lucero, Maria Luisa; Sologuren, Ander; Leal, Nerea; Rodríguez, Mónica

    2009-01-01

    To model the pharmacokinetic and pharmacodynamic relationship of bilastine, a new histamine H(1) receptor antagonist, from single- and multiple-dose studies in healthy adult subjects. The pharmacokinetic model was developed from different single-dose and multiple-dose studies. In the single-dose studies, a total of 183 subjects received oral doses of bilastine 2.5, 5, 10, 20, 50, 100, 120, 160, 200 and 220 mg. In the multiple-dose studies, 127 healthy subjects received bilastine 10, 20, 40, 50, 80, 100, 140 or 200 mg/day as multiple doses during a 4-, 7- or 14-day period. The pharmacokinetic profile of bilastine was investigated using a simultaneous analysis of all concentration-time data by means of nonlinear mixed-effects modelling population pharmacokinetic software NONMEM version 6.1. Plasma concentrations were modelled according to a two-compartment open model with first-order absorption and elimination. For the pharmacodynamic analysis, the inhibitory effect of bilastine (inhibition of histamine-induced wheal and flare) was assessed on a preselected time schedule, and the predicted typical pharmacokinetic profile (based on the pharmacokinetic model previously developed) was used. An indirect response model was developed to describe the pharmacodynamic relationships between flare or wheal areas and bilastine plasma concentrations. Finally, once values of the concentration that produced 50% inhibition (IC(50)) had been estimated for wheal and flare effects, simulations were carried out to predict plasma concentrations for the doses of bilastine 5, 10 and 20 mg at steady state (72-96 hours). A non-compartmental analysis resulted in linear kinetics of bilastine in the dose range studied. Bilastine was characterized by two-compartmental kinetics with a rapid-absorption phase (first-order absorption rate constant = 1.50 h(-1)), plasma peak concentrations were observed at 1 hour following administration and the maximal response was observed at approximately 4 hours

  3. 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.

  4. Blocking histamine H(1) improves learning and mnemonic dysfunction in mice with social isolation plus repeated methamphetamine injection.

    Science.gov (United States)

    Jia, Feiyong; Mobarakeh, Jalal Izadi; Dai, Hongmei; Kato, Motohisa; Xu, Ajing; Okuda, Tomohiro; Sakurai, Eiko; Okamura, Nobuyuki; Takahashi, Kazuhiro; Yanai, Kazuhiko

    2008-06-01

    The aim of this study was to investigate the effects of histamine H(1) and H(3) antagonists on learning and mnemonic dysfunction in mice. Two H(1) antagonists, pyrilamine and clozapine, and the prototypic H(3) antagonist thioperamide were used to study the role of histamine in mice with social isolation and repeated methamphetamine administration. Mice with social isolation and repeated methamphetamine administration showed significant disruption of prepulse inhibition as compared to both the socially-housed mice and isolation-housing mice. Furthermore, social isolation and repeated methamphetamine administration caused significant learning and mnemonic dysfunctions. Treatment with clozapine improved learning and mnemonic ability in all of the tasks. Pyrilamine treatment ameliorated performance in all the tests examined except for the passive avoidance test. Thioperamide, however, did not change the learning and mnemonic ability. Donepezil, an acetylcholinesterase inhibitor, reversed the learning and mnemonic dysfunction in all four tasks. The present study has shown that blockade of histamine H(1) receptor improved the learning and mnemonic ability in mice, raising the possibility that treatment with clozapine or pyrilamine may improve learning and mnemonic performance in certain patients with psychiatric diseases such as schizophrenic patients with cognitive dysfunction.

  5. New genetic variants of influenza A(H1N1)pdm09 detected in Cuba during 2011-2013.

    Science.gov (United States)

    Arencibia, Amely; Acosta, Belsy; Muné, Mayra; Valdés, Odalys; Fernandez, Leandro; Medina, Isel; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Goyenechea, Angel; Piñón, Alexander

    2015-06-01

    Influenza A(H1N1)pdm09 virus has evolved continually since its emergence in 2009. For influenza virus strains, genetic changes occurring in HA1 domain of the hemagglutinin cause the emergence of new variants. The aim of our study is to establish genetic associations between 35 A(H1N1)pdm09 viruses circulating in Cuba in 2011-2012 and 2012-2013 seasons, and A/California/07/2009 strain recommended by WHO as the H1N1 component of the influenza vaccine. The phylogenetic analysis revealed the circulation of clades 3, 6A, 6B, 6C and 7. Mutations were detected in the antigenic site or in the receptor-binding domains of HA1 segment, including S174P, S179N, K180Q, S202T, S220T and R222K. Substitutions S174P, S179N, K180Q and R222K were detected in Cuban strains for the first time. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Mechanistic Study of the Stereoselective Hydroxylation of [2-2 H1 ,3-2 H1 ]Butanes Catalyzed by Cytochrome P450 BM3 Variants.

    Science.gov (United States)

    Yang, Chung-Ling; Lin, Cheng-Hung; Luo, Wen-I; Lee, Tsu-Lin; Ramu, Ravirala; Ng, Kok Yaoh; Tsai, Yi-Fang; Wei, Guor-Tzo; Yu, Steve S-F

    2017-02-21

    Engineered bacterial cytochrome P450s are noted for their ability in the oxidation of inert small alkanes. Cytochrome P450 BM3 L188P A328F (BM3 PF) and A74E L188P A328F (BM3 EPF) variants are able to efficiently oxidize n-butane to 2-butanol. Esterification of the 2-butanol derived from this reaction mediated by the aforementioned two mutants gives diastereomeric excesses (de) of -56±1 and -52±1 %, respectively, with the preference for the oxidation occurring at the C-HS bond. When tailored (2R,3R)- and (2S,3S)-[2-2 H1 ,3-2 H1 ]butane probes are employed as substrates for both variants, the obtained de values from (2R,3R)-[2-2 H1 ,3-2 H1 ]butane are -93 and -92 % for BM3 PF and EPF, respectively; whereas the obtained de values from (2S,3S)-[2-2 H1 ,3-2 H1 ]butane are 52 and 56 % in the BM3 PF and EPF systems, respectively. The kinetic isotope effects (KIEs) for the oxidation of (2R,3R)-[2-2 H1 ,3-2 H1 ]butane are 7.3 and 7.8 in BM3 PF and EPF, respectively; whereas KIEs for (2S,3S)-[2-2 H1 ,3-2 H1 ]butanes are 18 and 25 in BM3 PF and EPF, respectively. The discrepancy in KIEs obtained from the two substrates supports the two-state reactivity (TSR) that is proposed for alkane oxidation in cytochrome P450 systems. Moreover, for the first time, experimental evidence for tunneling in the oxidation mediated by P450 is given through the oxidation of the C-HR bond in (2S,3S)-[2-2 H1 ,3-2 H1 ]butane. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells.

    Science.gov (United States)

    Wang, Xue; Tan, Jiying; Biswas, Santanu; Zhao, Jiangqin; Devadas, Krishnakumar; Ye, Zhiping; Hewlett, Indira

    2016-02-02

    Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.

  8. Properly folded bacterially expressed H1N1 hemagglutinin globular head and ectodomain vaccines protect ferrets against H1N1 pandemic influenza virus.

    Directory of Open Access Journals (Sweden)

    Surender Khurana

    2010-07-01

    Full Text Available In the face of impending influenza pandemic, a rapid vaccine production and mass vaccination is the most effective approach to prevent the large scale mortality and morbidity that was associated with the 1918 "Spanish Flu". The traditional process of influenza vaccine production in eggs is time consuming and may not meet the demands of rapid global vaccination required to curtail influenza pandemic.Recombinant technology can be used to express the hemagglutinin (HA of the emerging new influenza strain in a variety of systems including mammalian, insect, and bacterial cells. In this study, two forms of HA proteins derived from the currently circulating novel H1N1 A/California/07/2009 virus, HA1 (1-330 and HA (1-480, were expressed and purified from E. coli under controlled redox refolding conditions that favoured proper protein folding. However, only the recombinant HA1 (1-330 protein formed oligomers, including functional trimers that bound receptor and caused agglutination of human red blood cells. These proteins were used to vaccinate ferrets prior to challenge with the A/California/07/2009 virus. Both proteins induced neutralizing antibodies, and reduced viral loads in nasal washes. However, the HA1 (1-330 protein that had higher content of multimeric forms provided better protection from fever and weight loss at a lower vaccine dose compared with HA (1-480. Protein yield for the HA1 (1-330 ranged around 40 mg/Liter, while the HA (1-480 yield was 0.4-0.8 mg/Liter.This is the first study that describes production in bacterial system of properly folded functional globular HA1 domain trimers, lacking the HA2 transmembrane protein, that elicit potent neutralizing antibody responses following vaccination and protect ferrets from in vivo challenge. The combination of bacterial expression system with established quality control methods could provide a mechanism for rapid large scale production of influenza vaccines in the face of influenza pandemic

  9. Pathogenicity and transmissibility of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 genes in pigs.

    Science.gov (United States)

    Ma, Jingjiao; Shen, Huigang; Liu, Qinfang; Bawa, Bhupinder; Qi, Wenbao; Duff, Michael; Lang, Yuekun; Lee, Jinhwa; Yu, Hai; Bai, Jianfa; Tong, Guangzhi; Hesse, Richard A; Richt, Jürgen A; Ma, Wenjun

    2015-03-01

    At least 10 different genotypes of novel reassortant H3N2 influenza viruses with 2009 pandemic H1N1 [A(H1N1)pdm09] gene(s) have been identified in U.S. pigs, including the H3N2 variant with a single A(H1N1)pdm09 M gene, which has infected more than 300 people. To date, only three genotypes of these viruses have been evaluated in animal models, and the pathogenicity and transmissibility of the other seven genotype viruses remain unknown. Here, we show that three H3N2 reassortant viruses that contain 3 (NP, M, and NS) or 5 (PA, PB2, NP, M, and NS) genes from A(H1N1)pdm09 were pathogenic in pigs, similar to the endemic H3N2 swine virus. However, the reassortant H3N2 virus with 3 A(H1N1)pdm09 genes and a recent human influenza virus N2 gene was transmitted most efficiently among pigs, whereas the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes was transmitted less efficiently than the endemic H3N2 virus. Interestingly, the polymerase complex of reassortant H3N2 virus with 5 A(H1N1)pdm09 genes showed significantly higher polymerase activity than those of endemic and reassortant H3N2 viruses with 3 A(H1N1)pdm09 genes. Further studies showed that an avian-like glycine at position 228 at the hemagglutinin (HA) receptor binding site is responsible for inefficient transmission of the reassortant H3N2 virus with 5 A(H1N1)pdm09 genes. Taken together, our results provide insights into the pathogenicity and transmissibility of novel reassortant H3N2 viruses in pigs and suggest that a mammalian-like serine at position 228 in the HA is critical for the transmissibility of these reassortant H3N2 viruses. Swine influenza is a highly contagious zoonotic disease that threatens animal and public health. Introduction of 2009 pandemic H1N1 virus [A(H1N1)pdm09] into swine herds has resulted in novel reassortant influenza viruses in swine, including H3N2 and H1N2 variants that have caused human infections in the United States. We showed that reassortant H3N2 influenza viruses with 3 or 5

  10. Crystal structure of bis­(1-benzyl-1H-1,2,4-triazole) perchloric acid monosolvate

    Science.gov (United States)

    Qin, Yong-Qi; Xue, Jin-hui; Qiao, Yuan-Biao; Zhang, Zi-Feng

    2014-01-01

    The title compound, 2C9H9N3·HClO4, was prepared by reaction of 1-benzyl-1H-1,2,4-triazole and HClO4 in ethanol at room temperature. The asymmetric unit consists of two mol­ecules of 1-benzyl-1H-1,2,4-triazole and one of HClO4 mol­ecule. The benzene and triazole rings make dihedral angles of 85.45 (8) and 84.76 (8)° in the two mol­ecules. The H-atom position of the perchloric acid mol­ecule is split over two O atoms (real peaks on difference map), with site-occupation factors of 0.5. These H atoms form two classical hydrogen bonds [2.546 (5) and 2.620 (4) Å] with the same N atoms in both mol­ecules. Five inter­molecular non-classical C—H⋯O inter­actions, with C⋯O distances in the range 3.147 (5)–3.483 (5) Å, are found in the crystal structure. PMID:25553052

  11. Occupational therapy evaluation

    DEFF Research Database (Denmark)

    Nielsen, Kristina Tomra; Wæhrens, Eva Ejlersen

    2015-01-01

    Background: The Occupational Therapy Intervention Process Model (OTIPM) serves to guide occupational therapists in their professional reasoning. The OTIPM prescribes evaluation of task performance based on both self-report and observation. Although this approach seems ideal, many clinicians raise...

  12. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

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    Mora Xavier

    2007-05-01

    Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

  13. Prior infection with classical swine H1N1 influenza viruses is associated with protective immunity to the 2009 pandemic H1N1 virus.

    Science.gov (United States)

    Kash, John C; Qi, Li; Dugan, Vivien G; Jagger, Brett W; Hrabal, Rachel J; Memoli, Matthew J; Morens, David M; Taubenberger, Jeffery K

    2010-05-01

    The 2009 H1N1 pandemic emerged even though seasonal H1N1 viruses have circulated for decades. Epidemiological evidence suggested that the current seasonal vaccine did not offer significant protection from the novel pandemic, and that people over the age of 50 were less susceptible to infection. In a mouse challenge study with the 2009 pandemic H1N1 virus, we evaluated protective immune responses elicited by prior infection with human and swine influenza A viruses. Mice infected with A/Mexico/4108/2009 (Mex09) showed significant weight loss and 40% mortality. Prior infection with a 1976 classical swine H1N1 virus resulted in complete protection from Mex09 challenge. Prior infection with either a 2009 or a 1940 seasonal H1N1 influenza virus provided partial protection and a >100-fold reduction in viral lung titers at day 4 post-infection. These findings indicate that in experimental animals recently induced immunity to 1918-derived H1N1 seasonal influenza viruses, and to a 1976 swine influenza virus, afford a degree of protection against the 2009 pandemic virus. Implications of these findings are discussed in the context of accumulating data suggesting partial protection of older persons during the 2009 pandemic.

  14. Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics.

    Science.gov (United States)

    Bernier, Morgan; Luo, Yi; Nwokelo, Kingsley C; Goodwin, Michelle; Dreher, Sarah J; Zhang, Pei; Parthun, Mark R; Fondufe-Mittendorf, Yvonne; Ottesen, Jennifer J; Poirier, Michael G

    2015-12-09

    H1 linker histones are highly abundant proteins that compact nucleosomes and chromatin to regulate DNA accessibility and transcription. However, the mechanisms that target H1 regulation to specific regions of eukaryotic genomes are unknown. Here we report fluorescence measurements of human H1 regulation of nucleosome dynamics and transcription factor (TF) binding within nucleosomes. H1 does not block TF binding, instead it suppresses nucleosome unwrapping to reduce DNA accessibility within H1-bound nucleosomes. We then investigated H1 regulation by H3K56 and H3K122 acetylation, two transcriptional activating histone post translational modifications (PTMs). Only H3K56 acetylation, which increases nucleosome unwrapping, abolishes H1.0 reduction of TF binding. These findings show that nucleosomes remain dynamic, while H1 is bound and H1 dissociation is not required for TF binding within the nucleosome. Furthermore, our H3K56 acetylation measurements suggest that a single-histone PTM can define regions of the genome that are not regulated by H1.

  15. Mitochondrial haplogroup H1 in north Africa: an early holocene arrival from Iberia.

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    Claudio Ottoni

    Full Text Available The Tuareg of the Fezzan region (Libya are characterized by an extremely high frequency (61% of haplogroup H1, a mitochondrial DNA (mtDNA haplogroup that is common in all Western European populations. To define how and when H1 spread from Europe to North Africa up to the Central Sahara, in Fezzan, we investigated the complete mitochondrial genomes of eleven Libyan Tuareg belonging to H1. Coalescence time estimates suggest an arrival of the European H1 mtDNAs at about 8,000-9,000 years ago, while phylogenetic analyses reveal three novel H1 branches, termed H1v, H1w and H1x, which appear to be specific for North African populations, but whose frequencies can be extremely different even in relatively close Tuareg villages. Overall, these findings support the scenario of an arrival of haplogroup H1 in North Africa from Iberia at the beginning of the Holocene, as a consequence of the improvement in climate conditions after the Younger Dryas cold snap, followed by in situ formation of local H1 sub-haplogroups. This process of autochthonous differentiation continues in the Libyan Tuareg who, probably due to isolation and recent founder events, are characterized by village-specific maternal mtDNA lineages.

  16. Genetic correlation between current circulating H1N1 swine and human influenza viruses.

    Science.gov (United States)

    Lu, Lu; Yin, Yanbo; Sun, Zhongsheng; Gao, Lei; Gao, George F; Liu, Sidang; Sun, Lei; Liu, Wenjun

    2010-11-01

    H1N1 is the main subtype influenza A virus circulating in human and swine population, and has long been a threat to economy and public health. To explore the genetic correlation between current circulating H1N1 swine and human influenza viruses. Three new H1N1 swine influenza viruses (SIVs) were isolated and genomes sequencing were conducted followed by phylogenetic and molecular analysis of all swine and human H1N1 influenza viruses isolated in China in the past five years. Homology and phylogenetic analysis revealed that the three isolates possessed different characteristics: the genome of A/Swine/Shandong/1112/2008 was closely related to that of classical H1N1 SIV, while A/Swine/Shandong/1123/2008 was a reassortant with NS gene from the human-like H3N2 influenza virus and other genes from the classical H1N1 SIV, and A/Swine/Fujian/0325/2008 fell into a lineage of seasonal human H1N1 influenza viruses. Genetically, 2009 H1N1 influenza A viruses (2009 H1N1) in China were contiguous to the SIV lineages rather than the seasonal H1N1 human influenza virus's lineage. Furthermore, molecular analysis among human and swine influenza viruses provided more detail information for understanding their genetic correlation. These results suggested that in China in the past five years, the classical, avian-like and human-like H1N1 SIV existed in swine herds and the reassortment between H1N1 swine and H3N2 human influenza viruses was identified. In addition, the present data showed no evidence to support a strong correlation between the 2009 H1N1 and the swine influenza virus circulating in China. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Clinical differences between influenza A (H1N1 virus and respiratory infection between the two waves in 2009 and 2010

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    Zarogoulidis P

    2012-08-01

    Full Text Available Paul Zarogoulidis,1,2 Dimitrios Glaros,1 Ioannis Kioumis,2 Eirini Terzi,1 Konstantinos Porpodis,2 Anastasios Tsiotsios,2 Anastasios Kallianos,3 Georgia Trakada,4 Nikolaos Machairiotis,1 Aikaterini Stylianakil,1 Antonis Sakas,1 Ageliki Rapti,3 Nikolaos Courcoutsakis,5 Theodoros C Constantinidis,6 Efstartios Maltezos,1 Konstantinos Zarogoulidis21Unit of Infectious Diseases, General University Hospital of Alexandroupolis, Democritus University of Thrace, Komotini, 2Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 3Second Pulmonology Clinic, Hospital of Chest Diseases "Sotiria", Athens, 4Pulmonary Department, "Alexandra" General Hospital, University of Athens, Athens, 5Radiology Department, University General Hospital of Alexandroupolis, 6Laboratory of Hygiene and Environmental Protection, Occupational Medicine Section, Democritus University of Thrace, Komotini, GreeceBackground: The purpose of the present retrospective study was to examine the clinical differences between patients hospitalized with H1N1 virus and those hospitalized with nonvirus respiratory tract infection in 2009 and 2010.Methods: Adult patient data were collected from three tertiary hospital centers. Real-time reverse transcriptase polymerase chain reaction testing was used to confirm the diagnosis. We included 106 H1N1-positive patients (52 from 2009 and 54 from 2010. These data were compared with those from 108 patients with H1N1-negative respiratory tract infection (51 patients from 2009 and 57 from 2010.Results: In 2009, the mean age was 36.4 years for H1N1-positive patients versus 46.4 years for H1N1-negative patients, and mean body mass index (BMI was 26.4 kg/m2 patients and 28.1 kg/m2, respectively. In 2009, seven patients required intubation, six of whom were H1N1-positive. In 2010, the mean age was 43.8 years for H1N1-positive patients versus 60.2 years for H1N1-negative patients, and mean BMI was 32.3 kg/m2 and

  18. Reasons for Low Pandemic H1N1 2009 Vaccine Acceptance within a College Sample

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    Russell D. Ravert

    2012-01-01

    Full Text Available This study examined health beliefs associated with novel influenza A (H1N1 immunization among US college undergraduates during the 2009-2010 pandemic. Undergraduates (ages 18–24 years from a large Midwestern University were invited to complete an online survey during March, 2010, five months after H1N1 vaccines became available. Survey items measured H1N1 vaccine history and H1N1-related attitudes based on the health belief literature. Logistic regression was used to identify attitudes associated with having received an H1N1 vaccine, and thematic analysis of student comments was conducted to further understand influences on vaccine decisions. Among the 296 students who participated in the survey, 15.2% reported having received an H1N1 vaccine. In regression analysis, H1N1 immunization was associated with seasonal flu vaccine history, perceived vaccine effectiveness, perceived obstacles to vaccination, and vaccine safety concerns. Qualitative results illustrate the relationship of beliefs to vaccine decisions, particularly in demonstrating that students often held concerns that vaccine could cause H1N1 or side effects. Vaccine safety, efficacy, and obstacles to immunization were major considerations in deciding whether to accept the H1N1 pandemic vaccine. Therefore, focusing on those aspects might be especially useful in future vaccine efforts within the college population.

  19. Novel Influenza A (H1N1)-Associated Acute Necrotizing Encephalopathy: A Case Report

    OpenAIRE

    Kim, Ki Jung; Park, Eun Sook; Chang, Hyun Jung; Suh, Miri; Rha, Dong-Wook

    2013-01-01

    Several cases of acute necrotizing encephalopathy (ANE) with influenza A (H1N1) have been reported to date. The prognosis of ANE associated with H1N1 is variable; some cases resulted in severe neurologic complication, whereas other cases were fatal. Reports mostly focused on the diagnosis of ANE with H1N1 infection, rather than functional recovery. We report a case of ANE with H1N1 infection in a 4-year-old Korean girl who rapidly developed fever, seizure, and altered mentality, as well as ha...

  20. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

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    Charles Nfon

    Full Text Available There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI. In addition, heterologous cell mediated immunity (CMI was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  1. Retrospective analysis of premedication, glucocorticosteroids, and H1-antihistamines for preventing infusion reactions associated with cetuximab treatment of patients with head and neck cancer.

    Science.gov (United States)

    Ikegawa, Kiwako; Suzuki, Shinya; Nomura, Hisanaga; Enokida, Tomohiro; Yamazaki, Tomoko; Okano, Susumu; Endo, Kazushi; Saito, Shinichiro; Yamaguchi, Masakazu; Tahara, Makoto

    2017-08-01

    Objectives We evaluated infusion-related reactions associated with cetuximab combination chemotherapy comprising an H1-receptor antagonist plus dexamethasone as anti-allergy premedications for patients with head and neck cancer. Methods We retrospectively evaluated 248 patients who received a cetuximab combination regimen between December 2012 and August 2015. All patients received 5 mg intravenous dichlorpheniramine (H1-receptor antagonist), and dexamethasone (DEX) was adjusted from 6.6 mg to 13.2 mg according to the emetogenic risk. Results We identified 248 subjects, including 13 (5.2%) with infusion-related reactions (grade 1 in five [2.0%], grade 2 in seven [2.8%], and grade 4 in one [0.4%]). The incidence of these reactions in cetuximab combination regimens, each employing an H1-receptor antagonist, using a higher dose of dexamethasone (13.2 mg) was not significantly lower compared with those using 6.6 mg DEX (2.4% vs 8.3%, respectively; p = 0.43). Twelve patients experienced infusion-related reactions associated with the first cetuximab administration, and one reaction occurred after the third administration. Conclusions The incidence of infusion-related reactions was lower compared with those of previous studies. Dexamethasone combined with an H1-receptor antagonist was useful for preventing allergic responses. The incidence of infusion-related reactions was not lower with 13.2 mg dexamethasone, and 6.6 mg DEX prevented infusion-related reactions.

  2. Monitoring peanut allergen in food products by measuring Ara h 1.

    Science.gov (United States)

    Pomés, Anna; Helm, Ricki M; Bannon, Gary A; Burks, A Wesley; Tsay, Amy; Chapman, Martin D

    2003-03-01

    Peanut allergy is an important health problem in the United States, affecting approximately 0.6% of children. Inadvertent exposure to peanut is a risk factor for life-threatening food-induced anaphylaxis. The purpose of this investigation was to develop an immunoassay for a major peanut allergen, Ara h 1, to detect peanut allergen in foods so that the risk of inadvertent exposure can be reduced. A specific 2-site monoclonal antibody-based ELISA was developed to measure Ara h 1 in foods. The sensitivity of the assay was 30 ng/mL. Ara h 1 was measured in foods (n = 83) with or without peanut and in experiments to optimize allergen yield and to determine peanut contamination in spiked foods. Ara h 1 levels in food products ranged from less than 0.1 microg/g to 500 microg/g. Ara h 1 measured in ng/mL was transformed to microg/g for food products. Peanut butter contained the highest amounts of Ara h 1. Peanut extracts contained from 0.5 to 15 mg Ara h 1/g of peanut depending on the extraction conditions. Optimal extraction of Ara h 1 was obtained by using phosphate buffer with 1 mol/L NaCl and Tween at 60 degrees C. Ara h 1 was not always detected in presence of chocolate under the extraction conditions tested. Spiking experiments showed that the assay could detect approximately 0.1% Ara h 1 contamination of food with ground peanut. There was an excellent correlation between Ara h 1 levels and peanut content measured by using a commercial polyclonal antibody-based ELISA (r = 93, n = 31, P allergy.

  3. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1 mortality during the 2009-2010 H1N1 pandemic: an ecological study.

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    Paula E Miller

    Full Text Available BACKGROUND: The influenza A (H1N1 pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. METHODS: Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. RESULTS: After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR = 0.84 per log increase in oseltamivir supply. While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase. CONCLUSION: While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.

  4. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: an ecological study.

    Science.gov (United States)

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2012-01-01

    The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.

  5. Differential activation of NK cells by influenza A pseudotype H5N1 and 1918 and 2009 pandemic H1N1 viruses.

    Science.gov (United States)

    Du, Ning; Zhou, Jianfang; Lin, Xiaojing; Zhang, Yonghui; Yang, Xiaoxing; Wang, Yue; Shu, Yuelong

    2010-08-01

    Natural killer (NK) cells are the effectors of innate immunity and are recruited into the lung 48 h after influenza virus infection. Functional NK cell activation can be triggered by the interaction between viral hemagglutinin (HA) and natural cytotoxicity receptors NKp46 and NKp44 on the cell surface. Recently, novel subtypes of influenza viruses, such as H5N1 and 2009 pandemic H1N1, transmitted directly to the human population, with unusual mortality and morbidity rates. Here, the human NK cell responses to these viruses were studied. Differential activation of heterogeneous NK cells (upregulation of CD69 and CD107a and gamma interferon [IFN-gamma] production as well as downregulation of NKp46) was observed following interactions with H5N1, 1918 H1N1, and 2009 H1N1 pseudotyped particles (pps), respectively, and the responses of the CD56(dim) subset predominated. Much stronger NK activation was triggered by H5N1 and 1918 H1N1 pps than by 2009 H1N1 pps. The interaction of pps with NK cells and subsequent internalization were mediated by NKp46 partially. The NK cell activation by pps showed a dosage-dependent manner, while an increasing viral HA titer attenuated NK activation phenotypes, cytotoxicity, and IFN-gamma production. The various host innate immune responses to different influenza virus subtypes or HA titers may be associated with disease severity.

  6. Differential Activation of NK Cells by Influenza A Pseudotype H5N1 and 1918 and 2009 Pandemic H1N1 Viruses▿ ‡ ‖

    Science.gov (United States)

    Du, Ning; Zhou, Jianfang; Lin, Xiaojing; Zhang, Yonghui; Yang, Xiaoxing; Wang, Yue; Shu, Yuelong

    2010-01-01

    Natural killer (NK) cells are the effectors of innate immunity and are recruited into the lung 48 h after influenza virus infection. Functional NK cell activation can be triggered by the interaction between viral hemagglutinin (HA) and natural cytotoxicity receptors NKp46 and NKp44 on the cell surface. Recently, novel subtypes of influenza viruses, such as H5N1 and 2009 pandemic H1N1, transmitted directly to the human population, with unusual mortality and morbidity rates. Here, the human NK cell responses to these viruses were studied. Differential activation of heterogeneous NK cells (upregulation of CD69 and CD107a and gamma interferon [IFN-γ] production as well as downregulation of NKp46) was observed following interactions with H5N1, 1918 H1N1, and 2009 H1N1 pseudotyped particles (pps), respectively, and the responses of the CD56dim subset predominated. Much stronger NK activation was triggered by H5N1 and 1918 H1N1 pps than by 2009 H1N1 pps. The interaction of pps with NK cells and subsequent internalization were mediated by NKp46 partially. The NK cell activation by pps showed a dosage-dependent manner, while an increasing viral HA titer attenuated NK activation phenotypes, cytotoxicity, and IFN-γ production. The various host innate immune responses to different influenza virus subtypes or HA titers may be associated with disease severity. PMID:20484512

  7. HIV-1 and its gp120 inhibits the influenza A(H1N1pdm09 life cycle in an IFITM3-dependent fashion.

    Directory of Open Access Journals (Sweden)

    Milene Mesquita

    Full Text Available HIV-1-infected patients co-infected with A(H1N1pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1pdm09 life cycle in vitro. We show here that exposure of A(H1N1pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA gene from in vitro experiments and from samples of HIV-1/A(H1N1pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1pdm09 co-infected patients during the recent influenza form 2009/2010.

  8. HIV-1 and its gp120 inhibits the influenza A(H1N1)pdm09 life cycle in an IFITM3-dependent fashion.

    Science.gov (United States)

    Mesquita, Milene; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q; Abrantes, Juliana L; Costa, Eduardo; Temerozo, Jairo R; Siqueira, Marilda M; Bou-Habib, Dumith Chequer; Souza, Thiago Moreno L

    2014-01-01

    HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010.

  9. A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

    Energy Technology Data Exchange (ETDEWEB)

    Boonsathorn, Naphatsawan; Panthong, Sumolrat [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Koksunan, Sarawut [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Chittaganpitch, Malinee; Phuygun, Siripaporn; Waicharoen, Sunthareeya [National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Prachasupap, Apichai [Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Sasaki, Tadahiro [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); Yasugi, Mayo [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); Ono, Ken-ichiro [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano (Japan); Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST/JICA, SATREPS), Tokyo (Japan); Arai, Yasuha [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); and others

    2014-09-26

    Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

  10. Reduced levels of histones H1o and H1b, and unaltered content of methylated DNA in rainbow trout hepatocellular carcinoma chromatin.

    Science.gov (United States)

    Davie, J R; Delcuve, G P; Nickel, B E; Moirier, R; Bailey, G

    1987-10-15

    The levels of histone subtypes and DNA methylation of aflatoxin-induced rainbow trout hepatocellular carcinoma and adult liver nuclei were compared. The hepatocellular carcinoma nuclei were enriched in the ubiquitinated species of histone H2A and depleted in histones H1o and H1b. The 5-methylcytosine content and methylation patterns of the vitellogenin genes and the transcriptionally inactive TPG-3 protamine gene were not altered in the trout hepatocellular carcinoma DNA. Thus, undermethylation of DNA is not a general feature of chemically induced tumors in vivo.

  11. Implicações da influenza A/H1N1 no período gestacional = Implications of H1N1 influenza during pregnancy

    Directory of Open Access Journals (Sweden)

    Pastore, Ana Paula Winter

    2012-01-01

    Conclusões: Os estudos apontam que os possíveis fatores de morbidade e mortalidade entre gestantes acometidas pelo vírus influenza A/H1N1 foram síndrome de desconforto respiratório do adulto, embolia pulmonar, edema pulmonar, pneumonia bacteriana secundária e insuficiência renal. Além disso, as complicações durante a gravidez tendem a acontecer mais no segundo e terceiro trimestre. Medidas preventivas e um adequado tratamento provavelmente diminuirão o número de casos futuros de influenza pandêmica A/H1N1

  12. Pandemic H1N1 2009 virus in Danish pigs: Diagnosis and lack of surveillance

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Nielsen, L. P.; Breum, Solvej Østergaard

    in swine with a genetic profile similar to older circulating strains implied a challenge for the veterinary diagnostic laboratories. We report the development, validation and implementation of a diagnostic strategy for specific diagnosis of H1N1v in pigs and the results of tests of pigs performed...... likely would recognize the H1N1v virus and this was further confirmed in the laboratory by test of samples from pvH1N1 infected humans. However, these assays could not discriminate between the typical circulating strains and the H1N1v subtype. For specific detection of the H1N1v subtype, an rRT-PCR assay...... targeting the HA gene developed at the Staten Serum Institute for diagnosis of H1N1v in humans was validated for use on pig specimens. In silico analysis showed that the probe and primers had 100% identity to published H1N1v strains and 80- 95% identity to classical-swine H1N1 which do not circulate...

  13. Life threatening severe Influenza A Virus (H1N1) infection in ...

    African Journals Online (AJOL)

    We report a case of H1N1 influenza in a 23-year old female with 28 weeks of gestation, who developed acute respiratory distress syndrome, required mechanical ventilation and eventually recovered. KEYWORDS: H1N1; Acute Respiratory Distress Syndrome; Pregnancy; Influenza Internet Journal of Medical Update 2012 ...

  14. A retrospective evaluation of critically ill patients infected with H1N1 ...

    African Journals Online (AJOL)

    Background: H1N1 influenza A virus infections were first reported in April 2009 and spread rapidly, resulting in mortality worldwide. The aim of this study was to evaluate patients with H1N1 infection treated in the intensive care unit (ICU) in Bursa, Turkey. Methods: Demographic characteristics, clinical features, and outcome ...

  15. Reassortant Pandemic (H1N1) 2009 Virus in Pigs, United Kingdom

    Science.gov (United States)

    Howard, Wendy A.; Essen, Steve C.; Strugnell, Benjamin W.; Russell, Christine; Barrass, Laura; Reid, Scott M.

    2011-01-01

    Surveillance for influenza virus in pigs in the United Kingdom during spring 2010 detected a novel reassortant influenza virus. This virus had genes encoding internal proteins from pandemic (H1N1) 2009 virus and hemagglutinin and neuraminidase genes from swine influenza virus (H1N2). Our results demonstrate processes contributing to influenza virus heterogeneity. PMID:21749767

  16. Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus.

    Science.gov (United States)

    Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao

    2015-09-28

    The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.

  17. Absence of somatic histone H1 in oocytes and preblastula embryos of Xenopus laevis

    NARCIS (Netherlands)

    Hock, R.; Moorman, A.; Fischer, D.; Scheer, U.

    1993-01-01

    Available data on the occurrence and expression of somatic histone H1 during oogenesis and early embryogenesis of Xenopus laevis are contradictory. In particular the reported presence of a large storage pool of histone H1A in oocytes is difficult to reconcile with the high transcriptional activity

  18. Influenza A (H1N1) neuraminidase inhibitors from Vitis amurensis

    DEFF Research Database (Denmark)

    Nguyen, Ngoc Anh; Dao, Trong Tuan; Tung, Bui Thanh

    2011-01-01

    Recently, a novel H1N1 influenza A virus (H1N1/09 virus) was identified and considered a strong candidate for a novel influenza pandemic. As part of an ongoing anti-influenza screening programme on natural products, eight oligostilbenes were isolated as active principles from the methanol extract...

  19. Safety of pandemic H1N1 vaccines in children and adolescents

    NARCIS (Netherlands)

    E.G. Wijnans (Leonoor); S. de Bie (Sandra); J.P. Dieleman (Jeanne); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

    2011-01-01

    textabstractDuring the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of

  20. A retrospective evaluation of critically ill patients infected with H1N1 ...

    African Journals Online (AJOL)

    2009-11-12

    Nov 12, 2009 ... Abstract. Background: H1N1 influenza A virus infections were first reported in April 2009 and spread rapidly, resulting in mortality worldwide. The aim of this study was to evaluate patients with H1N1 infection treated in the intensive care unit (ICU) in. Bursa, Turkey. Methods: Demographic characteristics ...

  1. H1N1 Flu & U.S. Schools: Answers to Frequently Asked Questions

    Science.gov (United States)

    US Department of Education, 2009

    2009-01-01

    A severe form of influenza known as H1N1, commonly being called swine flu, has health officials around the world concerned. In the United States, the outbreak of H1N1 has prompted school closures and cancellation of school-related events. As the flu spreads, the Department of Education encourages school leaders, parents and students to know how to…

  2. 78 FR 69539 - Removal of Attestation Process for Facilities Using H-1A Registered Nurses

    Science.gov (United States)

    2013-11-20

    ... governing health care facilities using nonimmigrant foreign workers as registered nurses under the H-1A visa... legislation provided for extending the stay until September 30, 1997, of certain foreign workers who: (1... for foreign workers who were in, or had previously been given, nonimmigrant H-1A status as registered...

  3. Function and coding in the blowfly H1 neuron during naturalistic optic flow

    NARCIS (Netherlands)

    Hateren, J.H. van; Kern, R.; Schwerdtfeger, G.; Egelhaaf, M.

    2005-01-01

    Naturalistic stimuli, reconstructed from measured eye movements of flying blowflies, were replayed on a panoramic stimulus device. The directional movement-sensitive H1 neuron was recorded from blowflies watching these stimuli. The response of the H1 neuron is dominated by the response to fast

  4. Allergen Ara h 1 occurs in peanuts as a large oligomer rather than as a trimer

    NARCIS (Netherlands)

    Boxtel, E.L. van; Beers, M.M.C. van; Koppelman, S.J.; Broek, L.A.M. van den; Gruppen, H.

    2006-01-01

    Ara h 1, a major peanut allergen, is known as a stable trimeric protein. Nevertheless, upon purification of native Ara h 1 from peanuts using only size exclusion chromatography, the allergen appeared to exist in an oligomeric structure, rather than as a trimeric structure. The oligomeric structure

  5. Pandemic (H1N1) 2009 outbreak on pig farm, Argentina.

    Science.gov (United States)

    Pereda, Ariel; Cappuccio, Javier; Quiroga, Maria A; Baumeister, Elsa; Insarralde, Lucas; Ibar, Mariela; Sanguinetti, Ramon; Cannilla, Maria L; Franzese, Debora; Escobar Cabrera, Oscar E; Craig, Maria I; Rimondi, Agustina; Machuca, Mariana; Debenedetti, Rosa T; Zenobi, Carlos; Barral, Leonardo; Balzano, Rodrigo; Capalbo, Santiago; Risso, Adriana; Perfumo, Carlos J

    2010-02-01

    In June-July 2009, an outbreak of pandemic (H1N1) 2009 infection occurred on a pig farm in Argentina. Molecular analysis indicated that the virus was genetically related to the pandemic (H1N1) 2009 influenza virus strain. The outbreak presumably resulted from direct human-to-pig transmission.

  6. Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication.

    Science.gov (United States)

    Holmes, J Bradley; Akman, Gokhan; Wood, Stuart R; Sakhuja, Kiran; Cerritelli, Susana M; Moss, Chloe; Bowmaker, Mark R; Jacobs, Howard T; Crouch, Robert J; Holt, Ian J

    2015-07-28

    Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L. Primer retention does not lead immediately to depletion, as the persistent RNA is fully incorporated in mitochondrial DNA. However, the retained primers present an obstacle to the mitochondrial DNA polymerase γ in subsequent rounds of replication and lead to the catastrophic generation of a double-strand break at the origin when the resulting gapped molecules are copied. Hence, the essential role of RNase H1 in mitochondrial DNA replication is the removal of primers at the origin of replication.

  7. Structural and dynamic properties of linker histone H1 binding to DNA

    CERN Document Server

    Dootz, Rolf; Pfohl, Thomas

    2010-01-01

    Found in all eukaryotic cells, linker histones H1 are known to bind to and rearrange nucleosomal linker DNA. In vitro, the fundamental nature of H1/DNA interactions has attracted wide interest among research communities - for biologists from a chromatin organization deciphering point of view, and for physicists from the study of polyelectrolyte interactions point of view. Hence, H1/DNA binding processes, structural and dynamical information about these self-assemblies is of broad importance. Targeting a quantitative understanding of H1 induced DNA compaction mechanisms our strategy is based on using small angle X-ray microdiffraction in combination with microfluidics. The usage of microfluidic hydrodynamic focusing devices facilitate a microscale control of these self-assembly processes. In addition, the method enables time-resolved access to structure formation in situ, in particular to transient intermediate states. The observed time dependent structure evolution shows that the interaction of H1 with DNA ca...

  8. Novel Influenza A (H1N1)-Associated Acute Necrotizing Encephalopathy: A Case Report

    Science.gov (United States)

    Kim, Ki Jung; Park, Eun Sook; Chang, Hyun Jung; Suh, Miri

    2013-01-01

    Several cases of acute necrotizing encephalopathy (ANE) with influenza A (H1N1) have been reported to date. The prognosis of ANE associated with H1N1 is variable; some cases resulted in severe neurologic complication, whereas other cases were fatal. Reports mostly focused on the diagnosis of ANE with H1N1 infection, rather than functional recovery. We report a case of ANE with H1N1 infection in a 4-year-old Korean girl who rapidly developed fever, seizure, and altered mentality, as well as had neurologic sequelae of ataxia, intentional tremor, strabismus, and dysarthria. Brain magnetic resonance imaging showed lesions in the bilateral thalami, pons, and left basal ganglia. To our knowledge, this is the first report of ANE caused by H1N1 infection and its long-term functional recovery in Korea. PMID:23705127

  9. Occupant Controlled Lighting

    DEFF Research Database (Denmark)

    Logadóttir, Ásta

    2011-01-01

    The studies presented in this thesis explore opportunities and limitations of using the method of adjustment for occupant controlled lighting. The method of adjustment is studied with respect to occupant preferences and energy efficiency. The work presents three types of studies using the method...... of adjustment. Firstly, there was preliminary laboratory study exploring the influence of daylight on occupant controlled dynamic lighting in a laboratory office environment. Secondly, there was non-daylit laboratory study on occupant preferences for illuminance, and thirdly a scale model study on occupant...... preferences for correlated colour temperature (CCT). The results suggest that the method of adjustment, previously used in the lighting literature, is not adequate to generalize about occupant preferences for illuminance or CCT. Factors that influence occupants’ lighting preference when applying the method...

  10. OCCUPATIONAL EXPOSURE AND COPD

    DEFF Research Database (Denmark)

    Würtz, Else Toft

    Chronic Obstructive Pulmonary Disease (COPD) is a common disease. The main risk factor is smoking although 15% of the COPD cases are expected to be preventable if the occupational exposures from vapour, gas, dust, and fume were eliminated; the population attributable fraction (PAF). The thesis...... addresses the association between occupational exposure and COPD in a population-based cohort of Danes aged 45-84-years. 4717 participants were included at baseline and 2624 at the four year follow-up. COPD was defined by spirometry and the occupational exposure was based on specialist defined jobs...... and questionnaires. The main occupational exposure was organic dust and 49% reported no lifetime occupational exposure. The results suggest occupational exposures to be associated to COPD also in never smokers and women. We found an exposure-response relation in the cross sectional analyses. The results...

  11. Essential Occupational Health Services.

    Directory of Open Access Journals (Sweden)

    Yucel Demiral,Ali Naci Yildiz

    2010-12-01

    Full Text Available Coverage of the occupational health services varies between 15%-90% of the workforce. Available services do not always fit the requirements of the occupational health necessities. Moreover, the need for the occupational health services has been growing while the working life has changed in the globalization era. International Labor Office instruments and World Health Organisation primary health care approach and health for all strategy have suggested universal and comprehensive occupational health services. From this point of view, World Health Organisation / International Labor Office and International Commission on Occupational Health jointly developed and proposed basic occupational health services to tackle this challenge. [TAF Prev Med Bull 2010; 9(6.000: 673-676

  12. Novel influenza A(H1N1) 2009 in vitro reassortant viruses with oseltamivir resistance.

    Science.gov (United States)

    Ottmann, Michèle; Duchamp, Maude Bouscambert; Casalegno, Jean-Sébastien; Frobert, Emilie; Moulès, Vincent; Ferraris, Olivier; Valette, Martine; Escuret, Vanessa; Lina, Bruno

    2010-01-01

    With the recent emergence of the novel A(H1N1) virus in 2009, the efficacy of available drugs, such as neuraminidase (NA) inhibitors, is of great concern for good patient care. Influenza viruses are known to be able to acquire resistance. In 2007, A(H1N1) viruses related to A/Brisbane/59/2007 (H1N1) (A[H1N1] Brisbane-like virus), which are naturally resistant to oseltamivir, emerged. Resistance to oseltamivir can be acquired either by spontaneous mutation in the NA (H275Y in N1), or by reassortment with a mutated NA. It is therefore crucial to determine the risk of pandemic A(H1N1) 2009 virus acquiring resistance against oseltamivir by reassortment. We estimated the capacity of reassortment between the A(H1N1) 2009 virus and an oseltamivir-resistant A(H1N1) Brisbane-like virus by in vitro coinfections of influenza-permissive cells. The screening and the analysis of reassortant viruses was performed by specific reverse transcriptase PCRs and by sequencing. Out of 50 analysed reassortant viruses, two harboured the haemagglutinin (HA) segment from the pandemic A(H1N1) 2009 virus and the mutated NA originated from the A(H1N1) Brisbane-like virus. The replicating capacities of these viruses were measured, showing no difference as compared to the two parental strains, suggesting that acquisition of the mutated NA segment did not impair viral fitness in vitro. Our results suggest that the novel A(H1N1) 2009 virus can acquire by in vitro genetic reassortment the H275Y mutated NA segment conferring resistance to oseltamivir.

  13. nm23-H1 expression in non-Hodgkin and Hodgkin lymphomas.

    Science.gov (United States)

    Bircan, Sema; Inamdar, Kedar V; Rassidakis, George Z; Medeiros, L J

    2008-05-01

    We assessed for nm23-H1 expression in 262 lymphoid neoplasms including 191 B-cell non-Hodgkin lymphoma (NHL), 54 T-cell NHL, and 17 Hodgkin lymphoma (HL). We used a monoclonal anti-nm23-H1 antibody, routinely processed tissue, and immunohistochemical methods. We semiquantified the percentage of positive cells (0%, 75%) and also estimated staining intensity (1 to 3+). Some percentage of nm23-H1 positive cells was detected in almost all types of NHL and HL, but T-cell NHL (87%) and HL (94.1%) more frequently had >75% positive cells than B-cell NHL (47.6%) (T- NHL vs. B-NHL, Ptypes of NHL and HL the nm23-H1 immunoreactivity was predominantly cytoplasmic. However, in plasma cell myeloma (PCM) nm23-H1 immunoreactivity was predominantly nuclear. In B-cell NHL, the percentage of nm23-H1-positive cells and the intensity of staining was not significantly different between various lymphoma types with the exception of PCM. We conclude that nm23-H1 is expressed in most types of B-cell and T-cell NHLs and HL, with a greater number of positive cells and higher staining intensity in T-cell NHL and HL, and PCM often being negative. The abundant intracellular expression of nm23-H1 suggests that serum levels of nm23-H1 are a reflection of tumor content. Unlike the conclusions of earlier studies, nm23-H1 expression in B-cell NHL was not significantly increased in clinically aggressive versus indolent neoplasms.

  14. Suv39h1 Protects from Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Bo Yang

    2014-04-01

    Full Text Available Background: Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R injury under diabetic condition has not been evaluated. Methods: To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis. Results: Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-κB. Conclusion: Overexpression of Suv39h1 results in the de-activation of proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore, Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under diabetic condition.

  15. Productive infection of human skeletal muscle cells by pandemic and seasonal influenza A(H1N1 viruses.

    Directory of Open Access Journals (Sweden)

    Marion Desdouits

    Full Text Available Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1 in 2009. The pathogenesis of these influenza-associated myopathies (IAM remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1 isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes were highly susceptible to infection by both influenza A(H1N1 isolates, whereas undifferentiated cells (i. e. myoblasts were partially resistant. The receptors for influenza viruses, α2-6 and α2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients.

  16. Inflammatory skin responses induced by icatibant injection are mast cell mediated and attenuated by H(1)-antihistamines.

    Science.gov (United States)

    Maurer, Marcus; Church, Martin K

    2012-02-01

    Icatibant, a bradykinin-2 receptor antagonist, is administered by subcutaneous injection for the treatment of attacks of type I and type II hereditary angioedema. Following injection, patients feel transient pain followed by a short-lived wheal and flare response at the injection site. We hypothesized that the icatibant-induced wheal and flare response follows histamine release from activated skin mast cells and would therefore be reduced by an H(1)-antihistamine. Intradermal injection of 100 μl of 100 μg/ml histamine and 10 mg/ml icatibant into the forearms of health volunteers caused wheal and flare responses of a similar magnitude which were reduced by cetirizine pretreatment by 49% and 41% (histamine) and 35% and 41% (icatibant). Studies in vitro showed that icatibant at 1 × 10(-4) and 1 × 10(-5) M caused significant (P wheal and flare responses that may be reduced in severity by prophylactic administration of an H(1)-antihistamine. © 2011 John Wiley & Sons A/S.

  17. Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity

    Directory of Open Access Journals (Sweden)

    Assia L. Angelova

    2017-12-01

    Full Text Available Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV, show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01, H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients. The virus was able to cross the blood–brain (tumor barrier after intravenous infusion. Importantly, H-1PV treatment of glioblastoma patients was associated with immunogenic changes in the tumor microenvironment. Tumor infiltration with activated cytotoxic T cells, induction of cathepsin B and inducible nitric oxide (NO synthase (iNOS expression in tumor-associated microglia/macrophages (TAM, and accumulation of activated TAM in cluster of differentiation (CD 40 ligand (CD40L-positive glioblastoma regions was detected. These are the first-in-human observations of H-1PV capacity to switch the immunosuppressed tumor microenvironment towards immunogenicity. Based on this pilot study, we present a tentative model of H-1PV-mediated modulation of glioblastoma microenvironment and propose a combinatorial therapeutic approach taking advantage of H-1PV-induced microglia/macrophage activation for further (preclinical testing.

  18. Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin.

    Directory of Open Access Journals (Sweden)

    Ki Joon Cho

    Full Text Available Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01 and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The β-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus.

  19. Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia.

    Science.gov (United States)

    Banoei, Mohammad M; Vogel, Hans J; Weljie, Aalim M; Kumar, Anand; Yende, Sachin; Angus, Derek C; Winston, Brent W

    2017-04-19

    Metabolomics is a tool that has been used for the diagnosis and prognosis of specific diseases. The purpose of this study was to examine if metabolomics could be used as a potential diagnostic and prognostic tool for H1N1 pneumonia. Our hypothesis was that metabolomics can potentially be used early for the diagnosis and prognosis of H1N1 influenza pneumonia. (1)H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry were used to profile the metabolome in 42 patients with H1N1 pneumonia, 31 ventilated control subjects in the intensive care unit (ICU), and 30 culture-positive plasma samples from patients with bacterial community-acquired pneumonia drawn within the first 24 h of hospital admission for diagnosis and prognosis of disease. We found that plasma-based metabolomics from samples taken within 24 h of hospital admission can be used to discriminate H1N1 pneumonia from bacterial pneumonia and nonsurvivors from survivors of H1N1 pneumonia. Moreover, metabolomics is a highly sensitive and specific tool for the 90-day prognosis of mortality in H1N1 pneumonia. This study demonstrates that H1N1 pneumonia can create a quite different plasma metabolic profile from bacterial culture-positive pneumonia and ventilated control subjects in the ICU on the basis of plasma samples taken within 24 h of hospital/ICU admission, early in the course of disease.

  20. Teacher's Guide to Occupational Orientation.

    Science.gov (United States)

    National Evaluation Systems, Inc., Amherst, MA.

    This guide is specifically designed to accompany materials developed for occupational orientation (particularly in Illinois) in the following five cluster areas: Applied biological and agricultural occupations; personal and public service occupations; health occupations; business, marketing, and management occupations; and industrial oriented…

  1. The Neurological Manifestations of H1N1 Influenza Infection; Diagnostic Challenges and Recommendations

    Directory of Open Access Journals (Sweden)

    Ali Akbar Asadi-Pooya

    2011-03-01

    Full Text Available Background: World Health Organization declared pandemic phase of human infection with novel influenza A (H1N1 in April 2009. There are very few reports about the neurological complications of H1N1 virus infection in the literature. Occasionally, these complications are severe and even fatal in some individuals. The aims of this study were to report neurological complaints and/or complications associated with H1N1 virus infection. Methods: The medical files of all patients with H1N1 influenza infection admitted to a specified hospital in the city of Shiraz, Iran from October through November 2009 were reviewed. More information about the patients were obtained by phone calls to the patients or their care givers. All patients had confirmed H1N1 virus infection with real-time PCR assay. Results: Fifty-five patients with H1N1 infection were studied. Twenty-three patients had neurological signs and/or symptoms. Mild neurological complaints may be reported in up to 42% of patients infected by H1N1 virus. Severe neurological complications occurred in 9% of the patients. The most common neurological manifestations were headache, numbness and paresthesia, drowsiness and coma. One patient had a Guillain-Barre syndrome-like illness, and died in a few days. Another patient had focal status epilepticus and encephalopathy. Conclusions: The H1N1 infection seems to have been quite mild with a self-limited course in much of the world, yet there appears to be a subset, which is severely affected. We recommend performing diagnostic tests for H1N1influenza virus in all patients with respiratory illness and neurological signs/symptoms. We also recommend initiating treatment with appropriate antiviral drugs as soon as possible in those with any significant neurological presentation accompanied with respiratory illness and flu-like symptoms

  2. Site-specific glycosylation profile of influenza A (H1N1) hemagglutinin through tandem mass spectrometry.

    Science.gov (United States)

    Cruz, Esteban; Cain, Joel; Crossett, Ben; Kayser, Veysel

    2017-10-19

    The study of influenza virus evolution in humans has revealed a significant role of glycosylation profile alterations in the viral glycoproteins - hemagglutinin (HA) and neuraminidase (NA), in the emergence of both seasonal and pandemic strains. Viral antigenic drift can modify the number and location of glycosylation sites, altering a wide range of biological activities and the antigenic properties of the strain. In view of the key role of glycans in determining antigenicity, elucidating the glycosylation profiles of influenza strains is a requirement towards the development of improved vaccines. Sequence-based analysis of viral RNA has provided great insight into the role of glycosite modifications in altering virulence and pathogenicity. Nonetheless, this sequence-based approach can only predict potential glycosylation sites. Due to experimental challenges, experimental confirmation of the occupation of predicted glycosylation sites has only been carried out for a few strains. Herein, we utilized HCD/CID-MS/MS tandem mass spectrometry to characterize the site-specific profile of HA of an egg-grown H1N1 reference strain (A/New Caledonia/20/1999). We confirmed experimentally the occupancy of glycosylation sites identified by primary sequence analysis and determined the heterogeneity of glycan structures. Four glycosylation sequons on the stalk region (N28, N40, N304 and N498) and four on the globular head (N71, N104, N142 and N177) of the protein are occupied. Our results revealed a broad glycan microheterogeneity, i.e., a great diversity of glycan compositions present on each glycosite. The present methodology can be applied to characterize other viruses, particularly different influenza strains, to better understand the impact of glycosylation on biological activities and aid the improvement of influenza vaccines.

  3. Three-decade epidemiological analysis of Escherichia coli O15:K52:H1

    DEFF Research Database (Denmark)

    Olesen, Bente; Scheutz, Flemming; Menard, Megan

    2009-01-01

    The successful Escherichia coli O15:K52:H1 clonal group provides a case study for the emergence of multiresistant clonal groups of Enterobacteriaceae generally. Accordingly, we tested the hypotheses that, over time, the O15:K52:H1 clonal group has become increasingly (i) virulent and (ii) resistant...... to antibiotics. One hundred archived international E. coli O15:K52:[H1] clinical isolates from 100 unique patients (1975 to 2006) were characterized for diverse phenotypic and molecular traits. All 100 isolates derived from phylogenetic group D and, presumptively, sequence type ST393. They uniformly carried...

  4. Leadership and Occupational Stress

    Science.gov (United States)

    Stickle, Fred E.; Scott, Kelly

    2016-01-01

    In a leadership position, it is important to understand what stress is and how it affects others. In an occupational setting, stressors vary according to personality types, gender, and occupational rank. The purpose of this manuscript is to review the foundations of stress and to explore how personality characteristics influence stress.…

  5. [Hand and occupational diseases].

    Science.gov (United States)

    Bensefa-Colas, Lynda; Choudat, Dominique

    2013-12-01

    Hand is frequently the site of work accidents or occupational diseases. The musculoskeletal upper limb is the first recognized occupational disease and carpal tunnel syndrome is the most common of them. The most common location of occupational dermatoses is the hand. Their causes are often multifactorial, involving chemical irritants, physical, allergens and endogenous factors (mainly atopic dermatitis). Occupational exposure to microtrauma and iterative use of vibrating tools may also be the cause of hypothenar hammer syndrome and acrosyndromes. The frequent chronicity and functional impairment induced by these attacks can cause lasting disabilities, an inability to source workstation. Occupational physician is a focal point for helping to maintain the position and the prevention of socioprofessional disinsertion. Many pathologies of the hand related to professional activity may benefit from a statement in occupational disease and thus allow the patient to obtain compensation and employment protection. Prevention of occupational hand diseases should be made by all health actors, especially in occupations and industries at risk. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  6. Occupational Mortality, Background on

    DEFF Research Database (Denmark)

    Lynge, Elsebeth

    2016-01-01

    The study of occupational mortality involves the systematic tabulation of mortality by occupational or socioeconomic groups. Three main methods are used to conduct these studies: cross-sectional studies, death certificate studies, and follow-up studies. Cross-sectional studies were undertaken in ...... the mortality rates of blue- and white-collar workers....

  7. The American Occupational Structure.

    Science.gov (United States)

    Blau, Peter M.; Duncan, Otis Dudley

    The objective of this book is to present a systematic analysis of the American occupational structure, and, thus, of the major foundation of the stratification system in this society. Processes of social mobility from one generation to the next and from career beginnings to occupational destinations are considered to reflect the dynamics of the…

  8. Dimensions of Occupational Prestige

    Science.gov (United States)

    Haug, Marie R.; Widdison, Harold A.

    1975-01-01

    Eight dimensions of occupational prestige are examined for their effect on the general prestige ratings accorded various occupations within the medical profession. Stepwise multiple regression analyzes the relative weight of these dimension among 410 persons. The findings suggested that public stereotypes exert a normative pressure on individual…

  9. A single amino acid in the HA of pH1N1 2009 influenza virus affects cell tropism in human airway epithelium, but not transmission in ferrets.

    Directory of Open Access Journals (Sweden)

    Neeltje van Doremalen

    Full Text Available The first pandemic of the 21(st century, pandemic H1N1 2009 (pH1N1 2009, emerged from a swine-origin source. Although human infections with swine-origin influenza have been reported previously, none went on to cause a pandemic or indeed any sustained human transmission. In previous pandemics, specific residues in the receptor binding site of the haemagglutinin (HA protein of influenza have been associated with the ability of the virus to transmit between humans. In the present study we investigated the effect of residue 227 in HA on cell tropism and transmission of pH1N1 2009. In pH1N1 2009 and recent seasonal H1N1 viruses this residue is glutamic acid, whereas in swine influenza it is alanine. Using human airway epithelium, we show a differential cell tropism of pH1N1 2009 compared to pH1N1 2009 E227A and swine influenza suggesting this residue may alter the sialic acid conformer binding preference of the HA. Furthermore, both pH1N1 2009 E227A and swine influenza multi-cycle viral growth was found to be attenuated in comparison to pH1N1 2009 in human airway epithelium. However this altered tropism and viral growth in human airway epithelium did not abrogate respiratory droplet transmission of pH1N1 2009 E227A in ferrets. Thus, acquisition of E at residue 227 was not solely responsible for the ability of pH1N1 2009 to transmit between humans.

  10. Occupational stress among dentists

    DEFF Research Database (Denmark)

    Moore, Rod

    2011-01-01

    Dentists report a high degree of occupational stress.(Cooper, Mallinger, and Kahn, 1978;Coster, Carstens, and Harris, 1987;DiMatteo, Shugars, and Hays, 1993;Hakeberg et al., 1992;Möller and Spangenberg, 1996;Moore, 2000;Myers and Myers, 2004;O'Shea, Corah, and Ayer, 1984) This chapter reviews...... the literature of studies that elaborate on the circumstances of occupational stress of dentists. These will include the frequency of occurrence of occupational stress among dentists in several countries, frequency and intensity of identified stressors specific to dentistry, as well as the consequences...... of this occupational stress. The literature on consequences includes effects on dentists' physical health, personal and occupational performance, including "burnout" phenomena, as well as topics of alcohol or substance abuse and reports of suicidal behaviour among dentists. One specific and less conventionally...

  11. Occupational medicine and toxicology

    Directory of Open Access Journals (Sweden)

    Fischer Axel

    2006-02-01

    Full Text Available Abstract This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.

  12. Global Molecular Epidemiology of the O15:K52:H1 Extraintestinal Pathogenic Escherichia coli Clonal Group: Evidence of Distribution beyond Europe

    Science.gov (United States)

    Johnson, James R.; Stell, Adam L.; O'Bryan, Timothy T.; Kuskowski, Michael; Nowicki, Bogdan; Johnson, Candice; Maslow, Joel N.; Kaul, Anil; Kavle, Justine; Prats, Guillem

    2002-01-01

    Escherichia coli O15:K52:H1 is a significant extraintestinal pathogen in Europe (G. Prats et al., J. Clin. Microbiol. 38:201-209, 2000). To search for evidence of this clonal group outside of Europe, 75 non-European E. coli isolates of serogroup O15 were compared with five members of the O15:K52:H1 clonal group from Barcelona, Spain, according to genomic background, virulence genotypes, and antimicrobial resistance profiles. Amplification phylotyping showed that 16 (21%) of the 75 non-European O15 isolates corresponded with the O15:K52:H1 clonal group. The 16 non-European O15:K52:H1 clonal group members represented diverse geographic locales. They were isolated almost exclusively from humans with extraintestinal infections and accounted for 50% of all O15 isolates from five human clinical collections studied. Most non-European clonal group members exhibited a consensus virulence factor profile that included the F16 or F7-2 papA alleles (P fimbrial structural subunit), papG allele II (P fimbrial adhesin), iha (putative adhesin siderophore), and iutA (aerobactin receptor). This resembles the virulence profiles of (i) European representatives of the O15:K52:H1 clonal group and (ii) phylogenetically related “clonal group A,” a recently recognized significant contributor to trimethoprim-sulfamethoxazole resistance in the United States (A. R. Manges et al., N. Engl. J. Med. 345:1007-1013, 2001). Antimicrobial resistance profiles were variable, and resistance was inconsistently transferred by conjugation. These findings indicate that the O15:K52:H1 clonal group is broadly distributed beyond Europe, exhibits previously unrecognized phenotypic and genotypic diversity, and contributes significantly to extraintestinal infections in humans. PMID:12037043

  13. Pediatric Healthcare Response to Pandemic (H1N1) 2009 Influenza Stakeholder Meeting - Summary of Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    HCTT CHE

    2010-01-01

    The goal of the meeting was to bring together subject matter experts to develop tools and resources for use by the pediatric healthcare community in response to 2009 (H1N1) pandemic influenza activity during the 2009 influenza season.

  14. Piezoresistive measurement of Swine H1N1 Hemagglutinin peptide binding with microcantilever arrays

    Directory of Open Access Journals (Sweden)

    N. Bajwa

    2014-03-01

    Full Text Available Effective detection of Swine H1N1 Hemagglutinin peptide is crucial as it could be used as a positive control to screen for highly infectious flu strains such as Swine-Origin Influenza A (H1N1. Piezoresistive microcantilever arrays present a pathway towards highly sensitive and label-free detection of biomolecules by transducing the antigen-antibody binding into change in resistivity via induced surface stress variation. We demonstrate a mechanical transduction of Swine H1N1 Hemagglutinin peptide binding and suggest the employed technique may offer a potential platform for detection of the H1N1 virus, which could be clinically used to diagnose and provide subsequent relief.

  15. H1N1 infection in emergency surgery: A cautionary tale.

    LENUS (Irish Health Repository)

    Galbraith, J G

    2010-01-01

    Pandemic 2009 influenza A H1N1 has spread rapidly since its first report in Mexico in March 2009. This is the first influenza pandemic in over 40 years and it atypically affects previously healthy young adults, with higher rates of morbidity and mortality. The medical literature has been inundated with reports of H1N1 infection, the majority found in critical care and internal medicine journals with a relative paucity in the surgical literature. Despite this, it remains an important entity that can impact greatly on acute surgical emergencies. We present a case of previously healthy 31-year-old male who underwent open appendectomy. His post-operative recovery was complicated by acute respiratory distress syndrome secondary to H1N1 infection. This case report highlights the impact that H1N1 virus can have on acute surgical emergencies and how it can complicate the post-operative course.

  16. Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Rui; Ekiert, Damian C.; Krause, Jens C.; Hai, Rong; Crowe, Jr., James E.; Wilson, Ian A. (Sinai); (Scripps); (Vanderbilt)

    2010-05-25

    The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

  17. H1N1 and influenza viruses: why pregnant women might be hesitant to be vaccinated.

    Science.gov (United States)

    Mirdamadi, Kamelia; Einarson, Adrienne

    2011-09-01

    I have been encouraging pregnant women to receive both the H1N1 and influenza vaccines since I became aware of Health Canada's guidelines. However, some of the women in my practice have heard conflicting information, often from media sources, and they are hesitant to be vaccinated. What is the evidence behind these guidelines, and should I really be convincing these women to be vaccinated? Pregnant women and growing fetuses are considered a population vulnerable to H1N1 and influenza viruses. Health Canada published a report in late 2010 estimating that this population was at increased risk of hospitalization and severe outcomes of H1N1 infection. Recommendations included pregnant women as a priority group to receive the H1N1 vaccine as well as the influenza vaccine. This information should be explained unambiguously to pregnant women, and they should be made aware of the sensationalism of media reports, which are often based on opinion and not evidence.

  18. The seroprevalence of pandemic influenza H1N1 (2009 virus in China.

    Directory of Open Access Journals (Sweden)

    Cuiling Xu

    2011-04-01

    Full Text Available Mainland China experienced pandemic influenza H1N1 (2009 virus (pH1N1 with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1.Stored serum samples (n = 2,379 collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40 was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%. Among unvaccinated participants, those aged 6-15 years (32.9% and 16-24 years (30.3% had higher seroprevalence compared with participants aged 25-59 years (10.7% and ≥60 years (9.9%, P<0.0001. Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively. We estimated that 207.7 million individuals (15.9% experienced pH1N1 infection in China.The Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

  19. Seroepidemiology of pandemic influenza A (H1N1 2009 virus infections in Pune, India

    Directory of Open Access Journals (Sweden)

    Tandale Babasaheb V

    2010-08-01

    Full Text Available Abstract Background In India, Pune was one of the badly affected cities during the influenza A (H1N1 2009 pandemic. We undertook serosurveys among the risk groups and general population to determine the extent of pandemic influenza A (H1N1 2009 virus infections. Methods Pre-pandemic sera from the archives, collected during January 2005 to March 2009, were assayed for the determination of baseline seropositivity. Serosurveys were undertaken among the risk groups such as hospital staff, general practitioners, school children and staff and general population between 15th August and 11th December 2009. In addition, the PCR-confirmed pandemic influenza A (H1N1 2009 cases and their household contacts were also investigated. Haemagglutination-inhibition (HI assays were performed using turkey red blood cells employing standard protocols. A titre of ≥1:40 was considered seropositive. Results Only 2 (0.9% of the 222 pre-pandemic sera were positive. The test-retest reliability of HI assay in 101 sera was 98% for pandemic H1N1, 93.1% for seasonal H1N1 and 94% for seasonal H3N2. The sera from 48 (73.8% of 65 PCR-confirmed pandemic H1N1 cases in 2009 were positive. Seropositivity among general practitioners increased from 4.9% in August to 9.4% in November and 15.1% in December. Among hospital staff, seropositivity increased from 2.8% in August to 12% in November. Seropositivity among the schools increased from 2% in August to 10.7% in September. The seropositivity among students (25% was higher than the school staff in September. In a general population survey in October 2009, seropositivity was higher in children (9.1% than adults (4.3%. The 15-19 years age group showed the highest seropositivity of 20.3%. Seropositivity of seasonal H3N2 (55.3% and H1N1 (26.4% was higher than pandemic H1N1 (5.7% (n = 2328. In households of 74 PCR-confirmed pandemic H1N1 cases, 25.6% contacts were seropositive. Almost 90% pandemic H1N1 infections were asymptomatic or mild

  20. The Occupations of Literacy: Occupational Therapy's Role

    Science.gov (United States)

    Frolek Clark, Gloria

    2016-01-01

    Nationally, student proficiency in reading and writing is very low and requires ongoing focus from state and local agencies. With almost 25% of occupational therapists working in early intervention and school settings (AOTA, 2015), their role of facilitating literacy (e.g., reading, writing, speaking and listening) is critical. Occupational…

  1. Evolution and adaptation of the pandemic A/H1N1 2009 influenza virus

    Directory of Open Access Journals (Sweden)

    Ducatez MF

    2011-07-01

    Full Text Available Mariette F Ducatez, Thomas P Fabrizio, Richard J WebbyDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USAAbstract: The emergence of the 2009 H1N1 pandemic influenza virus [A(H1N1pdm09] has provided the public health community with many challenges, but also the scientific community with an opportunity to monitor closely its evolution through the processes of drift and shift. To date, and despite having circulated in humans for nearly two years, little antigenic variation has been observed in the A(H1N1pdm09 viruses. However, as the A(H1N1pdm09 virus continues to circulate and the immunologic pressure within the human population increases, future antigenic change is almost a certainty. Several coinfections of A(H1N1pdm09 and seasonal A(H1N1 or A(H3N2 viruses have been observed, but no reassortant viruses have been described in humans, suggesting a lack of fitness of reassortant viruses or a lack of opportunities for interaction of different viral lineages. In contrast, multiple reassortment events have been detected in swine populations between A(H1N1 pdm09 and other endemic swine viruses. Somewhat surprisingly, many of the well characterized influenza virus virulence markers appear to have limited impact on the phenotype of the A(H1N1pdm09 viruses when they have been introduced into mutant viruses in laboratory settings. As such, it is unclear what the evolutionary path of the pandemic virus will be, but the monitoring of any changes in the circulating viruses will remain a global public and animal health priority.Keywords: influenza, pandemic, evolution, adaptation

  2. Bleeding Follicular Conjunctivitis due to Influenza H1N1 Virus

    Directory of Open Access Journals (Sweden)

    Maria Jesus Lopez-Prats

    2010-01-01

    Full Text Available Influenza H1N1 or A virus is a new virus serotype capable of human-to-human transmission. This infection causes a flu syndrome similar to that of seasonal influenza, with only one case of conjunctivitis described and no clinical details or microbiological confirmation. Its diagnosis is performed by PCR of pharyngeal smear of the patients affected. We report the first well-documented case in the medical literature of conjunctivitis by H1N1 virus.

  3. Radiologic Findings of Influenza A (H1N1) Pneumonia: Report of Two Cases

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jin Kyoung; Ahn, Myeong Im; Jung, Jung Im; Han, Dae Hee; Park, Seog Hee; Park, Chan Kwon; Kim, Young Kyoon [Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

    2010-08-15

    Novel influenza A (H1N1) infection is a highly infectious disease, which has been rapidly spreading worldwide since it was first documented in March of 2009 in Mexico. We experienced and report two cases of Influenza A (H1N1) pneumonia, accompanied by chest radiographic and CT findings. The chest radiographs revealed diffuse haziness and extensive airspace consolidation, whereas the CT scans demonstrated multifocal areas of ground glass opacity and airspace consolidation with a CT halo sign.

  4. Pandemic (H1N1) 2009 and Hajj Pilgrims Who Received Predeparture Vaccination, Egypt

    Science.gov (United States)

    Kandeel, Amr; Abdel Kereem, Eman; El-Refay, Samir; Afifi, Salma; Abukela, Mohammed; Earhart, Kenneth; El-Sayed, Nasr; El-Gabaly, Hatem

    2011-01-01

    In Egypt, vaccination against pandemic (H1N1) 2009 virus was required of pilgrims departing for the 2009 Hajj. A survey of 551 pilgrims as they returned to Egypt found 542 (98.1% [weighted]) reported receiving the vaccine; 6 (1.0% [weighted]) were infected with influenza virus A (H3N2) but none with pandemic (H1N1) 2009 virus. PMID:21762583

  5. Nodal-Dependent Mesendoderm Specification Requires the Combinatorial Activities of FoxH1 and Eomesodermin

    Science.gov (United States)

    Slagle, Christopher E.; Aoki, Tsutomu; Burdine, Rebecca D.

    2011-01-01

    Vertebrate mesendoderm specification requires the Nodal signaling pathway and its transcriptional effector FoxH1. However, loss of FoxH1 in several species does not reliably cause the full range of loss-of-Nodal phenotypes, indicating that Nodal signals through additional transcription factors during early development. We investigated the FoxH1-dependent and -independent roles of Nodal signaling during mesendoderm patterning using a novel recessive zebrafish FoxH1 mutation called midway, which produces a C-terminally truncated FoxH1 protein lacking the Smad-interaction domain but retaining DNA–binding capability. Using a combination of gel shift assays, Nodal overexpression experiments, and genetic epistasis analyses, we demonstrate that midway more accurately represents a complete loss of FoxH1-dependent Nodal signaling than the existing zebrafish FoxH1 mutant schmalspur. Maternal-zygotic midway mutants lack notochords, in agreement with FoxH1 loss in other organisms, but retain near wild-type expression of markers of endoderm and various nonaxial mesoderm fates, including paraxial and intermediate mesoderm and blood precursors. We found that the activity of the T-box transcription factor Eomesodermin accounts for specification of these tissues in midway embryos. Inhibition of Eomesodermin in midway mutants severely reduces the specification of these tissues and effectively phenocopies the defects seen upon complete loss of Nodal signaling. Our results indicate that the specific combinations of transcription factors available for signal transduction play critical and separable roles in determining Nodal pathway output during mesendoderm patterning. Our findings also offer novel insights into the co-evolution of the Nodal signaling pathway, the notochord specification program, and the chordate branch of the deuterostome family of animals. PMID:21637786

  6. Synthesis, characterization, and pharmacological studies of ferrocene-1H-1,2,3-triazole hybrids

    Science.gov (United States)

    Haque, Ashanul; Hsieh, Ming-Fa; Hassan, Syed Imran; Haque Faizi, Md. Serajul; Saha, Anannya; Dege, Necmi; Rather, Jahangir Ahmad; Khan, Muhammad S.

    2017-10-01

    A series of ferrocene-1H-1,2,3-triazole hybrids namely 1-(4-nitrophenyl)-4-ferrocenyl-1H-1,2,3-triazole (1), 1-(4,4‧-dinitro-2-biphenyl)-4-ferrocenyl-1H-1,2,3-triazole (2), 1-(3-chloro-4-fluorophenyl)-4-ferrocenyl-1H-1,2,3-triazole (3), 1-(4-bromophenyl)-4-ferrocenyl-1H-1,2,3-triazole (4) and 1-(2-nitrophenyl)-4-ferrocenyl-1H-1,2,3-triazole (5) were designed and synthesized by copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction. All the new hybrids were characterized by microanalyses, NMR (1H and 13C), UV-vis, IR, ESI-MS and electrochemical techniques. Crystal structure of the compound (3) was solved by single crystal X-ray diffraction method. The structural (single crystal) and spectroscopic (UV-Vis. and IR) properties of the compound 3 have been analyzed and compared by complementary quantum modeling. Hybrids 1-5 exhibited low toxicity and demonstrated neuroprotective effect.

  7. H1N1 encephalitis with malignant edema and review of neurologic complications from influenza.

    Science.gov (United States)

    Akins, Paul Taylor; Belko, John; Uyeki, Timothy M; Axelrod, Yekaterina; Lee, Kenneth K; Silverthorn, James

    2010-12-01

    Influenza virus infection of the respiratory tract is associated with a range of neurologic complications. The emergence of 2009 pandemic influenza A (H1N1) virus has been linked to neurological complications, including encephalopathy and encephalitis. Case report and literature review. We reviewed case management of a 20-year old Hispanic male who developed febrile upper respiratory tract signs and symptoms followed by a confusional state. He had rapid neurologic decline and his clinical course was complicated by refractory seizures and malignant brain edema. He was managed with oseltamavir and peramavir, corticosteroids, intravenous gamma globulin treatment, anticonvulsants, intracranial pressure management with external ventricular drain placement, hyperosmolar therapy, sedation, and mechanical ventilation. Reverse transcriptase polymerase chain reaction analysis of nasal secretions confirmed 2009 H1N1 virus infection; cerebrospinal fluid (CSF) was negative for 2009 H1N1 viral RNA. Follow-up imaging demonstrated improvement in brain edema but restricted diffusion in the basal ganglia. We provide a review of the clinical spectrum of neurologic complications of seasonal influenza and 2009 H1N1, and current approaches towards managing these complications. 2009 H1N1-associated acute encephalitis and encephalopathy appear to be variable in severity, including a subset of patients with a malignant clinical course complicated by high morbidity and mortality. Since the H1N1 influenza virus has not been detected in the CSF or brain tissue in patients with this diagnosis, the emerging view is that the host immune response plays a key role in pathogenesis.

  8. Numerical Analysis of an H1-Galerkin Mixed Finite Element Method for Time Fractional Telegraph Equation

    Directory of Open Access Journals (Sweden)

    Jinfeng Wang

    2014-01-01

    Full Text Available We discuss and analyze an H1-Galerkin mixed finite element (H1-GMFE method to look for the numerical solution of time fractional telegraph equation. We introduce an auxiliary variable to reduce the original equation into lower-order coupled equations and then formulate an H1-GMFE scheme with two important variables. We discretize the Caputo time fractional derivatives using the finite difference methods and approximate the spatial direction by applying the H1-GMFE method. Based on the discussion on the theoretical error analysis in L2-norm for the scalar unknown and its gradient in one dimensional case, we obtain the optimal order of convergence in space-time direction. Further, we also derive the optimal error results for the scalar unknown in H1-norm. Moreover, we derive and analyze the stability of H1-GMFE scheme and give the results of a priori error estimates in two- or three-dimensional cases. In order to verify our theoretical analysis, we give some results of numerical calculation by using the Matlab procedure.

  9. Numerical analysis of an H1-Galerkin mixed finite element method for time fractional telegraph equation.

    Science.gov (United States)

    Wang, Jinfeng; Zhao, Meng; Zhang, Min; Liu, Yang; Li, Hong

    2014-01-01

    We discuss and analyze an H(1)-Galerkin mixed finite element (H(1)-GMFE) method to look for the numerical solution of time fractional telegraph equation. We introduce an auxiliary variable to reduce the original equation into lower-order coupled equations and then formulate an H(1)-GMFE scheme with two important variables. We discretize the Caputo time fractional derivatives using the finite difference methods and approximate the spatial direction by applying the H(1)-GMFE method. Based on the discussion on the theoretical error analysis in L(2)-norm for the scalar unknown and its gradient in one dimensional case, we obtain the optimal order of convergence in space-time direction. Further, we also derive the optimal error results for the scalar unknown in H(1)-norm. Moreover, we derive and analyze the stability of H(1)-GMFE scheme and give the results of a priori error estimates in two- or three-dimensional cases. In order to verify our theoretical analysis, we give some results of numerical calculation by using the Matlab procedure.

  10. Mechanisms of triggering H1 helix in prion proteins unfolding revealed by molecular dynamic simulation

    Science.gov (United States)

    Tseng, Chih-Yuan; Lee, H. C.

    2006-03-01

    In template-assistance model, normal Prion protein (PrP^C), the pathogen to cause several prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrP^Sc) through a transient interaction with PrP^Sc. Furthermore, conventional studies showed S1-H1-S2 region in PrP^C to be the template of S1-S2 β-sheet in PrP^Sc, and Prion protein's conformational conversion may involve an unfolding of H1 and refolding into β-sheet. Here we prepare several mouse prion peptides that contain S1-H1-S2 region with specific different structures, which are corresponding to specific interactions, to investigate possible mechanisms to trigger H1 α-helix unfolding process via molecular dynamic simulation. Three properties, conformational transition, salt-bridge in H1, and hydrophobic solvent accessible surface (SAS) are analyzed. From these studies, we found the interaction that triggers H1 unfolding to be the one that causes dihedral angle at residue Asn^143 changes. Whereas interactions that cause S1 segment's conformational changes play a minor in this process. These studies offers an additional evidence for template-assistance model.

  11. [Epidemiology of Pandemic Influenza (H1N1) 2009 in Aichi Medical University Hospital].

    Science.gov (United States)

    Tani, Hiroya; Yamagishi, Yuka; Fuzimaki, Eriko; Kishi, Takahiko; Goto, Minehiro; Mikamo, Hiroshige

    2010-01-01

    We have analyzed epidemiology of pandemic influenza (H1N1) 2009 in Aichi Medical University hospital. As a result, the characteristics of pandemic influenza (H1N1) 2009 was as follows. (1) The number of ordered rapid diagnostic test was 2.8 times compared with the seasonal influenza period. The number of ordered rapid diagnostic test of the seasonal influenza period had the peak in January to March. However, the peak in pandemic influenza (H1N1) 2009 was November. Also, the number of samples on the weekend had been more than that of the weekday. (2) Positive rate of each diagnostic kit did not have the difference between the seasonal influenza (31.3 ± 1.8%) and pandemic influenza (H1N1) 2009 (29.6%). (3) Age on most ordered samples were less than ten years old, and the number of samples in 11 to 20 years old was twice in comparison with the seasonal influenza. (4) Pandemic influenza (H1N1) 2009 in influenza A accounted for 96.9%. (5) Sensitivity and specificity of ESPLINE Influenza A&B-N (FUJIREBIO, Inc., Tokyo, Japan) to the pandemic influenza (H1N1) 2009 were 100% and 100%, respectively. Also, sensitivity and specificity of prorasuto Flu (Mitsubishi Chemical Medience Corporation, Tokyo, Japan) were 77.3%and 98.5%, respectively.

  12. Respiratory failure presenting in H1N1 influenza with Legionnaires disease: two case reports.

    Science.gov (United States)

    Iannuzzi, Michele; De Robertis, Edoardo; Piazza, Ornella; Rispoli, Fabio; Servillo, Giuseppe; Tufano, Rosalba

    2011-10-21

    Media sensationalism on the H1N1 outbreak may have influenced decisional processes and clinical diagnosis. We report two cases of patients who presented in 2009 with coexisting H1N1 virus and Legionella infections: a 69-year-old Caucasian man and a 71-year-old Caucasian woman. In our cases all the signs and symptoms, including vomiting, progressive respiratory disease leading to respiratory failure, refractory hypoxemia, leukopenia, lymphopenia, thrombocytopenia, and elevated levels of creatine kinase and hepatic aminotransferases, were consistent with critical illness due to 2009 H1N1 virus infection. Other infectious disorders may mimic H1N1 viral infection especially Legionnaires' disease. Because the swine flu H1N1 pandemic occurred in Autumn in Italy, Legionnaires disease was to be highly suspected since the peak incidence usually occurs in early fall. We do think that our immediate suspicion of Legionella infection based on clinical history and X-ray abnormalities was fundamental for a successful resolution. Our two case reports suggest that patients with H1N1 should be screened for Legionella, which is not currently common practice. This is particularly important since the signs and symptoms of both infections are similar.

  13. Respiratory failure presenting in H1N1 influenza with Legionnaires disease: two case reports

    Directory of Open Access Journals (Sweden)

    Iannuzzi Michele

    2011-10-01

    Full Text Available Abstract Introduction Media sensationalism on the H1N1 outbreak may have influenced decisional processes and clinical diagnosis. Case Presentation We report two cases of patients who presented in 2009 with coexisting H1N1 virus and Legionella infections: a 69-year-old Caucasian man and a 71-year-old Caucasian woman. In our cases all the signs and symptoms, including vomiting, progressive respiratory disease leading to respiratory failure, refractory hypoxemia, leukopenia, lymphopenia, thrombocytopenia, and elevated levels of creatine kinase and hepatic aminotransferases, were consistent with critical illness due to 2009 H1N1 virus infection. Other infectious disorders may mimic H1N1 viral infection especially Legionnaires' disease. Because the swine flu H1N1 pandemic occurred in Autumn in Italy, Legionnaires disease was to be highly suspected since the peak incidence usually occurs in early fall. We do think that our immediate suspicion of Legionella infection based on clinical history and X-ray abnormalities was fundamental for a successful resolution. Conclusion Our two case reports suggest that patients with H1N1 should be screened for Legionella, which is not currently common practice. This is particularly important since the signs and symptoms of both infections are similar.

  14. Numerical Analysis of an H 1-Galerkin Mixed Finite Element Method for Time Fractional Telegraph Equation

    Science.gov (United States)

    Wang, Jinfeng; Zhao, Meng; Zhang, Min; Liu, Yang; Li, Hong

    2014-01-01

    We discuss and analyze an H 1-Galerkin mixed finite element (H 1-GMFE) method to look for the numerical solution of time fractional telegraph equation. We introduce an auxiliary variable to reduce the original equation into lower-order coupled equations and then formulate an H 1-GMFE scheme with two important variables. We discretize the Caputo time fractional derivatives using the finite difference methods and approximate the spatial direction by applying the H 1-GMFE method. Based on the discussion on the theoretical error analysis in L 2-norm for the scalar unknown and its gradient in one dimensional case, we obtain the optimal order of convergence in space-time direction. Further, we also derive the optimal error results for the scalar unknown in H 1-norm. Moreover, we derive and analyze the stability of H 1-GMFE scheme and give the results of a priori error estimates in two- or three-dimensional cases. In order to verify our theoretical analysis, we give some results of numerical calculation by using the Matlab procedure. PMID:25184148

  15. Occupational Accidents Aboard Merchant Ships

    National Research Council Canada - National Science Library

    H. L. Hansen; D. Nielsen; M. Frydenberg

    2002-01-01

    Objectives: To investigate the frequency, circumstances, and causes of occupational accidents aboard merchant ships in international trade, and to identify risk factors for the occurrence of occupational...

  16. Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs.

    Science.gov (United States)

    Kong, Weili; Liu, Qinfang; Sun, Yipeng; Wang, Yu; Gao, Huijie; Liu, Lirong; Qin, Zhihua; He, Qiming; Sun, Honglei; Pu, Juan; Wang, Dayan; Guo, Xin; Yang, Hanchun; Chang, Kin-Chow; Shu, Yuelong; Liu, Jinhua

    2016-06-02

    Given the present extensive co-circulation in pigs of Eurasian avian-like (EA) swine H1N1 and 2009 pandemic (pdm/09) H1N1 viruses, reassortment between them is highly plausible but largely uncharacterized. Here, experimentally co-infected pigs with a representative EA virus and a pdm/09 virus yielded 55 novel reassortant viruses that could be categorized into 17 genotypes from Gt1 to Gt17 based on segment segregation. Majority of novel reassortants were isolated from the lower respiratory tract. Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs. The most transmissible reassortant genotypes demonstrated in guinea pigs (Gt2, Gt3, Gt7, Gt10 and Gt13) were also the most lethal in mice. Notably, nearly all these highly virulent reassortants (all except Gt13) were characterized with possession of EA H1 and full complement of pdm/09 ribonucleoprotein genes. Compositionally, we demonstrated that EA H1-222G contributed to virulence by its ability to bind avian-type sialic acid receptors, and that pdm/09 RNP conferred the most robust polymerase activity to reassortants. The present study revealed high reassortment compatibility between EA and pdm/09 viruses in pigs, which could give rise to progeny reassortant viruses with enhanced virulence and transmissibility in mice and guinea pig models.

  17. Seroprevalence of Pandemic A(H1N1) pmd09 Virus Antibodies in Mexican Health Care Workers Before and After Vaccination.

    Science.gov (United States)

    Aguilar-Madrid, Guadalupe; Castelán-Vega, Juan Arturo; Juárez-Pérez, Cuauhtémoc Arturo; Ribas-Aparicio, Rosa María; Estrada-García, Iris; Baltierra-Jasso, Laura; Cervantes-Servín, Nicté; Méndez-Ortega, Vanessa; Haro-García, Luis C; Sánchez-Román, Francisco Raúl; Ortiz-Navarrete, Vianney; Fabila-Castillo, Luis H; Magaña-Hernández, Anastasia; Chávez-Negrete, Adolfo; Salamanca-Gómez, Fabio Abdel; Jiménez-Alberto, Alicia

    2015-02-01

    In April 2009, a new strain of influenza A(H1N1) was identified in Mexico and in the U.S. In June 2009, WHO declared this a pandemic. Health care workers constituted a risk group for their close contact with infected individuals. The aim was to estimate seropositivity for A(H1N1)pdm09 in health staff at the Instituto Mexicano del Seguro Social. A two-stage cross-sectional study, before and after vaccination in the same workers, was performed on a random sample of health-care workers. A socio-occupational questionnaire was applied and serum antibodies against influenza A(H1N1)pdm09 were determined through neutralization of retroviral pseudotypes; two logistic regression models for both were constructed. The average (median/mean) age of 1378 participants from 13 work centers was 41.7 years and 68.7% (947) were women. Seroprevalence for the first stage was 26.5% (365) (7.4-43%) vs. 20.8% (11) in a control group from the blood bank; for the second stage, the vaccinated group was 33% (215) (18.2-47%) and 27% (196) (11.6-50%) for the unvaccinated group. In regression models, seropositivity was associated with occupational exposure to suspected influenza infected patients, being physicians, and being vaccinated. Seropositivity against pandemic virus is similar to what was reported, both for vaccinated (2.8-40.9%) and unvaccinated (18.8-64.7%). Low seroprevalence in the vaccinated group indicates that between 67% and 73% were susceptible to infection. Given the relatively low vaccine-induced seropositivity, it is imperative to increase, hygiene and safety for health staff and at-risk populations, and strengthen epidemiological surveillance. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  18. Alcoholism and occupation.

    Science.gov (United States)

    Olkinuora, M

    1984-12-01

    Occupational roles are a dominant force in many aspects of social life. Occupation signifies a complex of social and psychological factors that reflect intelligence, education, personality, ambition, social status, and life-style. The consumption of alcohol and alcoholism have many correlations with occupational roles. Mortality from cirrhosis of the liver reflects the per capita consumption of alcohol. In certain occupations such mortality rates are clearly above average. The highest risk is found in occupations associated with the serving of food and beverages. A Finnish study has shown that the alcohol-related use of health services among males is the highest among unskilled workers, painters, seamen, and construction workers and the lowest among executives and farmers. Many population studies have shown that blue-collar workers and laborers have the highest level of drinking. This pattern is not necessarily true among females. The risk factors associated with occupation include the availability of alcohol at work, social pressure to drink on the job, separation from normal social relationships, and freedom from supervision. The opportunity to obtain alcoholic beverages relatively inexpensively, when combined with social pressure by peers to drink heavily, is an especially powerful explanation for high rates of alcoholism within an occupation.

  19. Occupational skin cancers

    Energy Technology Data Exchange (ETDEWEB)

    Gawkrodger, D.J. [Royal Hallamshire Hospital, Sheffield (United Kingdom). Dept. of Dermatology

    2004-10-01

    Skin cancer due to occupation is more common than is generally recognized, although it is difficult to obtain an accurate estimate of its prevalence. Over the past two centuries, occupational skin cancers have particularly been due to industrial exposure of men (it seems more so than women) to chemical carcinogens such as polycyclic hydrocarbons (e.g. from coal tar products) or to arsenic. Industrial processes have improved in most Western countries to limit this type of exposure, but those with outdoor occupations are still exposed to solar ultraviolet irradiation without this being widely recognized as an industrial hazard. Ionizing radiation such as X-rays can also cause skin cancer. Occupational skin cancers often resemble skin tumours found in non-occupational subjects, e.g. basal cell carcinoma, squamous cell carcinoma and malignant melanoma, but some pre-malignant lesions can be more specific and point to an occupational origin, e.g. tar keratoses or arsenical keratoses. An uncommon but well-recognized cause of occupational skin cancer is that which results from scar formation following an industrial burn. In the future it will be necessary to focus on preventative measures, e.g. for outdoor workers, the need to cover up in the sun and use sun protective creams and a campaign for earlier recognition of skin cancers, which are usually curable if treated in their early stages.

  20. [Study on evolutionary origin of influenza A virus (H1N1) based on HA gene].

    Science.gov (United States)

    Lu, Yi-Han; Ju, Li-Wen; Jiang, Lu-Fang; Yang, Ji-Xing; Shi, Qiang; Jiang, Qing-Wu

    2009-07-01

    To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. A total of 344 H1 sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetically (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57 x 10(-3) substitutions/site per year averagely (95% Highest Posterior Density: 1.96 x 10(-3) - 3.03 x 10(-3)/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46 x 10(-3)/site per year and 0.97 x 10(-3)/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86 x 10(-3)/site per year and 5.02 x 10(-3)/site per year. The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.

  1. Intense Seasonal A/H1N1 Influenza in Mexico, Winter 2013–2014

    Science.gov (United States)

    Dávila-Torres, Javier; Chowell, Gerardo; Borja-Aburto, Víctor H.; Viboud, Cécile; Grajalez-Muñiz, Concepción; Miller, Mark. A.

    2014-01-01

    Background and Aims A recrudescent wave of pandemic influenza A/H1N1 affected Mexico during the winter of 2013–2014 following a mild 2012–2013 A/H3N2 influenza season. Methods We compared the demographic and geographic characteristics of hospitalizations and inpatient deaths for severe acute respiratory infection (SARI) and laboratory-confirmed influenza during the 2013–2014 influenza season compared to previous influenza seasons, based on a large prospective surveillance system maintained by the Mexican Social Security health care system. Results A total of 14,236 SARI hospitalizations and 1,163 inpatient deaths (8.2%) were reported between October 1, 2013 and March 31, 2014. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30–59 years and lower among younger age groups for the 2013–2014 A/H1N1 season compared to the previous A/H1N1 season in 2011–2012 (χ2 test, p <0.001). The reproduction number for the winter 2013–2014 influenza season in central Mexico was estimated at 1.3–1.4, in line with that reported for the 2011–2012 A/H1N1 season but lower than during the initial waves of pandemic A/H1N1 activity in 2009. Conclusions We documented a substantial increase in the number of A/H1N1-related hospitalizations and deaths during the period from October 2013–March 2014 in Mexico and a proportionate shift of severe disease to middle-aged adults, relative to the preceding A/H1N1 2011–2012 season. In the absence of clear antigenic drift in globally circulating A/H1N1 viruses in the post-2009 pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics. PMID:25446616

  2. Occupational cancer in Britain

    Science.gov (United States)

    Chen, Yiqun; Osman, John

    2012-01-01

    Although only a relatively small proportion of cancer is attributable to occupational exposure to carcinogenic agents, the estimated number of deaths due to occupational cancer is high when compared to other deaths due to work-related ill health and injury. However, risk from occupational exposure to carcinogens can be minimised through proportionate but effective risk management. The Health and Safety Executive (HSE) is the regulator of workplace health and safety in Great Britain. As part of its aim to reduce ill health arising from failures to control properly exposure to hazards at work, HSE commissioned the research presented elsewhere in this supplement to enable it to identify priorities for preventing occupational cancer. The research has shown that occupational cancer remains a key health issue and that low-level exposure of a large number of workers to carcinogens is important. The finding that a small number of carcinogens have been responsible for the majority of the burden of occupational cancer provides key evidence in the development of priorities for significant reduction of occupational cancer. Although the research presented in this supplement reflects the consequences of past exposures to carcinogens, occupational cancer remains a problem. The potential for exposure to the agents considered in this research is still present in the workplace and the findings are relevant to prevention of future disease. In this article, the principle approaches for risk reduction are described. It provides supporting information on some of the initiatives already being undertaken, or those being put in place, to reduce occupational cancer in Great Britain. The need also for systematic collection of exposure information and the importance of raising awareness and changing behaviours are discussed. PMID:22710673

  3. Phase 1 study of pandemic H1 DNA vaccine in healthy adults.

    Directory of Open Access Journals (Sweden)

    Michelle C Crank

    Full Text Available A novel, swine-origin influenza A (H1N1 virus was detected worldwide in April 2009, and the World Health Organization (WHO declared a global pandemic that June. DNA vaccine priming improves responses to inactivated influenza vaccines. We describe the rapid production and clinical evaluation of a DNA vaccine encoding the hemagglutinin protein of the 2009 pandemic A/California/04/2009(H1N1 influenza virus, accomplished nearly two months faster than production of A/California/07/2009(H1N1 licensed monovalent inactivated vaccine (MIV.20 subjects received three H1 DNA vaccinations (4 mg intramuscularly with Biojector at 4-week intervals. Eighteen subjects received an optional boost when the licensed H1N1 MIV became available. The interval between the third H1 DNA injection and MIV boost was 3-17 weeks. Vaccine safety was assessed by clinical observation, laboratory parameters, and 7-day solicited reactogenicity. Antibody responses were assessed by ELISA, HAI and neutralization assays, and T cell responses by ELISpot and flow cytometry.Vaccinations were safe and well-tolerated. As evaluated by HAI, 6/20 developed positive responses at 4 weeks after third DNA injection and 13/18 at 4 weeks after MIV boost. Similar results were detected in neutralization assays. T cell responses were detected after DNA and MIV. The antibody responses were significantly amplified by the MIV boost, however, the boost did not increased T cell responses induced by DNA vaccine.H1 DNA vaccine was produced quickly, was well-tolerated, and had modest immunogenicity as a single agent. Other HA DNA prime-MIV boost regimens utilizing one DNA prime vaccination and longer boost intervals have shown significant immunogenicity. Rapid and large-scale production of HA DNA vaccines has the potential to contribute to an efficient response against future influenza pandemics.Clinicaltrials.gov NCT00973895.

  4. [Influenza H1N1 in obstetric population of a general hospital in Oaxaca].

    Science.gov (United States)

    Calvo Aguilar, Omar; Canalizo Mendoza, Yazmín Ruth; Hernández Cuevas, Maritza Jenny

    2011-06-01

    In April 2009 are reported the first cases of H1N1 influenza in Mexico, presenting the first death from this cause in the city of Oaxaca in the same month. Different epidemiological reports of pandemics brought to the pregnant and high risk population for complications secondary to infection with influenza H1N1 due to immune status. describe the obstetric population infected with H1N1 influenza in the Hospital General Dr. Aurelio Valdivieso of Oaxaca. Retrospective and observational study conducted in pregnant women with suspected infection by the virus of the influenza A/H1N1 served in the General Hospital Aurelio Valdivieso of Oaxaca, Oax in 13 patients with influenza H1N1 confirmed by RT-PCR during the pandemic occurred from May 2009 to April 2010. We reported 27 suspected cases of H1N1 influenza in pregnant women of which 13 were positive by RT-PCR, the cumulative incidence was 1.6 per 1000 pregnant women during the period. The fatality rate was 7.6 per hundred pregnant women affected, one case of maternal death indirectly by fluid and electrolyte imbalance occurred and the attack rate was 0.16 per 100 pregnant women, the main complication of atypical pneumonia occurred in four cases followed by three cases of preeclampsia, infants showed no defects and perinatal outcomes were good to present two cases of admission to the NICU for iatrogenic prematurity without deaths. H1N1 influenza infection has a high fatality rate in late pregnancy. Perinatal outcomes did not worsen the condition or management.

  5. Pandemic influenza (H1N1 2009 is associated with severe disease in India.

    Directory of Open Access Journals (Sweden)

    Akhilesh C Mishra

    Full Text Available BACKGROUND: Pandemic influenza A (H1N1 2009 has posed a serious public health challenge world-wide. In absence of reliable information on severity of the disease, the nations are unable to decide on the appropriate response against this disease. METHODS: Based on the results of laboratory investigations, attendance in outpatient department, hospital admissions and mortality from the cases of influenza like illness from 1 August to 31 October 2009 in Pune urban agglomeration, risk of hospitalization and case fatality ratio were assessed to determine the severity of pandemic H1N1 and seasonal influenza-A infections. RESULTS: Prevalence of pandemic H1N1 as well as seasonal-A cases were high in Pune urban agglomeration during the study period. The cases positive for pandemic H1N1 virus had significantly higher risk of hospitalization than those positive for seasonal influenza-A viruses (OR: 1.7. Of 93 influenza related deaths, 57 and 8 deaths from Pune (urban and 27 and 1 death from Pune (rural were from pandemic H1N1 positive and seasonal-A positive cases respectively. The case fatality ratio 0.86% for pandemic H1N1 was significantly higher than that of seasonal-A (0.13% and it was in category 3 of the pandemic severity index of CDC, USA. The data on the cumulative fatality of rural and urban Pune revealed that with time the epidemic is spreading to rural areas. CONCLUSIONS: The severity of the H1N1 influenza pandemic is less than that reported for 'Spanish flu 1918' but higher than other pandemics of the 20(th century. Thus, pandemic influenza should be considered as serious health threat and unprecedented global response seems justified.

  6. Clinical profile and outcome of critically ill pregnant females with H1N1 influenza

    Directory of Open Access Journals (Sweden)

    Minal Shastri

    2016-12-01

    Full Text Available Background Record based review of the 2009 H1N1 Influenza pandemic suggests that pregnant women are at higher risk for hospitalization and death due to H1N1 Influenza. Aims To study the clinical profile and outcome of critically ill pregnant females admitted in intensive care unit (ICU with real-time recombinant polymerase chain reaction (rRT-PCR proven positive H1N1 cases. Methods A retrospective record-review based study was conducted at Sir SayajiRao General Hospital (SSGH and Medical College, Vadodara on data of confirmed rRT-PCR H1N1 pregnant females admitted during the pandemics of 2010and 2015. Demographics, clinical profile and laboratory investigations were recorded and outcomes (survived or expired were analysed. Results There were a total of 20 H1N1 positive pregnant females requiring ICU admission. With equal demographic distribution among rural and urban population, cough and fever were the most common presenting complaints. 65 per cent were in third trimester, the subgroup which also had the highest mortality. Mean days from onset until presentation was 5.05 days. 12 (60 per cent patients’ required invasive mode of ventilation and all died. Average hospital stay was 7 days. Foetus had favourable outcome in patients who recovered from H1N1 acute illness. Conclusion Pregnant females in our study had 60 per cent mortality. Thus, awareness, early diagnosis and treatment should be provided to them. Guidelines, policy changes and government protocols are required specifically for pregnant females with H1N1 Influenza A infection. Our study was an observational study and comparisons with non-pregnant females were not done, conclusions applicable to entire pregnant population was not derived.

  7. [Effects levocabastine ophthalmic solution (H1 receptor antagonist) on symptoms of vernal conjunctivitis. A prospective, randomized double-blind study].

    Science.gov (United States)

    Graue, E

    1994-01-01

    A double blind, prospective and randomized study was carried out in forty patients with clinical diagnosis of vernal conjunctivitis and eosinophilia in conjunctival scrapings. They were divided in two randomized groups of 20 patients each. One of the groups received levocabastine ophthalmic solution and the other saline solution drops. The mean age of the study group was 9.1 years old with a vernal conjunctivitis history of 44 months. The control group mean age was 10.1 years old and a history of vernal conjunctivitis of 48 months prior the enter of the study. One group received levocabastine 0.5 mgrs/ml while the other balanced saline solution, one drop every 12 hours per seven days. The patients evaluated their symptoms through a visual analogic scale (every day). Data collected was analyzed, for the first, third and seventh day, through U-Mann Whitney statistical analysis. Epiphora and photophobia showed a significant improvement. Itching, edema and foreign body sensation showed improvement in the levocabastine group but without statistical significance. Hyperthermia remained the same in both groups studied.

  8. Synthesis of ( sup 3 H)-1-(1-(3-isothiocyanatophenyl)cyclohexyl) piperidine (METAPHIT), an acylating agent for phencyclidine receptors

    Energy Technology Data Exchange (ETDEWEB)

    De Costa, B.R.; Lessor, R.A.; Thurkauf, A.; Highet, R.J.; Jacobson, A.E.; Rice, K.C. (National Insts. of Health, Bethesda, MD (USA))

    1989-09-01

    The preparation of ({sup 3}H)-labelled 1-(1-(3-isothiocyanatophenyl)cyclohexyl)piperidine (METAPHIT), an electrophilic acylating agent for the phencyclidine (PCP) site is described. Synthesis of ({sup 3}H)METAPHIT was accomplished in three steps starting from 1-(1-(3-nitrophenyl)cyclohexyl)piperidine. Introduction of the tritium-label in 20.6% radiochemical yield was achieved in the penultimate step. (author).

  9. The Target Residence Time of Antihistamines Determines Their Antagonism of the G Protein-Coupled Histamine H1 Receptor

    NARCIS (Netherlands)

    Bosma, Reggie; Witt, Gesa; Vaas, Lea A I; Josimovic, Ivana; Gribbon, Philip; Vischer, Henry F; Gul, Sheraz; Leurs, Rob

    2017-01-01

    The pharmacodynamics of drug-candidates is often optimized by metrics that describe target binding (Kd or Ki value) or target modulation (IC50). However, these metrics are determined at equilibrium conditions, and consequently information regarding the onset and offset of target engagement and

  10. Influenza A viral loads in respiratory samples collected from patients infected with pandemic H1N1, seasonal H1N1 and H3N2 viruses

    Directory of Open Access Journals (Sweden)

    Chuchottaworn Charoen

    2010-04-01

    Full Text Available Abstract Background Nasopharyngeal aspirate (NPA, nasal swab (NS, and throat swab (TS are common specimens used for diagnosis of respiratory virus infections based on the detection of viral genomes, viral antigens and viral isolation. However, there is no documented data regarding the type of specimen that yields the best result of viral detection. In this study, quantitative real time RT-PCR specific for M gene was used to determine influenza A viral loads present in NS, NPA and TS samples collected from patients infected with the 2009 pandemic H1N1, seasonal H1N1 and H3N2 viruses. Various copy numbers of RNA transcripts derived from recombinant plasmids containing complete M gene insert of each virus strain were assayed by RT-PCR. A standard curve for viral RNA quantification was constructed by plotting each Ct value against the log quantity of each standard RNA copy number. Results Copy numbers of M gene were obtained through the extrapolation of Ct values of the test samples against the corresponding standard curve. Among a total of 29 patients with severe influenza enrolled in this study (12 cases of the 2009 pandemic influenza, 5 cases of seasonal H1N1 and 12 cases of seasonal H3N2 virus, NPA was found to contain significantly highest amount of viral loads and followed in order by NS and TS specimen. Viral loads among patients infected with those viruses were comparable regarding type of specimen analyzed. Conclusion Based on M gene copy numbers, we conclude that NPA is the best specimen for detection of influenza A viruses, and followed in order by NS and TS.

  11. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wörmann, Xenia [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Lesch, Markus [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Steinbeis Innovation gGmbH, Center for Systems Biomedicine, Falkensee (Germany); Welke, Robert-William [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Okonechnikov, Konstantin; Abdurishid, Mirshat [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Sieben, Christian [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Geissner, Andreas [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Brinkmann, Volker [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Kastner, Markus [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Karner, Andreas [Center for Advanced Bioanalysis GmbH (CBL), Linz (Austria); Zhu, Rong; Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Anish, Chakkumkal [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Seeberger, Peter H. [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Herrmann, Andreas [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); and others

    2016-05-15

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA{sub 1} D130E, HA{sub 2} I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

  12. Gossip and Occupational Ideology

    Science.gov (United States)

    Rysman, Alexander R.

    1976-01-01

    Defines the transmission of gossip as an essential social process reflecting a shared group membership and discusses the ways in which gossip supports ideologies held by members of a specific occupation. (MH)

  13. Occupants' window opening behaviour

    DEFF Research Database (Denmark)

    Fabi, Valentina; Andersen, Rune Korsholm; Corgnati, Stefano

    2012-01-01

    and office buildings. The analysis of the literature highlights how a shared approach on identifying the driving forces for occupants' window opening and closing behaviour has not yet been reached. However, the reporting of variables found not to be drivers may reveal contradictions in the obtained results......Energy consumption in buildings is influenced by several factors related to the building properties and the building controls, some of them highly connected to the behaviour of their occupants.In this paper, a definition of items referring to occupant behaviour related to the building control...... systems is proposed, based on studies presented in literature and a general process leading to the effects on energy consumptions is identified.Existing studies on the topic of window opening behaviour are highlighted and a theoretical framework to deal with occupants' interactions with building controls...

  14. Occupational Noise Exposure

    Science.gov (United States)

    Powered by Translate UNITED STATES DEPARTMENT OF LABOR Facebook Twitter Instagram RSS Subscribe Search A TO Z INDEX UNITED STATES DEPARTMENT OF LABOR Facebook Twitter Instagram RSS Subscribe Occupational Safety and Health Administration English | ...

  15. Histone H1 Differentially Inhibits DNA Bending by Reduced and Oxidized HMGB1 Protein.

    Directory of Open Access Journals (Sweden)

    Michal Štros

    Full Text Available HMGB1 protein and linker histone H1 have overlapping binding sites in the nucleosome. HMGB1 has been implicated in many DNA-dependent processes in chromatin involving binding of specific proteins, including transcription factors, to DNA sites pre-bent by HMGB1. HMGB1 can also act as an extracellular signaling molecule by promoting inflammation, tumor growth a metastasis. Many of the intra- and extracellular functions of HMGB1 depend on redox-sensitive cysteine residues of the protein. Here we report that mild oxidization of HMGB1 (and much less mutation of cysteines involved in disulphide bond formation can severely compromise the functioning of the protein as a DNA chaperone by inhibiting its ability to unwind or bend DNA. Histone H1 (via the highly basic C-terminal domain significantly inhibits DNA bending by the full-length HMGB1, and the inhibition is further enhanced upon oxidization of HMGB1. Interestingly, DNA bending by HMGB1 lacking the acidic C-tail (HMGB1ΔC is much less affected by histone H1, but oxidization rendered DNA bending by HMGB1ΔC and HMGB1 equally prone for inhibition by histone H1. Possible consequences of histone H1-mediated inhibition of DNA bending by HMGB1 of different redox state for the functioning of chromatin are discussed.

  16. Binding of histone H1 to DNA is differentially modulated by redox state of HMGB1.

    Directory of Open Access Journals (Sweden)

    Eva Polanská

    Full Text Available HMGB1 is an architectural protein in chromatin, acting also as a signaling molecule outside the cell. Recent reports from several laboratories provided evidence that a number of both the intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein. In this study we demonstrate that redox state of HMGB1 can significantly modulate the ability of the protein to bind and bend DNA, as well as to promote DNA end-joining. We also report a high affinity binding of histone H1 to hemicatenated DNA loops and DNA minicircles. Finally, we show that reduced HMGB1 can readily displace histone H1 from DNA, while oxidized HMGB1 has limited capacity for H1 displacement. Our results suggested a novel mechanism for the HMGB1-mediated modulation of histone H1 binding to DNA. Possible biological consequences of linker histones H1 replacement by HMGB1 for the functioning of chromatin are discussed.

  17. Characteristics of US public schools with reported cases of novel influenza A (H1N1).

    Science.gov (United States)

    Hoen, Anne Gatewood; Buckeridge, David L; Chan, Emily H; Freifeld, Clark C; Keller, Mikaela; Charland, Katia; Donnelly, Christl A; Brownstein, John S

    2010-09-01

    The 2009 pandemic of influenza A (H1N1) has disproportionately affected children and young adults, resulting in attention by public health officials and the news media on schools as important settings for disease transmission and spread. We aimed to characterize US schools affected by novel influenza A (H1N1) relative to other schools in the same communities. A database of US school-related cases was obtained by electronic news media monitoring for early reports of novel H1N1 influenza between April 23 and June 8, 2009. We performed a matched case-control study of 32 public primary and secondary schools that had one or more confirmed cases of H1N1 influenza and 6815 control schools located in the same 23 counties as case schools. Compared with controls from the same county, schools with reports of confirmed cases of H1N1 influenza were less likely to have a high proportion of economically disadvantaged students (adjusted odds ratio (aOR) 0.385; 95% confidence interval (CI) 0.166-0.894) and less likely to have older students (aOR 0.792; 95% CI 0.670-0.938). We conclude that public schools with younger, more affluent students may be considered sentinels of the epidemic and may have played a role in its initial spread. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. Influenza A(H1N1)pdm09 during air travel.

    Science.gov (United States)

    Neatherlin, John; Cramer, Elaine H; Dubray, Christine; Marienau, Karen J; Russell, Michelle; Sun, Hong; Whaley, Melissa; Hancock, Kathy; Duong, Krista K; Kirking, Hannah L; Schembri, Christopher; Katz, Jacqueline M; Cohen, Nicole J; Fishbein, Daniel B

    2013-01-01

    The global spread of the influenza A(H1N1)pdm09 virus (pH1N1) associated with travelers from North America during the onset of the 2009 pandemic demonstrates the central role of international air travel in virus migration. To characterize risk factors for pH1N1 transmission during air travel, we investigated travelers and airline employees from four North American flights carrying ill travelers with confirmed pH1N1 infection. Of 392 passengers and crew identified, information was available for 290 (74%) passengers were interviewed. Overall attack rates for acute respiratory infection and influenza-like illness 1-7 days after travel were 5.2% and 2.4% respectively. Of 43 individuals that provided sera, 4 (9.3%) tested positive for pH1N1 antibodies, including 3 with serologic evidence of asymptomatic infection. Investigation of novel influenza aboard aircraft may be instructive. However, beyond the initial outbreak phase, it may compete with community-based mitigation activities, and interpretation of findings will be difficult in the context of established community transmission. Published by Elsevier Ltd.

  19. New Onset Refractory Status Epilepticus in a Young Man with H1N1 Infection

    Directory of Open Access Journals (Sweden)

    Faisal Ibrahim

    2014-01-01

    Full Text Available Objective. To report a case of refractory status epilepticus (SE as an unusual early manifestation of H1N1 influenza infection. Introduction. H1N1 neurological complications have been reported and consist mainly of seizures or encephalopathy occurring in children. However, we only found a single report of an adult developing complex partial SE with H1N1 infection. Case Report. A 21-year-old previously healthy man was brought to the emergency room (ER after a witnessed generalized tonic clonic seizure (GTCS. He was fully alert and afebrile upon ER arrival, but a second GTCS prompted treatment with Lorazepam and Fosphenytoin. The initial EEG showed diffuse slowing, but a repeat one requested as the patient failed to regain consciousness revealed recurrent focal seizures of independent bihemispheric origin, fulfilling the criteria for nonconvulsive SE. Chest X-ray, followed by chest CT scan, showed a left upper lobe consolidation. H1N1 infection was confirmed with PCR on bronchoalveolar lavage material. Despite aggressive treatment with Midazolam, Propofol, and multiple high dose antiepileptic drugs, the electrographic seizures recurred at every attempt to reduce the intravenous sedative drugs. The patient died two weeks after his initial presentation. Conclusion. H1N1 should be added to the list of rare causes of refractory SE, regardless of the patient’s age.

  20. Measles resurgence associated with continued circulation of genotype H1 viruses in China, 2005.

    Science.gov (United States)

    Ji, Yixin; Zhang, Yan; Xu, Songtao; Zhu, Zhen; Zuo, Shuyan; Jiang, Xiaohong; Lu, Peishan; Wang, Changyin; Liang, Yong; Zheng, Huanying; Liu, Yang; Mao, Naiying; Liang, Xiaofeng; Featherstone, David Alexander; Rota, Paul A; Bellini, William J; Xu, Wenbo

    2009-09-08

    Measles morbidity and mortality decreased significantly after measles vaccine was introduced into China in 1965. From 1995 to 2004, average annual measles incidence decreased to 5.6 cases per 100,000 population following the establishment of a national two-dose regimen. Molecular characterization of wild-type measles viruses demonstrated that genotype H1 was endemic and widely distributed throughout the country in China during 1995-2004. A total of 124,865 cases and 55 deaths were reported from the National Notifiable Diseases Reporting System (NNDRS) in 2005, which represented a 69.05% increase compared with 2004. Over 16,000 serum samples obtained from 914 measles outbreaks and the measles IgM positive rate was 81%. 213 wild-type measles viruses were isolated from 18 of 31 provinces in China during 2005, and all of the isolates belonged to genotype H1. The ranges of the nucleotide sequence and predicted amino acid sequence homologies of the 213 genotype H1 strains were 93.4%-100% and 90.0%-100%, respectively. H1-associated cases and outbreaks caused the measles resurgence in China in 2005. H1 genotype has the most inner variation within genotype, it could be divided into 2 clusters, and cluster 1 viruses were predominant in China throughout 2005.

  1. Stiffness-activated GEF-H1 expression exacerbates LPS-induced lung inflammation.

    Directory of Open Access Journals (Sweden)

    Isa Mambetsariev

    Full Text Available Acute lung injury (ALI is accompanied by decreased lung compliance. However, a role of tissue mechanics in modulation of inflammation remains unclear. We hypothesized that bacterial lipopolysacharide (LPS stimulates extracellular matrix (ECM production and vascular stiffening leading to stiffness-dependent exacerbation of endothelial cell (EC inflammatory activation and lung barrier dysfunction. Expression of GEF-H1, ICAM-1, VCAM-1, ECM proteins fibronectin and collagen, lysyl oxidase (LOX activity, interleukin-8 and activation of Rho signaling were analyzed in lung samples and pulmonary EC grown on soft (1.5 or 2.8 kPa and stiff (40 kPa substrates. LPS induced EC inflammatory activation accompanied by expression of ECM proteins, increase in LOX activity, and activation of Rho signaling. These effects were augmented in EC grown on stiff substrate. Stiffness-dependent enhancement of inflammation was associated with increased expression of Rho activator, GEF-H1. Inhibition of ECM crosslinking and stiffening by LOX suppression reduced EC inflammatory activation and GEF-H1 expression in response to LPS. In vivo, LOX inhibition attenuated LPS-induced expression of GEF-H1 and lung dysfunction. These findings present a novel mechanism of stiffness-dependent exacerbation of vascular inflammation and escalation of ALI via stimulation of GEF-H1-Rho pathway. This pathway represents a fundamental mechanism of positive feedback regulation of inflammation.

  2. [Epidemiological characteristics on the clustering nature of pandemic (H1N1) 2009 in China].

    Science.gov (United States)

    Shi, Jing-hong; Xiang, Ni-juan; Zhang, Yan-ping; Chen, Min; Sun, Shan-hua; Chen, Tao; Yuan, Fan; Wang, Li-jie; Yang, Jing; Yang, Li-mei; Li, Pei-long; Fan, Chun-xiang; Yang, Dao-wei; Zhao, Yong; Xu, Peng; Zhao, Qing-long; Zong, Jun; Zhang, Yang; Xu, Cui-ling; Shu, Yue-long; Feng, Zi-jian

    2012-01-01

    To study the epidemiological characteristics on the clustering nature of pandemic (H1N1) 2009 in China. Time and place distribution of pandemic (H1N1) 2009 on the nature of clustering through data from Public Health Emergency Management Information System were described. As of August 10, 2010, 2773 pandemic (H1N1) 2009 clusters, a total of 77 363 cases (including 20 deaths) were reported in the mainland of China. The most reported number of clusters was from schools and kindergartens with the total number of 2498 (accounted for 90.08% of the total number). Middle schools appeared the have the most clusters (1223, accounting for 48.96%). The number of clusters reported in the southern provinces (cities) accounted for 77.03% of the total, and was more than that in the northern provinces (cities). Two reported peaks in the southern provinces (cities) were in June and November, 2009, respectively. There was only one reported peak in the northern provinces in September, 2009. Time and place distribution characteristics on the clusters of pandemic (H1N1) 2009 were similar to the seasonal influenza, but the beginning of winter peak was much earlier and intensity of reporting was much higher on the clusters of pandemic (H1N1) 2009 than that of seasonal influenza.

  3. Measles Resurgence Associated with Continued Circulation of Genotype H1 Viruses in China, 2005

    Directory of Open Access Journals (Sweden)

    Featherstone David

    2009-09-01

    Full Text Available Abstract Measles morbidity and mortality decreased significantly after measles vaccine was introduced into China in 1965. From 1995 to 2004, average annual measles incidence decreased to 5.6 cases per 100,000 population following the establishment of a national two-dose regimen. Molecular characterization of wild-type measles viruses demonstrated that genotype H1 was endemic and widely distributed throughout the country in China during 1995-2004. A total of 124,865 cases and 55 deaths were reported from the National Notifiable Diseases Reporting System (NNDRS in 2005, which represented a 69.05% increase compared with 2004. Over 16,000 serum samples obtained from 914 measles outbreaks and the measles IgM positive rate was 81%. 213 wild-type measles viruses were isolated from 18 of 31 provinces in China during 2005, and all of the isolates belonged to genotype H1. The ranges of the nucleotide sequence and predicted amino acid sequence homologies of the 213 genotype H1 strains were 93.4%-100% and 90.0%-100%, respectively. H1-associated cases and outbreaks caused the measles resurgence in China in 2005. H1 genotype has the most inner variation within genotype, it could be divided into 2 clusters, and cluster 1 viruses were predominant in China throughout 2005.

  4. Occupational health in Mexico.

    Science.gov (United States)

    Carreón, Tania; Santos-Burgoa, Carlos; Baron, Sherry; Hernández, Sendy

    2002-01-01

    The authors discuss the maquiladoras and child labor, and offer an overview of the history of occupational safety and health in Mexico that covers laws and regulations, social security, unions, and enforcement of legislation. The organization and structure of the various institutions responsible for occupational safety and health (OSH), as well as administrative procedures, are described. This article concludes with a list of the new challenges for OSH in Mexico.

  5. Occupancy in continuous habitat

    Science.gov (United States)

    Efford, Murray G.; Dawson, Deanna K.

    2012-01-01

    The probability that a site has at least one individual of a species ('occupancy') has come to be widely used as a state variable for animal population monitoring. The available statistical theory for estimation when detection is imperfect applies particularly to habitat patches or islands, although it is also used for arbitrary plots in continuous habitat. The probability that such a plot is occupied depends on plot size and home-range characteristics (size, shape and dispersion) as well as population density. Plot size is critical to the definition of occupancy as a state variable, but clear advice on plot size is missing from the literature on the design of occupancy studies. We describe models for the effects of varying plot size and home-range size on expected occupancy. Temporal, spatial, and species variation in average home-range size is to be expected, but information on home ranges is difficult to retrieve from species presence/absence data collected in occupancy studies. The effect of variable home-range size is negligible when plots are very large (>100 x area of home range), but large plots pose practical problems. At the other extreme, sampling of 'point' plots with cameras or other passive detectors allows the true 'proportion of area occupied' to be estimated. However, this measure equally reflects home-range size and density, and is of doubtful value for population monitoring or cross-species comparisons. Plot size is ill-defined and variable in occupancy studies that detect animals at unknown distances, the commonest example being unlimited-radius point counts of song birds. We also find that plot size is ill-defined in recent treatments of "multi-scale" occupancy; the respective scales are better interpreted as temporal (instantaneous and asymptotic) rather than spatial. Occupancy is an inadequate metric for population monitoring when it is confounded with home-range size or detection distance.

  6. 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

  7. Occupational stressors in nursing

    Directory of Open Access Journals (Sweden)

    N. Nikpeyma

    2009-04-01

    Full Text Available Background and aimsNursing provides a wide range of potential workplace stressors as it is  a profession that requires a high level of skill, teamworking in a variety of situations and provision  of 24-hour delivery of care .Occupational stress is a major factor of Staff sickness an  absenteeism.This study investigates the main occupational stressors in nursing profession in the  hope of identification and reducing it.MethodsIn this study a questionnaire consisting of three parts:demoghraphic data,the nurses  background and questions about occupational stress from Revised index fulfilled by 140 nurses.ResultsLack of reward for work well done(48/6%, Heavy workload(46/4% ,lack of Participation in decisions (39/3% , poor Control of work place(38/4%and lack of job  development (36/4% have been the main sources of Occupational stress for nurses.chronic  diseases, Night Shift working and working hours were positively associated with occupstional  stress.Conclusion Analysis indicated that effects of work factors on occupational stress are more than demoghraphic data. The findings of this study can assist health service organisations to provide an attractive working climate in order to decrease side effects and consequences of occupational stress. Furthermore, understanding this situation can help to develop coping strategies in order to reduce work-related stress.

  8. Professional Differentiation and Occupational Earnings.

    Science.gov (United States)

    Cullen, John B.

    1985-01-01

    "Professional" and other occupational characteristics were selected as variables for predicting the earnings of occupational groups. Task complexity and education were significant predictors of occupational earnings. In support of some power theorists, the data suggested that some occupational groups derive additional earnings by influencing their…

  9. Occupational Employment Projections to 2010.

    Science.gov (United States)

    Hecker, Daniel E.

    2001-01-01

    Employment in professional and related occupations and service occupations will increase the fastest and add the most jobs from 2000 to 2010. Changes in technology or business operations will cause the largest declines in occupational demand. Occupations requiring a postsecondary award or academic degree will account for 42 percent of total job…

  10. Secondary Health Occupations Education Curriculum.

    Science.gov (United States)

    Matzen, Shelley; Muhl, V. Jane

    This color coded curriculum guide for secondary health occupations in Iowa provides units for the first phase of the curriculum, career exploration of the health occupations. The nine units cover the following topics: (1) introduction to health occupations; (2) health occupations career exploration; (3) communication skills; (4) self-care and…

  11. Occupational therapists' perception of the concept of occupational balance.

    Science.gov (United States)

    Yazdani, Farzaneh; Harb, Alia; Rassafiani, Mehdi; Nobakht, Laya; Yazdani, Nastaran

    2017-05-10

    Occupational balance is one of the concepts used by occupational therapists with no consensus on its definition. Literature demonstrates different perspectives when this concept is applied in practice and in its link to other concepts such as health and well-being. This study aims to explore how the concept of occupational balance is perceived and practised by occupational therapy practitioners. A qualitative methodology was employed. Fourteen occupational therapists volunteered for the study. Nine occupational therapy practitioners were interviewed individually and five attended a focus group. Thematic analysis was applied to analyze the data. Six themes were identified as follows: (1) occupational balance: what it is; (2) how occupational balance is formed; (3) occupational balance and well-being (4); subjective and objective representations of occupational balance (5); what disrupts/affects occupational balance; and (6) occupational balance/imbalance and occupational therapy practice. Both objective and subjective experiences of occupational balance need to be considered in order to make an informed decision in practice. The right occupational balance for each individual should be based on his/her values but with consideration of the principal of no harm to others.

  12. An overview of the novel H1-antihistamine bilastine in allergic rhinitis and urticaria.

    Science.gov (United States)

    Jáuregui, Ignacio; García-Lirio, Eduardo; Soriano, Ana María; Gamboa, Pedro M; Antépara, Ignacio

    2012-01-01

    Currently available second-generation H1-antihistamines include a wide group of drugs with a better therapeutic index (or risk-benefit ratio) than the classic antihistamines, although their properties and safety profiles may differ. Bilastine is a newly registered H1-antihistamine for the oral treatment of allergic rhinitis and urticaria, with established antihistaminic and antiallergic properties. Clinical studies in allergic rhinitis and chronic urticaria show that once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life, with at least comparable efficacy to other nonsedative H1-antihistamines. As far as studies in healthy volunteers, clinical assays and clinical experience can establish, bilastine's safety profile is satisfactory, since it lacks anticholinergic effects, does not impair psychomotor performance or actual driving, and appears to be entirely free from cardiovascular effects.

  13. De Quervain thyroiditis in the course of H1N1 influenza infection.

    Science.gov (United States)

    Michas, G; Alevetsovitis, G; Andrikou, I; Tsimiklis, S; Vryonis, E

    2014-01-01

    Viral infections have been frequently associated with subacute (De Quervain) thyroiditis and autoimmune thyroid diseases. In the present case report we document a rare case of De Quervain thyroiditis in the course of H1N1 influenza infection. A 17-year-old previously healthy female that was treated in the General Hospital of Kalamata developed an influenza-like syndrome that was accompanied by palpitations, thyroid enlargement, and increased C-reactive protein. Polymerase chain reaction assay confirmed the diagnosis of H1N1 virus infection. Serum thyroid-stimulating hormone was suppressed to zero while the levels of free thyroxine and triiodothyronine were increased. The patient was treated with non-steroidal anti-inflammatory drugs and thyroid function was gradually restored without evolving to a hypothyroid phase. To our knowledge this is the second case described in the literature of De Quervain thyroiditis associated with H1N1 influenza infection.

  14. Measurement and QCD Interpretation of the Inclusive Deep-Inelastic Scattering Cross Section by H1

    CERN Multimedia

    CERN. Geneva

    2001-01-01

    Deep inelastic electron proton collisions are a straightforward tool to study the QCD dynamics between quarks and gluons in the proton. A recent measurement and QCD analysis of the deep inelastic scattering cross section by the H1 experiment at HERA are presented. In a NLO QCD analysis of H1 structure function data, the gluon distribution in the proton is extracted to typically 3% experimental accuracy at low Bjorken x.. In a combined analysis of H1 and high precision µp data by the CERN muon experiment BCDMS, the gluon distribution at low x and the strong coupling constant as were for the first time extracted simultaneously.The strong coupling constant is determined with about 1% experimental accuracy, and QCD at NLO is confirmed over 5 orders of magnitude of Bjorken x at a new level of precision.

  15. Kompliceret influenza A (H1N1) hos gravid i andet trimester

    DEFF Research Database (Denmark)

    Ersboell, Anne Schjoedt; Hesselvig, Anne Brun; Hedegaard, Morten

    2012-01-01

    A 27-year-old woman at 25 weeks of gestation was admitted to hospital due to bilateral pneumonia with increasing hypoxia. She was tested positive for influenza A (H1N1) and successfully treated with oral oseltamivir. Nine days after the admission pathological umbilical flows were recorded and an ...... and an emergency caesarean was performed at 26 weeks + 2 days of gestation. The neonatal period was uncomplicated. Influenza A (H1N1) is especially dangerous in pregnant women and vaccination is important.......A 27-year-old woman at 25 weeks of gestation was admitted to hospital due to bilateral pneumonia with increasing hypoxia. She was tested positive for influenza A (H1N1) and successfully treated with oral oseltamivir. Nine days after the admission pathological umbilical flows were recorded...

  16. Mongrelised genetics of H1N1 virus: A bird′s eyeview

    Directory of Open Access Journals (Sweden)

    Nagarathna C

    2010-01-01

    Full Text Available H1N1 influenza, also known as "novel H1N1 virus" has led to a "global outcry." This virus is more virulent when compared with other seasonal flu viruses. Virulence may change as the adaptive mutation gene increases within the virus. A study at the US Centre for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain as they showed no cross-reactive antibody reaction when compared with adults aged 18-64 years, who showed a cross-reactive antibody reaction of 6-9% and older adults with 33% immunity. This review article depicts H1N1 virus, its virulence with genetic evolution potential and preventive protocol for the dental professionals. This would allow us to comprehend the changes in the disease process and contribute in its prevention as "prevention is better than cure."

  17. Acute disseminated encephalomyelitis associated with influenza A H1N1 infection.

    Science.gov (United States)

    Ozkale, Yasemin; Erol, Ilknur; Ozkale, Murat; Demir, Senay; Alehan, Füsun

    2012-07-01

    Acute disseminated encephalomyelitis is an immune-mediated inflammatory disorder of the central nervous system, characterized by demyelination. Acute disseminated encephalomyelitis predominantly involves the white matter of the brain and spinal cord, and often follows upper respiratory tract infection. We describe a case of acute disseminated encephalomyelitis associated with the influenza A (H1N1) virus. The H1N1 virus usually causes febrile respiratory signs, e.g., fever, cough, and sore throat. Although these signs exhibit a self-limited course, the frequencies of severe complications and death are increasing. To date, only a few reports of acute disseminated encephalomyelitis secondary to the H1N1 virus have been published. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line

    KAUST Repository

    Benavente, Ernest Diez

    2017-12-16

    Plasmodium knowlesi, a common parasite of macaques, is recognized as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites. The PkA1-H.1 reference will enhance the capabilities of the in vitro model to improve the understanding of P. knowlesi infection in humans.

  19. Effect of paramagnetic manganese cations on H-1 MRS of the brain

    DEFF Research Database (Denmark)

    Madsen, K. S.; Holm, David Alberg; Søgaard, L. V.

    2008-01-01

    Manganese cations (Mn2+) call be used as all intracellular contrast agent for structural, functional and neural pathway imaging applications. However, at high concentrations, Mn2+ is neurotoxic and play influence the concentration of H-1 MR-detectable metabolites. Furthermore, the paramagnetic Mn2......+ cations may also influence the relaxation of the metabolites under investigation. Consequently, the purpose of this study was to investigate the effect of paramagnetic Mn2+ cations on H-1-MR spectra of the brain using in vivo and phantom models at 4.7T. To investigate the direct paramagnetic effects of Mn...... be expected at this concentration. Consequently, this study indicates that. ill this model. the presence of Mn2+ cations does not significantly affect H-1-MR spectra despite possible toxic and paramagnetic effects....

  20. Transplantation of solid organs procured from influenza A H1N1 infected donors.

    Science.gov (United States)

    Cockbain, Andrew J; Jacob, Matthew; Ecuyer, Clare; Hostert, Lutz; Ahmad, Niaz

    2011-12-01

    Following the influenza A H1N1 (swine flu) pandemic, there remains little evidence informing the safety of transplanting organs from donors suspected or diagnosed with H1N1. Limited guidelines from the major transplant societies leave the use of such organs at the discretion of individual transplant centres, and practice varies considerably both nationally and internationally. We present the largest published series of outcome following transplantation of organs from H1N1 positive donors and demonstrate that these organs can be transplanted safely and with good short-term outcome. We discuss our local policy for treatment of recipients with Oseltamivir. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

  1. Occupational health in Brazil.

    Science.gov (United States)

    Bedrikow, B; Algranti, E; Buschinelli, J T; Morrone, L C

    1997-01-01

    Brazil is a recently industrialised country with marked contrasts in social and economic development. The availability of public/private services in its different regions also varies. Health indicators follow these trends. Occupational health is a vast new field, as in other developing countries. Occupational medicine is a required subject in graduation courses for physicians. Specialisation courses for university graduated professionals have more than 700 hours of lectures and train occupational health physicians, safety engineers and nursing staff. At the technical level, there are courses with up to 1300 hours for the training of safety inspectors. Until 1986 about 19,000 occupational health physicians, 18,000 safety engineers and 51,000 safety inspectors had been officially registered. Although in its infancy, postgraduation has attracted professionals at university level, through residence programmes as well as masters and doctors degrees, whereby at least a hundred good-quality research studies have been produced so far. Occupational health activities are controlled by law. Undertakings with higher risks and larger number of employees are required to hire specialised technical staff. In 1995 the Ministry of Labour demanded programmes of medical control of occupational health (PCMSO) for every worker as well as a programme of prevention of environmental hazards (PPRA). This was considered as a positive measure for the improvement of working conditions and health at work. Physicians specialising in occupational medicine are the professionals more often hired by the enterprises. Reference centres (CRSTs) for workers' health are connected to the State or City Health Secretariat primary health care units. They exist in more populated areas and are accepted by workers as the best way to accomplish the diagnosis of occupational diseases. There is important participation by the trade unions in the management of these reference centres. For 30 years now employers

  2. Occupational Experience, Mobility, and Wages

    DEFF Research Database (Denmark)

    Groes, Fane

    In this paper we present how occupational tenure relates to wage growth and occupational mobility in Danish data. We show that the Danish data produces qualitatively similar results as found in U.S. data with respect to an increase in average wages when experience in an occupation increases. In a...... also is true for workers switching occupation and rm. After ve years of experience in an occupation the average probability of switching any type of occupation, including occupation and rm switches, has fallen from 25% to 12%....

  3. The novel influenza A (H1N1 virus pandemic: An update

    Directory of Open Access Journals (Sweden)

    Petrosillo N

    2009-01-01

    Full Text Available In the 4 months since it was first recognized, the pandemic strain of a novel influenza A (H1N1 virus has spread to all continents and, after documentation of human-to-human transmission of the virus in at least three countries in two separate World Health Organization (WHO regions, the pandemic alert was raised to level 6. The agent responsible for this pandemic, a swine-origin influenza A (H1N1 virus (S-OIV, is characterized by a unique combination of gene segments that has not previously been identified among human or swine influenza A viruses. As of 31th July 2009, 168 countries and overseas territories/communities have each reported at least one laboratory-confirmed case of pandemic H1N1 infection. There have been a total of 162,380 reported cases and 1154 associated deaths. Influenza epidemics usually take off in autumn, and it is important to prepare for an earlier start this season. Estimates from Europe indicate that 230 millions Europe inhabitants will have clinical signs and symptoms of S-OIV this autumn, and 7– 35% of the clinical cases will have a fatal outcome, which means that there will be 160,000– 750,000 H1N1-related deaths. A vaccine against H1N1 is expected to be the most effective tool for controlling influenza A (H1N1 infection in terms of reducing morbidity and mortality and limiting diffusion. However, there are several issues with regard to vaccine manufacture and approval, as well as production capacity, that remain unsettled. We searched the literature indexed in PubMed as well as the websites of major international health agencies to obtain the material presented in this update on the current S-OIV pandemic.

  4. Pandemic influenza A (H1N1 2009 vaccine: An update

    Directory of Open Access Journals (Sweden)

    M K Goel

    2011-01-01

    Full Text Available The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 coun-tries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009 virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.

  5. H1-antihistamines for primary mast cell activation syndromes: a systematic review.

    Science.gov (United States)

    Nurmatov, U B; Rhatigan, E; Simons, F E R; Sheikh, A

    2015-09-01

    Primary mast cell activation syndromes (MCAS) are a group of disorders presenting with symptoms of mast cell mediator release. To assess the effectiveness and safety of orally administered H1 -antihistamines in the treatment of primary MCAS compared with placebo and other pharmacologic treatments. We systematically searched five databases and three trial repositories and contacted an international panel of experts to identify published and unpublished trials. A total of 36 potentially relevant studies were identified. Of these, five crossover trials, enrolling a total of 71 patients (63 adults), met the eligibility criteria. All five of these studies were judged to be at moderate or high risk of bias. Two studies compared an H1 -antihistamine with placebo, two compared two different H1 -antihistamines, and one study compared H1 - and H2 -antihistamines with oral cromolyn sodium. Four of the five randomized controlled trials were historic (reported from 1983-1993), small (enrolling 8-15 patients), and used agents and/or dosing regimens that are now less commonly used in clinical practice (i.e. azelastine, chlorpheniramine, hydroxyzine, and ketotifen). The fifth trial, which enrolled 33 adults with cutaneous and systemic mastocytosis found 4 weeks of treatment with the second-generation H1 -antihistamine rupatadine, compared with placebo, resulted in significant improvements in quality of life, symptom control (itching, wheals and flares, flushing, tachycardia, and headache, but not gastrointestinal symptoms), and reduction in itching and whealing after standardized skin provocation to elicit Darier's sign. There is an urgent need for large, well-designed, double-blind, placebo-controlled randomized trials investigating the effectiveness, cost-effectiveness, and safety of second-generation H1 -antihistamines in treatment of primary MCAS. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Sensitive and selective magnetoimmunosensing platform for determination of the food allergen Ara h 1

    Energy Technology Data Exchange (ETDEWEB)

    Montiel, V. Ruiz-Valdepeñas, E-mail: victor_lega90@hotmail.com [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Campuzano, S., E-mail: susanacr@quim.ucm.es [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Pellicanò, A., E-mail: alessandro.pellicano@unimi.it [Department of Food, Environmental and Nutritional Sciences (DEFENS), University of Milan, Via Celoria 2, 20133 Milan (Italy); Torrente-Rodríguez, R.M., E-mail: rebeca.magnolia@gmail.com [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Reviejo, A.J., E-mail: reviejo@quim.ucm.es [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Cosio, M.S., E-mail: stella.cosio@unimi.it [Department of Food, Environmental and Nutritional Sciences (DEFENS), University of Milan, Via Celoria 2, 20133 Milan (Italy); Pingarrón, J.M., E-mail: pingarro@quim.ucm.es [Departamento de Química Analítica, Facultad de CC. Químicas, Universidad Complutense de Madrid, E-28040 Madrid (Spain)

    2015-06-23

    Highlights: • First amperometric magnetoimmunosensor for Ara h 1 determination. • Sensitive and selective detection of Ara h 1 in 2 h. • LOD of 6.3 ng mL{sup −1}. • Determinations in food extracts and saliva. • Potential applicability in food safety and consumer protection. - Abstract: A highly sensitive disposable amperometric immunosensor based on the use of magnetic beads (MBs) is described for determination of Ara h 1, the major peanut allergen, in only 2 h. The approach uses a sandwich configuration involving selective capture and biotinylated detector antibodies and carboxylic acid-modified MBs (HOOC-MBs). The MBs bearing the immunoconjugates are captured by a magnet placed under the surface of a disposable screen-printed carbon electrode (SPCE) and the affinity reactions are monitored amperometrically at −0.20 V (vs a Ag pseudo-reference electrode) in the presence of hydroquinone (HQ) as electron transfer mediator and upon addition of H{sub 2}O{sub 2} as the enzyme substrate. The developed immunosensor exhibits a wide range of linearity between 20.8 and 1000.0 ng mL{sup −1} Ara h 1, a detection limit of 6.3 ng mL{sup −1}, a great selectivity, a good reproducibility with a RSD of 6.3% for six different immunosensors and a useful lifetime of 25 days. The usefulness of the immunosensor was demonstrated by determining Ara h 1 in different matrices (food extracts and saliva). The results correlated properly with those provided by a commercial ELISA method offering a reliable and promising analytical screening tool in the development of user-friendly devices for on-site determination of Ara h 1.

  7. Analysis of fatal outcomes from influenza A(H1N1pdm09 in Mongolia

    Directory of Open Access Journals (Sweden)

    Erdenebaatariin Soyolmaa

    2012-08-01

    Full Text Available Introduction: While influenza A(H1N1pdm09 usually causes mild illness in the majority of people, there have been reports of severe cases and deaths. As there is no documented evidence on fatal outcomes from influenza in Mongolia previously, we aimed to describe the epidemiology of fatal influenza A(H1N1pdm09 cases to provide recommendations to assist the national influenza prevention and control strategy.Methods: We selected influenza A(H1N1pdm09-confirmed deaths in hospitals between 12 October 2009 and 31 January 2010 in Mongolia from the national influenza surveillance system. The mortality rate and case fatality rate (CFR of influenza A(H1N1pdm09-hospitalized deaths were calculated. Using country prevalence of pregnancy and chronic diseases, we calculated the relative risk of death from influenza A(H1N1pdm09.Results: There were 29 deaths with a mortality rate of 1.0 per 100 000 population during the study period, which was highest in children under five and the middle-aged population. Crude CFR was 2.2%. Of all fatal cases, 62% had at least one underlying condition. Most (62% were provided antivirals, although none received these within 48 hours of symptom onset. Prevalence for pregnancy, cardiovascular and chronic liver diseases was five to 50 times higher in fatal cases compared to country prevalence.Discussion: Mortality and crude CFR in our study was higher than in other studies. However, due to the diagnostic policy change during the epidemic, this estimate is likely to have overestimated actual case fatalities. Pregnancy, cardiovascular and chronic liver diseases were suggestive risk factors for death from influenza A(H1N1pdm09. Strengthening hospital-based influenza surveillance is important in predicting severity of an epidemic and responding to influenza epidemics in a timely and appropriate manner.

  8. Analysis of fatal outcomes from influenza A(H1N1)pdm09 in Mongolia.

    Science.gov (United States)

    Baigalmaa, Jantsansengeegiin; Tuul, Tseesurengiin; Darmaa, Badarchyn; Soyolmaa, Erdenebaatariin

    2012-07-01

    While influenza A(H1N1)pdm09 usually causes mild illness in the majority of people, there have been reports of severe cases and deaths. As there is no documented evidence on fatal outcomes from influenza in Mongolia previously, we aimed to describe the epidemiology of fatal influenza A(H1N1)pdm09 cases to provide recommendations to assist the national influenza prevention and control strategy. We selected influenza A(H1N1)pdm09-confirmed deaths in hospitals between 12 October 2009 and 31 January 2010 in Mongolia from the national influenza surveillance system. The mortality rate and case fatality rate (CFR) of influenza A(H1N1)pdm09-hospitalized deaths were calculated. Using country prevalence of pregnancy and chronic diseases, we calculated the relative risk of death from influenza A(H1N1)pdm09. There were 29 deaths with a mortality rate of 1.0 per 100 000 population during the study period, which was highest in children under five and the middle-aged population. Crude CFR was 2.2%. Of all fatal cases, 62% had at least one underlying condition. Most (62%) were provided antivirals, although none received these within 48 hours of symptom onset. Prevalence for pregnancy, cardiovascular and chronic liver diseases was five to 50 times higher in fatal cases compared to country prevalence. Mortality and crude CFR in our study was higher than in other studies. However, due to the diagnostic policy change during the epidemic, this estimate is likely to have overestimated actual case fatalities. Pregnancy, cardiovascular and chronic liver diseases were suggestive risk factors for death from influenza A(H1N1)pdm09. Strengthening hospital-based influenza surveillance is important in predicting severity of an epidemic and responding to influenza epidemics in a timely and appropriate manner.

  9. MicroRNA expression in mice infected with seasonal H1N1, swine H1N1 or highly pathogenic H5N1.

    Science.gov (United States)

    Vela, Eric M; Kasoji, Manjula D; Wendling, Morgan Q; Price, Jennifer A; Knostman, Katherine A B; Bresler, Herbert S; Long, James P

    2014-09-01

    Influenza virus infections in humans remain a healthcare concern, and the need for vaccines, therapeutics and prophylactics remains a high priority. Understanding the molecular events associated with influenza-virus-induced pathology may lead to the identification of clinical disease biomarkers and novel antiviral targets. MicroRNAs (miRNAs) are well-conserved endogenous non-coding RNAs known to regulate post-transcriptional gene expression as well as play a major role in many biological processes and pathways. Animal studies have demonstrated that miRNAs are involved in viral disease and controlling inflammation. In this study, we examined the differences in the miRNA expression profiles associated with the lung in mice infected with influenza viruses that varied in virulence and pathogenicity. A statistical model was employed that utilized changes in miRNA expression to identify the virus that was used to infect the mice. This study identified a unique fingerprint of viral pathogenicity associated with seasonal H1N1, swine H1N1 and highly pathogenic H5N1 in the mouse model, and may lead to the identification of novel therapeutic and prophylactic targets. © 2014 The Authors.

  10. Population Health and Occupational Therapy.

    Science.gov (United States)

    Braveman, Brent

    2016-01-01

    Occupational therapy practitioners play an important role in improving the health of populations through the development of occupational therapy interventions at the population level and through advocacy to address occupational participation and the multiple determinants of health. This article defines and explores population health as a concept and describes the appropriateness of occupational therapy practice in population health. Support of population health practice as evidenced in the official documents of the American Occupational Therapy Association and the relevance of population health for occupational therapy as a profession are reviewed. Recommendations and directions for the future are included related to celebration of the achievements of occupational therapy practitioners in the area of population health, changes to the Occupational Therapy Practice Framework and educational accreditation standards, and the importance of supporting, recognizing, rewarding, and valuing occupational therapy practitioners who assume roles in which direct care is not their primary function. Copyright © 2016 by the American Occupational Therapy Association, Inc.

  11. Nosocomial Pandemic (H1N1) 2009, United Kingdom, 2009–2010

    OpenAIRE

    Enstone, JE; Myles, PR; Openshaw, PJM; Gadd, EM; Lim, WS; Semple, MG; Read, RC; Taylor, BL; McMenamin, J; Armstrong, C.; Bannister, B.; Nicholson, KG; Nguyen-Van-Tam, JS

    2011-01-01

    To determine clinical characteristics of patients hospitalized in the United Kingdom with pandemic (H1N1) 2009, we studied 1,520 patients in 75 National Health Service hospitals. We characterized patients who acquired influenza nosocomially during the pandemic (H1N1) 2009 outbreak. Of 30 patients, 12 (80%) of 15 adults and 14 (93%) of 15 children had serious underlying illnesses. Only 12 (57%) of 21 patients who received antiviral therapy did so within 48 hours after symptom onset, but 53% ne...

  12. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    Directory of Open Access Journals (Sweden)

    Paola Faverio

    2014-01-01

    Full Text Available We present the results of bronchoalveolar lavage (BAL performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS. Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage.

  13. Epidemiological characteristics of Pandemic Influenza A (H1N1-2009) in Zhanjiang, China

    OpenAIRE

    Fu, JinJian; Chen, SiDong; Chen, JiaLin; Wang, Jie; Ling, ChenWen

    2011-01-01

    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 Zhanjiang, China. Methods The case and outbreak reports of influenza-like illness (ILI) were collected from the Chinese information system of disease control and prevention an...

  14. Digested Ara h 1 Loses Sensitizing Capacity When Separated into Fractions

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Barkholt, Vibeke; Rigby, Neil M.

    2012-01-01

    The major peanut allergen Ara h 1 is an easily digestible protein under physiological conditions. The present study revealed that pepsin digestion products of Ara h 1 retained the sensitizing potential in a Brown Norway rat model, while this sensitizing capacity was lost by separating the digest ...... of the peptides being in an aggregated state resembling the intact molecule or that most peptides of the digests need to be present in the same solution, having a synergistic or adjuvant effect and thereby augmenting the immune response against other peptides....

  15. How Does Influenza A (H1N1 Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

    Directory of Open Access Journals (Sweden)

    Sinem Civriz Bozdağ

    2012-03-01

    Full Text Available Clinical course of H1N1 infection in Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT patients is contraversial. We report three AHSCT patients who were infected with Influenza A/H1N1 infection. All of the patients were diagnosed with different hematological diagnosis and were at different stages of transplantation.All of them were treated with oseltamivir,zanamivir was switched with oseltamivir in one patient. All of the three patients were survived without any complication. Swine flu, can display with different courses and progress with bacterial or other viral infections in immunsupressed patients.

  16. Seroprevalence and severity of 2009 pandemic influenza A H1N1 in Taiwan.

    Directory of Open Access Journals (Sweden)

    Chih-Jung Chen

    Full Text Available BACKGROUND: This study is to determine the seroprevalence of the pandemic influenza A H1N1 virus (pH1N1 in Taiwan before and after the 2009 pandemic, and to estimate the relative severity of pH1N1 infections among different age groups. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1544 and 1558 random serum samples were collected from the general population in Taiwan in 2007 and 2010, respectively. Seropositivity was defined by a hemagglutination inhibition titer to pH1N1 (A/Taiwan/126/09 ≥1:40. The seropositivity rate of pH1N1 among the unvaccinated subjects and national surveillance data were used to compare the proportion of infections that led to severe diseases and fatalities among different age groups. The overall seroprevalence of pH1N1 was 0.91% (95% confidence interval [CI] 0.43-1.38 in 2007 and significantly increased to 29.9% (95% CI 27.6-32.2 in 2010 (p<0.0001, with the peak attack rate (55.4% in 10-17 year-old adolescents, the lowest in elderly ≥65 years (14.1%. The overall attack rates were 20.6% (188/912 in unvaccinated subjects. Among the unvaccinated but infected populations, the estimated attack rates of severe cases per 100,000 infections were significantly higher in children aged 0-5 years (54.9 cases, odds ratio [OR] 4.23, 95% CI 3.04-5.90 and elderly ≥ 65 years (22.4 cases, OR 2.76, 95% CI 1.99-3.83 compared to adolescents aged 10-17 years (13.0 cases. The overall case-fatality rate was 0.98 per 100,000 infections without a significant difference in different age groups. CONCLUSIONS/SIGNIFICANCE: Pre-existing immunity against pH1N1 was rarely identified in Taiwanese at any age in 2007. Young children and elderly--the two most lower seroprotection groups showed the greatest vulnerability to clinical severity after the pH1N1 infections. These results imply that both age groups should have higher priority for immunization in the coming flu season.

  17. Palladium-catalyzed cross coupling reactions of 4-bromo-6H-1,2-oxazines

    Directory of Open Access Journals (Sweden)

    Reinhold Zimmer

    2009-09-01

    Full Text Available A number of 4-aryl- and 4-alkynyl-substituted 6H-1,2-oxazines 8 and 9 have been prepared in good yields via cross coupling reactions of halogenated precursors 2, which in turn are easily accessible by bromination of 6H-1,2-oxazines 1. Lewis-acid promoted reaction of 1,2-oxazine 9c with 1-hexyne provided alkynyl-substituted pyridine derivative 12 thus demonstrating the potential of this approach for the synthesis of pyridines.

  18. Antimicrobial and antioxidant activities of substituted 4H-1, 4-benzothiazines

    Science.gov (United States)

    Sharma, Praveen Kumar; Chaucer, Puneet; Kumar, Gulshan; Parihar, Leena

    2017-07-01

    Antioxidant and antimicrobial activity of substituted benzothiazine was investigated. Antioxidant activity of 3,7-dimethyl-2-(4'-morpholinylcarbonyl)-4H-1,4-benzothiazine was tested by the use of 2-diphenyl-1-picrylhydrazyl radical(DPPH). In addition 3,7-dimethyl-2-(4'-morpholinylcarbonyl)-4H-1,4-benzothiazine was examined for its antimicrobial activity against bacteria, Bacillus subtilis, B. flexus, B. alkalophilus, as well as their antifungal activity against Aspergillus nigrum, A. Flexus and show potential antimicrobial activities.

  19. Crystal structures of three substituted 3-aryl-2-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-ones

    Directory of Open Access Journals (Sweden)

    Hemant P. Yennawar

    2016-08-01

    Full Text Available Three ring-substituted 3-aryl analogs of 2-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-one, namely 3-(4-methoxyphenyl-2-phenyl-4H-1,3-benzothiazin-4-one, C21H17NO2S, (I, 2-phenyl-3-[4-(trifluoromethylphenyl]-2,3-dihydro-4H-1,3-benzothiazin-4-one toluene hemisolvate, C21H14F3NOS·0.5C7H8, (II, and 3-(3-bromophenyl-2-phenyl-2,3-dihydro-4H-1,3-benzothiazin-4-one toluene hemisolvate, C20H14BrNOS·0.5C7H8, (III, were synthesized and their crystal structures determined. The hemisolvates differ in that in (II, the asymmetric unit comprises two molecules of the benzothiazinone compound and a toluene solvent molecule, whereas in (III, the unit comprises one benzothiazinone molecule and a half-occupancy toluene solvent molecule. All crystals are of racemic mixtures of the chiral 2-C atom of the thiazine moiety, which in all structures has a screw-boat puckering, with the puckering amplitude values within the range 0.575–0.603 Å. In all three structures, the benzene plane of the benzothiazine system makes a dihedral angle in the range 78.60 (5 to 98.40 (5° with the unsubstituted benzene plane and in the range 70.50 (1 to 121.00 (5° with the substituted benzene plane. The CF3 substituent group in one of the molecules of (II shows positional disorder, with an occupancy ratio of 0.57 (3:0.43 (3. In the crystals of (I and (II, weak intermolecular C—H...O interactions are present, giving in (I, molecules arranged in a plane parallel to (010, and in (II, chains along a. In addition, all three structures show weak C—H...π interactions involving various aromatic rings.

  20. Local compartment changes and regulatory landscape alterations in histone H1-depleted cells

    NARCIS (Netherlands)

    Geeven, Geert; Zhu, Yun; Kim, Byung Ju; Bartholdy, Boris A; Yang, Seung-Min; Macfarlan, Todd S; Gifford, Wesley D; Pfaff, Samuel L; Verstegen, Marjon J A M; Pinto, Hugo; Vermunt, Marit W; Creyghton, Menno P|info:eu-repo/dai/nl/336269471; Wijchers, Patrick J|info:eu-repo/dai/nl/41399371X; Stamatoyannopoulos, John A; Skoultchi, Arthur I; de Laat, Wouter|info:eu-repo/dai/nl/169934497

    2015-01-01

    BACKGROUND: Linker histone H1 is a core chromatin component that binds to nucleosome core particles and the linker DNA between nucleosomes. It has been implicated in chromatin compaction and gene regulation and is anticipated to play a role in higher-order genome structure. Here we have used a

  1. Pandemic Influenza A (H1N1): knowledge among senior health ...

    African Journals Online (AJOL)

    Objective: This study was conducted to assess the level of knowledge of influenza A (H1N1) infection among health care workers in a secondary health care facility in Osogbo, Southwest Nigeria. Methods: A structured questionnaire assessing participants'knowledge of swine influenza viruses, mode of transmission, clinical ...

  2. Serological Evidence of Influenza A virus serotypes (H1 N1 and H5 ...

    African Journals Online (AJOL)

    Keywords: H1N1 and H5N1 influenza A, chicken Sera, Nigeria. One hundred sera samples from chicken flocks showing respiratory distress but failed to respond to treatment against chronic respiratory disease (CRD) were tested for avian influenza virus antibodies. The sera samples were collected from 5, 32, and 21 weeks ...

  3. De Quervain thyroiditis in the course of H1N1 influenza infection

    OpenAIRE

    Michas, G.; Alevetsovitis, G; Andrikou, I.; Tsimiklis, S; Vryonis, E

    2014-01-01

    Background/aim: Viral infections have been frequently associated with subacute (De Quervain) thyroiditis and autoimmune thyroid diseases. In the present case report we document a rare case of De Quervain thyroiditis in the course of H1N1 influenza infection.

  4. Pneumonia and Pandemic Influenza A H1N1 Virus Infection: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Servet Kayhan

    2014-01-01

    Full Text Available Influenza viruses cause seasonal epidemics and occasional pandemics. On 18 March 2009, A novel swine origin influenza A (H1N1 virus was seen in Mexico, then a global outbreak of respiratory illness started. The new H1N1 virus usually attaches to tracheobronchial epithelial cells and the clinical picture ranges from transient lower respiratory tract infections to severe pneumonia leading to acute respiratory distress syndrome. The main complication is extension of viral infection to the alveoli that causes primary viral pneumonia. The most common radiologic findings are unilateral or bilateral ground-glass opacities and multifocal areas of consolidations Bacterial coinfections, particularly Streptococcus pneumoniae and Staphylococcus aureus, increase the severity of illness. Patients with underlying cardiopulmonary comorbid conditions, pregnancy and obesity appear to be at higher risk of severe pneumonia. The severe cases have required admission to intensive care units and needs to mechanical ventilation. H1N1 influenza virus is now in post-pandemic period; however, localized outbreaks of various magnitudes are being reported. Keywords: H1N1; influenza; pandemic; pneumonia

  5. Pandemic influenza A/H1N1 virus incursion into Africa: countries ...

    African Journals Online (AJOL)

    Nucleotide sequence alignment and construction of phylogenetic trees were carried out with MEGA version 5 bioinformatics software and the neighbor-joining ClustalW method with 1000 bootstrap replicates. Earliest human cases of pandemic H1N1 in Africa were detected by June 2009 in Egypt, Morocco, South Africa and ...

  6. Quantitative analysis of chemically modified starches by H-1-NMR spectroscopy

    NARCIS (Netherlands)

    de Graaf, R.A.; Lammers, G; Janssen, L.P.B.M.; Beenackers, A.A C M

    1995-01-01

    A quantitative H-1-NMR method for the determination of the Molar Substitution (MS) of acetylated and hydroxypropylated starches was developed and tested for MS ranging from 0.09 to 0.5. Results were checked using the Johnson method and a titration method for hydroxypropylated and acetylated starch,

  7. Pandemic (H1N1) 2009 Outbreak at Camp for Children with Hematologic and Oncologic Conditions

    Science.gov (United States)

    Morrison, Cori; Maurtua-Neumann, Paola; Myint, Myo Thwin; Drury, Stacy S.

    2011-01-01

    An outbreak of influenza A pandemic (H1N1) 2009 occurred among campers and staff at a summer camp attended by children with hematologic and oncologic conditions. The overall attack rate was 36% and was highest among children and adolescents (43%), persons with cancer (48%), and persons with sickle cell disease (82%). PMID:21192861

  8. Determinants of Parental Acceptance of the H1N1 Vaccine

    Science.gov (United States)

    Hilyard, Karen M.; Quinn, Sandra Crouse; Kim, Kevin H.; Musa, Don; Freimuth, Vicki S.

    2014-01-01

    Although designated as a high-risk group during the 2009-2010 H1N1 pandemic, only about 40% of U.S. children received the vaccine, a relatively low percentage compared with high-risk groups in seasonal influenza, such as the elderly, whose vaccine rates typically top 70%. To better understand parental decision making and predictors of acceptance…

  9. Correlates of 2009 H1N1 Influenza Vaccine Acceptability among Parents and Their Adolescent Children

    Science.gov (United States)

    Painter, Julia E.; Gargano, Lisa M.; Sales, Jessica M.; Morfaw, Christopher; Jones, LaDawna M.; Murray, Dennis; DiClemente, Ralph J.; Hughes, James M.

    2011-01-01

    School-aged children were a priority group for receipt of the pandemic (2009) H1N1 influenza vaccine. Both parental and adolescent attitudes likely influence vaccination behaviors. Data were collected from surveys distributed to middle- and high-school students and their parents in two counties in rural Georgia. Multivariable logistic regression…

  10. Influenza A(H1N1)pdm09 in critically ill children admitted to a ...

    African Journals Online (AJOL)

    in a southern African paediatric intensive care unit (PICU), and to compare them with a similar group with respiratory virus infections other than ... Conclusions. Children admitted to the PICU with confirmed H1N1 tended to have longer ICU stays, prolonged ventilation, more severe ... Africa (SA) was diagnosed on 17 June ...

  11. IgE epitopes of intact and digested Ara h 1

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Nielsen, H.; Madsen, Charlotte Bernhard

    2012-01-01

    epitopes have been suggested to be of great importance. ObjectiveThe aim of this study was to identify IgE specific epitopes of intact and digested Ara h 1, and to compare epitope patterns between humans and rats. MethodsSera from five peanut allergic patients and five Brown Norway rats were used...... to identify intact and digested Ara h 1-specific IgE epitopes by competitive immunoscreening of a phage-displayed random hepta-mer peptide library using polyclonal IgE from the individual sera. The resulting peptide sequences were mapped on the surface of a three-dimensional structure of the Ara h 1 molecule...... to mimic epitopes using a computer-based algorithm. ResultsPatients as well as rats were shown to have individual IgE epitope patterns. All epitope mimics were conformational and found to cluster into three different areas of the Ara h 1 molecule. Five epitope motifs were identified by patient IgE, which...

  12. The accumulation of the maternal pool of histone H1A during oogenesis in Xenopus laevis

    NARCIS (Netherlands)

    van Dongen, W. M.; Moorman, A. F.; Destrée, O. H.

    1983-01-01

    The accumulation of the maternal pool of histone H1A in Xenopus laevis oocytes was measured by the use of a semi-quantitative immunoradiographic method. This method implies the size-fractionation of total basic protein extracts from oocytes on a polyacrylamide gel, blotting of the proteins to

  13. Peanut Allergen Ara h 1 Interacts with Proanthocyanidins into Higher Molecular Weight Complexes

    NARCIS (Netherlands)

    Boxtel, van E.L.; Broek, van den L.A.M.; Koppelman, S.J.; Vincken, J.P.; Gruppen, H.

    2007-01-01

    Mildly extracted peanut allergen Ara h 1 was previously reported to occur as an oligomeric complex. In this paper we describe how the protein in this oligomeric complex interacts noncovalently with phenolic compounds of the proanthocyanidin type. These interactions are being disrupted during anion

  14. H1N1 Preventive Health Behaviors in a University Setting

    Science.gov (United States)

    Katz, Rebecca; May, Larissa; Sanza, Megan; Johnston, Lindsay; Petinaux, Bruno

    2012-01-01

    Background: When H1N1 emerged in 2009, institutions of higher education were immediately faced with questions about how best to protect their community from the virus, yet limited information existed to help predict student preventive behaviors. Methods: The authors surveyed students at a large urban university in November 2009 to better…

  15. Early experience of the pandemic influenza H1N1 2009 epidemic in Taiwan

    Directory of Open Access Journals (Sweden)

    Tzong-Hann Yang

    2011-07-01

    Conclusion: When a patient presents with influenza-like acute febrile respiratory illness symptoms and is young in age, has a travel history involving an affected area, and is suffering from myalgia or leukopenia, physicians should be alerted to the possibility of novel H1N1 virus infection.

  16. Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

    NARCIS (Netherlands)

    Salmon, Daniel A.; Akhtar, Aysha; Mergler, Michelle J.; Vannice, Kirsten S.; Izurieta, Hector; Ball, Robert; Lee, Grace M.; Vellozzi, Claudia; Garman, Patrick; Cunningham, Francesca; Gellin, Bruce; Koh, Howard; Lurie, Nicole

    The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by

  17. Social capital and immunisation against the 2009 A(H1N1) pandemic in Sweden.

    Science.gov (United States)

    Rönnerstrand, Björn

    2013-12-01

    To investigate the connection between social capital indicators and immunisation. The national Society Opinion & Media (SOM) survey is an annual cross-sectional postal survey. In 2009, a random sample of persons aged 16-85 was drawn from the Swedish national register and yielded a 59% participation rate. The number of respondents analysed was 2130. A multiple logistic regression model was used to investigate the connection between the explanatory variables institutional trust and generalised trust and the outcome variable immunisation intent. The analyses included sex, age, education, self-rated health, and personal and societal concern about the 2009 A(H1N1) pandemic. For institutional trust in health care, the odds ratios for intention to vaccinate against the A(H1N1) pandemic were significantly higher in the Medium trust and High trust categories as compared to the Low trust reference category. For generalised trust, the odds ratio for vaccination intention was significantly higher in the High trust category as compared to the Low trust reference category. Two important social capital indicators - institutional trust in health care and generalised trust - seem to be independently associated with intention to accept vaccination against the 2009 A(H1N1) pandemic. The effect holds also when controlling for plausible confounders, such as education, self-rated health, and personal and societal concern about the 2009 A(H1N1) pandemic.

  18. Synthesis and structure-activity relationships of piperidinylpyrrolopyridine derivatives as potent and selective H1 antagonists.

    Science.gov (United States)

    Fonquerna, Silvia; Miralpeix, Montse; Pagès, Lluís; Puig, Carles; Cardús, Arantxa; Antón, Francisca; Vilella, Dolors; Aparici, Mónica; Prieto, José; Warrellow, Graham; Beleta, Jorge; Ryder, Hamish

    2005-02-15

    The synthesis and structure-activity relationships of piperidinylpyrrolopyridines as potent and selective H(1) antagonists are discussed. It was found that the nature of the acid chain bonded to piperidine was a key feature for maintaining both the duration of action in vivo and lack of sedative properties.

  19. Ethnic differences in susceptibilities to A(H1N1) flu: An epidemic ...

    African Journals Online (AJOL)

    The current A(H1N1) flu has showed sub-population dependent susceptibility and fatality as early as April and May of 2009 in its first wave of spreading. After the pandemic outbreak spreads globally for more than seven months, the subpopulation dependence of this flu, including ethnicity, age and gender selectivity, has ...

  20. Swine- Origin Influenza A (H1N1) Pandemic Revisited | Mathew ...

    African Journals Online (AJOL)

    Since the beginning of January 2008 sporadic cases of infections in humans caused by influenza A (H1N1) virus- resistant to available anti-influenza drugs have been reported worldwide [1,2]. The World Health Organization (WHO) in its report published on 18 March 2009 indicated that during weeks 1- 4 (28 December ...

  1. 11 CFR 103.2 - Depositories (2 U.S.C. 432(h)(1)).

    Science.gov (United States)

    2010-01-01

    ... Section 103.2 Federal Elections FEDERAL ELECTION COMMISSION GENERAL CAMPAIGN DEPOSITORIES (2 U.S.C. 432(h)) § 103.2 Depositories (2 U.S.C. 432(h)(1)). Each political committee shall designate one or more State... Savings and Loan Insurance Corporation, or the National Credit Union Administration, as its campaign...

  2. 11 CFR 102.10 - Disbursement by check (2 U.S.C. 432(h)(1)).

    Science.gov (United States)

    2010-01-01

    ..., AND RECORDKEEPING BY POLITICAL COMMITTEES (2 U.S.C. 433) § 102.10 Disbursement by check (2 U.S.C. 432(h)(1)). All disbursements by a political committee, except for disbursements from the petty cash... the committee's campaign depository or depositories under 11 CFR part 103. ...

  3. MAPT haplotype H1G is associated with increased risk of dementia with Lewy bodies.

    Science.gov (United States)

    Labbé, Catherine; Heckman, Michael G; Lorenzo-Betancor, Oswaldo; Soto-Ortolaza, Alexandra I; Walton, Ronald L; Murray, Melissa E; Allen, Mariet; Uitti, Ryan J; Wszolek, Zbigniew K; Smith, Glenn E; Kantarci, Kejal; Knopman, David S; Lowe, Val J; Jack, Clifford R; Ertekin-Taner, Nilüfer; Hassan, Anhar; Savica, Rodolfo; Petersen, Ronald C; Parisi, Joseph E; Maraganore, Demetrius M; Graff-Radford, Neill R; Ferman, Tanis J; Boeve, Bradley F; Dickson, Dennis W; Ross, Owen A

    2016-12-01

    The MAPT H1 haplotype has been associated with several neurodegenerative diseases. We were interested in exploring the role of MAPT haplotypic variation in risk of dementia with Lewy bodies (DLB). We genotyped six MAPT haplotype tagging SNPs and screened 431 clinical DLB cases, 347 pathologically defined high-likelihood DLB cases, and 1049 controls. We performed haplotypic association tests and detected an association with the protective H2 haplotype in our combined series (odds ratio [OR] = 0.75). We fine-mapped the locus and identified a relatively rare haplotype, H1G, that is associated with an increased risk of DLB (OR = 3.30, P = .0017). This association was replicated in our pathologically defined series (OR = 2.26, P = .035). These results support a role for H1 and specifically H1G in susceptibility to DLB. However, the exact functional variant at the locus is still unknown, and additional studies are warranted to fully explain genetic risk of DLB at the MAPT locus. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  4. Seroprevalence to influenza A(H1N1) 2009 virus--where are we?

    Science.gov (United States)

    Broberg, Eeva; Nicoll, Angus; Amato-Gauci, Andrew

    2011-08-01

    Age-specific seroprevalences for influenza virus make important contributions to estimating the burden of infection and determining the vulnerable populations. It is especially difficult to know the true clinical attack rates of the 2009 influenza A(H1N1) pandemic; however, we can estimate infection rates through analyses of seroprevalences based on national studies from different continents and countries with different demographics. After the 2009 influenza A(H1N1) pandemic, seroprevalence studies found 5 to 60% of populations across different continents and age groups having antibodies against the A(H1N1) 2009 virus. The seropositivity was highest in children and teenagers (20 to 60%) as well as in the elderly older than 80 years (20 to 40%). Preexisting cross-reactive antibodies against the virus were present mostly in sera of older people (born before 1950) who could have encountered viruses descended from the 1918 pandemic viruses. Experience with the 2009 pandemic indicates how essential early and timely serology data against the emerging virus can be for informing decisions on use of antivirals and vaccination campaigns, especially in regard to risk groups. The objectives of this review were to summarize the current data available on seroprevalence before and after the 2009 influenza A(H1N1) pandemic and the lessons learned for future pandemic preparedness.

  5. Antivirals Use During the Pandemic H1N1 2009 Outbreak

    Centers for Disease Control (CDC) Podcasts

    2012-01-23

    Charisma Atkins, CDC public health analyst, discusses antiviral use during the 2009 H1N1 pandemic flu outbreak.  Created: 1/23/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/23/2012.

  6. 20 CFR 655.736 - What are H-1B-dependent employers and willful violators?

    Science.gov (United States)

    2010-04-01

    ....g., copies of H-1B petitions; payroll records described in § 655.731(b)(1)). (6) Change in corporate structure or identity of employer. If an employer which experiences a change in its corporate structure as... this section). (See § 655.730(e), regarding change in corporate structure or identity of employer.) In...

  7. Experimental pandemic (H1N1) 2009 virus infection of cats

    NARCIS (Netherlands)

    J.M.A. van den Brand (Judith); K.J. Stittelaar (Koert); G. van Amerongen (Geert); M.W.G. van de Bildt (Marco); L.M.E. Leijten (Lonneke); T. Kuiken (Thijs); A.D.M.E. Osterhaus (Albert)

    2010-01-01

    textabstractTo demonstrate that pandemic (H1N1) 2009 virus may cause respiratory disease in cats, we intratracheally infected cats. Diffuse alveolar damage developed. Seroconversion of sentinel cats indicated cat-to-cat virus transmission. Unlike in cats infected with highly pathogenic avian

  8. Assessment of H1N1 influenza: A swine flu vaccination in Kumasi ...

    African Journals Online (AJOL)

    This study was carried out to assess H1N1 vaccination in the Kumasi metropolis of the Ashanti Region of Ghana. Questionnaires on the subject were administered to 504 individuals compris-ing of 254 health personnel and 250 from the general public (in a cross-sectional survey) after an initial interview of 1,686 individuals.

  9. Distribution and risk factors of 2009 pandemic influenza A (H1N1) in mainland China

    NARCIS (Netherlands)

    L-Q. Fang (Li-Qun); L-P. Wang (Li-Ping); S.J. de Vlas (Sake); S. Liang (Song); S-L. Tong (Shi-Lu); Y-L. Li (Yan-Li); Y-P. Li (Ya-Pin); Q. Qian (Quan); H. Yang (Hong); M-G. Zhou (Mai-Geng); X-F. Wang (Xiao-Feng); J.H. Richardus (Jan Hendrik); J-Q. Ma (Jia-Qi); W.C. Cao (Wu Chun)

    2012-01-01

    textabstractData from all reported cases of 2009 pandemic influenza A (H1N1) were obtained from the China Information System for Disease Control and Prevention. The spatiotemporal distribution patterns of cases were characterized through spatial analysis. The impact of travel-related risk factors on

  10. Factores genéticos en casos graves de gripe (H1N1 2009

    Directory of Open Access Journals (Sweden)

    Francesc Calafell i Majó

    2011-01-01

    Full Text Available La pandemia de gripe (H1N1 2009 generó una serie de cuestiones, entre las cuales estuvo que entre un 25 y un 30% de los casos graves de gripe no presentaron ningún factor de riesgo obvio. Hipotetizamos que un elemento que puede contribuir a la respuesta son factores de riesgo gené ticos del huésped involucrados en la mala progresió n de la enfermedad. Varios indicios nos llevaron a esta hipótesis: estudios de agregación familiar en islandeses y mormones de Utah muestran una cierta heredabilidad de la mortalidad por gripe; se conocen casi 300 genes humanos necesarios para la replicació n del virus de la gripe; y los pacientes más graves de gripe (H1N12009 mostraron una desregulació n del sistema inmune adaptativo. Estamos abordando este problema mediante un diseñ o caso-control (casos hospitalizados de gripe (H1N12009 confirmados contra casos ambulatorios, tambié n confirmados para (H1N12009, en el que se genotiparán más de un milló n de polimorfismos de cambios de nucleó tido (SNPs y de variació n de número de copia (CNVs en casos y controles.

  11. H-1 chemical shift imaging characterization of human brain tumor and edema

    NARCIS (Netherlands)

    Sijens, PE; Oudkerk, M

    Longitudinal (T1) and transverse (T2) relaxation times of metabolites in human brain tumor, peritumoral edema, and unaffected brain tissue were assessed from point resolved spectroscopy (PRESS) H-1 chemical shift imaging results at different repetition times (TR = 1500 and 5000 ms; T1: n = 19) and

  12. Learning from Successful School-based Vaccination Clinics during 2009 pH1N1

    Science.gov (United States)

    Klaiman, Tamar; O'Connell, Katherine; Stoto, Michael A.

    2014-01-01

    Background: The 2009 H1N1 vaccination campaign was the largest in US history. State health departments received vaccines from the federal government and sent them to local health departments (LHDs) who were responsible for getting vaccines to the public. Many LHD's used school-based clinics to ensure children were the first to receive limited…

  13. [Influenza A H1N1v treated with extra-corporal membrane oxygenation.

    DEFF Research Database (Denmark)

    Jensen, Reinhold; Severinsen, Inge Krogh; Terp, Kim

    2010-01-01

    . Polymerase chain reaction test for H1N1v was positive until day ten. No mutations were found in the virus. The patient was given oseltamivir tablets and inhalable zanamivir as well as antibiotics. The patient was treated with extra-corporal membrane oxygenation (EcmO) for 12 days followed by ventilator...

  14. Peanut allergen Ara h 1 interacts with proanthocyanidins into higher molecular weight complexes

    NARCIS (Netherlands)

    Boxtel, E.L. van; Broek, L.A.M. van den; Koppelman, S.J.; Vincken, J.-P.; Gruppen, H.

    2007-01-01

    Mildly extracted peanut allergen Ara h 1 was previously reported to occur as an oligomeric complex. In this paper we describe how the protein in this oligomeric complex interacts noncovalently with phenolic compounds of the proanthocyanidin type. These interactions are being disrupted during anion

  15. Histamine H4 receptor antagonists: the new antihistamines?

    Science.gov (United States)

    Fung-Leung, Wai-Ping; Thurmond, Robin L; Ling, Ping; Karlsson, Lars

    2004-11-01

    Antihistamines (histamine H1 receptor antagonists) are a mainstay treatment for atopic allergy, yet they are only partially effective in relieving the symptoms of the disease. They also have very limited value for the treatment of asthma, despite the well-characterized bronchoconstrictory effects of histamine. The recent discovery of a fourth histamine receptor (H4), and the realization that it is exclusively expressed on hematopoietic cell types that are most implicated in the development and symptomatology of allergy and asthma, suggests that pharmacological targeting of the H4 receptor, either alone or in combination with H1 receptor antagonists, may prove useful for treating both allergy and asthma. Here we review the known biology associated with the H4 receptor, as well the effects of a highly selective H1 receptor antagonist.

  16. Zoonoses as occupational diseases

    Directory of Open Access Journals (Sweden)

    Giorgio Battelli

    2008-12-01

    Full Text Available Zoonoses are discussed as occupational diseases, with special reference to animal husbandry and related activities. After quoting some historical references, occupational zoonoses are examined in relation to the evolution of the concept of occupational zoonosis, the involvement of the World Health Organization in this field, their socio-economic significance, the principal working activities, zoonoses of greatest importance (with special reference to the Mediterranean region, the evaluation of damage and risks. An outline is made of the transmission of zoonoses from farm workers to animals and the biological hazards from the environment. The present situation of occupational zoonoses and related risks in industrialised and traditional farming activities are presented and the importance of some emerging and re-emerging zoonoses for the health of workers is highlighted. The author concludes by stressing that the prevention of occupational zoonoses must be implemented jointly by both veterinary and medical services through preventive measures and epidemiological surveillance of human and animal health, risk evaluation, diagnosis of infections and prompt reporting. It is hoped that the future will offer better inter-disciplinary collaboration and that legislation will be timely and better tailored to safeguard working health and safety.

  17. Clinical outcomes of seasonal influenza and pandemic influenza A (H1N1 in pediatric inpatients

    Directory of Open Access Journals (Sweden)

    Budd Alicia

    2010-10-01

    Full Text Available Abstract Background In April 2009, a novel influenza A H1N1 (nH1N1 virus emerged and spread rapidly worldwide. News of the pandemic led to a heightened awareness of the consequences of influenza and generally resulted in enhanced infection control practices and strengthened vaccination efforts for both healthcare workers and the general population. Seasonal influenza (SI illness in the pediatric population has been previously shown to result in significant morbidity, mortality, and substantial hospital resource utilization. Although influenza pandemics have the possibility of resulting in considerable illness, we must not ignore the impact that we can experience annually with SI. Methods We compared the outcomes of pediatric patients ≤18 years of age at a large urban hospital with laboratory confirmed influenza and an influenza-like illness (ILI during the 2009 pandemic and two prior influenza seasons. The primary outcome measure was hospital length of stay (LOS. All variables potentially associated with LOS based on univariable analysis, previous studies, or hypothesized relationships were included in the regression models to ensure adjustment for their effects. Results There were 133 pediatric cases of nH1N1 admitted during 2009 and 133 cases of SI admitted during the prior 2 influenza seasons (2007-8 and 2008-9. Thirty-six percent of children with SI and 18% of children with nH1N1 had no preexisting medical conditions (p = 0.14. Children admitted with SI had 1.73 times longer adjusted LOS than children admitted for nH1N1 (95% CI 1.35 - 2.13. There was a trend towards more children with SI requiring mechanical ventilation compared with nH1N1 (16 vs.7, p = 0.08. Conclusions This study strengthens the growing body of evidence demonstrating that SI results in significant morbidity in the pediatric population. Pandemic H1N1 received considerable attention with strong media messages urging people to undergo vaccination and encouraging improved

  18. Calculating the potential for within-flight transmission of influenza A (H1N1

    Directory of Open Access Journals (Sweden)

    Blower Sally

    2009-12-01

    Full Text Available Abstract Background Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1. However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights. Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1. Methods We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment. Results The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case. Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected. We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class. Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight. However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class. Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class. During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full. Conclusions Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010. They show travel by one

  19. Communicating uncertainty - how Australian television reported H1N1 risk in 2009: a content analysis

    Directory of Open Access Journals (Sweden)

    Blood R Warwick

    2011-03-01

    Full Text Available Abstract Background Health officials face particular challenges in communicating with the public about emerging infectious diseases of unknown severity such as the 2009 H1N1(swine 'flu pandemic (pH1N1. Statements intended to create awareness and convey the seriousness of infectious disease threats can draw accusations of scare-mongering, while officials can be accused of complacency if such statements are not made. In these communication contexts, news journalists, often reliant on official sources to understand issues are pivotal in selecting and emphasising aspects of official discourse deemed sufficiently newsworthy to present to the public. This paper presents a case-study of news communication regarding the emergence of pH1N1. Methods We conducted a content analysis of all television news items about pH1N1. We examined news and current affairs items broadcast on 5 free-to-air Sydney television channels between April 25 2009 (the first report and October 9 (prior to the vaccine release for statements about 1 the seriousness of the disease 2 how the public could minimise contagion 3 government responses to emerging information. Results pH1N1 was the leading health story for eight of 24 weeks and was in the top 5 for 20 weeks. 353 news items were identified, yielding 3086 statements for analysis, with 63.4% related to the seriousness of the situation, 12.9% providing advice for viewers and 23.6% involving assurances from government. Coverage focused on infection/mortality rates, the spread of the virus, the need for public calm, the vulnerability of particular groups, direct and indirect advice for viewers, and government reassurances about effective management. Conclusions Overall, the reporting of 2009 pH1N1 in Sydney, Australia was generally non-alarmist, while conveying that pH1N1 was potentially serious. Daily infection rate tallies and commentary on changes in the pandemic alert level were seldom contextualised to assist viewers in

  20. French experience of 2009 A/H1N1v influenza in pregnant women.

    Science.gov (United States)

    Dubar, Grégory; Azria, Elie; Tesnière, Antoine; Dupont, Hervé; Le Ray, Camille; Baugnon, Thomas; Matheron, Sophie; Luton, Dominique; Richard, Jean-Christophe; Launay, Odile; Tsatsaris, Vassilis; Goffinet, François; Mignon, Alexandre

    2010-10-05

    The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of early oseltamivir treatment in this specific population.

  1. French experience of 2009 A/H1N1v influenza in pregnant women.

    Directory of Open Access Journals (Sweden)

    Grégory Dubar

    Full Text Available BACKGROUND: The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. METHODOLOGY/PRINCIPAL FINDINGS: A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes, 111 were hospitalized in obstetric or medical wards (moderate outcomes, and 164 were outpatients (mild outcomes. The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%, notably the severe patients (70%, were in the third trimester. Among the severe patients, twenty (50% underwent mechanical ventilation, and eleven (28% were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2-11.8 and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days (adjusted OR, 4.8; 95% CI, 1.9-12.1 and 61.2, 95% CI; 14.4-261.3, respectively. Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14% were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. CONCLUSIONS: This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the

  2. Influenza virus H1N1pdm09 infections in the young and old: evidence of greater antibody diversity and affinity for the hemagglutinin globular head domain (HA1 Domain) in the elderly than in young adults and children.

    Science.gov (United States)

    Verma, Nitin; Dimitrova, Milena; Carter, Donald M; Crevar, Corey J; Ross, Ted M; Golding, Hana; Khurana, Surender

    2012-05-01

    The H1N1 2009 influenza virus (H1N1pdm09) pandemic had several unexpected features, including low morbidity and mortality in older populations. We performed in-depth evaluation of antibody responses generated following H1N1pdm09 infection of naïve ferrets and of 130 humans ranging from the very young (0 to 9 years old) to the very old (70 to 89 years old). In addition to hemagglutination inhibition (HI) titers, we used H1N1pdm09 whole-genome-fragment phage display libraries (GFPDL) to evaluate the antibody repertoires against internal genes, hemagglutinin (HA), and neuraminidase (NA) and also measured antibody affinity for antigenic domains within HA. GFPDL analyses of H1N1pdm09-infected ferrets demonstrated gradual development of antibody repertoires with a focus on M1 and HA1 by day 21 postinfection. In humans, H1N1pdm09 infection in the elderly (>70 years old) induced antibodies with broader epitope recognition in both the internal genes and the HA1 receptor binding domain (RBD) than for the younger age groups (0 to 69 years). Importantly, post-H1N1 infection serum antibodies from the elderly demonstrated substantially higher avidity for recombinant HA1 (rHA1) (but not HA2) than those from younger subjects (50% versus elderly following H1N1pdm09 infection, indicative of recall of long-term memory B cells or long-lived plasma cells. These findings may help explain the age-related morbidity and mortality pattern observed during the H1N1pdm09 pandemic.

  3. Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Erjefält Jonas

    2010-02-01

    Full Text Available Abstract Background The CC-chemokine receptor-3 (CCR3 has emerged as a target molecule for pharmacological intervention in allergic inflammation. Objective To examine whether a dual CCR3 and H1-receptor antagonist (AZD3778 affects allergic inflammation and symptoms in allergic rhinitis. Methods Patients with seasonal allergic rhinitis were subjected to three seven days' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Symptoms and nasal peak inspiratory flow (PIF were monitored in the morning, ten minutes post challenge, and in the evening. Nasal lavages were carried out at the end of each challenge series and α2-macroglobulin, ECP, and tryptase were monitored as indices of allergic inflammation. Results Plasma levels of AZD3778 were stable throughout the treatment series. AZD3778 and the antihistamine (loratadine reduced rhinitis symptoms recorded ten minutes post challenge during this period. AZD3778, but not the anti-histamine, also improved nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening nasal symptoms from the last five days of the allergen challenge series showed statistically significant reductions for AZD3778, but not for loratadine. ECP was reduced by AZD3778, but not by loratadine. Conclusions AZD3778 exerts anti-eosinophil and symptom-reducing effects in allergic rhinitis and part of this effect can likely be attributed to CCR3-antagonism. The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis. Trial registration EudraCT No: 2005-002805-21.

  4. Safety and efficacy of a novel live attenuated influenza vaccine against pandemic H1N1 in swine

    Science.gov (United States)

    On June 11, 2009 the World Health Organization (WHO) declared that the outbreaks caused by novel swine-origin influenza A (H1N1) virus had reached pandemic proportions. The pandemic H1N1 (H1N1pdm) is the predominant influenza strain in the human population. It has also crossed the species barriers a...

  5. File list: Oth.PSC.10.Suv39h1.AllCell [Chip-atlas[Archive

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  11. 26 CFR 1.501(h)-1 - Application of the expenditure test to expenditures to influence legislation; introduction.

    Science.gov (United States)

    2010-04-01

    ... expenditures to influence legislation; introduction. 1.501(h)-1 Section 1.501(h)-1 Internal Revenue INTERNAL...) Exempt Organizations § 1.501(h)-1 Application of the expenditure test to expenditures to influence..., (except as otherwise provided in subsection (h)).” This requirement is called the substantial part test...

  12. File list: Oth.PSC.50.Suv39h1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.PSC.50.Suv39h1.AllCell mm9 TFs and others Suv39h1 Pluripotent stem cell SRX6042...54,SRX604255 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.PSC.50.Suv39h1.AllCell.bed ...

  13. 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...

  14. Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses.

    Science.gov (United States)

    Gras, Stephanie; Kedzierski, Lukasz; Valkenburg, Sophie A; Laurie, Karen; Liu, Yu Chih; Denholm, Justin T; Richards, Michael J; Rimmelzwaan, Guus F; Kelso, Anne; Doherty, Peter C; Turner, Stephen J; Rossjohn, Jamie; Kedzierska, Katherine

    2010-07-13

    Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 "Spanish flu" rather than more recent "seasonal" strains. We present immunological and structural analyses of cross-reactive CD8(+) T-cell-mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP(418-426) peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8(+) T-cell specificity was probed for 12 different NP(418) mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP(418) mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP(418) variant or the 1918-NP(418) variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8(+) T cells specific for the 2009-NP(418) and 1918-NP(418) epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.

  15. Hearing impairment in the P23H-1 retinal degeneration rat model

    Directory of Open Access Journals (Sweden)

    Jorge V. Sotoca

    2014-09-01

    Full Text Available The transgenic P23H line 1 (P23H-1 rat expresses a variant of rhodopsin with a mutation that leads to loss of visual function. This rat strain is an experimental model usually employed to study photoreceptor degeneration. Although the mutated protein should not interfere with other sensory functions, observing severe loss of auditory reflexes in response to natural sounds led us to study auditory brain response (ABR recording. Animals were separated into different hearing levels following the response to natural stimuli (hand clapping and kissing sounds. Of all the analyzed animals, 25.9% presented auditory loss before 50 days of age (P50 and 45% were totally deaf by P200. ABR recordings showed that all the rats had a higher hearing threshold than the control Sprague-Dawley (SD rats, which was also higher than any other rat strains. The integrity of the central and peripheral auditory pathway was analyzed by histology and immunocytochemistry. In the cochlear nucleus (CN, statistical differences were found between SD and P23H-1 rats in VGluT1 distribution, but none were found when labeling all the CN synapses with anti-Syntaxin. This finding suggests anatomical and/or molecular abnormalities in the auditory downstream pathway. The inner ear of the hypoacusic P23H-1 rats showed several anatomical defects, including loss and disruption of hair cells and spiral ganglion neurons. All these results can explain, at least in part, how hearing impairment can occur in a high percentage of P23H-1 rats. P23H-1 rats may be considered an experimental model with visual and auditory dysfunctions in future research.

  16. Impact of obesity in patients infected with 2009 influenza A(H1N1).

    Science.gov (United States)

    Díaz, Emili; Rodríguez, Alejandro; Martin-Loeches, Ignacio; Lorente, Leonardo; Del Mar Martín, María; Pozo, Juan Carlos; Montejo, Juan Carlos; Estella, Angel; Arenzana, Ángel; Rello, Jordi

    2011-02-01

    A large proportion of patients infected with 2009 influenza A(H1N1) (A[H1N1]) are obese. Obesity has been proposed as a risk factor influencing outcome in these patients. However, its role remains unclear. We evaluate the outcome of patients who are obese and infected with A(H1N1) in the ICU, determining whether obesity is a risk factor for mortality. This was a prospective, observational, and multicenter study performed in 144 ICUs in Spain. Data were obtained from the Grupo de Trabajo en Enfermedades Infecciosas de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (GTEI/SEMICYUC) registry. Adult patients with A(H1N1) that was confirmed by real-time polymerase chain reaction were included in the analysis. Patients who were obese (BMI > 30) were compared with patients who were nonobese. Cox regression analysis was used to determine adjusted mortality. Differences of P 40). Mechanical ventilation (MV) was more frequently applied in patients who were obese (64% vs 52.4%, P < .01) Patients with obesity remained on MV longer than patients who were nonobese (6.5 ± 10.3 days vs 9.3 ± 9.7 days, P = .02), had longer ICU length of stay (10.8 ± 12.1 days vs 13.7 ± 11.7 days, P = .03), and had longer hospitalization (18.2 ± 14.6 days vs 22.2 ± 16.5 days, P = .02). Mortality adjusted by severity and potential confounders identified that obesity was not significantly associated with ICU mortality (hazard ratio, 1.1; 95% CI, 0.69-1.75; P = .68). In our cohort, patients who were obese and infected with A(H1N1) did not have increased mortality. However, there was an association between obesity and higher ICU resource consumption.

  17. Serosurveillance for pandemic influenza A (H1N1) 2009 virus infection in domestic elephants, Thailand.

    Science.gov (United States)

    Paungpin, Weena; Wiriyarat, Witthawat; Chaichoun, Kridsada; Tiyanun, Ekasit; Sangkachai, Nareerat; Changsom, Don; Poltep, Kanaporn; Ratanakorn, Parntep; Puthavathana, Pilaipan

    2017-01-01

    The present study conducted serosurveillance for the presence of antibody to pandemic influenza A (H1N1) 2009 virus (H1N1pdm virus) in archival serum samples collected between 2009 and 2013 from 317 domestic elephants living in 19 provinces situated in various parts of Thailand. To obtain the most accurate data, hemagglutination-inhibition (HI) assay was employed as the screening test; and sera with HI antibody titers ≥20 were further confirmed by other methods, including cytopathic effect/hemagglutination based-microneutralization (microNT) and Western blot (WB) assays using H1N1pdm matrix 1 (M1) or hemagglutinin (HA) recombinant protein as the test antigen. Conclusively, the appropriate assays using HI in conjunction with WB assays for HA antibody revealed an overall seropositive rate of 8.5% (27 of 317). The prevalence of antibody to H1N1pdm virus was 2% (4/172) in 2009, 32% (17/53) in 2010, 9% (2/22) in 2011, 12% (1/8) in 2012, and 5% (3/62) in 2013. Notably, these positive serum samples were collected from elephants living in 7 tourist provinces of Thailand. The highest seropositive rate was obtained from elephants in Phuket, a popular tourist beach city. Young elephants had higher seropositive rate than older elephants. The source of H1N1pdm viral infection in these elephants was not explored, but most likely came from close contact with the infected mahouts or from the infected tourists who engaged in activities such as elephant riding and feeding. Nevertheless, it could not be excluded that elephant-to-elephant transmission did occur.

  18. Proteolysis of the peanut allergen Ara h 1 by an endogenous aspartic protease.

    Science.gov (United States)

    Wilson, Karl A; Tan-Wilson, Anna

    2015-11-01

    The 7S and 11S globulins of peanuts are subjected to proteolysis two days after seed imbibition, with Ara h 1 and the arachin acidic chains being among the first storage proteins to be mobilized. Proteolytic activity was greatest at pH 2.6-3 and is inhibited by pepstatin A, characteristic of an aspartic protease. This activity persists in seedling cotyledons up to at least 8 days after imbibition. In vitro proteolysis of Ara h 1 at pH 2.6 by extracts of cotyledons from seedlings harvested 24 h after seed imbibition generates newly appearing bands on SDS-PAGE. Partial sequences of Ara h 1 that were obtained through LC-MS/MS analysis of in-gel trypsin digests of those bands, combined with information on fragment size, suggest that proteolysis begins in the region that links the two cupin domains to produce two 33/34 kD fragments, each one encompassing an intact cupin domain. The later appearance of two 18 and 10/11 kD fragments can be explained by proteolysis within an exposed site in the cupin domains of each of the 33/34 kD fragments. The same or similar proteolytic activity was observed in developing seeds, but Ara h 1 remains intact through seed maturation. This is partly explained by the observation that acidification of the protein storage vacuoles, demonstrated by vacuolar accumulation of acridine orange that was dissipated by a membrane-permeable base, occurs only after germination. These findings suggest a method for use of the seed aspartic protease in reducing peanut allergy due to Ara h 1. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Initial human transmission dynamics of the pandemic (H1N1) 2009 virus in North America

    Science.gov (United States)

    Pourbohloul, Babak; Ahued, Armando; Davoudi, Bahman; Meza, Rafael; Meyers, Lauren A.; Skowronski, Danuta M.; Villaseñor, Ignacio; Galván, Fernando; Cravioto, Patricia; Earn, David J. D.; Dushoff, Jonathan; Fisman, David; Edmunds, W. John; Hupert, Nathaniel; Scarpino, Samuel V.; Trujillo, Jesús; Lutzow, Miguel; Morales, Jorge; Contreras, Ada; Chávez, Carolina; Patrick, David M.; Brunham, Robert C.

    2009-01-01

    Background  Between 5 and 25 April 2009, pandemic (H1N1) 2009 caused a substantial, severe outbreak in Mexico, and subsequently developed into the first global pandemic in 41 years. We determined the reproduction number of pandemic (H1N1) 2009 by analyzing the dynamics of the complete case series in Mexico City during this early period. Methods  We analyzed three mutually exclusive datasets from Mexico City Distrito Federal which constituted all suspect cases from 15 March to 25 April: confirmed pandemic (H1N1) 2009 infections, non‐pandemic influenza A infections and patients who tested negative for influenza. We estimated the initial reproduction number from 497 suspect cases identified prior to 20 April, using a novel contact network methodology incorporating dates of symptom onset and hospitalization, variation in contact rates, extrinsic sociological factors, and uncertainties in underreporting and disease progression. We tested the robustness of this estimate using both the subset of laboratory‐confirmed pandemic (H1N1) 2009 infections and an extended case series through 25 April, adjusted for suspected ascertainment bias. Results  The initial reproduction number (95% confidence interval range) for this novel virus is 1·51 (1·32–1·71) based on suspected cases and 1·43 (1·29–1·57) based on confirmed cases before 20 April. The longer time series (through 25 April) yielded a higher estimate of 2·04 (1·84–2·25), which reduced to 1·44 (1·38–1·51) after correction for ascertainment bias. Conclusions  The estimated transmission characteristics of pandemic (H1N1) 2009 suggest that pharmaceutical and non‐pharmaceutical mitigation measures may appreciably limit its spread prior the development of an effective vaccine. PMID:19702583

  20. Trust During the Early Stages of the 2009 H1N1 Pandemic

    Science.gov (United States)

    FREIMUTH, VICKI S.; MUSA, DON; HILYARD, KAREN; QUINN, SANDRA CROUSE; KIM, KEVIN

    2013-01-01

    Distrust of the government often stands in the way of cooperation with public health recommendations in a crisis. The purpose of this paper is to describe the public’s trust in government recommendations during the early stages of the H1N1 pandemic and identify factors that might account for these trust levels. We surveyed 1543 respondents about their experiences and attitudes related to H1N1 influenza between June 3, 2009 and July 6, 2009, during the first wave of the pandemic using the Knowledge Networks (KN) online panel. This panel is representative of the US population, and uses a combination of random-digit dial and address-based probability sampling frames covering 99% of the US household population to recruit participants. To ensure participation of low-income individuals and those without Internet access, KN provides hardware and access to the Internet if needed. Measures included standard demographics, a trust scale, trust ratings for individual spokespersons, involvement with H1N1, experience with H1N1, and past discrimination in health care. We found that trust of government was low (2.3 out of 4) and varied across demographic groups. Blacks and Hispanics reported higher trust in government than did Whites. Of the spokespersons included, personal health professionals received the highest trust ratings and religious leaders the lowest. Attitudinal and experience variables predicted trust better than demographic characteristics. Closely following the news about the flu virus, having some self-reported knowledge about H1N1, self-reporting of local cases and previously experiencing discrimination were the significant attitudinal and experience predictors of trust. Using a second longitudinal survey, trust in the early stages of the pandemic did predict vaccine acceptance later but only for white, non-Hispanic individuals. PMID:24117390

  1. Airport arrivals screening during pandemic (H1N1) 2009 influenza in New South Wales, Australia.

    Science.gov (United States)

    Gunaratnam, Praveena J; Tobin, Sean; Seale, Holly; Marich, Andrew; McAnulty, Jeremy

    2014-03-17

    To examine the effectiveness of airport screening in New South Wales during pandemic (H1N1) 2009 influenza. Analysis of data collected at clinics held at Sydney Airport, and of all notified cases of influenza A(H1N1)pdm09, between 28 April 2009 and 18 June 2009. Case detection rate per 100,000 passengers screened, sensitivity, positive predictive value and specificity of airport screening. The proportion of all cases in the period detected at airport clinics was compared with the proportion detected in emergency departments and general practice. Of an estimated 625,147 passenger arrivals at Sydney Airport during the period, 5845 (0.93%) were identified as being symptomatic or febrile, and three of 5845 were subsequently confirmed to have influenza A(H1N1)pdm09, resulting in a detection rate of 0.05 per 10,000 screened (95% CI, 0.02-1.14 per 10,000). Forty-five patients with overseas-acquired influenza A(H1N1)pdm09 in NSW would have probably passed through the airport during this time, giving airport screening a sensitivity of 6.67% (95% CI, 1.40%-18.27%). Positive predictive value was 0.05% (95% CI, 0.02%-0.15%) and specificity 99.10% (95% CI, 99.00%-100.00%). Of the 557 confirmed cases across NSW during the period, 290 (52.1%) were detected at emergency departments and 135 (24.2%) at general practices, compared with three (0.5%) detected at the airport. Airport screening was ineffective in detecting cases of influenza A(H1N1)pdm09 in NSW. Its future use should be carefully considered against potentially more effective interventions, such as contact tracing in the community.

  2. Inside the outbreak of the 2009 influenza A (H1N1v virus in Mexico.

    Directory of Open Access Journals (Sweden)

    Hector M Zepeda-Lopez

    Full Text Available BACKGROUND: Influenza viruses pose a threat to human health because of their potential to cause global disease. Between mid March and mid April a pandemic influenza A virus emerged in Mexico. This report details 202 cases of infection of humans with the 2009 influenza A virus (H1N1v which occurred in Mexico City as well as the spread of the virus throughout the entire country. METHODOLOGY AND FINDINGS: From May 1st to May 5th nasopharyngeal swabs, derived from 751 patients, were collected at 220 outpatient clinics and 28 hospitals distributed throughout Mexico City. Analysis of samples using real time RT-PCR revealed that 202 patients out of the 751 subjects (26.9% were confirmed to be infected with the new virus. All confirmed cases of human infection with the strain influenza (H1N1v suffered respiratory symptoms. The greatest number of confirmed cases during the outbreak of the 2009 influenza A (H1N1v were seen in neighbourhoods on the northeast side of Mexico City including Iztapalapa, Gustavo A. Madero, Iztacalco, and Tlahuac which are the most populated areas in Mexico City. Using these data, together with data reported by the Mexican Secretariat of Health (MSH to date, we plot the course of influenza (H1N1v activity throughout Mexico. CONCLUSIONS: Our data, which is backed up by MSH data, show that the greatest numbers of the 2009 influenza A (H1N1 cases were seen in the most populated areas. We speculate on conditions in Mexico which may have sparked this flu pandemic, the first in 41 years. We accept the hypothesis that high population density and a mass gathering which took in Iztapalapa contributed to the rapid spread of the disease which developed in three peaks of activity throughout the Country.

  3. Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.

    Science.gov (United States)

    Bao, Yanyan; Gao, Yingjie; Shi, Yujing; Cui, Xiaolan

    2017-06-01

    H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

  4. 2009 H1N1 flu pandemic among professional basketball players: data from 18 countries.

    Science.gov (United States)

    Kousoulis, Antonis A; Sergentanis, Theodoros N; Tsiodras, Sotirios

    2014-12-01

    Although influenza may be propagated in innumerable occasions and daily situations involving exposure, basketball may create many chances for close contact in which influenza could spread. This study aims to quantify and assess the impact of the 2009 H1N1 influenza pandemic among professional basketball players. A multi-step strategy was followed to gather the relevant data during the 2009-10 basketball season. Possible risk factors were recorded; logistic regression was performed to assess the impact of the former. Where data were only available in the press, cases were also verified by subsequent communication with the national basketball federations. Relevant data were available for 18 countries (218 teams, 3,024 players). In all, 52 H1N1 cases in 19 teams were reported. A larger number of players presented as a risk factor for the emergence of H1N1 cases to a borderline extent (Odds Ratio, OR 1.19, 95% CI 1.00-1.41, p 0.056). A borderline association also implicated the population of the city-basis (OR 1.01, 95% CI 1.00-1.02, p 0.094). On the other hand, no significant association with risk of H1N1 emergence was demonstrated regarding latitude and longitude of the city-basis. Even in environments where the best possible preventive and other medical care is provided influenza continues to be a threat. The microenvironment (crowding index, players per team) seemed to represent the most meaningful predictor regarding H1N1 emergence in a basketball team.

  5. Serosurveillance for pandemic influenza A (H1N1 2009 virus infection in domestic elephants, Thailand.

    Directory of Open Access Journals (Sweden)

    Weena Paungpin

    Full Text Available The present study conducted serosurveillance for the presence of antibody to pandemic influenza A (H1N1 2009 virus (H1N1pdm virus in archival serum samples collected between 2009 and 2013 from 317 domestic elephants living in 19 provinces situated in various parts of Thailand. To obtain the most accurate data, hemagglutination-inhibition (HI assay was employed as the screening test; and sera with HI antibody titers ≥20 were further confirmed by other methods, including cytopathic effect/hemagglutination based-microneutralization (microNT and Western blot (WB assays using H1N1pdm matrix 1 (M1 or hemagglutinin (HA recombinant protein as the test antigen. Conclusively, the appropriate assays using HI in conjunction with WB assays for HA antibody revealed an overall seropositive rate of 8.5% (27 of 317. The prevalence of antibody to H1N1pdm virus was 2% (4/172 in 2009, 32% (17/53 in 2010, 9% (2/22 in 2011, 12% (1/8 in 2012, and 5% (3/62 in 2013. Notably, these positive serum samples were collected from elephants living in 7 tourist provinces of Thailand. The highest seropositive rate was obtained from elephants in Phuket, a popular tourist beach city. Young elephants had higher seropositive rate than older elephants. The source of H1N1pdm viral infection in these elephants was not explored, but most likely came from close contact with the infected mahouts or from the infected tourists who engaged in activities such as elephant riding and feeding. Nevertheless, it could not be excluded that elephant-to-elephant transmission did occur.

  6. Inside the Outbreak of the 2009 Influenza A (H1N1)v Virus in Mexico

    Science.gov (United States)

    Zepeda-Lopez, Hector M.; Perea-Araujo, Lizbeth; Miliar-García, Angel; Dominguez-López, Aarón; Xoconostle-Cázarez, Beatriz; Lara-Padilla, Eleazar; Ramírez Hernandez, Jorge A.; Sevilla-Reyes, Edgar; Orozco, Maria Esther; Ahued-Ortega, Armando; Villaseñor-Ruiz, Ignacio; Garcia-Cavazos, Ricardo J.; Teran, Luis M.

    2010-01-01

    Background Influenza viruses pose a threat to human health because of their potential to cause global disease. Between mid March and mid April a pandemic influenza A virus emerged in Mexico. This report details 202 cases of infection of humans with the 2009 influenza A virus (H1N1)v which occurred in Mexico City as well as the spread of the virus throughout the entire country. Methodology and Findings From May 1st to May 5th nasopharyngeal swabs, derived from 751 patients, were collected at 220 outpatient clinics and 28 hospitals distributed throughout Mexico City. Analysis of samples using real time RT-PCR revealed that 202 patients out of the 751 subjects (26.9%) were confirmed to be infected with the new virus. All confirmed cases of human infection with the strain influenza (H1N1)v suffered respiratory symptoms. The greatest number of confirmed cases during the outbreak of the 2009 influenza A (H1N1)v were seen in neighbourhoods on the northeast side of Mexico City including Iztapalapa, Gustavo A. Madero, Iztacalco, and Tlahuac which are the most populated areas in Mexico City. Using these data, together with data reported by the Mexican Secretariat of Health (MSH) to date, we plot the course of influenza (H1N1)v activity throughout Mexico. Conclusions Our data, which is backed up by MSH data, show that the greatest numbers of the 2009 influenza A (H1N1) cases were seen in the most populated areas. We speculate on conditions in Mexico which may have sparked this flu pandemic, the first in 41 years. We accept the hypothesis that high population density and a mass gathering which took in Iztapalapa contributed to the rapid spread of the disease which developed in three peaks of activity throughout the Country. PMID:20949040

  7. Illinois department of public health H1N1/A pandemic communications evaluation survey.

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, D.; Decision and Information Sciences

    2010-09-16

    Because of heightened media coverage, a 24-hour news cycle and the potential miscommunication of health messages across all levels of government during the onset of the H1N1 influenza outbreak in spring 2009, the Illinois Department of Public Health (IDPH) decided to evaluate its H1N1 influenza A communications system. IDPH wanted to confirm its disease information and instructions were helping stakeholders prepare for and respond to a novel influenza outbreak. In addition, the time commitment involved in preparing, issuing, monitoring, updating, and responding to H1N1 federal guidelines/updates and media stories became a heavy burden for IDPH staff. The process and results of the H1N1 messaging survey represent a best practice that other health departments and emergency management agencies can replicate to improve coordination efforts with stakeholder groups during both emergency preparedness and response phases. Importantly, the H1N1 survey confirmed IDPH's messages were influencing stakeholders decisions to activate their pandemic plans and initiate response operations. While there was some dissatisfaction with IDPH's delivery of information and communication tools, such as the fax system, this report should demonstrate to IDPH that its core partners believe it has the ability and expertise to issue timely and accurate instructions that can help them respond to a large-scale disease outbreak in Illinois. The conclusion will focus on three main areas: (1) the survey development process, (2) survey results: best practices and areas for improvement and (3) recommendations: next steps.

  8. Modelling and analysis of influenza A (H1N1) on networks.

    Science.gov (United States)

    Jin, Zhen; Zhang, Juping; Song, Li-Peng; Sun, Gui-Quan; Kan, Jianli; Zhu, Huaiping

    2011-02-25

    In April 2009, a new strain of H1N1 influenza virus, referred to as pandemic influenza A (H1N1) was first detected in humans in the United States, followed by an outbreak in the state of Veracruz, Mexico. Soon afterwards, this new virus kept spreading worldwide resulting in a global outbreak. In China, the second Circular of the Ministry of Health pointed out that as of December 31, 2009, the country's 31 provinces had reported 120,000 confirmed cases of H1N1. We formulate an epidemic model of influenza A based on networks. We calculate the basic reproduction number and study the effects of various immunization schemes. The final size relation is derived for the network epidemic model. The model parameters are estimated via least-squares fitting of the model solution to the observed data in China. For the network model, we prove that the disease-free equilibrium is globally asymptotically stable when the basic reproduction is less than one. The final size will depend on the vaccination starting time, T, the number of infective cases at time T and immunization schemes to follow. Our theoretical results are confirmed by numerical simulations. Using the parameter estimates based on the observation data of the cumulative number of hospital notifications, we estimate the basic reproduction number R0 to be 1.6809 in China. Network modelling supplies a useful tool for studying the transmission of H1N1 in China, capturing the main features of the spread of H1N1. While a uniform, mass-immunization strategy helps control the prevalence, a targeted immunization strategy focusing on specific groups with given connectivity may better control the endemic.

  9. Occupation-centred, occupation-based, occupation-focused: same, same or different?

    Science.gov (United States)

    Fisher, Anne G

    2013-05-01

    Since the beginning of the occupational therapy profession, engagement in occupation has been valued as the primary therapeutic agent as well as the goal of intervention. While there are few today who would not support this idea, occupational therapists continue to struggle with implementing their beliefs through "what we do" and "how we do it". Contributing to this problem is their failure to use terminology in a manner that clearly defines what and how occupational therapists do what they do in occupational therapy research, education, and practice. The author will, therefore, first discuss some key occupational therapy terms and propose that they represent an occupation-related taxonomy that can be used to more clearly define and describe for occupational therapists and others what they do and how they do what they do as occupational therapists. Then, with a goal of fostering critical self-reflection among occupational scientists and occupational therapy researchers, educators, and practitioners, the author will go through the stages of the occupational therapy process outlined in the Occupational Therapy Intervention Process Model (OTIPM) and demonstrate how a more precise use of this occupation-related taxonomy can facilitate maximizing the power of occupation in practice.

  10. Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus.

    Science.gov (United States)

    Dunford, Paul J; Williams, Kacy N; Desai, Pragnya J; Karlsson, Lars; McQueen, Daniel; Thurmond, Robin L

    2007-01-01

    Histamine is a potent mediator of itch in humans, yet histamine H(1) receptor antagonists have been shown to be of limited use in the treatment of certain chronic pruritic diseases. The histamine H(4) receptor is a recently described histamine receptor, expressed on hematopoietic cells, linked to the pathology of allergy and asthma. The contribution of the novel histamine H(4) receptor to histaminergic and allergic pruritus was investigated. Histamine and a selective histamine H(4) receptor agonist caused scratching responses in mice, which were almost completely attenuated in histamine H(4) receptor knockout mice or by pretreatment with the selective histamine H(4) receptor antagonist, JNJ 7777120. Pruritus induced by allergic mechanisms was also potently inhibited with histamine H(4) receptor antagonist treatment or in histamine H(4) receptor knockout mice. In all cases, the inhibitory effect of histamine H(4) receptor antagonist was greater than those observed with histamine H(1) receptor antagonists. The histamine H(4) receptor-mediated pruritus was shown to be independent of mast cells or other hematopoietic cells and may result from actions on peripheral neurons. These results demonstrate that the histamine H(4) receptor is involved in pruritic responses in mice to a greater extent than the histamine H(1) receptor. Histamine H(4) receptor antagonists may have therapeutic utility for treating chronic pruritic diseases in humans where histamine H(1) receptor antagonists are not effective.

  11. Pharmacologic Evaluation of Antidepressant Activity and Synthesis of 2-Morpholino-5-phenyl-6H-1,3,4-thiadiazine Hydrobromide

    Directory of Open Access Journals (Sweden)

    Alexey P. Sarapultsev

    2016-05-01

    Full Text Available Substituted thiadiazines exert a reliable therapeutic effect in treating stress, and a schematic description of their ability to influence all aspects of a stress response has been depicted. This study was conducted to pharmacologically evaluate compound L-17, a substituted thiadiazine, (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide for possible anti-psychotic/antidepressant activity. Compound L-17 was synthesized by cyclocondensation of α-bromoacetophenone with the original morpholine-4-carbothionic acid hydrazide. Pharmacologic evaluations were conducted using methods described by E.F. Lavretskaya (1985, and in accordance with published guidelines for studying drugs for neuroleptic activity. Compound L-17 was evaluated for various possible mechanisms of action, including its effects on cholinergic system agonists/antagonists, dopaminergic neurotransmission, the adrenergic system, and 5-HT3 serotonin receptors. One or more of these mechanisms may be responsible for the beneficial effects shown by thiadiazine compounds in experiments conducted to evaluate their activity in models of acute stress and acute myocardial infarction.

  12. In silico molecular modeling of neuraminidase enzyme H1N1 avian influenza virus and docking with zanamivir ligands

    Directory of Open Access Journals (Sweden)

    Muthiyan Ramachandran

    2012-12-01

    Full Text Available Objective: Neuraminidase is an enzyme aspartic protease that is essential for the life cycle of H1N1. Methods: Constructed a model of Neuraminidase enzyme the 3D structure as template using with Modeller software. The Neuraminidase enzyme model was predicted and validated by Procheck, What check, Errat, Verify-3D and AutoDock web server for reliability. Results: The Modeller homology-modeling algorithm was demonstrated excellent accuracy in blind predictions. The Neuraminidase enzyme model built with little, 35% identity could be accurate enough to be successfully used in receptor based rational drug design. The closest homologue with the highest sequence identity 100% was selected. Zanamivir drug and analogues were retrieved from PubChem database, as well as subjected to docking interaction with Neuraminidase enzyme used AutoDock programme. Based on the root mean square deviation and lowest binding energy values the best docking orientation was selected. The better lowest binding energy value -6.91 was selected of CID_25209232. Conclusions: This study will be used in broad screening of inhibitors of the protein. However, further implemented experimental and clinical verification is needed to establishment these analogues as drug.

  13. Occupational skin diseases

    DEFF Research Database (Denmark)

    Mahler, Vera; Aalto-Korte, Kristiina; Alfonso, Jose Hernan

    2017-01-01

    and rehabilitation in different European countries. METHODS: A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation...... is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. CONCLUSION: OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness...

  14. Dopamine D₂/₃ occupancy of ziprasidone across a day: a within-subject PET study.

    Science.gov (United States)

    Suzuki, Takefumi; Graff-Guerrero, Ariel; Uchida, Hiroyuki; Remington, Gary; Caravaggio, Fernando; Borlido, Carol; Pollock, Bruce; Mulsant, Benoit; Deluca, Vincenzo; Ismail, Zahinoor; Mamo, David

    2013-07-01

    Ziprasidone is an atypical antipsychotic recommended to be administered twice daily. The purpose of this study was to investigate whether occupancy of the dopamine D2/3 receptors by ziprasidone is maintained across a day employing a within subject design. Positron emission tomography (PET) scans with [(11)C]-raclopride were performed in 12 patients with schizophrenia while treated with ziprasidone 60 mg twice daily. Each patient completed [(11)C]-raclopride PET scans at 5, 13 and 23 h after the last dose of ziprasidone. Dopamine D2/3 receptor occupancy was estimated with reference to binding potential data of 44 age- and sex-matched control subjects in the caudate, putamen and ventral striatum. Eleven scans were available at each time point, and the mean occupancies at 5-, 13- and 23-h scans were 66, 39 and 2 % in the putamen; 62, 35 and -6 % in the caudate; and 68, 47 and 11 % in the ventral striatum, respectively. The time-course of receptor occupancy across the regions indicated an occupancy half-life of 8.3 h. The serum level of ziprasidone associated with 50 % D2/3 receptors occupancy was estimated to be 204 nmol/L (84 ng/ml). Prolactin levels were highest at 5-h post-dose and none showed hyperprolactinemia at 23-h scans. The absence of ziprasidone striatal D2/3 receptor binding 23 h after taking 60 mg under steady-state conditions is consistent with its peripheral half-life. The results support our earlier report that ziprasidone 60 mg administered twice daily appears to be the minimal dose expected to achieve therapeutic central dopamine D2/3 receptor occupancy (i.e. 60 %). 24-Hour Time Course of Striatal Dopamine D2 Receptor Occupancy of Ziprasidone: A PET Study, www.clinicaltrials.gov/ct2/show/NCT00818298 , NCT00818298.

  15. Histamine, histamine receptors and antihistamines: new concepts.

    Science.gov (United States)

    Criado, Paulo Ricardo; Criado, Roberta Fachini Jardim; Maruta, Celina W; Machado Filho, Carlos d'Apparecida

    2010-01-01

    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 is essential for a better medical care, especially that offered to pregnant women, children, the elderly, and patients with comorbidities.

  16. Histamine H2 receptor - Involvement in gastric ulceration

    Science.gov (United States)

    Brown, P. A.; Vernikos-Danellis, J.; Brown, T. H.

    1976-01-01

    The involvement of the H1 and H2 receptors for histamine in the pathogenesis of gastric ulcers was investigated in rats. Metiamide, an H2 receptor antagonist, reliably reduced ulceration produced by stress alone or by a combination of stress and aspirin. In contrast, pyrilamine, which blocks only the H1 receptor, was without effect under these same conditions. The results support the hypothesis that histamine mediates both stress and stress plus aspirin induced ulceration by a mechanism involving the H2 receptor.