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1.
001-es BibID:
BIBFORM003869
Első szerző:
Elekes Krisztián
Cím:
Inhibitory effects of synthetic somatostatin receptor subtype 4 agonists on acute and chronic airway inflammation and hyperreactivity in the mouse / Krisztián Elekes, Zsuzsanna Helyes, László Kereskai, Katalin Sándor, Erika Pintér, Gábor Pozsgai, Valéria Tékus, Ágnes Bánvölgyi, József Németh, Tamás Szűts, György Kéri, János Szolcsányi
Dátum:
2008
Megjegyzések:
Somatostatin released fromactivated capsaicin-sensitive afferents of the lung inhibits inflammation and related bronchial hyperreactivity presumably via somatostatin 4 receptors (sst4). The aim of this studywas to examine the effects of TT-232, a heptapeptide sst4/sst1 receptor agonist and J-2156, a high affinity sst4 receptor-selective peptidomimetic agonist in airway inflammation models. Acute pneumonitis was evoked by intranasal lipopolysaccharide 24 h before measurement. Chronic inflammation was induced by ovalbumin inhalation on days 28, 29 and 30 after i.p. sensitization on days 1 and 14. Semiquantitative histopathological scoring was based on perivascular/peribronchial oedema, neutrophil/macrophage infiltration, goblet cell hyperplasia in the acute model and eosinophil infiltration,mucosal oedema,mucus production and epithelial cell damage in chronic inflammation.Myeloperoxidase activity of the lung was measured spectrophotometrically to quantify granulocyte accumulation and the broncoalveolar lavage fluid was analysed by flow cytometry. Carbachol-induced bronchoconstriction was assessed by unrestrained whole body plethysmography and its calculated indicator, enhanced pause (Penh)was determined. TT-232 and J-2156 induced similar inhibition on granulocyte recruitment and histopathological changes in both models, although macrophage infiltration in LPS-induced inflammation was unaltered by either compounds. Both agonists diminished inflammatory airway hyperresponsiveness. Since their single administration after the development of the inflammatory reactions also inhibited carbachol-induced bronchoconstriction, somatostatin sst4 receptor activation on bronchial smooth muscle cells is likely to be involved in their anti-hyperreactivity effect. These results suggest that stable, somatostatin sst4 receptor-selective agonists could be potential candidates for the development of a completely novel group of anti-inflammatory drugs for the treatment of airway inflammation and hyperresponsiveness.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
Somatostatin sst4 receptor
Interleukin-1beta
Whole body plethysmography
Ovalbumin
Lipopolysaccharide
Bronchial hyperreactivity
Airway inflammation
Megjelenés:
European Journal of Pharmacology. - 578 : 2-3 (2008), p. 313-322. -
További szerzők:
Helyes Zsuzsanna
Kereskai László
Sándor Katalin
Pintér Erika
Pozsgai Gábor
Tékus Valéria
Bánvölgyi Ágnes
Németh József (1954-) (vegyész, analitikus)
Szűts Tamás
Kéri György
Szolcsányi János (Pécs)
Internet cím:
elektronikus változat
DOI
Borító:
Saját polcon:
2.
001-es BibID:
BIBFORM002463
Első szerző:
Elekes Krisztián
Cím:
Role of capsaicin-sensitive afferents and sensory neuropeptides / Krisztián Elekes, Zsuzsanna Helyes, József Németh, Katalin Sándor, Gábor Pozsgai, László Kereskai, Rita Börzsei, Erika Pintér, Árpád Szabó, János Szolcsányi
Dátum:
2007
Megjegyzések:
Substance P (SP) and calcitonin gene-related peptide (CGRP) released from capsaicin-sensitive afferents induce neurogenic inflammation via NK1, NK2 and CGRP1 receptor activation. This study examines the role of capsaicin-sensitive fibres and sensory neuropeptides in endotoxininduced airway inflammation and consequent bronchial hyperreactivity with functional, morphological and biochemical techniques in mice. Carbachol-induced bronchoconstriction was measured with whole body plethysmography 24 h after intranasal lipopolysaccharide administration. SP and CGRP were determined with radioimmunoassay, myeloperoxidase activity with spectrophotometry, interleukin-1? with ELISA and histopathological changes with semiquantitative scoring from lung samples. Treatments with resiniferatoxin for selective destruction of capsaicinsensitive afferents, NK1 antagonist SR 140333, NK2 antagonist SR 48968, their combination, or CGRP1 receptor antagonist CGRP(8-37) were performed. Lipopolysaccharide significantly increased lung SP and CGRP concentrations, which was prevented by resiniferatoxin pretreatment. Resiniferatoxin-desensitization markedly enhanced inflammation, but decreased bronchoconstriction. CGRP(8-37) or combination of SR 140333 and SR 48968 diminished neutrophil accumulation, MPO levels and IL-1? production, airway hyperresponsiveness was inhibited only by SR 48968. This is the first evidence that capsaicin-sensitive afferents exert a protective role in endotoxin-induced airway inflammation, but contribute to increased bronchoconstriction. Activation of CGRP1 receptors or NK1+NK2 receptors participate in granulocyte accumulation, but NK2 receptors play predominant role in enhanced airway resistance.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
Whole body plethysmography
Myeloperoxidase activity
NK1 receptor
NK2 receptor
CGRP1 receptor
Somatostatin
Megjelenés:
Regulatory Peptides. - 141 : 1-3 (2007), p. 44-54. -
További szerzők:
Helyes Zsuzsanna
Sándor Katalin
Pozsgai Gábor
Kereskai László
Börzsei Rita
Pintér Erika
Szabó Árpád
Szolcsányi János (Pécs)
Németh József (1954-) (vegyész, analitikus)
Internet cím:
elektronikus változat
DOI
Borító:
Saját polcon:
3.
001-es BibID:
BIBFORM061062
Első szerző:
Helyes Zsuzsanna
Cím:
Pituitary Adenylate Cyclase-Activating Polypeptide Is Upregulated in Murine Skin Inflammation and Mediates Transient Receptor Potential Vanilloid-1-Induced Neurogenic Edema / Zsuzsanna Helyes, Jozsef Kun, Nora Dobrosi, Katalin Sándor, Jozsef Németh, Aniko Perkecz, Erika Pintér, Krisztina Szabadfi, Balazs Gaszner, Valeria Tékus, Janos Szolcsányi, Martin Steinhoff, Hitoshi Hashimoto, Dora Reglődi, Tamas Bíró
Dátum:
2015
ISSN:
0022-202X
Megjegyzések:
Although pituitary adenylate cyclase-activating polypeptide (PACAP) was described as a key vasoregulator inhuman skin, little is known about its expression in mouse skin. As it is important to investigate PACAP signaling intranslational mouse dermatitis models, we determined its presence, regulation, and role in neurogenic and nonneurogeniccutaneous inflammatory mechanisms. The mRNA of PACAP and its specific receptor PAC1 wasdetected with real-time PCR in several skin regions at comparable levels. PACAP-38-immunoreactivity measuredwith radioimmunoassay was similar in plantar and dorsal paw skin and the ear but significantly smaller in theback skin. PACAP and PAC1 mRNA, as well as PACAP-38 and PAC1 protein expression, significantly increased in theplantar skin after intraplantar administration of capsaicin (50 ?l, 100 ?gml?1), an agonist of the transient receptorpotential vanilloid 1 (TRPV1) receptor, evoking chiefly neurogenic inflammation without inflammatory cellaccumulation. Intraplantar complete Freund's adjuvant (CFA; 50 ?l, 1mgml?1) also increased PACAP/PAC1 mRNAbut not the PACAP peptide. Capsaicin-induced neurogenic paw edema, but not CFA-evoked non-neurogenicswelling, was significantly smaller in PACAP-deficient mice throughout a 24-hour period. To our knowledge, weprovide previously unreported evidence for PACAP and PAC1 expression upregulation during skin inflammation ofdifferent mechanisms and for its pro-inflammatory function in neurogenic edema formation.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
cross-talk
sebaceous gland
sebocytes
skin homeostasis
Megjelenés:
Journal Of Investigative Dermatology 135 : 9 (2015), p. 2209-2218. -
További szerzők:
Kun József
Dobrosi Nóra (1981-) (molekuláris biológus)
Sándor Katalin
Németh József (1954-) (vegyész, analitikus)
Perkecz Anikó
Pintér Erika
Szabadfi Krisztina (Pécsi Egyetem)
Gaszner Balázs (Neuroanatómia)
Tékus Valéria
Szolcsányi János (Pécs)
Steinhoff, Martin
Hashimoto, Hitoshi
Reglődi Dóra (Idegtudományok)
Bíró Tamás (1968-) (élettanász)
Pályázati támogatás:
OTKA-104984
OTKA
OTKA-PD100706
OTKA
OTKA-101761
OTKA
OTKA105369
OTKA
TÁMOP-4.2.2./A-11/1/KONV-2012-0025
TÁMOP
TÁMOP-4.2.4.A/ 2- 11/1-2012-0001
TÁMOP
Internet cím:
Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:
4.
001-es BibID:
BIBFORM002464
Első szerző:
Helyes Zsuzsanna
Cím:
Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced / Zsuzsanna Helyes, Krisztián Elekes, József Németh, Gábor Pozsgai, Katalin Sándor, László Kereskai, Rita Börzsei, Erika Pintér, Árpád Szabó, János Szolcsányi
Dátum:
2007
Megjegyzések:
Airways are densely innervated by capsaicin-sensitive sensory neurons expressing transient receptor potential vanilloid 1 (TRPV1) receptors/ion channels, which play an important regulatory role in inflammatory processes via the release of sensory neuropeptides. The aim of the present study was to investigate the role of TRPV1 receptors in endotoxin-induced airway inflammation and consequent bronchial hyperreactivity with functional, morphological, and biochemical techniques using receptor gene-deficient mice. Inflammation was evoked by intranasal administration of Escherichia coli lipopolysaccharide (60 gammal, 167 gammag/ml) in TRPV1 knockout (TRPV1-/-) mice and their wild-type counterparts (TRPV1+/+) 24 h before measurement. Airway reactivity was assessed by unrestrained whole body plethysmography, and its quantitative indicator, enhanced pause (Penh), was calculated after inhalation of the bronchoconstrictor carbachol. Histological examination and spectrophotometric myeloperoxidase measurement was performed from the lung. Somatostatin concentration was measured in the lung and plasma with radioimmunoassay. Bronchial hyperreactivity, histological lesions (perivascular/peribronchial edema, neutrophil/ macrophage infiltration, goblet cell hyperplasia), and myeloperoxidase activity were significantly greater in TRPV-/- mice. Inflammation markedly elevated lung and plasma somatostatin concentrations in TRPV1+/+ but not TRPV1-/- animals. In TRPV1-/- mice, exogenous administration of somatostatin-14 (4 x 100 gamma g/kg ip) diminished inflammation and hyperreactivity. Furthermore, in wildtype mice, antagonizing somatostatin receptors by cyclo-somatostatin (4 x 250 gamma g/kg ip) increased these parameters. This study provides the first evidence for a novel counterregulatory mechanism during endotoxin-induced airway inflammation, which is mediated by somatostatin released from sensory nerve terminals in response to activation of TRPV1 receptors of the lung. It reaches the systemic circulation and inhibits inflammation and consequent bronchial hyperreactivity.
Tárgyszavak:
Orvostudományok
Elméleti orvostudományok
idegen nyelvű folyóiratközlemény külföldi lapban
capsaicin-sensitive afferents
inflammatory airway hyperreactivity
Megjelenés:
American journal of physiology. Lung cellular and molecular physiology. - 292 (2007), p. L1173-L1181. -
További szerzők:
Sándor Katalin
Szolcsányi János (Pécs)
Szabó Árpád
Pintér Erika
Börzsei Rita
Kereskai László
Pozsgai Gábor
Elekes Krisztián
Németh József (1954-) (vegyész, analitikus)
Internet cím:
elektronikus változat
DOI
Borító:
Saját polcon:
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