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A Szentágothai János Kutatóközpont a PTE korszerű, nemzetközi tudományszervezési és menedzsment normák szerint kialakított új intézménye, amely az élettudományi, élettelen természettudományi, valamint környezettudományi oktatás...

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Molecular Pharmacology Research Group

  • Research concept
  • Members
  • Publications
  • Awarded projects
  • R and D results
  • Services
  • Laboratories, instruments
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Complex analysis of the role of capsaicin-sensitive afferents, the released neuropeptides and their receptors, as well as the pathophysiological importance of neuro-immune interactions in complex animal models of pain, inflammation, and tumor development. Identification of new pharmacological targets and preclinical investigation of analgesic and anti-inflammatory drug candidates in these systems.

  • Acute and chronic joint inflammation: Mouse/rat models of arthritis (kaoline, carrageenan-induced acute monoarthritis, complete Freund’s adjuvant-induced chronic polyarthritis, autoantibody-transfer and proteoglycane-induced polyarthritis, iodoacetate-induced osteoarthritis).
  • Acute and chronic airway inflammation: Mouse models (endotoxin-induced non-allergic and dust mite antigen-induced allergic lung inflammation, ovalbumine-induced asthma, cigarette smoke-evoked chronic bronchitis).
  • Acute and chronic cutaneous inflammation: mouse/rat models (irritant-induced acute inflammation, oxazolone-evoked allergic contact dermatitis, murine psoriasis models, bleomycine-induced scleroderma-model).
  • Chronic gastric and bowel inflammation: Mouse models of inflammatory gastrointestinal conditions (gastritis, autoimmune colon inflammation, Crohn-disease models).
  • Migraine and chronic neuropathy: Mouse/rat models of traumatic mononeuropathy, diabetic polyneuropathy, toxic polyneuropathy, and bone metastasis-induced neuropathic pain.

Role of pituitary adenylate-cyclase-activating polypeptide in nociception and migraine Running title: PACAP: nociception and migraine. Tajti J, Tuka B, Botz B, Helyes Z, Vecsei L. CNS Neurol Disord Drug Targets. 2015 Apr 29. [Epub ahead of print].
http://benthamscience.com/journal/abstracts.php?journalID=cnsnddt&articleID=130827

Pituitary Adenylate-Cyclase Activating Polypeptide is up-Regulated in Murine Skin Inflammation and Mediates Transient Receptor Potential Vanilloid-1-Induced Neurogenic Edema. Helyes Z, Kun J, Dobrosi N, Sándor K, Németh J, Perkecz A, Pintér E, Szabadfi K, Gaszner B, Tékus V, Szolcsányi J, Steinhoff M, Hashimoto H, Reglődi D, Bíró T. J Invest Dermatol. 2015 Apr 23. doi: 10.1038/jid.2015.156. [Epub ahead of print]
http://www.nature.com/jid/journal/vaop/naam/abs/jid2015156a.html

Effects of Some Natural Carotenoids on TRPA1- and TRPV1-Induced Neurogenic Inflammatory Processes In Vivo in the Mouse Skin. Horváth G, Kemény Á, Barthó L, Molnár P, Deli J, Szente L, Bozó T, Pál S, Sándor K, Szőke É, Szolcsányi J, Helyes Z. J Mol Neurosci. 2015;56:113-21. doi: 10.1007/s12031-014-0472-7.
http://link.springer.com/article/10.1007%2Fs12031-014-0472-7

Hydrophobic cyanine dye-doped micelles for optical in vivo imaging of plasma leakage and vascular disruption.Botz B, Bölcskei K, Kemény Á, Sándor Z, Tékus V, Sétáló G Jr, Csepregi J, Mócsai A, Pintér E, Kollár L, Helyes Z. J Biomed Opt. 2015;20:016022. doi: 10.1117/1.JBO.20.1.016022.
http://biomedicaloptics.spiedigitallibrary.org/article.aspx?articleid=2108060

Hemokinin-1 is an important mediator of endotoxin-induced acute airway inflammation in the mouse. Hajna Z, Borbély É, Kemény Á, Botz B, Kereskai L, Szolcsányi J, Pintér E, Paige CJ, Berger A, Helyes Z. Peptides. 2015;64:1-7. doi: 10.1016/j.peptides.2014.12.002.
http://www.sciencedirect.com/science/article/pii/S0196978114003441

Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis. Borbély É, Botz B, Bölcskei K, Kenyér T, Kereskai L, Kiss T, Szolcsányi J, Pintér E, Csepregi JZ, Mócsai A, Helyes Z. Brain Behav Immun. 2015;45:50-9. doi: 10.1016/j.bbi.2014.12.012.
http://www.sciencedirect.com/science/article/pii/S0889159114005753

Analgesic topical capsaicinoid therapy increases somatostatin-like immunoreactivity in the human plasma.Horváth K, Boros M, Bagoly T, Sándor V, Kilár F, Kemény A, Helyes Z, Szolcsányi J, Pintér E. Neuropeptides. 2014;48:371-8. doi: 10.1016/j.npep.2014.10.001.
http://www.neuropeptidesjournal.com/article/S0143-4179(14)00084-5/abstract

Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions. Pintér E, Pozsgai G, Hajna Z, Helyes Z, Szolcsányi J. Br J Clin Pharmacol. 2014;77:5-20. doi: 10.1111/bcp.12097.
http://onlinelibrary.wiley.com/doi/10.1111/bcp.12097/full

Upregulation of the transient receptor potential ankyrin 1 ion channel in the inflamed human and mouse colon and its protective roles. Kun J, Szitter I, Kemény A, Perkecz A, Kereskai L, Pohóczky K, Vincze A, Gódi S, Szabó I, Szolcsányi J, Pintér E, Helyes Z. PLoS One. 2014;9:e108164. doi: 10.1371/journal.pone.0108164.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108164

The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a direct role in leukocyte recruitment. Kovács M, Németh T, Jakus Z, Sitaru C, Simon E, Futosi K, Botz B, Helyes Z, Lowell CA, Mócsai A. J Exp Med. 2014;211:1993-2011. doi: 10.1084/jem.20132496.
http://jem.rupress.org/content/211/10/1993.long

Age-Related Decline of Autocrine Pituitary Adenylate Cyclase-Activating Polypeptide Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells. Banki E, Sosnowska D, Tucsek Z, Gautam T, Toth P, Tarantini S, Tamas A, Helyes Z, Reglodi D, Sonntag WE, Csiszar A, Ungvari Z. J Gerontol A Biol Sci Med Sci. 2014 Aug 18. pii: glu116. [Epub ahead of print]
http://biomedgerontology.oxfordjournals.org/content/70/6/665.long

Differential regulatory role of pituitary adenylate cyclase-activating polypeptide in the serum-transfer arthritis model. Botz B, Bölcskei K, Kereskai L, Kovács M, Németh T, Szigeti K, Horváth I, Máthé D, Kovács N, Hashimoto H, Reglődi D, Szolcsányi J, Pintér E, Mócsai A, Helyes Z. Arthritis Rheumatol. 2014;66:2739-50. doi: 10.1002/art.38772.
http://onlinelibrary.wiley.com/doi/10.1002/art.38772/abstract;jsessionid=54D2E88E0CA3D21BB8F206F04866C4C9.f04t02

Changes of PACAP level in cerebrospinal fluid and plasma of patients with severe traumatic brain injury. Bukovics P, Czeiter E, Amrein K, Kovacs N, Pal J, Tamas A, Bagoly T, Helyes Z, Buki A, Reglodi D.
http://www.sciencedirect.com/science/article/pii/S0196978114001909

The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin. Banki E, Hajna Z, Kemeny A, Botz B, Nagy P, Bolcskei K, Toth G, Reglodi D, Helyes Z. Neuropharmacology. 2014;85:538-47. doi: 10.1016/j.neuropharm.2014.06.019.
http://www.sciencedirect.com/science/article/pii/S002839081400241X

Irritable eye syndrome: neuroimmune mechanisms and benefits of selected nutrients. Feher J, Pinter E, Kovács I, Helyes Z, Kemény A, Markovics A, Plateroti R, Librando A, Cruciani F. Ocul Surf. 2014;12:134-45. doi: 10.1016/j.jtos.2013.09.002.
http://www.theocularsurfacejournal.com/article/S1542-0124(13)00166-3/abstract

Role of neurokinin 1 receptors in dextran sulfate-induced colitis: studies with gene-deleted mice and the selective receptor antagonist netupitant. Szitter I, Pintér E, Perkecz A, Kemény A, Kun J, Kereskai L, Pietra C, Quinn JP, Zimmer A, Berger A, Paige CJ, Helyes Z. Inflamm Res. 2014;63:399-409. doi: 10.1007/s00011-014-0712-x
http://link.springer.com/article/10.1007%2Fs00011-014-0712-x

Plasma somatostatin-like immunoreactivity increases in the plasma of septic patients and rats with systemic inflammatory reaction: experimental evidence for its sensory origin and protective role. Suto B, Szitter I, Bagoly T, Pinter E, Szolcsányi J, Loibl C, Nemeth T, Tanczos K, Molnar T, Leiner T, Varnai B, Bardonicsek Z, Helyes Z. Peptides. 2014;54:49-57. doi: 10.1016/j.peptides.2014.01.006.
http://www.sciencedirect.com/science/article/pii/S0196978114000096

Neuropeptides in learning and memory. Borbély E, Scheich B, Helyes Z. Neuropeptides. 2013;47:439-50. doi: 10.1016/j.npep.2013.10.012.
http://www.neuropeptidesjournal.com/article/S0143-4179(13)00078-4/abstract

A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome. Tékus V, Hajna Z, Borbély É, Markovics A, Bagoly T, Szolcsányi J, Thompson V, Kemény Á, Helyes Z, Goebel A. Pain. 2014;155:299-308. doi: 10.1016/j.pain.2013.10.011.
http://journals.lww.com/pain/pages/articleviewer.aspx?year=2014&issue=02000&article=00013&type=abstract

Current approaches in the treatment of neuropathic and phantom limb pain. Helyes Zs., Botz B.: In: Emberi életfolyamatok idegi szabályozása - a neurontól a viselkedésig, Ed: Komoly S., Budapest: Dialóg-Campus Kiadó, e-könyv. 2014.
http://neurotamop.aok.pte.hu/

Role of tachykinin 1 and 4 gene-derived neuropeptides and the neurokinin 1 receptor in adjuvant-induced chronic arthritis of the mouse. Borbély E, Hajna Z, Sándor K, Kereskai L, Tóth I, Pintér E, Nagy P, Szolcsányi J, Quinn J, Zimmer A, Stewart J, Paige C, Berger A, Helyes Z. PLoS One. 2013;8:e61684. doi: 10.1371/journal.pone.0061684.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0061684

Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients. Tuka B, Helyes Z, Markovics A, Bagoly T, Szolcsányi J, Szabó N, Tóth E, Kincses ZT, Vécsei L, Tajti J. Cephalalgia. 2013;33:1085-95. doi: 10.1177/0333102413483931.
http://cep.sagepub.com/content/33/13/1085.full

Alterations in mucosal neuropeptides in patients with irritable bowel syndrome and ulcerative colitis in remission: a role in pain symptom generation? Keszthelyi D, Troost FJ, Jonkers DM, Helyes Z, Hamer HM, Ludidi S, Vanhoutvin S, Venema K, Dekker J, Szolcsányi J, Masclee AA. Eur J Pain. 2013;17:1299-306. doi:
10.1002/j.1532-2149.2013.00309.x.
http://onlinelibrary.wiley.com/doi/10.1002/j.1532-2149.2013.00309.x/abstract

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions. Botz B, Imreh A, Sándor K, Elekes K, Szolcsányi J, Reglődi D, Quinn JP, Stewart J, Zimmer A, Hashimoto H, Helyes Z. Peptides. 2013;43:105-12. doi: 10.1016/j.peptides.2013.03.003.
http://www.sciencedirect.com/science/article/pii/S0196978113000776

Examination of PACAP38-like immunoreactivity in different milk and infant formula samples. Csanaky K, Reglődi D, Bánki E, Tarcai I, Márk L, Helyes Z, Ertl T, Gyarmati J, Horváth K, Sántik L, Tamás A. Acta Physiol Hung. 2013;100:28-36. doi: 10.1556/APhysiol.100.2013.1.2.
http://www.akademiai.com/doi/pdf/10.1556/APhysiol.100.2013.1.2

 

  1. SROP-4 2 2 A-11-1-KONV-2012-0024 (2012-2014): Integrative investigation of neuropeptide-mediated mechanisms in vascular, inflammatory and immune functions.
    Principal investigator: Prof. Dr. Zsuzsanna Helyes
  2. Richter Gedeon collaborative project (2012-2014): Establishing and validating model systems for the investigation of the trigeminovascular activation.
    Principal investigator: Prof. Dr. Zsuzsanna Helyes
  3. OTKA112171 (2013-2016): Investigation of the role of polysulfides, TRPA 1 receptors and somatostatin sst4 receptors in animal models of inflammatory and neuropathic pain, as well as rheumatoid arthritis.
    Principal investigator: Dr. Gábor Pozsgai 
  4. OTKA 114458 (2015-2018): Investigation of TRP channel-mediated effects of hydrogen sulphide in animal models of acute and chronic arthritis.
    Principal investigator: Dr. Erika Pintér
  5. Hungarian Brain Research Project A KTIA_NAP_13-1-2013-0001 (2013-2017): The role and significance of TRPA1 channel activation in the nervous system.
    Principal investigator: Dr. Erika Pintér
  6. Hungarian Brain Research Project B KTIA-NAP-13-2014-0022 (2014-2017): Role of neuro-immune interactions in chronic pain: analysing central sensitization mechanisms and identifying novel analgesic targets. 
    Principal investigator: Dr. Zsuzsanna Helyes
  7. TÁMOP- 4.1.1.C (2013-2015): Supporting regional, interdisciplinary collaborations, and promoting higher education integration in the convergence regions.
    Principal investigator: Dr. Erika Pintér
  8. Pain Relief Foundation (2015-2017): Development of the Complex Regional Pain Syndrome (CRPS) Passive-Transfer-Trauma Model for Drug Research.
    Principal investigators: Dr. Andreas Goebel (Univeryity of Liverpool) and Dr. Zsuzsanna Helyes (co-applicants)

 

Individual scholarships and awards – National Excellence Program:

  1. Bálint Botz (Apáczai Csere János Scholarship)
  2. József Kun (Apáczai Csere János Scholarship)
  3. Éva Borbély (Apáczai Csere János Scholarship)
  4. Ádám Horváth (Eötvös Loránd Scholarship)
  5. Valéria Tékus (Jedlik Ányos Scholarship)
  6. Adrienn Markovics (Erdős Pál Scholarship)
  7. Erika Pintér (Szentágothai János Scholarship)

1. Patents:

Waczek F, Helyes Zs, Őrfi L, Kéri G, Szűts T, Pintér E, Szolcsányi J, Szőke É. New agents for treating neurogenic inflammation and neuropathic hyperalgesia related disorders. 2014. Hungarian and USA PCT P1400432 (University of Pécs and Vichem Ltd.)

Helyes Zs, Matyus P, Tekus V, Scheich B. Semicarbazide-sensitive amine-oxidase inhibitors, as analgesics in traumatic neuropathy and neurogenic inflammation. 2014. Hungarian and USA PCT P1400205 (University of Pécs).

G. Pozsgai, E. Pintér, M. Boros, L. Nagy, G. Nagy: H2S sensor for in vivo measurements. 2013. Reg. No.: U1200173 (University of Pécs)

 

2. Industrial Collaborations:

  • Pharmnovo Ltd. – Bengt von Mentzer, migraine, pain
  • Soft Flow Hungary – microcirculation
  • Varga Herb Manufactory – inflammation models
  • Richter Gedeon Plc.-Establishing and validating model systems for the investigation of the trigeminovascular activation

Complex pharmacological investigations in acute or chronic mouse models of painful/inflammatory conditions using functional, morphological, immunological, and imaging techniques. Examination of complex pathophysiological processes and integrative analysis of the effects of drug candidates in vivo and in vitro.

 

1.) Fluorescent and luminescent functional imaging of living, anesthetized mice/rats, excised tissue samples, and cell cultures

Analysis of the expression and distribution of various biological markers (enzyme activity, receptors, structural components, free radicals) using fluorescent contrast agents, and bioluminescent/chemiluminescent substrates.

Instruments:

  • PerkinElmer FMT 2000 – Fluroescent molecular tomography system
  • PerkinElmer Lumina II - Luminescent/fluorescent imaging system

Earlier contract/cooperation: Scientific collaborations with the Institute of Physiology, Semmelweis University, and the Institute of Experimental Medicine, Hungarian Academy of Sciences

Contact: Prof. Dr. Zsuzsanna Helyes, zsuzsanna.helyes@aok.pte.hu, +36 72/501-500/35591 or +36 72/501-500/29043

 

2.) Intravital microscopy examinations

Real time monitoring of vasodilation, plasma protein extravastion, leukocyte accumulation, etc. in murine inflammation models. Imaging and quantitative analysis of these parameters in the skin, brain surface, joints, and internal organs.

Instruments:

  • NIKON intravital microscope with camera and image analysis software

Contact: Prof. Dr. Zsuzsanna Helyes, zsuzsanna.helyes@aok.pte.hu, +36 72/501-500/35591 or +36 72/501-500/29043

 

3.) In vivo imaging of microcirculation in mice/rats, large animals and humans (skin, mucous membrane)

Measurement of microcirculation in animal models of inflammation, vasoregulatory disorders, and migraine. Noninvasive investigation of local skin blood flow in human subjects.

Instruments:

  • PeriScan PIM II laser Doppler imager with inbuilt blood flow sensor
  • PeriFlux 5000 Laser Doppler Flowmeter – monitoring of microcirculation and PO2/PCO2. Optional application of temperature and pressure stimuli.
  • PeriCam laser speckle imager – Capable of monitoring rapid/transient changes of microcirculation

Earlier contract/cooperation:

  • Soft-Flow Ltd.,
  • Richter Gedeon Plc.,
  • University of Szeged, Dept. of Neurology

Contact: Prof. Dr. Zsuzsanna Helyes, zsuzsanna.helyes@aok.pte.hu, +36 72/501-500/35591 or +36 72/501-500/29043

Intravital and surgical videomicroscope with camera and image analysis software: With the aid of ex vivo or in vivo labeling techniques vascular responses and the movement of labeled immune cells can be visualized, quantified, and monitored in real time. The technique is suitable to examine the surface of organs in situ.

Further informations about the instrument:

 

Pericam PSI laser speckle imager, PIM-II laser Doppler scanner, Periflux 5000 laser Doppler perfusion monitor (Perimed): Continous visual monitoring and precise quantification of skin, joint, and brain microcirculation. Suitable for both preclinical models and clinical studies.

Further informations about the instruments:

 

Micro-Computer Tomograph (Bruker): High resolution CT-imaging of anesthetized rodents (inbuilt cardiac and respiratory monitoring), excised organs, and tissue samples. Structural examination of various organic/inorganic materials is also possible. Enables long term follow-up of disease models in the same set of subjects. Particulary suitable for in vivo structural imaging studies (bone remodeling, lung architecture).

Further informations about the instrument:

 

Luminescent-fluorescent imaging workstation (Perkin-Elmer): Bioluminescent/fluorescent in vivoimaging enables the examination of the expression of proteins, receptors, and enzymes, production of free radicals in murine models. Luminescent imaging utilises either free radical-specific chemiluminescent substrates, or light emitted during the luciferase-luciferin enzyme reaction. During fluorescence imaging studies specific dyes and fluorescent probes are used. The instrument is capable of imaging in vivo(mice/rats), ex vivo (organ and tissue samples), or in vitro (e.g. cell cultures) samples.

Further informations about the instrument:

 

Fluorescence Molecular Tomograph (Perkin-Elmer): The instrument is capable of monitoring diverse mouse disease models using dedicated fluorescent near-infrared contrast agents (excitation at 680 or 750 nm wavelengths). Possible areas of use are: inflammatory/tumor-induced vascular leakage, receptor expression pattern, inflammatory enzyme activity, bone remodeling, etc. The same set of mice can be examined repeatedly in a noninvasive manner. The instrument is capable of 3D reconstruction of fluorophore distribution, and absolute (picomolar) quantification of the amount of fluorescent probes. Combination of fluorescent tomographic and structural CT-scans (multimodal image reconstruction) is also possible.

Further informations about the instrument: