Poprad Slovakia - Martin 2020 - Conference Martin...2-nd ICPMS Poprad 2018 10 CONFERENCE ROOM...

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CONFERENCE BOOK Poprad Slovakia 21-23 September 2018

Transcript of Poprad Slovakia - Martin 2020 - Conference Martin...2-nd ICPMS Poprad 2018 10 CONFERENCE ROOM...

  • CONFERENCE BOOK

    Poprad Slovakia 21-23 September 2018

  • Copyright© 2018 by Faculty of Pharmacy Jagiellonian University Medical

    College & ZOZ Ośrodek UMEA SHINODA-KURACEJO

    The initiators of organization of the first ICPMS CONFERENCE were:

    Prof. UJ dr hab. Jacek SAPA, Prof. UJ dr hab. Bożena MUSZYŃSKA,

    Prof. UJ dr hab. Włodzimierz OPOKA

    Chief Editor

    Bożena MUSZYŃSKA

    Cover design

    Bożena MUSZYŃSKA

    Jacek LELEK

    Typeset

    Joanna PIOTROWSKA

    Katarzyna SUŁKOWSKA-ZIAJA

    Marek BEDNARSKI

    Published by ZOZ Ośrodek UMEA SHINODA-KURACEJO

    31-851 Kraków, os. Albertyńskie 1-2, Poland

    [email protected]

    ISBN 978-83-946124-3-6

  • 3

    PART I

    INTRODUCTION

    COMMITTEES

    SPONSORS

    LETTERS

    PROGRAMME

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    HONORARY SUPPORT

    Vice-Rector of the Jagiellonian University for the Medical College

    Prof. dr hab. Tomasz GRODZICKI

    SUPPORT

    Dean of the Faculty of Pharmacy Jagiellonian University Medical College

    Prof. UJ dr hab. Jacek SAPA

    Dean of the Jessenius Faculty of Medicine, Comenius University of

    Bratislava Prof. Ján DANKO, M.D., PhD.

    Dean of the Faculty of Health Sciences Jagiellonian University

    Medical College Prof. dr hab. Tomasz BRZOSTEK

    Dean of the Faculty of Medicine Jagiellonian University

    Medical College Prof. dr hab. Maciej MAŁECKI

    President of the Polish Pharmaceutical Society

    Prof. dr hab. Janusz PLUTA

    President of the Polish Chamber of Physicians

    Prof. dr hab. Andrzej MATYJA

    Chair of the Supreme Pharmaceutical Council

    Mgr Elżbieta PIOTROWSKA-RUTKOWSKA

    MAIN ORGANIZERS

    Jagiellonian University Medical College, Faculty of Pharmacy; Polish

    Pharmaceutical Society (the Kraków Branch); STOP Illegal

    Pharmaceuticals Association for Health Protection and The Rule of Law;

    Polish Chamber of Physicians; Regional Pharmaceutical Chamber in

    Kraków

    SCIENTIFIC COMMITTEE

    Prof. dr hab. Dariusz ADAMEK – President; Prof. UJ dr hab. Bożena

    MUSZYŃSKA – Vice-President; Dr Marek BEDNARSKI – Secretary

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    Members of Scientific Committee

    Prof. dr hab. Marek Sanak; Prof. UJ dr hab. Jacek SAPA, Prof. Gabriela

    NOSÁĹOVÁ, M.D., D.Sc.; Prof. dr hab. Anna WESOŁOWSKA;

    Prof. dr hab. Gabriel NOWAK; Prof. dr hab. Jolanta PYTKO-

    POLOŃCZYK; Prof. dr hab. Małgorzata SCHLEGEL-ZAWADZKA;

    Prof. dr hab. Tomasz BRZOZOWSKI; Prof. dr hab. Andrzej PILC;

    Prof. dr hab. Zbigniew FIJAŁEK; Prof. dr hab. Ewa POLESZAK; Prof.

    dr hab. Edmund GRZEŚKOWIAK; Dr hab. Maria WALCZAK;

    Dr hab. Joanna GDULA-ARGASIŃSKA

    ORGANIZING COMMITTEE

    Prof. UJ dr hab. Bożena MUSZYŃSKA – President; Prof. dr hab.

    Włodzimierz OPOKA – Vice-President; Dr Katarzyna SUŁKOWSKA-

    ZIAJA – Secretary; Dr hab. Małgorzata ZYGMUNT – Treasurer; Dr

    Joanna PIOTROWSKA – Coordinator of Organizing Committee

    Members of Organizing Committee

    Dr Marek BEDNARSKI; Dr Barbara JĘKOT; Dr Piotr

    KACZMARCZYK; Mgr Katarzyna KAŁA; Jan LAZUR; Dr Agata

    KRYCZYK; Oliwia Sara SIOMAK; Dr Robert STĘPIEŃ; Dr Jerzy

    SZEWCZYŃSKI; Dr Jerzy SKUCIŃSKI

    JURY FOR THE BEST PRESENTATION OF YOUNG

    SCIENTISTS

    Prof. dr hab. Zbigniew FIJAŁEK; Dr Gerhard MIKOLAICZIK;

    Prof. dr hab. Jolanta PYTKO-POLOŃCZYK; Prof. dr hab. Małgorzata

    SCHLEGEL-ZAWADZKA; Prof. dr hab. Anna WESOŁOWSKA

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    SPONSORS

    Marszałek

    Województwa

    Małopolskiego

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    LETTER FROM DEAN OF THE FACULTY OF

    PHARMACY JAGIELLONIAN UNIVERSITY

    MEDICAL COLLEGE

    Dear Colleagues,

    I would like welcome you all to the 2nd International Conference on

    Pharmaceutical and Medical Sciences.

    This conference will be very good platform for discussions about a lot

    scientific problems in pharmacy and medicine.

    The Faculty of Pharmacy at the Jagiellonian University is one of the

    oldest faculties in Poland and also in Europe. The first Polish Chair of

    Pharmacy and Medical Matter was established in 1783. So, we have a long

    history.

    Today in our Faculty of Pharmacy there are over 1000 students

    studying pharmacy, medical analytics and cosmetology at Master’s and

    PhD studies and industrial pharmacy, medical analytics, clinical studies of

    pharmaceutical products and enology at postgraduate studies. Since this

    year, we have opened a new field of study - Drug Discovery and

    Development (DDD). We have a very good scientific staff and modern

    scientific and teaching laboratories.

    The Faculty of Pharmacy has been involved in the European

    Association of Faculties of Pharmacy. Our Faculty also cooperates with

    the District Chamber of Apothecaries and Pharmaceutical Inspectorate in

    the scope of pharmaceutical training. The Faculty of Pharmacy has

    achieved a high position in the parametric evaluation (A+) and possesses

    accreditation of specializations.

    In this year, like before, we were recognized again as the best field of

    study – pharmacy – all over the country.

    I wish the fruitful discussions, successful meeting and unforgettable

    time in Poprad.

    Sincerely,

    Prof. UJ dr hab. Jacek Sapa

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    LETTER FROM PRESIDENT OF THE

    SCIENTIFIC COMMITTEE OF 2-ND ICPMS

    POPRAD 2018

    Our bodies are exposed to the uncountable hazardous or toxic

    chemicals and elements present in our food, water, and air. The pollution

    of the environment is a well-known culprit of dozens multifarious

    diseases, though their pathomechanisms still not always are clear.

    Awareness of the danger due to contamination of the environment

    including not only air or water but also food increases, but still there is

    lots of to do to improve the situation. And the situation itself becomes

    more and more complicated. The market is flooded by diverse food

    additives and diet supplements with unknown or poorly tested impact on

    our health. Another potential source of danger is microbiological content

    of food, air and water which includes new antibiotic-resistant strains of

    bacteria, recombinant viruses, other microbes and prions or even prion-

    like behaving proteins. A special category of dangerous and potentially

    even lethal agents are fake medicines and pharmaceutical products and

    diet additives that put our health to danger. As for the medicines,

    situation is somewhat special, since nobody can deny that they must be

    “toxic” as if by simple virtue of “drug”, and to have some, even serious

    side effects, which is unavoidable. Nevertheless in this case, one has to

    be sure that the inevitable risk of side effects is balanced with

    unequivocal pharmacological activity of the agent. However an

    enormous industry is flourishing which produce fake, counterfeited

    medicines and other medical products which, being equally or even more

    harmful that originals, show little or even no effectiveness.

    To sum up, considering all the aforementioned dangers and the

    necessity to enhance ways of counteraction it seems to be justified to

    introduce a concept of “biomedical security”, which encompasses all

    diverse methods to identify dangers to our health, all undertakings to

    guard society and individuals against toxic and harmful agents and all

    ways of counteractivity.

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    We would like to make at least a little contribution into biomedical

    security, in particular in the struggle to diminish risk related to toxic,

    poisonous or in whichever way harmful constituents of food, medicines

    and any pharmaceutical products and to create an opportunity to gain

    better insight into ways and methods that can be used in unbiased

    assessment of the real, objective impact of toxic constituents of

    environment on our health organizing a conference: "Biomedical

    Security – A Multi-disciplinary Approach For A Multifaceted Problem".

    The particular aim of the conference is to present the current

    research on potentially toxic components of drugs, food products, dietary

    supplements and other pharmaceutical products used in medicine,

    dietetics, veterinary medicine and cosmetology, their impact on the

    environment and on the human health and to get better acquaintance of

    the newest methodology that is or can be employed in the struggle for

    better biomedical security.

    We cordially invite anybody, who represents any of medical

    professions, various medical and pharmaceutical disciplines and health

    and biological sciences, who are interested in issues of broadly

    understood biosecurity/biomedical security, as well as all who work on

    whatever technology that is or can be applied in detection of poisonous,

    toxic chemicals to participate in our conference.

    Prof. dr hab. Dariusz Adamek

  • 2-nd ICPMS Poprad 2018

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    CONFERENCE ROOM

    Aquapark Poprad s.r.o.

    Športová 1397/1

    058 01 Poprad

    Slovenská Republika

    PROGRAMME

    Friday, 21 September 2018

    14.30‒15.00 Registration of the Participants

    15.15‒15.30 Opening Ceremony

    15.30‒16.30 Lecture session I

    Presidents: prof. dr hab. Gabriel NOWAK, Prof. dr hab.

    Roman NOWOBILSKI

    15.30‒15.50 Prof. dr hab. Marek SANAK

    Molecular forensic tools against medicinal products

    forgery

    15.50‒16.10 Prof. dr hab. Peter RAČAY

    History and Present of Biomedical Center Martin

    16.10‒16.30 Prof. dr hab. Zbigniew FIJAŁEK

    Pharmaceutical crime - a deadly epidemic of the 21st

    century

    16.30‒16.45 Coffee break

    16.45‒17.40 Lecture session II

    Presidents: Prof. dr hab. Jolanta PYTKO-POLOŃCZYK,

    Prof. dr hab. Károly BODNÁR

    16.45‒17.05 Prof. dr hab. inż. Marek LANKOSZ

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    Some hideous elements from the “elements” of Nature…

    Analysis of toxic elements in human tissues and body

    fluids with the use of synchrotron radiation

    microspectroscopic techniques

    17.05‒17.25 Ks. prof. dr hab. Zenon UCHNAST

    To feel secure and safe: what does it really mean –

    psychological aspects of social and individual security

    17.25‒17.40 Dr Grzegorz BRZOSKOWSKI (Sanofi)

    Counterfeit pharmaceutical products and illegal

    distribution channels

    19.00 Welcome party

    Saturday, 22 September 2018

    9.15‒10.15 Lecture session III & Short lectures

    Presidents: Prof. dr hab. Małgorzata SCHLEGEL-

    ZAWADZKA, Prof. dr hab. Dariusz ADAMEK

    9.15‒9.30 Dr Gerhard MIKOLAICZIK

    Intestine - a suitcase with a double bottom - research,

    prevention, demands

    9.30‒9.45 Dr Agnieszka POLOŃCZYK

    Bioterrorism - a global challenge in the 21st Century.

    Should we feel defenseless or protected?

    9.45–9.55 Prof. dr hab. Károly BODNÁR

    Prevention of coccidiosis with medicinal herbs as

    natural coccidiostatics in rabbit production

    9.55–10.05 Dr hab. Urszula KOSIKOWSKA

    The presence of blaTEM genes in tonB-positive and tonB-

    negative pasteurellaceae isolates from respiratory

    microbiota

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    10.05–10.15 Prof. dr hab. Roman NOWOBILSKI

    Phantom phenomena, body scheme and level of limb

    amputation. Efficiency of “mirror therapy”

    10.15‒10.30 Coffee break

    10.30‒12.30 Short presentations I

    Presidents: Prof. dr hab. Anna WESOŁOWSKA,

    Prof. dr hab. Peter RAČAY

    12.30‒14.00 Lunch break

    14.00‒15.30 Short presentations II

    Presidents: Prof. dr hab. Małgorzata SCHLEGEL-

    ZAWADZKA, Prof. dr hab. Marek W. LANKOSZ

    15.45‒16.30 Jury proceeding

    16.30‒18.00 Conference discussion with coffee

    Sunday, 23 September 2018

    9.00‒10.00 Closing Ceremony

  • PART II

    LECTURES & SHORT LECTURES

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    MOLECULAR FORENSIC TOOLS AGAINST MEDICINAL

    PRODUCTS FORGERY

    Marek Sanak

    Division of Molecular Biology and Clinical Genetics

    Jagiellonian University Medical College, Krakow, Poland

    Counterfeit drugs is a public health issue because during last

    decades this illegal activity affected 10-30% medicines sold in

    developing countries and at least 1% in the industrialized ones. The total

    annual market of counterfeit medicines reached 200 billion dollars.

    Among the most frequently counterfeited were pharmacy beauty

    products, e.g. Pfitzer’s ChapSticks or anti-malaria drugs sold in Africa.

    According to WHO estimates 16% counterfeit drugs contain wrong

    ingredient, a similar percentage has wrong level of active ingredients,

    whereas 30% do not contain any active ingredient. A famous case of

    counterfeit bevacizumab (Avastin) seized in 2012 did not contain this

    biologics at all. Among measures taken to control counterfeit was to

    stamp on every package of the drug unique codes and serial numbers,

    which could help tracking its sells all around the world. Some other

    actions taken against their trafficking were recommendations of Food

    and Drug Administration (2011) to use physical-chemical identifiers

    (PCIDs) in solid oral dosage forms (SODFs) and RFID tags with

    encoded data to confirm the supply chain. This year, by international

    ratification the use of uniform 2-dimensional data-matrix labels on any

    medicinal was imposed to be effective in Europe from February 2019.

    However, molecular tags based on artificial and unique short double

    stranded DNA sequences seems one of promising solutions to protect

    medicines against forgery.

    Most commonly the identity and quantification of the active

    pharmaceutical ingredient (API) is accomplished by HPLC. SODFs

    require dissolution before the test. Since average cost of a single sample

    pharmacopeial analysis in WHO-prequalified laboratory exceeds 1500

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    dollars, there is a need for less expensive solutions applicable in

    developing countries. Two currently used approaches are near-infrared

    Raman spectroscopy, with a hand-held instrument available, or thin-

    layer chromatography mini-lab. Using the Minilab provided by the

    Global Pharma Health Found, samples of antibacterial or anti-malaria

    drugs were readily screened on site in Africa to reveal counterfeit

    batches with no API, API content between 7.1-81% or dissolution failure

    of SODFs. Among these counterfeit were antibiotics (amoxycilline),

    anti-malaria dihydroartemisinin, chloroquine or quinine manufactured in

    China, India, Cyprus but also in United Kingdom.

    Since falsifying drugs is a profitable crime, there is urgent need to

    establish anti-fraud screening, which can test drugs whenever a new

    manufacturer or distribution channel is established. Detection of DNA

    tags admixed to the drug and providing unique signature, alike private

    key in the protection of encrypted data, would cost much less and bind

    the product to the manufacturer. Usage of common technology of DNA

    amplification and mini-sequencing, affordable and verified in detection

    of GMO food admixtures is suggested. This kind of prevention could

    avoid many casualties due to counterfeit drugs.

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    HISTORY AND PRESENT OF BIOMEDICAL CENTER MARTIN

    Peter Račay, Erika Halašová, Kamil Javorka, Zora Lasabová,

    Gabriela Nosáľová

    Biomedical Center, Jessenius Faculty of Medicine, Comenius University,

    Martin, Slovakia

    Biomedical Center Jessenius Faculty of Medicine Comenius

    University Martin (BioMed JFM CU Martin) was established in May

    2015 within the projects co-financed from EU sources and European

    Regional Development Fund (ITMS code 26220220187).

    The BioMed objectives:

    • to capture the progressive trends in science,

    • to promote concentration of scientific teams,

    • to avoid the inefficiency and fragmentation in research,

    • to ensure a close connection between experimental results and their

    application in clinical practice,

    • to strengthen the position of JFMED CU both in domestic as well as

    international context.

    Recently, BioMed Martin is one of the leading institutes in Slovak

    Republic for biomedical basic and translation research. Daily, more than

    50 young scientists under supervision of the project leaders investigate

    molecules, cells and whole organisms in order to achieve a deeper

    understanding of the molecular basis of diseases of nervous and

    respiratory systems as well as malignant diseases. The scientists at the

    BioMed are laying the foundation for the development of new strategies

    in the diagnostics and treatment of mentioned diseases. In addition,

    scientific activity is focused on the biomedical and molecular principles

    of regenerative medicine. Structure of BioMed comprises four

    independent but collaborating Divisions (Molecular medicine,

    Neuroscience, Oncology and Respirology) with a strong scientific

    infrastructure. Each Division is divided to Departments that include

    functional laboratories. Finally, Central animal house is also part of

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    BioMed Martin. Current scientific projects of BioMed Martin are

    focused on genomics, epigenetics and transcriptomics of gynaecologic

    malignancies and colorectal cancer; respiratory distress syndrome of

    new-borns and mechanisms of cough; molecular mechanisms of

    proliferation and differentiation of selected stem and tumour cells and

    application of stem cells in regenerative medicine; mechanisms of

    neurodegeneration associated with Parkinson disease, ischemia-

    reperfusion injury, sclerosis multiplex; regulation of cardiovascular

    system by autonomous nervous system associated with obesity,

    metabolic diseases and mental stress.

    In conclusion, BioMed Martin is modern and open biomedical

    research institute with a strong personal and scientific infrastructure that

    is loaded in favour of the domestic and international scientific

    collaboration.

    This work was supported by the project Biomedical Center Martin (ITMS:

    26220220187) co-financed from EU sources.

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    PHARMACEUTICAL CRIME – A DEADLY EPIDEMIC OF THE

    21ST CENTURY

    Zbigniew Fijałek1, 2

    1 Department of Bioanalysis and Drug Analysis, Faculty of Pharmacy, Warsaw

    Medical University 2 "STOP Illegal Pharmaceuticals" Association For Health Protection And The

    Rule Of Law

    Pharmaceutical crime is a serious public health problem that puts

    human lives at risks, causes direct harm to patients and undermines

    people’s confidence in the entire health system; affecting the reputation

    of manufacturers, wholesalers, pharmacists, doctors, private organisation

    and governments alike. The criminal market for counterfeit medicines

    was estimated to be worth approximately EUR 120 billion in 2017.

    Counterfeiting affects all medical products: medicines,

    pharmaceutical ingredients, medical devices, diagnostics and dietary

    supplements (including products containing false information about the

    composition, origin, effects, usage and history). All types of medicines

    are being falsified: lifestyle medicines, doping substances, cheap or

    expensive medicines such as those for the treatment of AIDS and cancer.

    There is also an increase illicit traffic of illegal or stolen medicines. The

    consequence of the use of falsified products can be extremely dramatic.

    Falsified medicines can kill either through direct poisoning or by not

    treating a life-threatening disease. There are also more and more data

    about hospitalisations and deaths of people who used preparations of

    unknown origin, purchased from online offers and turnovers outside

    legal pharmaceutical supply chain (eg. oriental medicine clinics, sex

    shops, gyms), where no one asks for prescription and informs about the

    adverse effects or interactions with other medical products.

    The online sale of medicines took off in the early 2000s and,

    although various platforms have been used, online pharmacies have been

    a primary source of distribution. In the early days, the most popular

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    products to be supplied on the web were natural and herbal medicinal

    products, smoking cessation aids, and beauty and sexual performance

    enhancement products. More recently, the market for enhancement drugs

    such as muscle builders, diet pills and sunless self-tanning sprays has

    been expanding and there have been reports of cancer drugs and stem

    cells being marketed over the internet. The central role of the internet in

    facilitating and enhancing this global market is widely acknowledged,

    posing an increased threat to public health. According to the WHO,

    FDA, Interpol and Alliance of Safe Online Pharmacy (ASOP EU; 2018

    Report), around 50% to 90% of the medicines and dietary supplements

    sold online from illegal sites concealing their physical identity are

    counterfeits. Internet provides the ideal channel to buy illegally

    distributed fake medicines. Price, convenience and secrecy have driven

    consumer demand, creating the perfect environment for over 35000

    illegally operating websites.

    At the European level, there is not a common legislative approach to

    tackling the problem of counterfeit medicines and dietary supplements

    containing undeclared active pharmaceutical ingredients or their analogs.

    These products present still an ongoing challenge to analysts,

    toxicologists, and law enforcement agencies. To effectively combat the

    problems associated with pharmaceutical crime, a collective effort needs

    to be in place from pharmaceutical scientists, health professionals, and

    law enforcement authorities.

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    SOME HIDEOUS ELEMENTS FROM THE “ELEMENTS” OF

    NATURE… ANALYSIS OF TOXIC ELEMENTS IN HUMAN

    TISSUES AND BODY FLUIDS WITH THE USE OF

    SYNCHROTRON RADIATION MICROSPECTROSCOPIC

    TECHNIQUES

    Marek W. Lankosz

    AGH University of Science and Technology, Faculty of Physics and Applied

    Computer Sciences, al. Mickiewicza 30, 30-059 Kraków, Poland

    In antiquity it was thought that the elements are simple substances.

    In accordance to Greek philosopher’s water, fire, air, earth and ether

    were counted to them. These five elements connect everything on our

    planet. Though their origin continues to be a mystery, they remain

    integral to life and its evolution. Democritus defined the element as an

    indivisible part of matter. The evolution of our planet is not yet fully

    understood, but it is known that everything began with “Big Bang”. The

    nucleosynthesis and nuclear reactions caused by neutrons created all

    elements in the Universe.

    According to the current state of knowledge, it is known that many

    elements determine the proper functioning of living organisms and must

    be delivered to them with diet. The elements in physiological terms can

    be classified as elements necessary for the life (bio elements), neutral

    elements without which metabolic reactions can normally occur and

    toxic elements having a harmful effect on the human body. Different

    studies from around the world have shown that minerals and trace

    elements can prevent and treat various disorders. Up to now, some

    sixteen toxic elements in our environment have been identified, of which

    lead, cadmium, nickel, mercury and aluminum are the most prevalent.

    Many elements present in the human body play an important role in

    the pathophysiology of cancer and neurodegeneration. Molecular

    medicine requires the use of methods that enable the monitoring of

    biochemical processes and interactions of elements in tissues involved in

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  • 2-nd ICPMS Poprad 2018

    21

    the neoplastic processes and neurodegeneration. Synchrotron X-ray

    fluorescence micro spectroscopy (SRXRF), was used to study the

    elemental composition in brain and ovarian tissues. The studies showed

    that the elemental composition of tissues differs and are depending on

    the pathological processes. The obtained results enable us for better

    understanding of metabolic processes in neoplastic disease and

    neurodegeneration processes and may be useful in histopathological

    diagnostics.

    References

    1. Chmura Ł., Grzelak M., Czyzycki M., Wrobel P., Brzyszczyk M., Jach R.,

    Adamek D., Lankosz M., J Physiol Pharmacol 2017, 68(5), 699–707.

    2. Wandzilak A., Czyzycki M., Radwańska E., Adamek D., Geraki K.,

    Lankosz M., Spectrochim Acta Part B At Spectrosc 2015, 114, 52–57.

    3. Szczerbowska-Boruchowska M., Chwiej J., Lankosz M., Wojcik S., Adamek

    D., Krygowska-WajsA., Alzheimers Dement 2009, 5 iss. 4 suppl., 215.

    4. Golasik M., Wrobel P., Olbert M., Nowak B., Czyzycki M., Librowski T.,

    Lankosz M., Piekoszewski W., Biometals 2016, 29 iss. 3, 487–494.

    https://pl.pons.com/tłumaczenie/angielski-polski/thehttps://pl.pons.com/tłumaczenie/angielski-polski/neoplastichttps://pl.pons.com/tłumaczenie/angielski-polski/processhttps://pl.pons.com/tłumaczenie/angielski-polski/Synchrotronhttps://pl.pons.com/tłumaczenie/angielski-polski/X-rayhttps://pl.pons.com/tłumaczenie/angielski-polski/fluorescencehttps://pl.pons.com/tłumaczenie/angielski-polski/SRXRFhttps://pl.pons.com/tłumaczenie/angielski-polski/sedhttps://pl.pons.com/tłumaczenie/angielski-polski/tohttps://pl.pons.com/tłumaczenie/angielski-polski/studyhttps://pl.pons.com/tłumaczenie/angielski-polski/thehttps://pl.pons.com/tłumaczenie/angielski-polski/elementalhttps://pl.pons.com/tłumaczenie/angielski-polski/compositionhttps://pl.pons.com/tłumaczenie/angielski-polski/inhttps://pl.pons.com/tłumaczenie/angielski-polski/rainhttps://pl.pons.com/tłumaczenie/angielski-polski/andhttps://pl.pons.com/tłumaczenie/angielski-polski/ovarianhttps://pl.pons.com/tłumaczenie/angielski-polski/tissueshttps://pl.pons.com/tłumaczenie/angielski-polski/Thehttps://pl.pons.com/tłumaczenie/angielski-polski/studieshttps://pl.pons.com/tłumaczenie/angielski-polski/showedhttps://pl.pons.com/tłumaczenie/angielski-polski/thathttps://pl.pons.com/tłumaczenie/angielski-polski/thehttps://pl.pons.com/tłumaczenie/angielski-polski/elementalhttps://pl.pons.com/tłumaczenie/angielski-polski/compositionhttps://pl.pons.com/tłumaczenie/angielski-polski/ofhttps://pl.pons.com/tłumaczenie/angielski-polski/tissueshttps://pl.pons.com/tłumaczenie/angielski-polski/dependinghttps://pl.pons.com/tłumaczenie/angielski-polski/onhttps://pl.pons.com/tłumaczenie/angielski-polski/thehttps://pl.pons.com/tłumaczenie/angielski-polski/Thehttps://pl.pons.com/tłumaczenie/angielski-polski/obtainedhttps://pl.pons.com/tłumaczenie/angielski-polski/resultshttps://pl.pons.com/tłumaczenie/angielski-polski/enablehttps://pl.pons.com/tłumaczenie/angielski-polski/etterhttps://pl.pons.com/tłumaczenie/angielski-polski/nderstandinghttps://pl.pons.com/tłumaczenie/angielski-polski/ofhttps://pl.pons.com/tłumaczenie/angielski-polski/metabolichttps://pl.pons.com/tłumaczenie/angielski-polski/processeshttps://pl.pons.com/tłumaczenie/angielski-polski/inhttps://pl.pons.com/tłumaczenie/angielski-polski/andhttps://pl.pons.com/tłumaczenie/angielski-polski/mayhttps://pl.pons.com/tłumaczenie/angielski-polski/behttps://pl.pons.com/tłumaczenie/angielski-polski/sefulhttps://pl.pons.com/tłumaczenie/angielski-polski/inhttps://pl.pons.com/tłumaczenie/angielski-polski/histopathologicalhttps://pl.pons.com/tłumaczenie/angielski-polski/diagnostics

  • 2-nd ICPMS Poprad 2018

    22

    TO FEEL SECURE AND SAFE: WHAT DOES IT REALLY

    MEAN – PSYCHOLOGICAL ASPECTS OF SOCIAL

    AND INDIVIDUAL SECURITY

    Zenon Uchnast

    Jesuit University Ignatianum in Kraków, Institute of Psychology, Kopernika 26,

    31-501 Kraków, Poland

    Abraham Maslow (1908-1970) can still inspire to the search of the

    real sense of the individual and the social sense of safety. I would like to

    present three Maslow's exploratory approaches. The first Maslow’s

    original exploratory question was about psychopatho-genesis: “What

    makes people neurotic?”. Maslow’s answer on this question is in

    “Motivation and personality” (1954), that neurosis seemed at its core,

    and in its beginning, to be a deficiency disease. Finally he assumed that

    most neuroses involved ungratified basic needs for safety,

    belongingness, close love relationships, and for respect and prestige.

    Then, the identification of pre-conditions for satisfaction of these needs

    was very important in the area of Maslow’s growth theory as well.

    In the second approach presented in “Toward a psychology of

    being” (1962) Maslow pointed out the growth-motivated and self-

    actualizing individual, assuming that every human being has both sets of

    forces within him. One set clings to safety and defensiveness out of fear,

    the other set of forces impels him forward toward wholeness of Self and

    uniqueness of Self, toward full functioning of all his capacities, toward

    confidence in the face of the external world. Therefore he assumed the

    process of healthy growth to be a never ending series of free choice

    situations, confronting each individual at every point throughout his life,

    in which he must choose between the delights of safety and growth,

    dependence and independence, regression and progression, immaturity

    and maturity. Then, in that situations safety could have both anxieties

    and delights, and growth could have both anxieties and delights as well.

    However, in the last chapter of this monograph Maslow (1962, p. 190)

    sincerely confesses: “Though, in principle, self-actualization is easy, in

  • 2-nd ICPMS Poprad 2018

    23

    practice it rarely happens (by my criteria, certainly in less than 1% of the

    adult population)”.

    The third approach to the process of the safe and healthy growth

    Maslow (1964) assumed in the paper “Synergy in the society and in the

    individual” (1964). Synergic self-actualization is understood as

    individual achievement in the ability to express and actualize one’s

    potential through adequate participation and cooperation in interpersonal

    and social relationships. Z. Uchnast’s Self-Actualization Styles

    Questionnaire (2000, 2010) and included in it the structural scale of

    Synergic self-actualization could be used as the measurement instrument

    of individual differences in the bipolar dimension: synergic proactivity

    and growth – safety and defensiveness.

  • 2-nd ICPMS Poprad 2018

    24

    COUNTERFEIT PHARMACEUTICAL PRODUCTS AND

    ILLEGAL DISTRIBUTION CHANNELS

    Grzegorz Brzoskowski

    Security Director CEE/Nordic, SANOFI/Genzyme/Pasteur/Nepentes, Warsaw,

    Poland

    Sanofi has been involved for nearly 10 years in preventing and

    fighting fake medicines. Since 2008, a Sanofi laboratory in Tours,

    France has analyzed suspected counterfeit products and has improved

    knowledge of counterfeit medicines around the world. Counterfeiting

    medication is very profitable for organize crime groups, they take

    advantage of the good reputation of products and brands that brand

    owners established.

    Current supply channels and organize crime activity in Europe and

    Middle East and the examples of dismantling medicines trafficking

    networks worldwide.

  • 2-nd ICPMS Poprad 2018

    25

    INTESTINE A SUITCASE WITH A DOUBLE BOTTOM

    RESEARCH, PREVENTION, DEMANDS

    Gerhard Mikolaiczik

    International Research Group of Apllied Preventive Medicine

    Währinger Str. 63 A-1090 Wien, Austria

    The development of preventive medicine and biological sciences let

    us have a better and better understanding of the relations of intestine and

    microbiota with metabolism, immunology, mental condition, skin

    condition, child development, cognitive skills, depression, metabolic

    disorders. Intestinal microbiota has a significant influence on human

    health. It modulates immune response, provides the body with vitamins,

    takes part in food digestion, supplies energy-producing short-chain fatty

    acids to intestinal epithelium, and stimulates intestinal peristalsis.

    The microbiome also plays a significant role in xenobiotic

    detoxification. Changes in the microbiome are causative agents of some

    diseases such as obesity, non-alcoholic fatty liver disease, diabetes,

    coronary disease, tumours, allergies, and skin diseases. One of the

    significant intestinal disorders is also a leaky gut syndrome – a well-

    documented phenomenon which contributes even to obesity in youth.

    In the past, it was believed that a few “good” strains of bacteria are

    enough to restore the intestine to the right condition. Nowadays we know

    that such belief is far from truth. The capabilities of microorganisms

    living in the intestine to manipulate human brain and metabolism are

    surprising: from aggression-causing toxins to lignans pretending human

    signal molecules.

    In the light of new research, the most important parameters of

    a good condition of a healthy intestine, which seems to be the “health

    guard”, are biodiversity, the right pH, integrity of mucous membranes,

    a proper Firmicutes/Bacteroides ratio, the presence of a sufficient

    number of butyrate-producing bacteria, immunogenic bacteria, oxalate-

    decomposing bacteria, bacteria stabilizing the intestinal environment,

    absence of histamine and histamine-producing bacteria in the intestine,

    and normal inflammatory markers. The thesis which is the easiest to

  • 2-nd ICPMS Poprad 2018

    26

    verify but extremely important for a healthy intestine is a proposal to

    limit the desired pH value in faeces to the range of 6-6.5.

    References

    1. P.C. Konturek et al., J Physiol Pharmacol 2015, 66, 4, 483-491.

    2. Küme T. et al., J Clin Res Pediatr Endocrinol 2017, 9(1), 31–38.

    3. Fasano A., Am J Clin Nutr 2017, 105, 3–4.

    4. Fasano A., Physiol Rev 2011, 91, 151–75.

    5. Louis J. Cohen et al., Nature 2017, 7, 48–53.

    https://www.ncbi.nlm.nih.gov/pubmed/28854168

  • 2-nd ICPMS Poprad 2018

    27

    BIOTERRORISM – A GLOBAL CHALLENGE IN THE 21ST

    CENTURY. SHOULD WE FEEL DEFENSELESS OR

    PROTECTED?

    Agnieszka Polończyk

    Institute of Security Education and Civil Education, Pedagogical University of

    Kraków, Poland

    The aim of the paper is to present the phenomenon of bioterrorism

    which is a form of terrorism that involves the intentional release or

    dissemination of biological agents like bacteria, viruses, toxins or fungi.

    Using biological weapon, in naturally occurring or in a human-modified

    form, can lead to many illnesses, disability or even death of people,

    animals, or plants. It is also worth mentioning, that pathogenic germs can

    be transmitted by means of missiles, aerial bombs, containers or letter

    items. Bioterrorist attacks are difficult to detect, because microorganisms

    are easy to hide and transport, and even a small number of them is

    dangerous and effective. Important is, that nowadays, the risk of

    biological attacks increases, but there is still little awareness about the

    phenomenon of bioterrorism among many of the societies.

    In the first part of the paper, the term of bioterrorism will be defined

    and the history of this phenomenon will be brought closer. Interesting is,

    that the history of the use of biological weapons goes back to ancient

    times, however the greatest development of biological weapons is to be

    observed in the period of the Second World War and in the post-war

    times. Then, the classification of the biological threats according to the

    American Center for Disease Control and Prevention will be pointed.

    Particular attention will be paid to the characteristic features of

    a bioterrorist attack and the procedures in the case of its occurrence on

    the example of Poland. Finally, an attempt will be made to answer the

    question, how to prevent and counteract the bioterrorist attack and if the

    real threat of bioterrorism really occurs.

  • 2-nd ICPMS Poprad 2018

    28

    References

    1. Barras V., Greub G., Clin Microbiol Infect 2014, 20, 497–502.

    2. Center for Disease Control and Prevention, Bioterrorism Overview,

    https://www.cdc.gov.

    3. Chomiczewski K., Przegl Epidemiol 2003, 57, 363–368.

    4. Khan A.S., Swerdlow D. L., Juranek D. D., Public Health Rep 2001, 116 (1),

    3–14.

    5. Prakash N., Sharada P., Pradeep G.L., J Forensic Dent Sci 2010, 2(2), 59–

    62.

  • 2-nd ICPMS Poprad 2018

    29

    PREVENTION OF COCCIDIOSIS WITH MEDICINAL HERBS

    AS NATURAL COCCIDIOSTATICS IN RABBIT PRODUCTION

    Károly Bodnár

    Faculty of Agricultural and Economic Studies, Szent Istvan University,

    Szabadsag 1-3. H-5540 Szarvas, Hungary

    In meat rabbit production coccidiosis caused by Eimeria species is

    a serious animal health, production, management and economic problem.

    The disease can be prevented by medicated feed (coccidiostat drugs),

    which may cause the resistance of the parasites; vaccines are exist, but

    they are too expensive for rabbit farming. A lot of researches were made

    on the use of medicinal herbs as an alternative way of reduction of

    oocyst number. Recent paper is a short literature based summary on the

    prophylaxis of coccidiosis with natural plant materials. The most

    frequently researched plants are genus Thymus, genus Origanum, genus

    Artemisia, Allium sativum, Allium cepa, Salvia officinalis, Nigella sativa,

    Matricaria chamomilla, Rosmarinus officinalis, Commifora molmol,

    Sophora flavescens, Sideritis scardica, Sinapis alba, Curcuma longa,

    Musa paradisiaca. The application of herbs can take several forms: oral

    administration in the feed pellet or with the drinking water; the whole

    dried plant or parts of it (leaves, flowers, roots) and often the essential oil

    extracts are used. The use of essential oils makes possible a more precise

    dosage, but it is more expensive. Dried herbs can be used easier in

    practice. The relative high concentration (1-5%) and the comparatively

    strong bitter tastes of them usually do not have negative effect on the

    palatability of rabbit feed. The authors state that the examined herbal

    additives to prevent coccidiosis can reduce the number of oocysts with

    the provision of adequate nutrition and good hygienic condition. Further

    positive effects of the examined medicinal herbs are also reported.

    Increased daily weight gain and reduced mortality was observed. Some

    of the preparations which have also bactericidal or fungicidal effects

    seem more suitable for prevention. There are no harmful drug residues in

  • 2-nd ICPMS Poprad 2018

    30

    the carcass and the faeces or urine of rabbits. If the rabbit meat contains

    residues of essential oils, it will make the meat tastier because some of

    the examined plants (thyme, oregano, garlic) are traditional seasonings

    of the meals from rabbit.

  • 2-nd ICPMS Poprad 2018

    31

    THE PRESENCE OF blaTEM GENES IN tonB-POSITIVE AND

    tonB-NEGATIVE PASTEURELLACEAE ISOLATES FROM

    RESPIRATORY MICROBIOTA

    Urszula Kosikowska1, Edyta Chwiejczak1, Patrycja Mrozik2,

    Artur Niedzielski3, Anna Malm1

    1 Department of Pharmaceutical Microbiology with Laboratory for

    Microbiological Diagnostics, Medical University of Lublin, Chodzki 1,

    Lublin, Poland

    2 Students Scientific Association at the Department of Pharmaceutical

    Microbiology with Laboratory for Microbiological Diagnostics, Medical

    University of Lublin, Chodźki 1, Lublin, Poland 3 Otoneurology Lab, Medical University of Lublin, Gebali 6, Lublin, Poland

    The tonB protein (coded by the tonB gene) in TonB systems of

    Gram-negative bacteria is very important for active transport of iron and

    other specific substrates, e.g. vitamins, into the periplasmic space [1,2].

    It is essential for the growth and pathogenesis of these microorganisms

    in the host body, where iron is limited. Only some haemophili species

    (Pasteurellaceae), representing the respiratory microbiota components,

    posses the tonB gene coding TonB protein, which is the known virulence

    factor of Haemophilus influenzae. The aim of this study was to detect the

    presence of blaTEM gene encoding beta-lactamases production with and

    without tonB gene in Haemophilus spp. and Aggregatibacter spp.

    isolated from respiratory microbiota.

    The study included 27 randomly selected isolates from the

    Pasteurellaceae family: H. influenzae (2), H. haemolyticus (3), H.

    parainfluenzae (16) i Aggregatibacter aphrophilus (6) identified on the

    basis of protein profile using MALDI-TOF MS technique. The tonB and

    blaTEM genes were detected by PCR method. The antimicrobial

    sensitivity was detected on the basis of MIC (minimal inhibitory

    concentration) using gradient-diffusion method.

  • 2-nd ICPMS Poprad 2018

    32

    Among the tested Pasteurellaceae species tonB gene was detected

    in H. influenzae, H. haemolyticus, H. parainfluenzae and A. aphrophilus

    isolates. The blaTEM gene occurred in H. influenzae, H. parainfluenzae

    and A. aphrophilus isolates. Either tonB and blaTEM genes occurred in

    total of 5/27 (18.5%) isolates (2 H. influenzae, 2 H. parainfluenzae

    and 1 A. aphrophilus). These bacteria were mainly resistant or in less

    level the intermediate to ampicilin and cefuroxime according to

    EUCAST categories.

    The presence of a blaTEM and tonB gene among Pasteurellaceae

    isolates within respiratory microbiota may increase their virulence and

    have the effect on the occurrence of therapeutic problems due to

    production of beta-lactams inactivating enzymes.

    References

    1. Koebnik R., Trends Microbiol 2005, 13, 343–347.

    2. Reeves S.A. et al., Infect Immun. 2000, 68, 6329–6336 .

  • 2-nd ICPMS Poprad 2018

    33

    PHANTOM PHENOMENA, BODY SCHEME AND LEVEL OF

    LIMB AMPUTATION. EFFICIENCY OF “MIRROR THERAPY”

    Roman Nowobilski1, Tomasz Włoch2, Aneta Pirowska3,

    Arkadiusz Berwecki2, Sławomir Szczupacki4

    1 Jagiellonian University Medical College, Faculty of Public Health, Krakow,

    Poland 2 University School of Physical Education, Krakow, Poland

    3 Institut Robert Merle d'Aubigné, Artificial Limb Centre (CRA – Centre de

    Reeducation et d'Appareillage), Valenton, France 4 Orthopaedic Laboratory, Kraków, Poland

    About 70% of the amputees will sooner or later experience phantom

    phenomena. Phantom sensations and phantom pain may occur

    immediately after the limb amputation or many months, even years later.

    One of the factors affecting the intensity of phantom phenomena is

    height of limb amputation.

    The aim of the study was to assess the relationship between height

    of limb amputation and the type of phantom phenomena. The benefits of

    mirror therapy and early introduction of prosthesis and applying

    functional prosthesis were tested. The study included 45 adults after

    single or multiple-limb amputations: 35 men and 10 women. The mean

    age was 68,24 ± 13.9 years. No sex differences in age (p = 0.226).

    The pilot study used a survey questionnaire, numerical scale and McGill

    Pain Questionnaire.

    The relationships were demonstrated between the height of limb

    amputation, age and the intensity of phantom phenomena (rho=-31,

    p

  • 34

    PART III

    SHORT PRESENTATIONS

  • 2-nd ICPMS Poprad 2018

    35

    HYPOTENSIVE, ANTIARRHYTMIC AND α1-ADRENOLYTIC

    ACTIVITY OF THE NEW ARRYLPIPERAZINE DERIVATIVES

    OF 5,5-DIMETHYLPHYDANTOIN

    Małgorzata Belczyk1, Joanna Knutelska1, Małgorzata Zygmunt1,

    Marek Bednarski1, Adrian Bryła1, Jadwiga Handzlik2,

    Magdalena Kotańska1, Jacek Sapa1

    1 Department of Pharmacological Screening, Chair of Pharmacodynamics

    2 Department of Technology and Biotechnology of Medicinal Products,

    Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland

    The arylpiperazine group is an important structural element of α1-

    adrenergic receptor ligands. It occurs in the structure of many chemical

    compounds and also in the structure of some drugs affect the

    symphatetic nervous system. Drugs having an arylpiperazine group in

    their structure are for example naphthopidil and urapidil, which have

    significant α1-adrenolytic activity. It is the reason why they are used in

    the pharmacotherapy of cardiovascular diseases (1-4).

    A series of new arylpiperazine derivatives of 5,5-dimethylhydantoin

    has been synthesized and evaluated for effects on the normal rat

    electrocardiogram in vivo, antiarrhythmic activity in the adrenaline

    arrhythmia model, antihypertensive activity and affinity for α1-

    adrenergic receptors. Pharmacological studies have shown that all tested

    compounds have affinity for the α1-adrenergic receptors, however MG-

    15 compund (Ki=12,7 nM) displaced 3H-prazosin in the rat cortex the

    most. Only the MG-15 compound completely protected animals from the

    onset of post-adrenaline disorders - bradycardia, bigeminia,

    atrioventricular blocks, extrasystoles and before death. The calculated

    ED50 value of the MG-15 compound in this arrythmia model was 0,21

    mg/kg, while the ED50 value of the Urapidil (reference compound) was

    1,041 mg/kg.

    Assessing the effect of arylpiperazine hydantoin derivatives on

    blood pressure in a normotensive rat after intravenous administration, it

  • 2-nd ICPMS Poprad 2018

    36

    was found that MG-15 compound had the strongest hypotensive effect

    (similar to the reference compound – Urapidil).

    The obtained results of pharmacological studies indicate that among

    the new arylpiperazine derivatives of hydantoin the compound with

    a very strong hypotensive and antiarrhythmic effect (stronger than

    Urapidyl) and with an affinity for α1-adrenergic receptors was selected.

    Hypotensive and antiarrhythmic activity of this compound may arise

    from the blockade of the α1-adrenergic receptor.

    References

    1. Malawska B. et al., Eur J Med Chem 2002, 37, 183–195.

    2. Kulig K. et al., Eur J Med Chem 2004, 44, 3994–4003.

    3. Muramatsu I., Yamanaka K ., Kigoshi S., Jap J Pharmacol 1991, 55, 391–

    398.

    4. Kubacka M. et al., Eur J Pharmacol 2013, 698, 335–344.

    The research was financed from the statutory research project No.

    K/ZDS/005548.

  • 2-nd ICPMS Poprad 2018

    37

    THE ANALYSIS OF ABILITY OF BIOFILM FORMATION IN

    VITRO AND GRF10 GENE EXPRESSION IN CANDIDA

    ALBICANS ISOLATED FROM ORAL CAVITY

    Anna Biernasiuk1, Rafał Sawicki2, Radosław Siwiec1, Anna Malm1

    1 Department of Pharmaceutical Microbiology with Laboratory for

    Microbiological Diagnostics, Medical University of Lublin, Chodźki 1,

    20-093 Lublin, Poland 2 Department of Biochemistry and Biotechnology, Medical University of Lublin,

    Chodźki 1, 20-093 Lublin, Poland

    The number of fungal infections, caused especially by commensal

    yeast species belonging to Candida spp., mainly Candida albicans, has

    progressively increased during last years. C. albicans and other Candida

    species are present in the oral cavity of up to 75% of the population.

    Under predisposing conditions these microorganisms may cause

    endogenous infections called as candidiases [1]. Several factors may

    contribute to the pathogenic potential of Candida spp. Among them, the

    ability of biofilm formation play an important role in the candidiases

    pathogenesis [2]. The biofilm formation by C. albicans is determined by

    the expression of several genes, e.g. grf10 (Growth-regulating factor

    10), involved in filamentous growth of yeasts [3]. The aim of this study

    was to analyze the expression of grf10 gene during biofilm formation by

    C. albicans strains colonizing the oral cavity.

    A total of 31 C. albicans strains isolated from oral cavity of patients

    with hepatitis C were studied. Biofilm formation was examined during

    the stationary culture in vitro in 96-well polystyrene microplates with

    a 0.1 % crystal violet. The prevalence of grf10 gene and its expression

    analysis was studied, using the PCR and qPCR reactions, respectively.

    For relative quantification of transcript levels, target gene was

    normalized to the housekeeping gene tef1. PCR reactions were

    performed with LightCycler® 480 thermal cycler (Roche).

  • 2-nd ICPMS Poprad 2018

    38

    It was found that 27 (87.10%) C. albicans strains showed the ability

    to biofilm formation. Among them, 10 (32.26%) strains formed biofilm

    strongly. In these strains grf10 gene was detected. During biofilm

    formation by them the total RNA was isolated and relative expression of

    grf10 gene was measured after 48 h and 72 h. In some C. albicans strains

    five to ten times increase of relative expression of grf10 gene could be

    noticed, while in others the amount of grf10 transcript was lower in

    comparison to calibrator.

    These data indicate that expression of grf10 gene in C. albicans

    seems to be rather strain-dependent and to be correlated with expression

    of other genes involved in biofilm formation. This requires further

    studies with the usage of RNA sequencing allowing to compare the

    entire transcriptome of different strains.

    References

    1. Millsop J.W., Clin Dermatol. 2016, 34, 487–494.

    2. Gulati M., Microbes Infect 2016, 18, 310–321.

    3. Ghosh A.K., FEMS Yeast Res 2015, 15 (8), pii: fov093.

    https://www.ncbi.nlm.nih.gov/pubmed/?term=Ghosh%20AK%5BAuthor%5D&cauthor=true&cauthor_uid=26472755https://www.ncbi.nlm.nih.gov/pubmed/26472755

  • 2-nd ICPMS Poprad 2018

    39

    IS THE INHIBITION OF ALDEHYDE DEHYDROGENASE BY

    DISULFIRAM PREVENTED OR REVERSED BY LIPOIC ACID

    AND DIHYDROLIPOIC ACID IN VITRO? DOES LIPOIC ACID

    ALLEVIATE THE TOXICITY OF THE CONCOMITANT USE

    OF ETHANOL AND DISULFIRAM IN RATS?

    Anna Bilska-Wilkosz1, Magdalena Kotańska2, Magdalena Górny1,

    Małgorzata Iciek1, Danuta Kowalczyk-Pachel1, Inga Kwiecień3,

    Barbara Filipek2

    1 Chair of Medical Biochemistry, Jagiellonian University Medical College,

    7 Kopernika Street, 31-034 Kraków, Poland 2 Chair of Pharmacodynamics, Jagiellonian University Medical College,

    Medyczna 9, 30-688 Kraków, Poland 3 Chair and Department of Pharmaceutical Botany, Jagiellonian University

    Medical College, Medyczna 9, 30-688 Kraków, Poland

    The inhibition of aldehyde dehydrogenase (ALDH) by disulfiram

    (DSF) in vitro can be prevented and/or reversed by dithiothreitol (DTT)

    which is a well-known low molecular weight non-physiological redox

    reagent commonly used in laboratory experiments.

    This observation inspired us to ask the question whether the

    inhibition of ALDH by DSF can be protected or abolished also by

    dihydrolipoic acid (DHLA) which is the only known today low

    molecular weight physiological dithiol in the body of humans and other

    animals. It can even be metaphorized that DHLA is an “endogenous

    DTT”. Lipoic acid (LA) is the oxidized form of DHLA. The exogenous

    LA is succesfully used as a drug in the treatment of many diseases (1).

    We investigated in vitro the inactivation of yeast ALDH by DSF in

    the presence and absence of LA and DHLA. In vivo studies were

    performed to answer the question whether LA administration to rats can

    attenuate ethanol (EtOH) toxicity when ALDH activity is blocked by

    DSF. For this purpose we conducted electrocardiographic (ECG), and

  • 2-nd ICPMS Poprad 2018

    40

    systolic and diastolic blood pressure measurements and estimated

    mortality of rats.

    The in vitro results showed that DHLA but not LA could protect

    ALDH against DSF-induced blockade, while neither LA nor DHLA

    were able to restore the ALDH activity when it already had been

    inhibited by DSF. The in vivo study demonstrated that LA could partially

    atttenuate the cardiac arrhythmia induced by EtOH. The results

    demonstrated also that LA administration reduced the EtOH-induced

    mortality of animals. These results reveal that LA may have a potential

    for use in acute EtOH intoxication.

    References

    1. Bilska A., Włodek L., Pharmacol Rep 2005, 57, 570–577.

  • 2-nd ICPMS Poprad 2018

    41

    CONSUMPTION OF CAFFEINE IN A GROUP OF YOUNG

    PEOPLE FROM SOUTHERN POLAND

    Ewa Błaszczyk-Bębenek, Paweł Jagielski, Beata Piórecka,

    Jaśmina Żwirska, Małgorzata Schlegel-Zawadzka

    Human Nutrition Department, Institute of Public Health, Faculty of Health

    Sciences, Jagiellonian University Medical College, Grzegórzecka 20,

    31-531 Kraków, Poland

    Caffeine-derived products in the diet are equally popular among

    adults as well as in younger age groups [1,2]. Many Agencies, including

    the European Food Safety Authority, stress the difficulty in determining

    the safe level of caffeine intake for the group of children and adolescents

    [3,4].

    The aim of the study was to evaluate caffeine consumption and to

    determine its sources in the diet of adolescents from the Southern

    Poland.

    A retrospective observational study was conducted (in 2014-15)

    among young people aged 16-18 (Bioethical Commission consent No.

    KBET/62/B/2013). The research tool to assess caffeine intake along with

    the diet was a questionnaire containing questions about the frequency

    and amount of consumed products being a source of caffeine in the diet.

    Frequency intervals proposed to assess the frequency of calcium intake

    along with diet (ADOS-Ca) were used to assess the average daily

    caffeine intake, [5]. To assess the safety of caffeine intake by subjects,

    doses considered safe with usual consumption (3 mg/kg body mass) [4]

    and causing sleep disorders (1.4 mg/kg body mass) or anxiety and

    anxiety (2.25 mg/kg body mass) [6]. The non-parametric U Mann-

    Whitney and Chi2 tests were used at the assumed significance level

    α=0.05.

    The mean caffeine intake by the study group was 95.54 mg/day

    (1.54 mg/kg body mass). The main sources of caffeine included black tea

    (26.9%) and green tea (16.2%), as well as energy drinks (13.3%). The

  • 2-nd ICPMS Poprad 2018

    42

    most commonly consumed products being a source of caffeine in the

    study diet were black tea, cola drinks, which were more often used by

    boys (p=0.0401) and milk chocolate. Boys also significantly more often

    reached for bitter chocolate (p=0.0219) and girls for instant coffee

    (p

  • 2-nd ICPMS Poprad 2018

    43

    PROTON POMP INHIBITORS – ABUSE AND USE

    INCOMPATIBLE WITH EXISTING MEDICAL GUIDELINES

    Adrian Bryła1,2, Małgorzata Zygmunt1, Katarzyna Dziewic2

    1 Department of Pharmacological Screening, Chair of Pharmacodynamics,

    Jagiellonian University Medical College, 9, 30-688 Kraków, Poland 2 Ludwik Rydygier’s Memorial Hospital, os. Złotej Jesieni 1,

    31-826 Kraków, Poland

    Proton pump inhibitors (PPI) are a group of drugs which block

    gastric acid production in parietal cells what lowering the pH in the

    gastric lumen. PPI are mainly used in the treatment of gastroesophageal

    reflux disease (GERD) and gastric and duodenal ulcers. Compared with

    previously used agents such as histamine H2 receptor antagonists,

    synthetic prostaglandin analogs or anticholinergic drugs, PPI have shown

    better tolerance and safety. Over recent years usage of proton pump

    inhibitors has increased dramatically. Due to the affordable price and

    high efficacy their use is prevalent and often is not compatible with

    existing medical guidelines. Ulcer prophylaxis among patients with low

    risk of bleeding, routine “gastroprotective” medication during treatment

    and non-specific abdominal symptoms are the most common patterns of

    off-label use of PPI.

    The problem of abuse or incorrect use of PPI is connected not only

    with hospital wards. PPI are avaliable (without a prescription) in

    pharmacies, shops and petrol stations. Patients often take these

    medicines despite the lack of indications, without any control of doctor

    or pharmacist. Observing patients (especially older patients) admitted to

    hospital, great habit to PPI is noticeable. Patients often demand this kind

    of drugs in their therapy during being in the hospital and they get it

    (treatment of older people with PPI is 25% - 85% unfounded). This

    feature and the fact that these people often suffer from many chronic

    disease (that require using a significant amount of different medications)

    makes older people the most exposed group to various drug-related

    interactions and other side effects of PPI. Another aspect related to the

  • 2-nd ICPMS Poprad 2018

    44

    wrong using of PPI is the financial aspect what is significant in relation

    to expenditure on these medications in hospitals during all year.

    Inapropriate using of PPI, too high costs, less money for other therapies.

    Is it right way?

    References

    1. Sanders S.W., Clin Ther 1996, 18, 2–34.

    2. Forgacs I., Loganayagam A., BMJ 2008, 336(7634), 2–3.

    3. Pasina L., Nobili A., Tettamanti M., Salerno F., Corrao S., Eur J Intern Med

    2011, 22, 205–210.

  • 2-nd ICPMS Poprad 2018

    45

    EFFECT OF USING NATURAL VEGETABLE OILS IN THE

    DIET ON ALCOHOL DETOXIFICATION IN HUMAN

    Aleksandra M. Buchaj1, Jakub A. Knurek2

    1 Department of Botany and Mycology, Maria Curie-Skłodowska University of

    Lublin, Akademicka 19, 20-400 Lublin 2 Department of department of Biochemistry and Biotechnology, Medical

    University of Lublin, Chodźki 1, 20-093 Lublin

    Worldwide, 3.3 million deaths every year result from harmful use of

    alcohol. Addiction to alcohol is a common cause of many diseases and

    injuries like hormonal disorders, cancer, immunodeficiency disorders,

    peripheral polyneuropathy, atrophy of the cerebellum, cirrhosis of the

    liver, bruised liver, acute or chronic pancreatitis, dilated cardiomyopathy,

    arrhythmia, anemia, gastritis and peptic ulcer disease. It is approved by

    the social acceptance mechanism, which leads to difficulties in its

    systemic combating.

    The aim of our lecture is to describe the influence of selected

    vegetable natural oils on alcohol metabolism and to prove the

    relationship between the composition of active ingredients (with

    particular reference to fatty acids) and pharmacological action. In the

    research, we included studies on sunflower oil, linseed oil, rapeseed oil

    and borage oil, which contain a different ratio of fatty acids. We hope

    that our work will significantly affect the intensification of research in

    this field.

    References

    1. Beroual K., Agabou A., Abdeldjelil M. C., Boutaghane N., Haouam S.,

    Hamdi-Pacha Y., Afr J Tradit Complement Altern Med. 2017, 14, 280–286.

    2. Bocianowski J., Mikołajczyk K., Bartkowiak-Broda I., J Appl Genet. 2012,

    53, 27–30.

  • 2-nd ICPMS Poprad 2018

    46

    3. Lu X., Sun D., Chen Z., Ye J., Wang R., Li L., Zeng S., Jiang H., Pharmazie

    2011, 66, 600–605.

    4. Orsavova J., Misurcova L., Ambrozova J. V., Vicha R., Mlcek J., Int J Mol

    Sci. 2015, 16, 12871–12890.

  • 2-nd ICPMS Poprad 2018

    47

    5HT1A AND MGLUR4 INTERACTION, POSSIBLE LINK TO

    SCHIZOPHRENIA?

    Grzegorz Burnat1, Piotr Brański1, Joanna Solich2,

    Magdalena Kolasa2, Barbara Chruścicka1, Marta Dziedzicka-

    Wasylewska2, Andrzej Pilc1

    1 Department of Neurobiology Institute of Pharmacology PAS, Kraków, Poland 2 Department of Pharmacology Institute of Pharmacology PAS, Kraków, Poland

    In previous reports our group showed the antipsychotic-like actions

    of mGlu4 and 5HT1a receptor activators (Wierońska et al., 2015, 2017).

    In present study we examined the heteromerization of members two

    different classes of G protein coupled receptors (GPCRs). The first one -

    metabotropic glutamate receptor 4 (mGlu4) is a representative of class C.

    Like other members of group III mGlu receptors its activation inhibits

    the activity of adenylate cyclase leading to a decrease of cAMP

    concentration in cells. In the central nervous system (CNS) mGlu4

    receptors are predominantly expressed pre-synaptically. The highest

    expression is observed in the cerebellum as well as in the cerebral cortex

    and in the hippocampus. The second one the 5HT1a receptor belongs to

    class A of GPCRs. Similarly to mGlur4 it is preferentially coupled with

    Gi protein to inhibit cAMP formation. The 5HT1a receptor in most brain

    structures is located post-synapticaly. The highest densities are in the

    hippocampus, amygdala and the cortical limbic areas. Moderate

    expression is observed in the raphe nuclei (pre-synaptic localization as

    an autoreceptor).

    Due to high expression of mGluR4 and 5HT1a in the hippocampus

    and cortex both receptors seem to be promising pharmacological targets

    for treatment of anxiety and schizophrenia.

    To analyze distribution of both receptors in the mouse brain

    a double immunofluorescence labelling with DAPI on cortical sections

    was performed. The occurrence of mGluR4-5HT1a hetero complex was

    studied in the brain regions where co-localization was observed. The

  • 2-nd ICPMS Poprad 2018

    48

    PLA red dots indicates close proximity

  • 2-nd ICPMS Poprad 2018

    49

    THE INFLUENCE OF LUNG CANCER ON THROAT

    COLONIZATION WITH CANDIDA SPP. AND STREPTOCOCCUS

    PNEUMONIAE

    Edyta Chwiejczak1, Urszula Kosikowska1, Katarzyna Kurek2,

    Barbara Mackiewicz2, Anna Malm1

    1 Department of Pharmaceutical Microbiology with Laboratory for

    Microbiological Diagnostics, Medical University of Lublin, Chodźki 1,

    20-093 Lublin, Poland 2 Department of Pneumonology, Oncology and Allergology, Medical University

    of Lublin, Chodźki 1, 20-093 Lublin, Poland

    Microorganisms that inhabit a given region of the body, create its

    microbiota, which protect the host’s organism from the harmful effects

    of external factors.. The composition of microbiota depends on many

    factors, e.g. health condition, diet type, lifestyle and frequency of

    antibiotics administration. However, in a state of weaken immunity

    microorganisms from microbiota may be the cause of opportunistic

    infections. Frequent etiological factors of them include yeasts that can

    cause candidiasis and Streptococcus pneumoniae, one of the most

    common etiologic agents of bacterial pneumonia.

    The aim of the study was to assess the prevalence of yeast and

    S. pneumoniae in the upper respiratory tract microbiota of people with

    lung cancer.

    The study included 13 patients with lung cancer before

    chemotherapy and 13 healthy volunteers (control group). The swabs

    from throat were cultured on agar media for bacteria and fungi. The

    cultures were incubated at 350C. The isolates were identified using mass

    spectrometry MALDI-TOF MS.

    In throat of 6/13 (46%) patients with lung cancer and 3/13 (23%)

    healthy people yeats were found. In the group of cancer patients

    4 species of yeasts were found: Candida albicans (3/6, 50%),

    C. tropicalis (1/6, 16.6%), C. glabrata (1/6, 16.6%), Sacchcaromyces

  • 2-nd ICPMS Poprad 2018

    50

    cerevisiae (1/6, 16.6%), while in the control group 2/3 (67%) patients

    were colonized with C. albicans and 1/3 (33%) with C. glabrata.

    Colonization of the throat with S. penumoniae was found in 6/13 (46%)

    of cancer patients and 3/13 (23%) in the control group.

    The cancer can cause significant disorders in the host immune

    system, reducing its efficiency. It can cause meaningful changes in the

    respiratory microbiota and favor the colonization by opportunistic

    microorganisms that can cause infections dangerous for health and life of

    patient.

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    51

    DRUG – DRUG INTERACTIONS STUDY

    Monika Dąbrowska, Żaneta Binert-Kusztal, Małgorzata Starek,

    Włodzimierz Opoka

    Department of Inorganic and Analytical Chemistry, Jagiellonian University

    Medical College, Faculty of Pharmacy, Medyczna 9, 30-688 Kraków, Poland

    In recent years, the matter of drug – drug interactions has received

    a large thing of attention from the scientific and health care communities

    worldwide. A large amount of drugs are admited every year and new

    interactions amongst medicines are progressively published. Drug – drug

    interactions can modify the drug’s absorption, distribution, metabolism,

    excretion or even real clinical action [1].

    Antibiotics is one of the most widely used group of drugs,

    prescribed from common cold to life threatening septicemia. Broad

    spectrum antibiotics (e.g. second and third cephalosporins generation

    and quinolones, amoxicillin and clavulanic acid) are being widely used

    for various indications, necessarily or otherwise [2].

    The risk of drug interactions is increased with polypharmacy,

    especially that it’s a popular practice among physicians to prescribe

    multiple medicines to a single patient. Beside from infections in

    otherwise units, a large number of patients are suffering from chronic

    diseases (e.g. diabetes, arthritis, hypertension) for which they must take

    long-life cures, so in these people the possibility of drug ˗ drug

    interactions are yet higher [3]. Another warning impact is the emergence

    of strains of bacteria resistant to many generation of antibiotics. This fact

    resulted in injudicious use of many antibiotics in conjugation with other

    drugs, without much heed given to the resultant drug – drug interactions

    [4].

    We designed this work to study drug – drug interactions and their

    potential effects on the stability of tested compunds.

    The TLC-densitometric conditions for the simultaneous

    determination of chosen therapeutic substances: cefuroxime axetil,

    cefepime, paracetamol, acetylsalicylic acid, ibuprofen, naproxen,

  • 2-nd ICPMS Poprad 2018

    52

    ketoprofen, caffeine, propranolol, gestodene, estradiol were developed.

    Selected drugs were used to prepare triple mixtures, most likely to occur

    during the combined therapy. Additionally, the impact of temperature,

    UV-VIS radiation, and the incubation time on the durability of the

    components was tested.

    The results obtained by the developed analytical method allow to

    state that the composition of tested mixture affects the stability of drugs,

    especially in the case of cefuroxime axetil. In addition, it was found that

    the temperature and the incubation time have an impact on the stability

    of analyzed components.

    References

    1. Farkas D., Shader RI., von Moltke LL., Greenblatt DJ. Mechanisms and

    consequences of drug-drug interactions. In: Gad S.C. Preclinical

    Development Handbook: ADME and Biopharmaceutical Properties.

    Philadelphia: Wiley, 2008, 879–917.

    2. Marshall WF., Blair JE., Mayo Clin. Proc. 1999, 74,187–195.

    3. Schmidt L.E. & Dalhoff K., Drugs 2002, 62, 1481–1502.

    4. Thummel K.E. & Wilkinson G.R., Annu. Rev. Pharmacol. Toxicol. 1998,

    38, 389–430.

  • 2-nd ICPMS Poprad 2018

    53

    EICOSAPENTAENOIC ACID SUPPLEMENTATION AFFECTS

    PRO-INFLAMMATORY PROTEIN LEVELS IN CaCo-2 CELLS

    ACTIVATED WITH LPS AND/OR TOXIN A

    Mirosław Dróżdż1, Jacek Czepiel2, Artur Jurczyszyn3, Anna Zając4,

    Katarzyna Sroczyńska4, Tadeusz Librowski4,

    Joanna Gdula-Argasińska4

    1 Saint Ann's Hospital, Miechów, Poland 2 Department of Infectious and Tropical Diseases, Jagiellonian University

    Medical College, Kraków, Poland 3 Department of Hematology, Jagiellonian University Medical College, Kraków,

    Poland 4 Department of Radioligands, Faculty of Pharmacy, Jagiellonian University

    Medical College, Kraków, Poland

    Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid,

    precursor of anti-inflammatory and pro-resolving mediators.

    Supplementation with this fatty acid may have a beneficial effect on

    reducing the risk of a various inflammatory pathologies.

    The purpose of this study was to determine the effect of EPA

    supplementation on cyclooxygenase-2 (COX-2), prostaglandin E2

    (cPEGS), aromatic hydrocarbon (AHR) protein expression and an

    interleukin 6 (IL-6) content in the intestinal epithelial CaCo-2 cells

    activated with lipopolysaccharide (LPS) and/or Toxin A, isolated from

    Clostridium difficile.

    CaCo-2 cells were incubated with 10 μmol and 25 μmol of EPA for

    24h and 48h, followed by LPS/Toxin A activation. Western blot

    technique was used to determine COX-2, cPGES, AHR receptor

    expression and an ELISA technique was used to determine IL-6

    concentration. It has been shown that statistically the highest expression

    of pro-inflammatory proteins in LPS and Toxin A-activated intestinal

    cells.

    In CaCo-2 cells after EPA supplementation and LPS/Toxin A

    activation, the levels of pro-inflammatory proteins have been

  • 2-nd ICPMS Poprad 2018

    54

    significantly reduced, suggesting that this fatty acid exhibits anti-

    inflammatory and pro-resolving activity.

    It seems necessary to carry out further research regarding on the

    action of eicosapentaenoic acid on intestinal epithelial cells.

  • 2-nd ICPMS Poprad 2018

    55

    INVOLVEMENT OF THE HOMER1A PROTEINS IN THE

    MECHANISM OF ACTION OF ANTIDEPRESSANT DRUGS

    Ewelina Frąckiewicz1, Agata Siwek1, Tadeusz Librowski1,

    Andrzej Pilc1,2, Gabriel Nowak1,2

    1 Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University

    Medical College, Medyczna 9, 30-688 Kraków, Poland 2 Polish Academy of Sciences, Institute of Pharmacology, Smętna 12,

    31-343 Kraków, Poland

    Depression is one of the most common mental disorders in the

    world and can be connected with other serious health problems. There

    are many theories that explain their patomechanism and the action of

    current antidepressant drugs. One of the most prevalent theory is linked

    with the dysregulation of the glutamatergic system and with neuronal

    plasticity disorders [2].

    Postsynaptic density (PSD) is a makromolecular complex located

    in the postsynaptic membrane and plays a significant role in signal

    transduction. Homer 1 is one of the most significant proteins that links

    mGluR5 to downstream targets such as inositol triphosphate receptors.

    This protein can also act as a moderator of the NMDA/mGluR5 complex

    involved in stress-induced neuropsychiatric pathologies, along with

    depression [1, 3 4].

    The aim of this research was to explore changes after acute,

    subchronic and chronic administration of antidepressants in the level of

    the Homer 1a protein in rat brain. Protein levels in rat hippocampus and

    prefronal cortex of Homer 1a were measured by the Western blot

    technique.

    The results show an increase of the level of Homer1a protein in

    hippocampus, but not in the prefrontal cortex, after acute antidepressants

    administration (imipramine, reboxetine). Our results indicate that a rapid

    increase in the level of Homer 1a in the hippocampus may be important

    in the mechanism of action of some antidepressants. This study shows

  • 2-nd ICPMS Poprad 2018

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    that further research is needed to study the involved postsynaptic density

    of signal transduction in the cell and the mechanism of action of

    antidepressant drugs.

    References

    1. Luo P., Li X., Fei Z., Poon W., Neurochem Int 2012, 61(5), 731–738.

    2. Nicoletti F., Bruno V., Ngomba R. T., Gradini R., Battaglia G., Curr Opin

    Pharmacol 2015, 20, 89–94.

    3. Tomasetti C., Iasevoli F., Filomena Buonaguro E., De Berardis D., Fornaro

    M., Lucia A., De Bartolomeis A., Int. J. Mol. Sci 2017, 18(1), 135.

    4. Wagner K. V, Hartmann J., Labermaier C., Häusl A. S., Zhao G., Harbich

    D., Schmidt M. V., Neuropsychopharmacology 2015, 40(5), 1222–1233.

  • 2-nd ICPMS Poprad 2018

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    ANALGESIC ACTIVITY OF AMBROXOL AND

    AMITRIPTYLINE IN A MODEL OF OXALIPLATIN-

    INDUCED NEUROPATHIC PAIN IN MICE

    Anna Furgała, Kinga Sałat

    Chair of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University,

    Medical College, Medyczna 9, 30-688 Kraków, Poland

    Providing a long-lasting quality of life to patients after anticancer

    treatment is extremely important, especially considering the increasing

    efficacy of currently applied anti-cancer therapies. Chemotherapy-

    induced peripheral neuropathy (CIPN) remains one of the main adverse

    effects of anti-cancer therapy, manifested by the occurrence of thermal

    and mechanical allodynia and spontaneous pain episodes.

    In vivo tests were performed in adult male Albino Swiss (CD-1)

    mice. To induce neuropathic pain intraperitoneal oxaliplatin at a single

    dose of 10 mg/kg was used. Cold allodynia in response to a thermal

    stimulus of 2.5 C was measured in the cold plate test 3 h and 7 days

    after oxaliplatin administration. Ambroxol was tested at doses of 12.5

    and 37.5 mg/kg, 0.5 h, 4 h, 6 h and 12 h after its intravenous

    administration. Amitriptyline was tested at doses 1, 2.5 and 10 mg/kg

    1 h after its intraperitoneal administration. Ambroxol was also used in

    combination with amitriptyline.

    Administration of oxaliplatin resulted in statistically significant

    decrease of thermal nociceptive threshold in response to low temperature

    (development of thermal allodynia). An antiallodynic activity was shown

    for both drugs - ambroxol at a dose of 37.5 mg/kg, 0.5 h after

    administration, as well as for amitriptyline at doses 2.5 and 10 mg/kg, 1h

    after administration. Also, a statistically significant analgesic activity

    was observed in the cold plate test as a result of co-administration of the

    tested drugs.

    Our study showed that ambroxol and amitriptyline administered in

    combination, or as a single drugs cause a significant pain relief in the

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    oxaliplatin-induced neuropathic pain model in mice. Thus, using these

    drugs may be an interesting option for the treatment of neuropathic pain

    in patients with peripheral neuropathy caused by chemotherapy.

    This study was supported by the National Science Centre grant UMO-

    2015/17/B/NZ7/02937.

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    F13714 AND F15599 - SELECTIVE 5-HT1A BIASED AGONISTS

    AS A NEW PHARMAGOLOGICAL TOOLS IN THE

    DEVELOPMENT OF TREATMENT OF

    NEURODEGENERATIVE AND PSYCHIATRIC DISORDERS

    Monika Głuch-Lutwin1, Joanna Śniecikowska1, Karolina Pytka1,

    Adam Bucki1, Kinga Sałaciak1, Alicja Gawalska1, Mark Varney2,

    Adrian Newman-Tancredi2, Marcin Kołaczkowski1

    1 Jagiellonian University, Medical College, Medyczna 9,

    30-688 Kraków, Poland 2 Neurolixis Inc. 34145 Pacific Coast Highway #504, Dana Point,

    CA 92629 USA

    Robert J. Lefkowitz, said that “biased agonists may represent an

    entirely novel form of therapeutic agent". The functional selectivity of

    drugs at G protein-coupled receptors is the ability to activate specific

    signaling pathways preferentially. In neurodegenerative and psychiatric

    disorders serotonin 5-HT1A receptors are attractive targets. These

    receptor are expressed both as pre-synaptic located on 5-HT cell bodies

    in the raphe nuclei and as post-synaptic in brain areas associated with

    mood, cognition and pain [1]. The compounds, F13714 and F15599, are

    the first brain-region selective biased agonists at 5-HT1A receptors

    (5-HT1A). The F15599 preferentially targets post-synaptic cortical

    serotonin receptor, while F13714 targets pre-synaptic 5-HT1A

    autoreceptors [2]. The brain-region selectivity of these compounds

    corresponds with biochemical mechanisms which may determine their

    unique pharmacological profiles.

    The compounds with high affinity for the serotonin receptor on four

    cell signaling pathways were tested: ERK phosphorylation (pERK),

    adenylyl cyclase (cAMP) inhibition, calcium mobilization and β-arrestin

    recruitment assay. In in vivo studies we used mouse model of

    corticosterone-induced depression. As behavioral endpoint we used

    forced swim test (antidepressant-like activity). We also investigated the

    influence on locomotor activity of mice.

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    Functional assays show F15599 significantly prefers pERK

    signaling pathways and is a partial agonist at Ca2+ mobilization. In

    contrast, F13714 does not discriminate between pERK, cAMP and

    β-arrestin but significantly less potently stimulates Ca2+ mobilization

    (although being a full agonist). It is noticed, serotonin shows no

    discrimination between all four signaling pathways. Studies in vivo show

    none of the compounds affected locomotor activity.

    Both tested compounds activated different cell signaling pathway

    (pERK, Ca2+, cAMP and β-arrestin). F15599 but not F13714 decreased

    the immobility of rodents in mouse model of corticosterone-induced

    depression. Only F15599 showed antidepressnt-like activity after acute

    administration in mouse model of corticosterone-induced depression.

    References

    1. Newman-Tancredi A., Br. J. Pharmacol. 2009, 156, 338–353.

    2. Newman-Tancredi A., Neuropsychiatry 2011, 1, 149–164.

    The research was supported by the Polish National Science Center grant No

    DEC-2015/19/B/NZ7/03543 and Jagiellonian University, Medical College

    (K/DSC/005294).

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    THE EFFECT OF LIPONATE (LA) AND HYDROGEN

    PEROXIDE (H2O2) ON ENZYMATIC ACTIVITY OF

    GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE

    (GAPDH) IN HUMAN MELANOMA CELLS

    Magdalena Górny1, Barbara Ostrowska1, Dorota Kusior1,

    Inga Kwiecień2, Małgorzata Iciek1, Anna Bilska-Wilkosz1, Danuta

    Kowalczyk-Pachel1

    1 Chair of Medical Biochemistry, Jagiellonian University, Medical College,

    Kopernika 7, 31-034 Kraków, Poland 2 Department of Pharmaceutical Botany, Jagiellonian University, Medical

    College, Medyczna 9, 30-688 Kraków, Poland

    Glyceraldehyde-3-phosphate dehydrogenase is a moonlighting

    protein [1, 2]. The catalytic activity of this enzyme is greatly affected by

    the redox modifications of the reactive cysteine residue in its active

    center (Cys-150). Most post-translational modifications of GAPDH lead

    to the inhibition of its enzymatic activity and induction of new activities

    not related to the primary glycolytic function, which in the aspect of

    cancer therapy could have significance [3].

    The aim of the study was to examine the effect of liponate (1,2-

    dithiolane 3-pentanoic acid, LA) and hydrogen peroxide (H2O2) on

    GAPDH enzymatic activity in human melanoma cells (lines WM266.4

    and WM115) and proliferation and survival of these cell lines. LA is

    considered a powerful antioxidant because it can be reduced in

    biological systems to dihydrolipoic acid (6,8-dimercapto-octanoic acid,

    DHLA).

    In the present experiments on WM115 cells, a downward trend in

    GAPDH activity was observed after 48 h incubation with 0.5 mM LA. In

    WM266.4 line cell cultures, the reduction of enzyme activity occurred

    only in the presence of 1 mM LA. In both cell lines, LA-dependent

    inhibition of proliferation was observed. Incubation with 50 μM H2O2 for

    24 h caused a 50% decrease in survival in the case of WM226.4 and

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    WM115 cell lines and in the case of WM 266.4 cells, a decrease in

    enzyme activity by 20% was observed.

    The obtained results show that the Cys-150 present in the catalytic

    center of GAPDH may react with reactive oxygen species (ROS) and

    low molecular weight compounds, such as LA. Under the influence of

    H2O2 disulfide bonds between the catalytically active Cys-150 and