Publications by authors named "Piotr Wroczynski"

51 Publications

Oxidative Stress Markers Differ in Two Placental Dysfunction Pathologies: Pregnancy-Induced Hypertension and Intrauterine Growth Restriction.

Oxid Med Cell Longev 2020 30;2020:1323891. Epub 2020 Jun 30.

Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

Aim: Pregnancy-induced hypertension (PIH) and intrauterine growth restriction (IUGR) are both multisystemic disorders of pregnancy that cause perinatal morbidity and mortality. Recently, researchers focused on the role of oxidative stress (OS) as a pathophysiological mechanism in the development of these pathologies. The aim of this study was to compare OS in placental-related pathologies (PIH and IUGR) and uncomplicated pregnancies. We also investigated which salivary OS markers reflect systemic oxidative status and which only reflect the state of the oral cavity. . A total of 104 pregnant women ( = 104; 27 with PIH, 30 with IUGR, and 47 controls) were evaluated. Malondialdehyde (MDA), total antioxidant capacity (ORAC), aldehyde dehydrogenase (ALDH), and activity of glutathione peroxidase (GPx) and glutathione transferase (GST) in plasma/whole blood and/or saliva were analysed. Dietary nutrient intake was calculated using a Semiquantitative Food Frequency Questionnaire (SFFQ). Oral health was assessed to eliminate patients with bleeding, severe periodontitis, and other dental pathologies.

Results: In the IUGR group, increased concentration of ORAC was observed both in saliva and plasma. Also, lower plasma levels of MDA in IUGR compared to the control group was detected. No sign of oxidative stress was confirmed in the PIH group. The examined groups did not differ regarding diet and markers of inflammation. ORAC in saliva was correlated with its level in plasma. No such correlations for MDA were observed. In the IUGR group, there were no differences in OS markers in plasma, but there was a lower ALDH level in the blood compared to the control group. It confirms OS occurrence in IUGR. In IUGR, a higher activity of salivary ALDH was probably due to worse oral health.

Conclusion: Oxidative stress differs between IUGR and PIH groups: the presence of oxidative stress was confirmed only in the IUGR group. Salivary ORAC can be used to estimate ORAC in plasma. The activity of salivary ALDH reflects the state of the oral cavity.
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http://dx.doi.org/10.1155/2020/1323891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346256PMC
June 2020

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Authors:
Jean Bousquet Josep M Anto Claus Bachert Tari Haahtela Torsten Zuberbier Wienczyslawa Czarlewski Anna Bedbrook Sinthia Bosnic-Anticevich G Walter Canonica Victoria Cardona Elisio Costa Alvaro A Cruz Marina Erhola Wytske J Fokkens Joao A Fonseca Maddalena Illario Juan-Carlos Ivancevich Marek Jutel Ludger Klimek Piotr Kuna Violeta Kvedariene Ltt Le Désirée E Larenas-Linnemann Daniel Laune Olga M Lourenço Erik Melén Joaquim Mullol Marek Niedoszytko Mikaëla Odemyr Yoshitaka Okamoto Nikos G Papadopoulos Vincenzo Patella Oliver Pfaar Nhân Pham-Thi Christine Rolland Boleslaw Samolinski Aziz Sheikh Mikhail Sofiev Charlotte Suppli Ulrik Ana Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Sian Williams Arzu Yorgancioglu Ioana Agache Cezmi A Akdis Rute Almeida Ignacio J Ansotegui Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagaña Eric D Bateman Annabelle Bédard Martin Bedolla-Barajas Sven Becker Kazi S Bennoor Samuel Benveniste Karl C Bergmann Michael Bewick Slawomir Bialek Nils E Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Matteo Bonini Philippe Bonniaud Isabelle Bosse Jacques Bouchard Louis-Philippe Boulet Rodolphe Bourret Koen Boussery Fluvio Braido Vitalis Briedis Andrew Briggs Christopher E Brightling Jan Brozek Guy Brusselle Luisa Brussino Roland Buhl Roland Buonaiuto Moises A Calderon Paulo Camargos Thierry Camuzat Luis Caraballo Ana-Maria Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Niels H Chavannes Ekaterine Chkhartishvili Derek K Chu Cemal Cingi Jaime Correia de Sousa David J Costa Anne-Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejan Dokic Yves Dauvilliers Giulia De Feo Govert De Vries Philippe Devillier Stefania Di Capua Gerard Dray Ruta Dubakiene Stephen R Durham Mark Dykewicz Motohiro Ebisawa Mina Gaga Yehia El-Gamal Enrico Heffler Regina Emuzyte John Farrell Jean-Luc Fauquert Alessandro Fiocchi Antje Fink-Wagner Jean-François Fontaine José M Fuentes Perez Bilun Gemicioğlu Amiran Gamkrelidze Judith Garcia-Aymerich Philippe Gevaert René Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam Yunuen R Huerta Villalobos Marc Humbert Guido Iaccarino Despo Ierodiakonou Tomohisa Iinuma Ewa Jassem Guy Joos Ki-Suck Jung Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Musa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Rostislav Kouznetsov Marek L Kowalski Vicky Kritikos Inger Kull Stefania La Grutta Lisa Leonardini Henrik Ljungberg Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Catarina Lopes-Pereira Claudia C Loureiro Renaud Louis Alpana Mair Bassam Mahboub Michaël Makris Joao Malva Patrick Manning Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Pedro Carreiro-Martins Mika Makela Eve Mathieu-Dupas Marcus Maurer Esteban De Manuel Keenoy Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Yann Micheli Neven Miculinic Florin Mihaltan Branislava Milenkovic Dimitirios I Mitsias Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralph Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leyla Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Björn Nordlund Ettore Novellino Dieudonné Nyembue Robyn O'Hehir Ken Ohta Kimi Okubo Gabrielle L Onorato Valentina Orlando Solange Ouedraogo Julia Palamarchuk Isabella Pali-Schöll Peter Panzner Hae-Sim Park Gianni Passalacqua Jean-Louis Pépin Ema Paulino Ruby Pawankar Jim Phillips Robert Picard Hilary Pinnock Davor Plavec Todor A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Fotis Psarros Benoit Pugin Francesca Puggioni Pablo Quinones-Delgado Filip Raciborski Rojin Rajabian-Söderlund Frederico S Regateiro Sietze Reitsma Daniela Rivero-Yeverino Graham Roberts Nicolas Roche Erendira Rodriguez-Zagal Christine Rolland Regina E Roller-Wirnsberger Nelson Rosario Antonino Romano Menachem Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Joaquin Sastre Glenis K Scadding Sophie Scheire Peter Schmid-Grendelmeier Holger J Schünemann Faradiba Sarquis Serpa Mohamed Shamji Juan-Carlos Sisul Mikhail Sofiev Dirceu Solé David Somekh Talant Sooronbaev Milan Sova François Spertini Otto Spranger Cristiana Stellato Rafael Stelmach Michel Thibaudon Teresa To Mondher Toumi Omar Usmani Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Marilyn Urrutia Pereira Rianne van der Kleij Michiel Van Eerd Olivier Vandenplas Tuula Vasankari Antonio Vaz Carneiro Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Yun Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Osman M Yusuf Heather J Zar Stéphane Zeng Mario E Zernotti Luo Zhang Nan Shan Zhong Mihaela Zidarn

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

Detection of ALDH3B2 in Human Placenta.

Int J Mol Sci 2019 Dec 13;20(24). Epub 2019 Dec 13.

Department of Bioanalysis and Drug Analysis, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland.

Aldehyde dehydrogenase 3B2 () gene contains a premature termination codon, which can be skipped or suppressed resulting in full-length protein expression. Alternatively, the longest putative open reading frame starting with the second in-frame start codon would encode short isoform. No unequivocal evidence of ALDH3B2 expression in healthy human tissues is available. The aim of this study was to confirm its expression in human placenta characterized by the highest mRNA abundance. DNA and mRNA were sequenced. The expression was investigated using western blot. The identity of the protein was confirmed using mass spectrometry (MS). The predicted tertiary and quaternary structures, subcellular localization, and phosphorylation sites were assessed using bioinformatic analyses. All DNA and mRNA isolates contained the premature stop codon. In western blot analyses, bands corresponding to the mass of full-length protein were detected. MS analysis led to the identification of two unique peptides, one of which is encoded by the nucleotide sequence located upstream the second start codon. Bioinformatic analyses suggest cytoplasmic localization and several phosphorylation sites. Despite premature stop codon in DNA and mRNA sequences, full-length ALDH3B2 was found. It can be formed as a result of premature stop codon readthrough, complex phenomenon enabling stop codon circumvention.
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http://dx.doi.org/10.3390/ijms20246292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941052PMC
December 2019

Acute exposure of zebrafish (Danio rerio) larvae to environmental concentrations of selected antidepressants: Bioaccumulation, physiological and histological changes.

Comp Biochem Physiol C Toxicol Pharmacol 2020 Mar 13;229:108670. Epub 2019 Nov 13.

Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, Warsaw PL-02097, Poland.

Antidepressants have been detected in surface waters worldwide at ng-μg/L concentration. These compounds can exert adverse effects on fish even at low levels. But, all previous analyses have concentrated on adult fish. The aim of the study was to assess the effect of environmental concentrations of sertraline, paroxetine, fluoxetine and mianserin, and their mixtures on such unusual endpoints as physiological and histological changes of zebrafish (Danio rerio) larvae. We also determined the bioconcentration of the pharmaceuticals. Fish Embryo Toxicity test was used to analyze the influence on developmental progression. Histological sections were stained with hematoxylin and eosin. Proliferating cells in liver were determined immunohistochemically by detection of Proliferating Cell Nuclear Antigens. The bioconcentration factor was measured by liquid chromatography coupled to mass spectrometry. Pharmaceuticals were used at low, medium and high concentrations in mixtures and at medium concentration as single compound. Exposure to the analyzed pharmaceuticals increased the rate of abnormal embryo and larvae development, accelerated the hatching time and affected the total hatching rate. Three-times lower proliferation of hepatocytes was observed in larvae exposed to paroxetine, mianserin, sertraline and the mixture of the pharmaceuticals at the highest concentrations. The highest bioaccumulation factor (BCF) was obtained for sertraline. The BCF of the analyzed compounds was higher if the organisms were exposed to the mixtures than to single pharmaceuticals. To conclude, the exposure of zebrafish larvae to selected antidepressants and their mixtures may cause disturbances in the organogenesis of fish even at environmental concentrations.
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http://dx.doi.org/10.1016/j.cbpc.2019.108670DOI Listing
March 2020

Cloud Point Extraction in the Determination of Drugs in Biological Matrices.

J Chromatogr Sci 2020 Jan;58(2):151-162

Department of Bioanalysis and Drug Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

Cloud point extraction (CPE) is a simple, safe and environment-friendly technique used in the preparation of various samples. It was primarily developed for the assessment of environmental samples, especially analyzed for metals. Recently, this technique has been used in the extraction and determination of various chemical compounds (e.g., drugs, pesticides and vitamins), in various matrices (e.g., human plasma, human serum, milk and urine). In this review, we show that CPE is a reliable method of extraction and can be used in analytical laboratories in combination with other techniques that can be used in the determination of drugs and other chemicals in the human biological matrix. According to the literature, a combination of different methods provides good recovery and can be used in the simultaneous determination of many drugs in a single analysis. CPE can be optimized by changing its conditions (e.g., type of surfactant used, incubation temperature, pH and the addition of salts). In this review, we present the optimized CPE methods used in the determination of various pharmaceuticals and describe how the conditions affect the performance of extraction. This data might support future designing of the new CPE applications that are simple and more accurate. We compared CPE with other extraction methods and also showed the advantages and disadvantages of various extraction techniques along with a discussion on their environmental impact. According to the publications reviewed, it is obvious that CPE is an easy, safe, rapid and inexpensive method of extraction.
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http://dx.doi.org/10.1093/chromsci/bmz064DOI Listing
January 2020

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases.

Authors:
J Jean Bousquet Holger J Schünemann Alkis Togias Marina Erhola Peter W Hellings Torsten Zuberbier Ioana Agache Ignacio J Ansotegui Josep M Anto Claus Bachert Sven Becker Martin Bedolla-Barajas Michael Bewick Sinthia Bosnic-Anticevich Isabelle Bosse Louis P Boulet Jean Marc Bourrez Guy Brusselle Niels Chavannes Elisio Costa Alvaro A Cruz Wienczyslawa Czarlewski Wytske J Fokkens Joao A Fonseca Mina Gaga Tari Haahtela Maddalena Illario Ludger Klimek Piotr Kuna Violeta Kvedariene L T T Le Desiree Larenas-Linnemann Daniel Laune Olga M Lourenço Enrica Menditto Joaquin Mullol Yashitaka Okamoto Nikos Papadopoulos Nhân Pham-Thi Robert Picard Hilary Pinnock Nicolas Roche Regina E Roller-Wirnsberger Christine Rolland Boleslaw Samolinski Aziz Sheikh Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria-Teresa Ventura Samantha Walker Sian Williams Cezmi A Akdis Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagana Eric Bateman Anna Bedbrook K S Bennoor Samuel Benveniste Karl C Bergmann Slawomir Bialek Nils Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Mateo Bonini Philippe Bonniaud Jacques Bouchard Vitalis Briedis Christofer E Brightling Jan Brozek Roland Buhl Roland Buonaiuto Giorgo W Canonica Victoria Cardona Ana M Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Eka Chkhartishvili Derek K Chu Cemal Cingi Elaine Colgan Jaime Correia de Sousa Anne Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejand Dokic Yves Dauvilliers Antoni Dedeu Giulia De Feo Philippe Devillier Stefania Di Capua Marc Dykewickz Ruta Dubakiene Motohiro Ebisawa Yaya El-Gamal Esben Eller Regina Emuzyte John Farrell Antjie Fink-Wagner Alessandro Fiocchi Jean F Fontaine Bilun Gemicioğlu Peter Schmid-Grendelmeir Amiran Gamkrelidze Judith Garcia-Aymerich Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam John O'B Hourihane Marc Humbert Guido Iaccarino Despo Ierodiakonou Maddalena Illario Juan C Ivancevich Guy Joos Ki-Suck Jung Marek Jutel Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Mussa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Marek L Kowalski Vicky Kritikos Inger Kull Lisa Leonardini Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Claudia C Loureiro Renaud Louis Alpana Mair Gert Marien Bassam Mahboub Joao Malva Patrick Manning Esteban De Manuel Keenoy Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Eve Mathieu-Dupas Poalo M Matricardi Eric Melén Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Neven Miculinic Florin Mihaltan Branislava Milenkovic Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralf Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leila Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Enrico Novellino Dieudonné Nyembue Robin O'Hehir Ken Ohta Kimi Okubo Gabrielle Onorato Solange Ouedraogo Isabella Pali-Schöll Susanna Palkonen Peter Panzner Hae-Sim Park Jean-Louis Pépin Ana-Maria Pereira Oliver Pfaar Ema Paulino Jim Phillips Robert Picard Davor Plavec Ted A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Benoit Pugin Filip Raciborski Rojin Rajabian-Söderlund Sietze Reitsma Xavier Rodo Antonino Romano Nelson Rosario Menahenm Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Juan-Carlos Sisul Dirceu Solé David Somekh Talant Sooronbaev Milan Sova Otto Spranger Cristina Stellato Rafael Stelmach Charlotte Suppli Ulrik Michel Thibaudon Teresa To Ana Todo-Bom Peter V Tomazic Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Rianne van der Kleij Olivier Vandenplas Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Y Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heahter J Zar Stéphane Zeng Mario Zernotti Luo Zhang Nan S Zhong Mihaela Zidarn

Clin Transl Allergy 2019 9;9:44. Epub 2019 Sep 9.

260University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.

Main Body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care.

Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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http://dx.doi.org/10.1186/s13601-019-0279-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734297PMC
September 2019

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Authors:
Sinthia Bosnic-Anticevich Elisio Costa Enrica Menditto Olga Lourenço Ettore Novellino Slawomir Bialek Vitalis Briedis Roland Buonaiuto Henry Chrystyn Biljana Cvetkovski Stefania Di Capua Vicky Kritikos Alpana Mair Valentina Orlando Ema Paulino Johanna Salimäki Rojin Söderlund Rachel Tan Dennis M Williams Piotr Wroczynski Ioana Agache Ignacio J Ansotegui Josep M Anto Anna Bedbrook Claus Bachert Mike Bewick Carsten Bindslev-Jensen Jan L Brozek Giorgio Walter Canonica Victoria Cardona Warner Carr Thomas B Casale Niels H Chavannes Jaime Correia de Sousa Alvaro A Cruz Wienczyslawa Czarlewski Giuseppe De Carlo Pascal Demoly Philippe Devillier Mark S Dykewicz Mina Gaga Yehia El-Gamal João Fonseca Wytske J Fokkens Maria Antonieta Guzmán Tari Haahtela Peter W Hellings Maddalena Illario Juan Carlos Ivancevich Jocelyne Just Igor Kaidashev Musa Khaitov Nikolai Khaltaev Thomas Keil Ludger Klimek Marek L Kowalski Piotr Kuna Violeta Kvedariene Désirée E Larenas-Linnemann Daniel Laune Lan T T Le Karin C Lodrup Carlsen Bassam Mahboub Dieter Maier Joao Malva Patrick J Manning Mário Morais-Almeida Ralph Mösges Joaquim Mullol Lars Münter Ruth Murray Robert Naclerio Leyla Namazova-Baranova Kristof Nekam Tshipukane Dieudonné Nyembue Kimi Okubo Robyn E O'Hehir Ken Ohta Yoshitaka Okamoto Gabrielle L Onorato Susanna Palkonen Petr Panzner Nikolaos G Papadopoulos Hae-Sim Park Ruby Pawankar Oliver Pfaar Jim Phillips Davor Plavec Todor A Popov Paul C Potter Emmanuel P Prokopakis Regina E Roller-Wirnsberger Menachem Rottem Dermot Ryan Bolesław Samolinski Mario Sanchez-Borges Holger J Schunemann Aziz Sheikh Juan Carlos Sisul David Somekh Cristiana Stellato Teresa To Ana Maria Todo-Bom Peter Valentin Tomazic Sanna Toppila-Salmi Antonio Valero Arunas Valiulis Errka Valovirta Maria Teresa Ventura Martin Wagenmann Dana Wallace Susan Waserman Magnus Wickman Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heather J Zar Mario E Zernotti Luo Zhang Mihaela Zidarn Torsten Zuberbier Jean Bousquet

Allergy 2019 07 30;74(7):1219-1236. Epub 2019 Apr 30.

MACVIA-France, Fondation Partenariale FMC VIA-LR, Montpellier, France.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.
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http://dx.doi.org/10.1111/all.13701DOI Listing
July 2019

Oxidative stress markers in saliva and plasma differ between diet-controlled and insulin-controlled gestational diabetes mellitus.

Diabetes Res Clin Pract 2019 Feb 6;148:72-80. Epub 2018 Dec 6.

Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

Objectives: The aims of the study were as follows: to investigate possible differences between plasma oxidative status (OS) in late-onset GDM and well-characterized healthy pregnant women (oral health, diet); to verify the existence of possible differences between GDMG1 (diet-treated) and GDMG2 (insulin-treated GDM); to determine whether oxidative stress markers could be detected in saliva.

Material And Methods: A total of 89 pregnant women (n = 89; 59 with GDM and 30 controls) were evaluated. Malondialdehyde (MDA), total antioxidant capacity (ORAC), inactivation of aldehyde dehydrogenase (I), activity of glutathione peroxidase (GPx) and glutathione transferase (GST)) in plasma and/or saliva were analyzed.

Results: The activity of GPx and GST in plasma was higher in GDMG2 as compared to GDMG1 and controls. Also, in GDMG2, elevated concentrations of salivary MDA and higher I were observed. In contrast, GDMG1 had higher plasma ORAC and lower GPx activity as compared to controls, probably due to low-energy diet, high in antioxidants and fibers. Salivary and plasma OS were correlated and most significant for ORAC.

Conclusion: Oxidative stress were not observed in GDMG1 but were confirmed to be moderate in GDMG2. However, large variability of the analyzed markers in GDM groups encourages screening of all patients, regardless of the treatment option. Saliva may be considered useful for the estimation of oxidative stress levels in GDM populations.
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http://dx.doi.org/10.1016/j.diabres.2018.11.021DOI Listing
February 2019

Effects of Selol 5% supplementation on tissue antioxidant enzyme levels and peroxidation marker in healthy mice.

Pharmacol Rep 2018 Dec 18;70(6):1073-1078. Epub 2018 Jun 18.

Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, Warszawa, Poland.

Background: Selenium (Se) is an essential micronutrient for animals and humans used in the prevention or treatment of cancer. Selol is a mixture of selenitetriglycerides, containing Se(IV). It does not exhibit mutagenic activity and is less toxic than inorganic sodium selenite containing Se(IV). The antioxidant properties of the Selol were demonstrated using the blood of healthy animals. The aim of the study was to evaluate Selol as a Se supplement by determining the effect of its administration on the Se level and the antioxidant status in the tissues.

Methods: We examined the effect of long-term (28-day) Selol 5% supplementation on the activity of antioxidant enzymes, including the main selenoenzymes in healthy mice organs, such as liver, brain, lungs, and testis. Enzyme activities of the tissue homogenates and the concentration of malondialdehyde (MDA) as a biomarker of oxidative stress were measured using spectrophotometric methods. The selenium concentrations in the tissues were determined by inductively coupled plasma mass spectrometer (ICP-MS) as well.

Results: A significant increase in glutathione peroxidase, thioredoxin reductase, and glutathione S-transferase activity as well as the MDA concentration was observed in most of the studied tissues during the Selol 5% supplementation.

Conclusions: Long-term supplementation with the new Se(IV) compound - Selol 5% significantly affects the activity of antioxidant enzymes and the redox state in healthy mice organs. In the healthy population Selol 5% seems to be a promising new antioxidant compound.
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http://dx.doi.org/10.1016/j.pharep.2018.06.003DOI Listing
December 2018

The utility of saliva testing in the estimation of uremic toxin levels in serum.

Clin Chem Lab Med 2018 12;57(2):230-237

Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Warsaw, Poland.

Background p-Cresol sulfate (pCS) and indoxyl sulfate (IS) are uremic toxins, high concentrations of which are related to renal failure progression. Saliva could become the first-line diagnostic sample of choice, especially for monitoring purposes. Recently, a method for determination of pCS and IS in saliva was developed. Since no data exist on correlations between the levels of toxins in saliva and serum, the applicability of saliva as a diagnostic material is yet to be established. Here, we present a study on the assessment of the utility of saliva testing in the estimation of uremic toxin levels in serum. Methods The study material included serum and unstimulated, fasting saliva obtained from healthy volunteers (n=26) and patients at all stages of chronic kidney diseases (CKD, n=93). The concentration of pCS and IS in saliva and serum (total and unbound fractions) was determined. The daytime variation of the toxins was studied. Results A correlation was found between pCS and IS in saliva and biological active fractions in serum (0.74; 0.81). The variation of the serum/saliva ratio during the day was negligible, with a median of 10% for pCS and 6% for IS, making saliva a reliable material for the estimation of the uremic toxins in circulation at any time of the day. Significant correlations were observed between salivary toxin levels and estimated glomerular filtration rate (pCS: -0.61; IS: -0.70) as well as significant differences in toxin levels between the stages of CKD. Conclusions Saliva could be a valuable diagnostic material for the estimation of toxin levels in circulation.
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http://dx.doi.org/10.1515/cclm-2018-0087DOI Listing
December 2018

Albumin Apheresis for Artificial Liver Support: In Vitro Testing of a Novel Filter.

Ther Apher Dial 2018 Aug 16;22(4):399-409. Epub 2018 May 16.

Department of Surgical and Transplantation Nursing and Extracorporeal Therapies, Medical University of Warsaw, Warsaw, Poland.

Currently there is no direct therapy for liver failure. We have previously described selective plasma exchange therapy using a hemofilter permeable to substances that have a molecular mass of up to 100 kDa. The proof-of-concept studies and a Phase I study in patients with decompensated cirrhosis demonstrated that hemofiltration using an albumin-leaking membrane is safe and effective in removing target molecules, alleviating severe encephalopathy and improving blood chemistry. In this study a novel large-pore filter for similar clinical application is described. The performance of the filter was studied in vitro; it was found to effectively remove a wide spectrum of pathogenic factors implicated in the pathophysiology of hepatic failure, including protein bound toxins and defective forms of circulating albumin. Data on mass transport characteristics and functionality using various modes of filtration and dialysis provide rationale for clinical evaluation of the filter for artificial liver support using albumin apheresis.
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http://dx.doi.org/10.1111/1744-9987.12665DOI Listing
August 2018

Occurrence of antimicrobial agents, drug-resistant bacteria, and genes in the sewage-impacted Vistula River (Poland).

Environ Sci Pollut Res Int 2018 Feb 12;25(6):5788-5807. Epub 2017 Dec 12.

Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02097, Warsaw, Poland.

Antimicrobial agents (antimicrobials) are a group of therapeutic and hygienic agents that either kill microorganisms or inhibit their growth. Their occurrence in surface water may reveal harmful effects on aquatic biota and challenge microbial populations. Recently, there is a growing concern over the contamination of surface water with both antimicrobial agents and multidrug-resistant bacteria. The aim of the study was the determination of the presence of selected antimicrobials at specific locations of the Vistula River (Poland), as well as in tap water samples originating from the Warsaw region. Analysis was performed using the liquid chromatography-electrospray ionization-tandem mass spectrometry method. In addition, the occurrence of drug-resistant bacteria and resistance genes was determined using standard procedures. This 2-year study is the first investigation of the simultaneous presence of antimicrobial agents, drug-resistant bacteria, and genes in Polish surface water. In Poland, relatively high concentrations of macrolides are observed in both surface and tap water. Simultaneous to the high macrolide levels in the environment, the presence of the erm B gene, coding the resistance to macrolides, lincosamides, and streptogramin, was detected in almost all sampling sites. Another ubiquitous gene was int1, an element of the 5'-conserved segment of class 1 integrons that encode site-specific integrase. Also, resistant isolates of Enterococcus faecium and Enterococcus faecalis and Gram-negative bacteria were recovered. Multidrug-resistant bacteria isolates of Gram-negative and Enterococcus were also detected. The results show that wastewater treatment plants (WWTP) are the main source of most antimicrobials, resistant bacteria, and genes in the aquatic environment, probably due to partial purification during wastewater treatment processes.
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http://dx.doi.org/10.1007/s11356-017-0861-xDOI Listing
February 2018

Analysis of fire deaths in Poland and influence of smoke toxicity.

Forensic Sci Int 2017 Aug 9;277:77-87. Epub 2017 Jun 9.

Centre for Fire Hazards and Science, School of Physical Sciences and Computing, University of Central Lancashire, Preston PR1 2HE, UK. Electronic address:

Dwelling fires have changed over the years because building contents and the materials used in then have changed. They all contribute to an ever-growing diversity of chemical species found in fires, many of them highly toxic. These arise largely from the changing nature of materials in interior finishes and furniture, with an increasing content of synthetic materials containing higher levels of nitrogen, halogen and phosphorus additives. While there is still a belief that carbon monoxide is the major lethal toxic agent in fires, the hydrogen cyanide and acid gases released from these additives are now well-recognised as major contributory causes of incapacitation, morbidity and mortality in domestic fires. Data for the total number of 263 fire death cases in the Mazowieckie region (mainly Warsaw area) of Poland between 2003-2011 for dwellings fires were obtained from pathologists, forensic toxicologists, fire fighters and analysed. Factors contributing to the death such as the findings of the full post mortem examination (age, sex, health status, burns), the toxicological analysis (carbon monoxide, alcohol etc.), and a thorough investigation of the scene (fire conditions, fuel, etc.) were taken into account and are summarised.
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http://dx.doi.org/10.1016/j.forsciint.2017.05.018DOI Listing
August 2017

Selol, an organic selenium donor, prevents lipopolysaccharide-induced oxidative stress and inflammatory reaction in the rat brain.

Neurochem Int 2017 Sep 24;108:66-77. Epub 2017 Feb 24.

Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland. Electronic address:

Neuroinflammation and oxidative stress are key intertwined pathological factors in many neurological, particularly neurodegenerative diseases, such as Alzheimer's and Parkinson's disorders as well as autism. The present study was conducted to evaluate the protective effects of Selol, an organic selenium donor, against lipopolysaccharide (LPS)-mediated inflammation in rat brain. The results demonstrated that the peripheral administration of LPS in a dose of 100 μg/kg b.w. evoked typical pathological reaction known as systemic inflammatory response. Moreover, we observed elevated blood levels of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, as well as increased concentration of tumor necrosis factor-α (TNF-α) in LPS-treated animals. Selol significantly prevented these LPS-evoked changes. Subsequently, Selol protected against LPS-induced up-regulation of proinflammatory cytokines (Tnfa, Ifng, Il6) in rat brain cortex. The molecular mechanisms through which Selol prevented the neuroinflammation were associated with the inhibition of oxidized glutathione (GSSG) accumulation and with an increase of glutathione-associated enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR) as well as thioredoxin reductase (TrxR) activity and expression. Finally, we observed that Selol administration effectively protected against LPS-induced changes in the expression of brain-derived neurotrophic factor (Bdnf). In conclusion, our studies indicated that Selol effectively protects against LPS-induced neuroinflammation by inhibiting pro-inflammatory cytokine release, by boosting antioxidant systems, and by augmenting BDNF level. Therefore, Selol could be a multi-potent and effective drug useful in the treatment and prevention of brain disorders associated with neuroinflammation.
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http://dx.doi.org/10.1016/j.neuint.2017.02.014DOI Listing
September 2017

Antazoline-insights into drug-induced electrocardiographic and hemodynamic effects: Results of the ELEPHANT II substudy.

Ann Noninvasive Electrocardiol 2017 Sep 25;22(5). Epub 2017 Feb 25.

Department of Cardiology, Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.

Background: Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters.

Methods: Antazoline was given intravenously in three 100 mg boluses to 10 healthy volunteers (four males, mean age 40 + 11 years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]. Plasma concentration of antazoline was also measured.

Results: Antazoline caused significant prolongation of P wave, QRS as well as QT and QTcF (101 ± 10 vs 110 ± 16 ms, p < .05, and 101 ± 12 vs 107 ± 12 ms, p < .05, 399 ± 27 vs 444 ± 23 ms, p < .05, and 403 ± 21 vs 448 ± 27 ms, p < .05, respectively). Also, a significant decrease in SV was noted (94.9 ± 21.8 vs 82.4 ± 19.6 ml, p < .05). A significant correlation between changes in plasma drug concentration and changes in CO, HR, and dBP was found.

Conclusions: Antazoline impairs slightly hemodynamics, significantly reducing SV. Significant prolongation of P wave and QRS duration corresponds to drug-induced prolongation of conduction, whereas QT prolongation represents drug-induced prolongation of repolarization.
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http://dx.doi.org/10.1111/anec.12441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931461PMC
September 2017

Application of 2-Aminothiazoline-4-carboxylic Acid as a Forensic Marker of Cyanide Exposure.

Chem Res Toxicol 2017 02 7;30(2):516-523. Epub 2017 Feb 7.

Bioanalysis and Drugs Analysis Department, Faculty of Pharmacy, Medical University of Warsaw , 1 Banacha Street, 02-097 Warsaw, Poland.

Cyanides are infamous for their highly poisonous properties. Accidental cyanide poisoning occurs frequently, but occasionally, intentional poisonings also occur. Inhalation of fumes generated by fire may also cause cyanide poisoning. There are many limitations in direct analysis of cyanide. 2-Aminothiazoline-4-carboxylic acid (ATCA), a cyanide metabolite, seems to be the only surrogate that is being used in the detection of cyanide because of its stability and its cyanide-dependent quality in a biological matrix. Unfortunately, toxicokinetic studies on diverse animal models suggest significant interspecies differences; therefore, the attempt to extrapolate animal models to human models may be unsuccessful. The aim of the present study was to evaluate the use of ATCA as a forensic marker of cyanide exposure. For this purpose, post-mortem materials (blood and organs) from fire victims (n = 32) and cyanide-poisoned persons (n = 3) were collected. The distribution of ATCA in organs and its thermal stability were evaluated. The variability of cyanides in a putrid sample and in the context of their long-term and higher temperature stability was established. The presence of ATCA was detected by using an LC-MS/MS method and that of cyanide was detected spectrofluorimetrically. This is the first report on the endogenous ATCA concentrations and the determination of ATCA distribution in tissues of fire victims and cyanide-poisoned persons. It was found that blood and heart had the highest ATCA concentrations. ATCA was observed to be thermally stable even at 90 °C. Even though the cyanide concentration was not elevated in putrid samples, it was unstable during long-term storage and at higher temperature, as expected. The relationship between ATCA and cyanides was also observed. Higher ATCA concentrations were related to increased levels of cyanide in blood and organs (less prominent). ATCA seems to be a reliable forensic marker of exposure to lethal doses of cyanide.
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http://dx.doi.org/10.1021/acs.chemrestox.6b00219DOI Listing
February 2017

Occurrence of cardiovascular drugs in the sewage-impacted Vistula River and in tap water in the Warsaw region (Poland).

Environ Sci Pollut Res Int 2016 Dec 21;23(23):24337-24349. Epub 2016 Sep 21.

Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, PL-02097, Warsaw, Poland.

In recent years, cardiovascular diseases were the second most common cause of death worldwide. Therefore, the consumption of drugs used to treat cardiovascular diseases is high. So far, there were no such comprehensive reports regarding the presence of cardiovascular drugs in surface and tap waters, particularly in Central and Eastern Europe. The aim of our study was to determine the presence of 30 pharmaceutically active compounds and some of their metabolites, at specific points of the Vistula River and in tap water samples in the Warsaw region. The analysis was performed using the liquid chromatography-electrospray ionization-tandem mass spectrometry method, coupled to solid-phase extraction. To the best of the authors' knowledge, this is the first time where the presence of ciprofibrate in the environment was investigated. Cardiovascular drugs found at the highest concentrations (reaching 1 μg/L or higher) in surface water were beta-blockers, sartans and diuretics. In tap water samples, trace amounts of pharmaceuticals were detected, for almost all target compounds. This highlights their inadequate elimination by the treatment facility used in the Warsaw region. The presence of cardiovascular compounds in the aquatic environment could have a long-term effect even at a low exposure level, since synergy effects amongst pharmaceuticals may occur.
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http://dx.doi.org/10.1007/s11356-016-7668-zDOI Listing
December 2016

Protective Effects of Selol Against Sodium Nitroprusside-Induced Cell Death and Oxidative Stress in PC12 Cells.

Neurochem Res 2016 Dec 2;41(12):3215-3226. Epub 2016 Sep 2.

Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland.

Selol is an organic selenitetriglyceride formulation containing selenium at +4 oxidation level that can be effectively incorporated into catalytic sites of of Se-dependent antioxidants. In the present study, the potential antioxidative and cytoprotective effects of Selol against sodium nitroprusside (SNP)-evoked oxidative/nitrosative stress were investigated in PC12 cells and the underlying mechanisms analyzed. Spectrophoto- and spectrofluorimetic methods as well as fluorescence microscopy were used in this study; mRNA expression was quantified by real-time PCR. Selol dose-dependently improved the survival and decreased the percentage of apoptosis in PC12 cells exposed to SNP. To determine the mechanism of this protective action, the effect of Selol on free radical generation and on antioxidative potential was evaluated. Selol offered significant protection against the elevation of reactive oxidative species (ROS) evoked by SNP. Moreover, this compound restored glutathione homeostasis by ameliorating the SNP-evoked disturbance of GSH/GSSG ratio. The protective effect exerted by Selol was associated with the prevention of SNP-mediated down-regulation of antioxidative enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR), and thioredoxin reductase (TrxR). Finally, GPx inhibition significantly abolished the cytoprotective effect of Selol. In conclusion, these results suggest that Selol effectively protected PC12 cells against SNP-induced oxidative damage and death by adjusting free radical levels and antioxidant system, and suppressing apoptosis. Selol could be successfully used in the treatments of diseases that involve oxidative stress and resulting apoptosis.
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http://dx.doi.org/10.1007/s11064-016-2046-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116319PMC
December 2016

A Search for the Optimum Selenium Source to Obtain Mushroom-Derived Chemopreventive Preparations.

Int J Med Mushrooms 2016 ;18(4):279-89

Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, Warsaw, Poland.

The objective of this research was to test whether selenium-yeast (Se-yeast) is a better source of selenium than sodium selenite for accumulation in mycelia and immunoactive cell wall polysaccharides. Culture media were enriched in selenium to a concentration of 20 µg/mL. Selenium was added to the medium either in the form of sodium selenite or in form of Se-yeast (Sel-Plex; Alltech Inc., Lexington, KY). The total selenium concentrations in the mycelium biomass and in the isolated crude polysaccharides were determined using atomic absorption spectroscopy. We found that selenium accumulated more efficiently in cultures enriched with Se-yeast. A higher concentration of selenium was also found in the crude polysaccharide fractions isolated from the mycelium grown in Se-yeast-enriched media. With the use of the needle trap gas chromatography-mass spectrometry method, we found that there are significant differences in the composition of the volatile aroma and flavor compounds secreted by the mycelia cultivated in different media.
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http://dx.doi.org/10.1615/IntJMedMushrooms.v18.i4.10DOI Listing
April 2017

Cloud-point extraction is compatible with liquid chromatography coupled to electrospray ionization mass spectrometry for the determination of antazoline in human plasma.

J Pharm Biomed Anal 2016 Sep 24;128:294-301. Epub 2016 May 24.

Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

Cloud-point extraction (CPE) is attracting increasing interest in a number of analytical fields, including bioanalysis, as it provides a simple, safe and environmentally-friendly sample preparation technique. However, there are only few reports on the application of this extraction technique in liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this study, CPE was used for the isolation of antazoline from human plasma. To date, only one method of antazoline isolation from plasma exists-liquid-liquid extraction (LLE). The aim of this study was to prove the compatibility of CPE and LC-ESI-MS/MS and the applicability of CPE to the determination of antazoline in spiked human plasma and clinical samples. Antazoline was isolated from human plasma using Triton X-114 as a surfactant. Xylometazoline was used as an internal standard. NaOH concentration, temperature and Triton X-114 concentration were optimized. The absolute matrix effect was carefully investigated. All validation experiments met international acceptance criteria and no significant relative matrix effect was observed. The compatibility of CPE and LC-ESI-MS/MS was confirmed using clinical plasma samples. The determination of antazoline concentration in human plasma in the range 10-2500ngmL(-1) by the CPE method led to results which are equivalent to those obtained by the widely used liquid-liquid extraction method.
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http://dx.doi.org/10.1016/j.jpba.2016.05.042DOI Listing
September 2016

Age-dependent increase in serum levels of indoxyl sulphate and p-cresol sulphate is not related to their precursors: Tryptophan and tyrosine.

Geriatr Gerontol Int 2017 Jun 31;17(6):1022-1026. Epub 2016 May 31.

Department of Immunology, Transplantology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.

Aim: Retention of indoxyl sulphate and p-cresol sulphate is associated with many diseases. The aim of the present study was to examine serum levels of indoxyl sulphate and p-cresol sulphate, the dynamics of their changes according to age, and their precursors.

Methods: The study included 180 healthy individuals aged 20-90 years (n = 180), divided into subgroups by decade (n = 30 in each subgroup) and into subgroups of ≥65 years (n = 42) or <65 years (n = 138). Serum indoxyl sulphate and p-cresol sulphate, tryptophan, and tyrosine were measured using high-performance liquid chromatography-mass spectrometry.

Results: The 70-90 years age group had higher indoxyl sulphate than the 50-59 years age group (P = 0.033). The 70-90 years age group had higher p-cresol sulphate than the 20-29 years (P < 0.001), 30-39 years (P < 0.001), 40-49 years (P = 0.007) and 50-59 years (P = 0.001) age groups; the 60-69 years age group had higher p-cresol sulphate than the 20-29 years (P = 0.043) and 30-39 years (P = 0.011) age groups. Indoxyl sulphate and p-cresol sulphate serum levels were higher in those aged ≥65 years. Indoxyl sulphate and p-cresol sulphate serum levels correlated positively with age, but not with tryptophan and tyrosine, respectively.

Conclusions: Healthy aging is associated with indoxyl sulphate and p-cresol sulphate serum level increases, which are not linked to tryptophan and tyrosine serum levels. Geriatr Gerontol Int 2017; 17: 1022-1026.
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http://dx.doi.org/10.1111/ggi.12811DOI Listing
June 2017

Application of a novel liquid chromatography/tandem mass spectrometry method for the determination of antazoline in human plasma: Result of ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study.

J Pharm Biomed Anal 2016 May 1;123:113-9. Epub 2016 Feb 1.

Bioanalysis and Drugs Analysis Department, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

Antazoline is a first-generation antihistaminic agent with antiarrhythmic quinidine-like properties. In some countries, it is widely used for termination of cardiac arrhythmias, especially atrial fibrillation (AF). However, no human pharmacokinetic studies have been conducted with intravenous antazoline. The aim of our study was to develop and validate a novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of antazoline in human plasma: the ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study. Antazoline was extracted from plasma using liquid-liquid extraction. The concentration of the analyte was measured by LC-MS/MS with xylometazoline as an internal standard. The method was validated for linearity, precision, accuracy, stability (freeze/thaw stability, stability in autosampler, short and long term stability), dilution integrity and matrix effect. The analyzed validation criteria were fulfilled. The method was applied to a pharmacokinetic study involving 10 healthy volunteers. Following a single intravenous dose of antazoline mesylate (100 mg), the plasma concentration profile showed a relative fast elimination with a terminal elimination half-life of 2.29 h. A relatively high volume of distribution was observed (Vss=315 L). The values of mean residence time (MRT∞), area under the curve (AUC∞) and clearance were 3.45 h, 0.91 mg h L(-1) and 80.5 L h(-1), respectively. One volunteer showed significant differences in pharmacokinetic parameters. In conclusion, the proposed new LC-MS/MS method was successfully used for the first time for the determination of antazoline in human plasma.
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http://dx.doi.org/10.1016/j.jpba.2016.01.060DOI Listing
May 2016

Development and validation of a LC-MS/MS method for quantitative analysis of uraemic toxins p-cresol sulphate and indoxyl sulphate in saliva.

Talanta 2016 Apr 30;150:593-8. Epub 2015 Dec 30.

Bioanalysis and Drugs Analysis Department, Pharmacy Faculty, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

p-Cresol sulphate (pCS) and indoxyl sulphate (IS) are uraemic toxins, the concentration of which in serum correlate with the stage of renal failure. The aim of this study was to develop and validate a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of pCS and IS in saliva. This is the first time, to our knowledge, that such a method has been developed using saliva. Unstimulated, fasting saliva was collected from healthy volunteers in the morning and pooled for validation assay. The method was validated for linearity, precision, accuracy, stability (freeze/thaw stability, stability in autosampler, short- and long-term stability, stock solution stability), dilution integrity and matrix effect. The analysed validation criteria were fulfilled. No influence of salivary flow (pCS: p=0.678; IS: p=0.238) nor type of swab in the Salivette device was detected. Finally, using the novel validated method, the saliva samples of healthy people (n=70) of various ages were analysed. We observed a tendency for an increase of concentration of toxins in saliva in the elderly. This could be a result of age-related diseases, e.g., diabetes and kidney function decline. We can conclude that the novel LC-MS/MS method can be used for the determination of pCS and IS in human saliva. The results encourage the validation of saliva as a clinical sample for monitoring toxin levels in organisms.
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http://dx.doi.org/10.1016/j.talanta.2015.12.075DOI Listing
April 2016

LC-MS/MS method development and validation for quantitative analyses of 2-aminothiazoline-4-carboxylic acid--a new cyanide exposure marker in post mortem blood.

Talanta 2016 Apr 30;150:586-92. Epub 2015 Dec 30.

Bioanalysis and Drugs Analysis Department, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

2-aminothiazoline-4-carboxylic acid (ATCA) is a hydrogen cyanide metabolite that has been found to be a reliable biomarker of cyanide poisoning, because of its long-term stability in biological material. There are several methods of ATCA determination; however, they are restricted to extraction on mixed mode cation exchange sorbents. To date, there has been no reliable method of ATCA determination in whole blood, the most frequently used material in forensic analysis. This novel method for ATCA determination in post mortem specimen includes protein precipitation, and derivatization of interfering compounds and their later extraction with ethyl acetate. ATCA was quantitatively analyzed via high performance liquid chromatography-tandem mass spectrometry with positive electrospray ionization detection using a hydrophilic interaction liquid chromatography column. The method satisfied all validation criteria and was tested on the real samples with satisfactory results. Therefore, this analytical approach has been proven to be a tool for measuring endogenous levels of ATCA in post mortem specimens. To conclude, a novel, accurate and sensitive method of ATCA determination in post mortem blood was developed. The establishment of the method provides new possibilities in the field of forensic science.
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http://dx.doi.org/10.1016/j.talanta.2015.12.076DOI Listing
April 2016

THE MEASUREMENT OF ANTIOXIDANT CAPACITY AND POLYPHENOL CONTENT IN SELECTED FOOD SUPPLEMENTS.

Acta Pol Pharm 2015 Sep-Oct;72(5):877-87

Oxidative stress (OS), defined as a disturbance in the balance between the production of reactive oxygen species (ROS) and antioxidant defenses, can result in the development of many serious diseases like diabetes or cancer. Moreover, the role of oxidative stress in the acceleration of the aging process is also confirmed. ROS are constantly produced in the natural biochemical processes, mainly during cellular respiration. Their enhanced production may be the result of e.g., an inappropriate diet high in saturated fats, low in fiber, fruits and vegetables, insufficient physical activity or smoking. To prevent oxidative stress, besides changes in life style, the additional supplementation of antioxidants is proposed. On the Polish market, the number of food supplements with declared antioxidant activity is still increasing. However, their antioxidant properties are rarely confirmed experimentally. The aim of our study was to determine the antioxidant potential of selected dietary supplements available on the market and recommended in chronic fatigue syndrome. The antioxidant potential was measured using four methods: FRAP, ORAC, HORAC, EPR/DPPH. Moreover, the content of polyphenols in the dietary supplements was also determined.
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January 2016

Cloud-point extraction is compatible with liquid chromatography coupled to electrospray ionization mass spectrometry for the determination of bisoprolol in human plasma.

J Chromatogr A 2015 Dec 29;1423:39-46. Epub 2015 Oct 29.

Bioanalysis and Drugs Analysis Department, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

Cloud-point extraction (CPE) draws increasing interest in a number of analytical fields including bioanalysis, but combining CPE and LC-MS with electrospray ionization (ESI) in the determination of drugs in biological fluids such as plasma, serum or blood has not been reported so far. Bisoprolol was determined in human plasma by CPE using Trition X-114 as a surfactant and metoprolol as the internal standard. NaOH concentration, temperature and Trition X-114 concentration were optimized. All analyses were performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). All validation experiments met international acceptance criteria and no significant matrix effect was observed. The compatibility of CPE and LC-ESI-MS/MS was confirmed using clinical plasma samples and appropriate statistical tests. The determination of bisoprolol concentration in human plasma in the range 1.0-70ngmL(-1) by the CPE method leads to the results which are equivalent to those obtained by the widely used liquid-liquid extraction method. The results revealed that a structural analogue may be an appropriate internal standard when CPE is used as the extraction technique. CPE offers significant practical advantages over the classical extraction methods, including a positive impact on the environment, therefore its wider application in future pharmacokinetic studies is justifiable.
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http://dx.doi.org/10.1016/j.chroma.2015.10.076DOI Listing
December 2015

Selenium in the Therapy of Neurological Diseases. Where is it Going?

Curr Neuropharmacol 2016 ;14(3):282-99

Department of Cellular Signaling, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland.

Selenium (34Se), an antioxidant trace element, is an important regulator of brain function. These beneficial properties that Se possesses are attributed to its ability to be incorporated into selenoproteins as an amino acid. Several selenoproteins are expressed in the brain, in which some of them, e.g. glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) or selenoprotein P (SelP), are strongly involved in antioxidant defence and in maintaining intercellular reducing conditions. Since increased oxidative stress has been implicated in neurological disorders, including Parkinson's disease, Alzheimer's disease, stroke, epilepsy and others, a growing body of evidence suggests that Se depletion followed by decreased activity of Se-dependent enzymes may be important factors connected with those pathologies. Undoubtedly, the remarkable progress that has been made in understanding the biological function of Se in the brain has opened up new potential possibilities for the treatment of neurological diseases by using Se as a potential drug. However, further research in the search for optimal Se donors is necessary in order to achieve an effective and safe therapeutic income.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857624PMC
http://dx.doi.org/10.2174/1570159x14666151223100011DOI Listing
December 2016

Activity of Cathepsin B in Serum of Patients after Kidney Transplantation Depends on Glucocorticosteroids Treatment.

Ann Transplant 2015 Oct 15;20:622-6. Epub 2015 Oct 15.

Department of Immunology, Transplantology and Internal Diseases, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland.

Background: Kidney diseases are characterized by deterioration of the function of this organ, often leading to irreversible failure, where transplantation is the only alternative to permanent dialysis. Proteolytic enzymes, including cathepsins B, cleave the peptide bond by hydrolysis reaction. They are also involved in pathological processes such as carcinogenesis and inflammatory processes. The aim of this study was to determine the activity of cathepsin B in the serum of patients after kidney transplantation and to assess the correlation with glucocorticosteroids treatment.

Material And Methods: In the study, blood samples of 100 renal transplant recipients were used. The subjects were divided into groups according to the time elapsed since transplantation and the use of steroids in the current and primary treatment. Enzyme activity was measured by spectrofluorometric technique.

Results: The study showed significant correlations of cathepsin B with the time since renal transplantation (p<0.05) and steroid used in the primary and current treatment. Steroid treatment is associated with a decrease of the activity of cathepsin B in serum.

Conclusions: The obtained results show decreasing activity of cathepsin B with longer time elapsed since transplantation. We have shown that steroids decrease activity of cathepsin B after renal transplantation. A significant increase in cathepsin B activity is observed mainly in cancer and atherosclerosis. Decreased activity of cathepsin B is probably due to the stabilizing action of steroids on the lysosomal membrane. The impact of steroid therapy for patients with these diseases appears to be significant.
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http://dx.doi.org/10.12659/aot.893811DOI Listing
October 2015

A highly selective molecularly imprinted sorbent for extraction of 2-aminothiazoline-4-carboxylic acid--Synthesis, characterization and application in post-mortem whole blood analysis.

J Chromatogr A 2015 Nov 1;1420:16-25. Epub 2015 Oct 1.

Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.

In this paper, the optimized synthesis and detailed characterization of novel imprinted material for selective extraction of 2-aminothiazoline-4-carboxylic acid (ATCA) were described. The prepolymeric system contained 1-allyl-2-thiourea and ethylene glycol dimethacrylate in methanol, tetrahydrofuran and dimethyl sulfoxide porogenic mixture and 2-aminothiazole-4-carboxylic acid which was used as the template for ATCA. This structural analog of the target analyte was found to provide the imprinted polymer with sufficient binding capacity (60.7 ± 0.9 μg g(-1)) and high selectivity (imprinting factor equal to 18.4) toward ATCA. The adsorption of ATCA was analyzed by the Langmuir model. The heterogeneous population of binding sites on the imprinted polymer was characterized by dissociation constants equal to 3.72 μg L(-1) and 435 μg L(-1) for high and low affinity binding sites, respectively. The morphology of the polymer was studied employing SEM and BET analyses and the composition was confirmed by EDS and (13)C CP/MAS NMR analyses. Adsorption of amino acids on the imprinted material was tested to analyze the impact of the sample components. The superiority of the imprinted sorbent was proved in a novel dispersive solid phase extraction procedure of ATCA from post-mortem whole blood with respect to the extraction efficacy on the commercial ion-exchange sorbents. The limit of quantification and limit of detection of ATCA in the new analytical method were 12 μg L(-1) and 3.5 μg L(-1), respectively. The recovery of ATCA was in the range of 81-89% and the precision of the method ranged from 1.5 to 2.7%.
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http://dx.doi.org/10.1016/j.chroma.2015.09.083DOI Listing
November 2015

Determination of selected cardiovascular active compounds in environmental aquatic samples--Methods and results, a review of global publications from the last 10 years.

Chemosphere 2015 Nov 3;138:642-56. Epub 2015 Aug 3.

Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, Warsaw PL-02097, Poland.

In recent years cardiovascular diseases were the second most common cause of death worldwide. Therefore, the consumption of cardiovascular drugs is high, which might result in an increase of them in the environment. The major source of aquatic environmental contamination is still effluents of wastewater treatment plants (WWTPs). Unfortunately removal of cardiovascular active compounds and/or their metabolites in WWTP is still unsatisfactory. Among microbial and abiotic degradation of these compounds during wastewater processes, photolysis and photodegradation of cardiovascular drugs also play an important role. New formed compounds may be more toxic or retain the properties of parent compounds. Thus the main goal of this paper was to provide a detailed and comprehensive review of used analytical methods, coupled to liquid chromatography-tandem mass spectrometry, to determine the presence of cardiovascular compounds in surface waters as well as WTTPs effluents and influents. Exhaustive preparation for mass spectrometry detection and quantitation including samples pre-treatment, and the common problem of the matrix effect are thoroughly explored in this paper. Additionally, the article provides some hints in respect of recently noted problematic issue related to the availability of specific standards for the analysis of drug's metabolites. Furthermore, information concerning the metabolism of cardiovascular active compounds including differences in metabolism within enantiomers is described. This article also touches on the problems associated with environmental risk assessment due to the presence of cardiovasculars in the environment. The paper also tries to explain differences in concentrations among cardiovascular compounds between countries worldwide.
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http://dx.doi.org/10.1016/j.chemosphere.2015.07.056DOI Listing
November 2015