Publications by authors named "Agnieszka Wróbel"

22 Publications

  • Page 1 of 1

Synthesis, Biological Activity, and Molecular Dynamics Study of Novel Series of a Trimethoprim Analogs as Multi-Targeted Compounds: Dihydrofolate Reductase (DHFR) Inhibitors and DNA-Binding Agents.

Int J Mol Sci 2021 Apr 1;22(7). Epub 2021 Apr 1.

Department of Organic Chemistry, Medical University of Bialystok, 15-222 Bialystok, Poland.

Eighteen previously undescribed trimethoprim (TMP) analogs containing amide bonds () were synthesized and compared with TMP, methotrexate (MTX), and netropsin (NT). These compounds were designed as potential minor groove binding agents (MGBAs) and inhibitors of human dihydrofolate reductase (DHFR). The all-new derivatives were obtained via solid phase synthesis using 4-nitrophenyl Wang resin. Data from the ethidium displacement test confirmed their DNA-binding capacity. Compounds (49.89% and 43.85%) and (41.68% and 42.99%) showed a higher binding affinity to pBR322 plasmid than NT. The possibility of binding in a minor groove as well as determination of association constants were performed using calf thymus DNA, T4 coliphage DNA, poly (dA-dT), and poly (dG-dC). With the exception of compounds (IC50 = 56.05 µM) and (IC50 = 55.32 µM), all of the compounds showed better inhibitory properties against DHFR than standard, which confirms that the addition of the amide bond into the TMP structures increases affinity towards DHFR. Derivatives , , , , and were found to be the most potent DHFR inhibitors. This molecular modelling study shows that they interact strongly with a catalytically important residue Glu-30.
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http://dx.doi.org/10.3390/ijms22073685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037161PMC
April 2021

Design and Characterization of a Novel Tool for the Antigenic Enrichment of Outer Membrane.

Pathogens 2020 Dec 2;9(12). Epub 2020 Dec 2.

Department of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870 Frederiksberg C, Copenhagen, Denmark.

Production and isolation of recombinant proteins are costly and work-intensive processes, especially in immunology when tens or hundreds of potential immunogens need to be purified for testing. Here we propose an alternative method for fast screening of immunogen candidates, based on genetic engineering of recombinant bacterial strains able to express and expose selected antigens on their outer membrane. In , a Gram-negative porcine pathogen responsible for extensive economic losses worldwide, we identified a conserved general secretion pathway (GSP) domain in the N-terminal part of the outer membrane protein ApfA (ApfA stem: ApfA). ApfA was used as an outer membrane anchor, to which potential immunogens can be attached. To enable confirmation of correct positioning, ApfA was cloned in combination with the modified acyl carrier protein (ACP) fluorescent tag ACP mini (ACP) and the putative immunogen VacJ. The chimeric construct was inserted in the pMK-express vector, subsequently transformed into for expression. Flow cytometry, fluorescence imaging and mass spectrometry analysis were employed to demonstrate that the outer membrane of the transformed strain was enriched with the chimeric ApfA-ACP-VacJ antigen. Our results confirmed correct positioning of the chimeric ApfA-ACP-VacJ antigen and supported this system's potential as platform technology enabling antigenic enrichment of the outer membrane of .
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http://dx.doi.org/10.3390/pathogens9121014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761619PMC
December 2020

The inverse autotransporters of Yersinia ruckeri, YrInv and YrIlm, contribute to biofilm formation and virulence.

Environ Microbiol 2020 07 17;22(7):2939-2955. Epub 2020 May 17.

Department of Biosciences, University of Oslo, 0316, Oslo, Norway.

Yersinia ruckeri causes enteric redmouth disease (ERM) that mainly affects salmonid fishes and leads to significant economic losses in the aquaculture industry. An increasing number of outbreaks and the lack of effective vaccines against some serotypes necessitates novel measures to control ERM. Importantly, Y. ruckeri survives in the environment for long periods, presumably by forming biofilms. How the pathogen forms biofilms and which molecular factors are involved in this process, remains unclear. Yersinia ruckeri produces two surface-exposed adhesins, belonging to the inverse autotransporters (IATs), called Y. ruckeri invasin (YrInv) and Y. ruckeri invasin-like molecule (YrIlm). Here, we investigated whether YrInv and YrIlm play a role in biofilm formation and virulence. Functional assays revealed that YrInv and YrIlm promote biofilm formation on different abiotic substrates. Confocal microscopy revealed that they are involved in microcolony interaction and formation, respectively. The effect of both IATs on biofilm formation correlated with the presence of different biopolymers in the biofilm matrix, including extracellular DNA, RNA and proteins. Moreover, YrInv and YrIlm contributed to virulence in the Galleria mellonella infection model. Taken together, we propose that both IATs are possible targets for the development of novel diagnostic and preventative strategies to control ERM.
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http://dx.doi.org/10.1111/1462-2920.15051DOI Listing
July 2020

Trimethoprim: An Old Antibacterial Drug as a Template to Search for New Targets. Synthesis, Biological Activity and Molecular Modeling Study of Novel Trimethoprim Analogs.

Molecules 2019 Dec 27;25(1). Epub 2019 Dec 27.

Department of Organic Chemistry, Medical University of Bialystok, 15222 Bialystok, Poland.

A new series of trimethoprim (TMP) analogs containing amide bonds (-) have been synthesized. Molecular docking, as well as dihydrofolate reductase (DHFR) inhibition assay were used to confirm their affinity to bind dihydrofolate reductase enzyme. Data from the ethidium displacement test showed their DNA-binding capacity. Tests confirming the possibility of DNA binding in a minor groove as well as determination of the association constants were performed using calf thymus DNA, T4 coliphage DNA, poly (dA-dT) and poly (dG-dC). Additionally, the mechanism of action of the new compounds was studied. In conclusion, some of our new analogs inhibited DHFR activity more strongly than TMP did, which confirms, that the addition of amide bonds into the analogs of TMP increases their affinity towards DHFR.
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http://dx.doi.org/10.3390/molecules25010116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983048PMC
December 2019

Recent Design and Structure-Activity Relationship Studies on the Modifications of DHFR Inhibitors as Anticancer Agents.

Curr Med Chem 2021 ;28(5):910-939

Department of Organic Chemistry, Faculty of Pharmacy, Medical University, Białystok, Poland.

Background: Dihydrofolate reductase (DHFR) has been known for decades as a molecular target for antibacterial, antifungal and anti-malarial treatments. This enzyme is becoming increasingly important in the design of new anticancer drugs, which is confirmed by numerous studies including modelling, synthesis and in vitro biological research. This review aims to present and discuss some remarkable recent advances in the research of new DHFR inhibitors with potential anticancer activity.

Methods: The scientific literature of the last decade on the different types of DHFR inhibitors has been searched. The studies on design, synthesis and investigation structure-activity relationships were summarized and divided into several subsections depending on the leading molecule and its structural modification. Various methods of synthesis, potential anticancer activity and possible practical applications as DHFR inhibitors of new chemical compounds were described and discussed.

Results: This review presents the current state of knowledge on the modification of known DHFR inhibitors and the structures and searches for about eighty new molecules, designed as potential anticancer drugs. In addition, DHFR inhibitors acting on thymidylate synthase (TS), carbon anhydrase (CA) and even DNA-binding are presented in this paper.

Conclusion: Thorough physicochemical characterization and biological investigations highlight the structure-activity relationship of DHFR inhibitors. This will enable even better design and synthesis of active compounds, which would have the expected mechanism of action and the desired activity.
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http://dx.doi.org/10.2174/0929867326666191016151018DOI Listing
April 2021

Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.

J Antibiot (Tokyo) 2020 01 2;73(1):5-27. Epub 2019 Oct 2.

Department of Organic Chemistry, Medical University of Białystok, Mickiewicza Street 2a, 15-222, Białystok, Poland.

The development of new mechanisms of resistance among pathogens, the occurrence and transmission of genes responsible for antibiotic insensitivity, as well as cancer diseases have been a serious clinical problem around the world for over 50 years. Therefore, intense searching of new leading structures and active substances, which may be used as new drugs, especially against strain resistant to all available therapeutics, is very important. Dihydrofolate reductase (DHFR) has attracted a lot of attention as a molecular target for bacterial resistance over several decades, resulting in a number of useful agents. Trimethoprim (TMP), (2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine) is the well-known dihydrofolate reductase inhibitor and one of the standard antibiotics used in urinary tract infections (UTIs). This review highlights advances in design, synthesis, and biological evaluations in structural modifications of TMP as DHFR inhibitors. In addition, this report presents the differences in the active site of human and pathogen DHFR. Moreover, an excellent review of DHFR inhibition and their relevance to antimicrobial and parasitic chemotherapy was presented.
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http://dx.doi.org/10.1038/s41429-019-0240-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102388PMC
January 2020

Synthesis and cellular effects of novel 1,3,5-triazine derivatives in DLD and Ht-29 human colon cancer cell lines.

Invest New Drugs 2020 08 13;38(4):990-1002. Epub 2019 Sep 13.

Department of Organic Chemistry, Medical University of Bialystok, Białystok, Poland.

This study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell lines. A novel series of 2,4,6-trisubstituted 1,3,5-triazine derivatives bearing 2-chloroethyl and oligopeptide moieties was designed and synthesized. The most cytotoxic derivative was triazine with an Ala-Ala-OMe substituent on the ring (compound 7b). This compound induced time- and dose-dependent cytotoxicity in the DLD-1 and HT-29 colon cancer cell lines. The triazine derivative furthermore induced apoptosis through intracellular signaling pathway attenuation. Compound 7b may be a candidate for further evaluation as a chemotherapeutic agent against colorectal cancer.
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http://dx.doi.org/10.1007/s10637-019-00838-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340680PMC
August 2020

Overcoming Fish Defences: The Virulence Factors of .

Genes (Basel) 2019 09 11;10(9). Epub 2019 Sep 11.

Department of Biosciences, University of Oslo, 0316 Oslo, Norway.

is the causative agent of enteric redmouth disease, a bacterial infection of marine and freshwater fish. The disease mainly affects salmonids, and outbreaks have significant economic impact on fish farms all over the world. Vaccination routines are in place against the major serotypes of but are not effective in all cases. Despite the economic importance of enteric redmouth disease, a detailed molecular understanding of the disease is lacking. A considerable number of mostly omics-based studies have been performed in recent years to identify genes related to virulence. This review summarizes the knowledge on virulence factors. Understanding the molecular pathogenicity of will aid in developing more efficient vaccines and antimicrobial compounds directed against enteric redmouth disease.
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http://dx.doi.org/10.3390/genes10090700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770984PMC
September 2019

Carbocyclic Analogues of Distamycin and Netropsin.

Mini Rev Med Chem 2019 ;19(2):98-113

Department of Organic Chemistry, Medical University, Bialystok 15-222, Mickiewicza Street 2c, Poland.

The DNA as the depository of genetic information is a natural target for chemotherapy. A lot of anticancer and antimicrobial agents derive their biological activity from their selective interaction with DNA in the minor groove and from their ability to interfere with biological processes such as enzyme catalysis, replication and transcription. The discovery of the details of minor groove binding drugs, such as netropsin and distamycin A, oligoamides built of 4-amino-1-methylpyrrole-2-carboxylic acid residues, allowed to develop various DNA sequence-reading molecules, named lexitropsins, capable of interacting with DNA precisely, strongly and with a high specificity, and at the same time exhibiting significant cytotoxic potential. Among such compounds, lexitropsins built of carbocyclic sixmembered aromatic rings occupy a quite prominent place in drug research. This work is an attempt to present current findings in the study of carbocyclic lexitropins, their structures, syntheses and biological investigations such as DNA-binding and antiproliferative activity.
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http://dx.doi.org/10.2174/1389557518666181009143203DOI Listing
January 2019

pYR4 From a Norwegian Isolate of Is a Putative Virulence Plasmid Encoding Both a Type IV Pilus and a Type IV Secretion System.

Front Cell Infect Microbiol 2018 30;8:373. Epub 2018 Oct 30.

Department of Biosciences, University of Oslo, Oslo, Norway.

Enteric redmouth disease caused by the pathogen is a significant problem for fish farming around the world. Despite its importance, only a few virulence factors of have been identified and studied in detail. Here, we report and analyze the complete DNA sequence of pYR4, a plasmid from a highly pathogenic Norwegian isolate, sequenced using PacBio SMRT technology. Like the well-known pYV plasmid of human pathogenic , pYR4 is a member of the IncFII family. Thirty-one percent of the pYR4 sequence is unique compared to other plasmids. The unique regions contain, among others genes, a large number of mobile genetic elements and two partitioning systems. The G+C content of pYR4 is higher than that of the NVH_3758 genome, indicating its relatively recent horizontal acquisition. pYR4, as well as the related plasmid pYR3, comprises operons that encode for type IV pili and for a conjugation system (). In contrast to other plasmids, pYR4 cannot be cured at elevated temperatures. Our study highlights the power of PacBio sequencing technology for identifying mis-assembled segments of genomic sequences. Comparative analysis of pYR4 and other plasmids and genomes, which were sequenced by second and the third generation sequencing technologies, showed errors in second generation sequencing assemblies. Specifically, in the 150 and ATCC29473 genome assemblies, we mapped the entire pYR3 plasmid sequence. Placing plasmid sequences on the chromosome can result in erroneous biological conclusions. Thus, PacBio sequencing or similar long-read methods should always be preferred for genome sequencing. As the operons of pYR3, although misplaced on the chromosome during the genome assembly process, were demonstrated to have an effect on virulence, and type IV pili are virulence factors in many bacteria, we suggest that pYR4 directly contributes to virulence.
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http://dx.doi.org/10.3389/fcimb.2018.00373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232867PMC
September 2019

The repeat structure of two paralogous genes, Yersinia ruckeri invasin (yrInv) and a "Y. ruckeri invasin-like molecule", (yrIlm) sheds light on the evolution of adhesive capacities of a fish pathogen.

J Struct Biol 2018 02 6;201(2):171-183. Epub 2017 Sep 6.

Department of Biosciences, University of Oslo, 0316 Oslo, Norway. Electronic address:

Inverse autotransporters comprise the recently identified type Ve secretion system and are exemplified by intimin from enterohaemorrhagic Escherichia coli and invasin from enteropathogenic Yersiniae. These proteins share a common domain architecture and promote bacterial adhesion to host cells. Here, we identified and characterized two putative inverse autotransporter genes in the fish pathogen Yersinia ruckeri NVH_3758, namely yrInv (for Y. ruckeri invasin) and yrIlm (for Y. ruckeri invasin-like molecule). When trying to clone the highly repetitive genes for structural and functional studies, we experienced problems in obtaining PCR products. PCR failures and the highly repetitive nature of inverse autotransporters prompted us to sequence the genome of Y. ruckeri NVH_3758 using PacBio sequencing, which produces some of the longest average read lengths available in the industry at this moment. According to our sequencing data, YrIlm is composed of 2603 amino acids (7812bp) and has a molecular mass of 256.4kDa. Based on the new genome information, we performed PCR analysis on four non-sequenced Y. ruckeri strains as well as the sequenced. Y. ruckeri type strain. We found that the genes are variably present in the strains, and that the length of yrIlm, when present, also varies. In addition, the length of the gene product for all strains, including the type strain, was much longer than expected based on deposited sequences. The internal repeats of the yrInv gene product are highly diverged, but represent the same bacterial immunoglobulin-like domains as in yrIlm. Using qRT-PCR, we found that yrIlm and yrInv are differentially expressed under conditions relevant for pathogenesis. In addition, we compared the genomic context of both genes in the newly sequenced Y. ruckeri strain to all available PacBio-sequenced Y. ruckeri genomes, and found indications of recent events of horizontal gene transfer. Taken together, this study demonstrates and highlights the power of Single Molecule Real-Time technology for sequencing highly repetitive proteins, and sheds light on the genetic events that gave rise to these highly repetitive genes in a commercially important fish pathogen.
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http://dx.doi.org/10.1016/j.jsb.2017.08.008DOI Listing
February 2018

ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation.

Open Biol 2016 Apr 27;6(4):150263. Epub 2016 Apr 27.

Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14A, Wrocław 50-383, Poland Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, Wrocław 53-114, Poland

In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins.
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http://dx.doi.org/10.1098/rsob.150263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852455PMC
April 2016

Yersinia adhesins: An arsenal for infection.

Proteomics Clin Appl 2016 10 17;10(9-10):949-963. Epub 2016 May 17.

Evolution and Genetics, Department of Biosciences, University of Oslo, Oslo, Norway.

The Yersiniae are a group of Gram-negative coccobacilli inhabiting a wide range of habitats. The genus harbors three recognized human pathogens: Y. enterocolitica and Y. pseudotuberculosis, which both cause gastrointestinal disease, and Y. pestis, the causative agent of plague. These three organisms have served as models for a number of aspects of infection biology, including adhesion, immune evasion, evolution of pathogenic traits, and retracing the course of ancient pandemics. The virulence of the pathogenic Yersiniae is heavily dependent on a number of adhesin molecules. Some of these, such as the Yersinia adhesin A and invasin of the enteropathogenic species, and the pH 6 antigen of Y. pestis, have been extensively studied. However, genomic sequencing has uncovered a host of other adhesins present in these organisms, the functions of which are only starting to be investigated. Here, we review the current state of knowledge on the adhesin molecules present in the Yersiniae, and their functions and putative roles in the infection process.
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http://dx.doi.org/10.1002/prca.201600012DOI Listing
October 2016

Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera.

Nat Commun 2015 Sep 29;6:8322. Epub 2015 Sep 29.

Key Laboratory of Dairy Biotechnology and Engineering, Education Ministry of China, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia 010018, China.

Lactobacilli are a diverse group of species that occupy diverse nutrient-rich niches associated with humans, animals, plants and food. They are used widely in biotechnology and food preservation, and are being explored as therapeutics. Exploiting lactobacilli has been complicated by metabolic diversity, unclear species identity and uncertain relationships between them and other commercially important lactic acid bacteria. The capacity for biotransformations catalysed by lactobacilli is an untapped biotechnology resource. Here we report the genome sequences of 213 Lactobacillus strains and associated genera, and their encoded genetic catalogue for modifying carbohydrates and proteins. In addition, we describe broad and diverse presence of novel CRISPR-Cas immune systems in lactobacilli that may be exploited for genome editing. We rationalize the phylogenomic distribution of host interaction factors and bacteriocins that affect their natural and industrial environments, and mechanisms to withstand stress during technological processes. We present a robust phylogenomic framework of existing species and for classifying new species.
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http://dx.doi.org/10.1038/ncomms9322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667430PMC
September 2015

IgG4-related inflammatory orbital pseudotumors - a retrospective case series.

Folia Neuropathol 2015 ;53(2):111-20

Krzysztof Oles, Department of Otolaryngology, Head and Neck Surgery, Jagiellonian University, Krakow, Poland, e-mail:

Orbital diseases may be divided into congenital defects of the orbit, infectious and inflammatory diseases, orbital tumors (including malignant and benign tumors) and injuries. Idiopathic inflammatory syndromes are often encountered within the orbit and are usually classified as orbital pseudotumors. The etiology of pseudotumors of the vision organ is unknown. Infectious agents, autoimmune disorders and improper healing are taken into consideration in the pathogenesis of this disorder. Thanks to detailed studies conducted in recent years, a new disease syndrome was identified in 2001. It is known as IgG4-related disease, and its differentiation is based on the analysis of IgG4 levels in the affected tissues. Orbital locations of the disease were first reported in Japan as late as at the end of 2009. This finding triggered the European studies on this subject. To date, no such studies have been conducted in Poland. The starting study population consisted of 167 patients with isolated infiltrative tumor diseases within the orbital region treated at the Department of Otolaryngology, Head and Neck Surgery of the Medical College Jagiellonian University in Krakow. Detailed analysis and diagnostic screening for IgG4-related disease was performed in a total of 17 patients diagnosed with orbital pseudotumor.
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http://dx.doi.org/10.5114/fn.2015.52407DOI Listing
December 2016

[PREVFNAIT prevention of foetal/neonatal alloimmune thrombocytopenia (FNAIT) in Polish foetuses and newborns--the PREVFNAIT program].

Ginekol Pol 2015 Jan;86(1):62-6

The scientific goals related to the grant include 1) estimation of FNAIT prevalence in Poland and 2) search for biomarkers to predict the risk of the antibody production and severity of fetal thrombocytopenia. Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) is caused by destruction of fetal blood platelets due to maternal antibodies. This condition, which most commonly results from incompatibility between the mother and the fetus for the Human Platelet Antigen-1a (HPA-1a), may lead to intracranial hemorrhage, damage of the central nervous system (CNS) and even death of the fetus or the newborn. It can be the cause of strokes in term newborns. FNAIT is usually attributed to the presence of anti-HPA-1a antibodies. Its incidence rate is estimated at approximately 1/1000-2000 live births. In the absence of a screening program, it is usually diagnosed after birth of a child with symptoms of thrombocytopenia or CNS hemorrhage. Monitoring of antibody production and thrombocytopenia treatment to effectively minimize the risk of stroke are therefore launched only at the next pregnancy. Testing indications are broader to include fetal ultrasound for symptoms of stroke to the CNS, ventricular enlargement or hydrocephalus, and obstetric failure. Diagnostic process is also recommended prior to the planned cordocentesis, in vitro fertilization and in sisters of mothers with children with FNAIT history. HPA-1a testing remains the best method for diagnosing pregnancies at risk. The detection frequency for FNAIT in Poland remains low. Therefore, the Institute of Hematology and Transfusion Medicine (IHTM) will have performed such HPA-1a antigen testing in 30 000 Polish women within the framework of the PREVFNAIT program by March 2016. HPA-1a negative women (2% of the population) are a risk group for production of anti- HPA-1a antibodies responsible for FNAIT therefore all of them will be monitored for the presence and activity of anti-HPA-1a antibodies. Such testing will be performed free of charge for the women.
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http://dx.doi.org/10.17772/gp/1901DOI Listing
January 2015

Smell impairment in chronic rhinosinusitis – evaluation of endoscopic sinus surgery results and review of literature concerning olfactory function predictors.

Otolaryngol Pol 2015 ;69(1):33-44

Katedra i Klinika Otolaryngologii, Uniwersytet Jagielloński, Collegium Medicum, Kraków, Polska.

Introduction: Endoscopic sinus surgery (ESS) is the treatment of choice for patients with chronic rhinosinusitis (CRS) refractory to medical therapy. ESS successfully reduces most symptoms of CRS, but its effect on olfaction is always uncertain.

Aim Of The Study: The aim of this study was to assess the influence of sinus surgery on olfaction and to analyze the predictors of olfactory function before and after ESS in the context of a literature review.

Material And Methods: The study group comprised of 153 patients with CRS refractory to medical treatment. The patients evaluated their olfactory function before ESS, 3-6 months after ESS (121 individuals) and 12 months after ESS (58 individuals). Statistical analysis concerned the postoperative olfactory improvement as well as the influence of various predictors on the impairment of smell before and after surgery.

Results And Conclusions: Olfactory dysfunction was significantly reduced after ESS. The smell impairment before and after surgery depended on different predictors. Patients with severe preoperative olfactory dysfunction and extensive pathological changes in the nose and sinuses, including nasal polyps, reported most pronounced improvement after ESS. However, severely hyposmic subjects with nasal polyposis, asthma or aspirin intolerance as well as older patients reported worse postoperative smell scores.
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http://dx.doi.org/10.5604/00306657.1131143DOI Listing
January 2017

[Evaluation of the impact of symptomatic gastroesophageal reflux disease on the result of surgical treatment with the use of endoscopic techniques and postoperative pharmacological treatment in patients with chronic sinusitis].

Przegl Lek 2013 ;70(7):421-6

Katedra i Klinika Otolaryngologii UJ CM w Krakowie, Kraków.

It is estimated that in Europe 10% of adults suffer from chronic sinusitis. Chronic sinusitis can be caused by many different diseases that share chronic inflammation of the sinuses as a common symptom. Rhinitis can be caused by stomach acid coming up from the stomach into the esophagus, which successively can result in chronic sinusitis. The current gold standard for diagnosing GERD is--bothersome for the patient--24 h esophageal pH monitoring. This method can be unpleasant for the patients, which makes it less acceptable. Because of that the criteria for symptomatic GERD were made an alternative diagnostic way. We acknowledge that the presence of heartburn and stomach acid coming up from the stomach into the esophagus at least once a week can be diagnosed as symptomatic GERD. The aim of the study is the assessment of the frequency of symptomatic GERD in patients operated because of chronic sinusitis and impact of symptomatic GERD on the follow-up treatment up to 12 months after endoscopic nasal surgery. The authors analysed 144 patients operated at the JUCM Otolaryngological Clinic in Kraków between 2011 and 2013 because of sinusitis. The inclusion criteria were: diagnosed chronic sinusitis, indications for endoscopic sinus surgery, and a written consent for the research. Each patient was examined laryngologically and surveyed. Patients were divided into two groups: with and without symptomatic GERD. We analysed the symptoms in patients treated for sinusitis with or without GERD before, between 3 and 6 as well as in the 12th month after endonasal surgery. Moreover, we analysed the intensity of the global symptoms (expressed in the VAS scale) and separately for each of the 13 symptoms of chronic sinusitis (expressed on a scale 0 - 3). We established that 33 out of the 144 patients (22.9%) qualified for the first survey reported the symptoms of GERD. In the second survey, which was conducted between 3 and 6 month after ESS, 24 out of 119 (20%) people reported the symptoms and in the third survey, which took place in the 12th month after ESS, 14 out of 52 patients reported symptomatic GERD. The intensity of global symptoms rated in the VAS scale in patients with chronic sinusitis during the first survey was 7.8 and in the second and third survey the intensity was 4.2 and 4.3 respectively. But in patients without any symptoms they were 7.4, 2.8, 3.2. We also analysed 13 symptoms of chronic sinusitis rated on a scale 0 - 3. The result of the research was that in patients with symptomatic GERD, even after FESS and the appropriate follow-up, we can still suspect such symptoms as streaming the fluid over the back side of the throat, cough, pain or the feeling of fullness in the ear, headache or halitosis. We should take it under consideration during qualification for the surgery as well as predicting the results of the treatment. Further research is required to state if and how different methods and procedures used in case of patients with symptomatic GERD can reduce the uncomfortable influence of this disease on the effects of chronic sinusitis treatment.
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December 2013

[Orbital tumors treated at the University Hospital Otolaryngology Clinic in Kraków between 1997 and 2011].

Przegl Lek 2013 ;70(7):417-20

Katedra i Klinika Otolaryngologii, UJ CM w Krakowie, Kraków.

The main aim of the study was to establish the frequency of orbital tumor occurrence in the patients of the University Hospital Otolaryngology Clinic in Kraków as well as to analyze the clinical features, location in the orbit and to identify the group of patients with the highest risk of orbital tumor. The authors retrospectively analyzed 46 patients (29 women and 17 men) between the ages of 23 and 87. This group of patients was compared to a group of 80 patients who were surgically treated at the same clinic 10 years ago and to a group of 70 patients treated 15 years ago. We established that the tumors localized in the orbit were mainly benign. A variety of histological types of tumors arises in the orbit but it was significant that inflammatory pseudotumors were the most common cases in all three groups of patients treated in our clinic now, about 10 and about 15 years ago. Referring to the group of patients at the highest risk, we established that orbital tumors are definitely most common in women than men. It has turned out to be statistically significant that benign tumors were most common in younger patients and malignant in older people. That suggests the conclusion that being female is a risk factor for orbital tumors and age is a risk factor for them being malignant. Comparing different approaches for the resection of orbital tumors, we established that the lateral orbitotomy provides access to orbital tumors in the most common locations (intraconal and in the top corner of the orbit). Malignant and extensive tumors have to be treated by orbital exenteration.
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December 2013

[Extensive neck trauma in material of Otolaryngology Department of the Jagiellonian University in Krakow 2009-2012].

Otolaryngol Pol 2013 Mar-Apr;67(2):95-9. Epub 2013 Jan 10.

Katedra i Klinika Otolaryngologii, Collegium Medicum, UJ, Kraków, Poland.

Isolated laryngeal fractures quite rarely can occur following trauma to the neck region, but because of the variety and dynamic growth of symptoms or possible injury of the main structures on the neck may be life-threatening. The appropriate treatment of these patients is quick surgical intervention proceeded by imaging techniques. Here we report the cases of three patients treated in our Department between 2009 and 2012: two of them with penetrating injury and one with blunt trauma. The appropriate treatment of these patients requires that airway patency be the first priority and if possible quick reconstruction. These cases illustrate the individualized treatment and multidisciplinary approach in managing such cases.
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http://dx.doi.org/10.1016/j.otpol.2013.01.001DOI Listing
July 2013

Lysophosphatidylcholines: bioactive lipids generated during storage of blood components.

Arch Immunol Ther Exp (Warsz) 2012 Feb 14;60(1):55-60. Epub 2011 Dec 14.

Department of Immunohaematology and Immunology of Transfusion Medicine, Institute of Haematology and Transfusion Medicine, Warsaw, Poland.

Transfusion-related acute lung injury (TRALI) is suggested to be a "two hit" event, resulting from priming and activation of pulmonary neutrophils. It is known that neutrophil activation may result from infusion of lysophosphatidylcholines (LysoPCs) accumulated during storage of blood components. The aim of our study was to verify whether the LysoPCs are released into the storage medium of blood components. We measured the LysoPCs concentration in the supernatants from stored apheresis platelet concentrates (PLTs), packed non-leukoreduced red blood cell concentrates (RBCs), leukoreduced red blood cell concentrates (L-RBCs), fresh frozen plasma (FFP) and donor plasma (control). Lipids were separated on high-performance thin-layer chromatography, detected by primulin spray and quantified by photodensitometric scanning. The LysoPCs concentration in donor plasma was similar to that in FFP. During storage the LysoPCs content in PLTs increased almost two-fold as compared to the fresh isolated platelets. In RBCs and L-RBCs the LysoPC level was very low or below detection limit and did not increase throughout the storage period. According to our observations bioactive LysoPCs may be considered a neutrophil-activating factor only following PLT transfusions but not RBCs transfusions.
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http://dx.doi.org/10.1007/s00005-011-0154-xDOI Listing
February 2012

Analysis of the organization of nursing care provided for disabled children in special education institutions in northwest Poland.

Cent Eur J Public Health 2009 Jun;17(2):71-4

Laboratory of Family Nursing, Pomeranian Medical University, Szczecin, Poland.

Introduction: It often happens that handicapped children and teenagers need to be taught in special educational centres. One of the specialists working in a special school should be a nurse having appropriate professional and methodical skills.

Material And Methods: The research involved nurses employed in 36 special education institutions in 2006/2007 in the area of North-West Poland. The organization of work was analysed on the basis of specially constructed questionnaires.

Results: The average working time of nurses employed in special education institutions was 16 hours and 12 minutes per week. In the group of nurses examined, 69% persons have completed qualifications and 5% specialty courses. Nurses cooperate mainly with speech therapists, educationalists, psychologists, rehabilitators, specialists in surdo-pedagogy and oligophreno-pedagogy. However, they attended meetings with parents very occasionally (8%) and rarely participated in staff meetings (8%). Besides, 29% of participants met with parents exclusively in case of emergency.

Conclusions: Nurses' working time in special education institutions according to the norms or work organization. Not all nurses working with disabled pupils have the required qualifications such as the completed specialty or qualification courses. Nurses working in special education do not fully use the possibility of cooperation with the families of disabled pupils and specialists in the therapeutic team.
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http://dx.doi.org/10.21101/cejph.a3510DOI Listing
June 2009