Publications by authors named "Piotr Radziwon"

42 Publications

Sex-dependent dysregulation of human neutrophil responses by bisphenol A.

Environ Health 2021 Jan 7;20(1). Epub 2021 Jan 7.

Department of Immunology, Medical University of Bialystok, ul. Waszyngtona 15A, 15-269, Bialystok, Poland.

Background: In the present study, we aimed to investigate selected functions of human neutrophils exposed to bisphenol A (BPA) under in vitro conditions. As BPA is classified among xenoestrogens, we compared its action and effects with those of 17β-estradiol (E2).

Methods: Chemotaxis of neutrophils was examined using the Boyden chamber. Their phagocytosis and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity were assessed via Park's method with latex beads and Park's test with nitroblue tetrazolium. To assess the total concentration of nitric oxide (NO), the Griess reaction was utilized. Flow cytometry was used to assess the expression of cluster of differentiation (CD) antigens. The formation of neutrophil extracellular traps (NETs) was analyzed using a microscope (IN Cell Analyzer 2200 system). Expression of the investigated proteins was determined using Western blot.

Results: The analysis of results obtained for both sexes demonstrated that after exposure to BPA, the chemotactic capacity of neutrophils was reduced. In the presence of BPA, the phagocytic activity was found to be elevated in the cells obtained from women and reduced in the cells from men. Following exposure to BPA, the percentage of neutrophils with CD14 and CD284 (TLR4) expression, as well as the percentage of cells forming NETs, was increased in the cells from both sexes. The stimulatory role of BPA and E2 in the activation of NADPH oxidase was observed only in female cells. On the other hand, no influence of E2 on the expression of CD14 and CD284, chemotaxis, phagocytosis, and the amount of NET-positive neutrophils was found for both sexes. The study further showed that BPA intensified NO production and iNOS expression in the cells of both sexes. In addition, intensified expression of all tested PI3K-Akt pathway proteins was observed in male neutrophils.

Conclusions: The study demonstrated the influence of BPA on neutrophil functions associated with locomotion and pathogen elimination, which in turn may disturb the immune response of these cells in both women and men. Analysis of the obtained data showed that the effect of this xenoestrogen on the human neutrophils was more pronounced than E2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12940-020-00686-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791670PMC
January 2021

Maintaining plasma quality and safety in the state of ongoing epidemic - The role of pathogen reduction.

Transfus Apher Sci 2020 Sep 28:102953. Epub 2020 Sep 28.

Regional Centre for Transfusion Medicine, Bialystok, Poland; Department of Haematology, Medical University of Bialystok, Bialystok, Poland.

In the field of transfusion medicine, many pathogen reduction techniques (PRTs) are currently available, including those based on photochemical (PI) and photodynamic inactivation (PDI). This is particularly important in the face of emerging viral pathogens that may pose a threat to blood recipients, as in the case of the COVID-19 pandemic. However, PRTs have some limitations, primarily related to their adverse effects on coagulation factors, which should be considered before their intended use. A comprehensive search of PubMed, Wiley Online Library and Science Direct databases was conducted to identify original papers. As a result, ten studies evaluating fresh plasma and frozen-thawed plasma treated with different PI/ PDI methods and evaluating concentrations of coagulation factors and natural anticoagulants both before and after photochemical treatment were included in the review. The use of PI and PDI is associated with a significant decrease in the activity of all analysed coagulation factors, while the recovery of natural anticoagulants remains at a satisfactory level, variable for individual inactivation methods. In addition, the published evidence reviewed above does not unequivocally favour the implementation of PI/PDI either before freezing or after thawing as plasma products obtained with these two approaches seem to satisfy the existing quality criteria. Based on current evidence, if implemented responsibly and in accordance with the current guidelines, both PI and PDI can ensure satisfactory plasma quality and improve its safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transci.2020.102953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832281PMC
September 2020

A 63-Year-Old Woman with SARS-CoV-2 Infection, Who Developed Severe COVID-19 Pneumonia and Was Supported with Convalescent Plasma Therapy.

Am J Case Rep 2020 Sep 29;21:e927662. Epub 2020 Sep 29.

Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, Białystok, Poland.

BACKGROUND There is no evidence-based treatment for coronavirus disease 2019 (COVID-19). We report the case of a 63-year-old woman with SARS-CoV-2 infection who developed severe COVID-19 pneumonia and was treated with convalescent plasma. CASE REPORT A 63-year-old woman who presented with severe and prolonged course of COVID-19 disease (fever up to 39.4°C, persistent cough, and dyspnea) received a convalescent plasma transfusion, which led to complete recovery. The diagnosis was confirmed by RT-PCR testing using the CFX96 Real-Time System (Bio-Rad, USA) from nasopharyngeal swabs. In laboratory tests, an increase in acute-phase parameters was observed. Chest computed tomography (CT) showed abnormalities typical for COVID-19. On days 9 and 11 of the disease, she received the convalescent plasma prepared from a single plasmapheresis donation from a male donor. This male donor was qualified as a convalescent plasma donor according to Polish guidelines, which are compliant with European guidelines. He donated plasma at the Regional Centre for Transfusion Medicine in Białystok, Poland. The therapy with convalescent plasma led to clinical improvement and normalization of inflammatory parameters. CONCLUSIONS This report presents a case of severe COVID-19 pneumonia in a 63-year-old woman who was given supportive treatment with convalescent plasma. Ongoing clinical trials will determine whether convalescent plasma therapy is an effective treatment for SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/AJCR.927662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532526PMC
September 2020

Elevated Microparticles, Thrombin-antithrombin and VEGF Levels in Colorectal Cancer Patients Undergoing Chemotherapy.

Pathol Oncol Res 2020 Oct 24;26(4):2499-2507. Epub 2020 Jun 24.

Bioactive Lipids Research Program, Department of Pathology-School of Medicine, Wayne State University, Detroit, MI, 48202, USA.

Hypercoagulable state and neoangiogenesis are common phenomena associated with malignancy. Cancer patients have increased levels of circulating endothelium-derived microparticles (EMPs), which have been hypothesized to be involved in numerous pathophysiological processes. Hemostasis and angiogenesis are also activated in colorectal cancer (CRC) patients. The study aimed to investigate potential influence of chemotherapy on EMPs, thrombin anti-thrombin complex (TAT) and vascular endothelial growth factor (VEGF) levels in CRC patients undergoing chemotherapy. The study group consisted of 18 CRC patients: 8 stage III colon cancer (CC) and 10 stage IV rectal cancer (RC) patients. EMPs, TAT and VEGF levels were assessed before chemotherapy and after the third course. Results were compared with 10 healthy subjects. EMP concentration was measured by flow cytometry, while TAT and VEGF concentrations were assayed employing ELISA. Compared to the control group, CC and RC patients had significantly higher levels of tissue factor (TF)-bearing and non-TF-bearing EMPs before and after three courses of chemotherapy. VEGF concentrations in CRC patients were higher than in the control groups and increased following chemotherapy. TAT levels were elevated in CRC patients before chemotherapy compared to healthy subjects and significantly increased after the third course of chemotherapy. No significant correlation was found either between EMP and TAT levels, or between EMP concentrations and VEGF levels in the study group. CRC patients have increased EMPs, and TAT as well as VEGF levels tend to increase during chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12253-020-00854-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471181PMC
October 2020

Molecular characterisation of clinical pandrug-resistant Alcaligenes faecalis strain MUB14.

Int J Antimicrob Agents 2020 Jun 20;55(6):105939. Epub 2020 Apr 20.

Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijantimicag.2020.105939DOI Listing
June 2020

Effect of bisphenol A on human neutrophils immunophenotype.

Sci Rep 2020 02 20;10(1):3083. Epub 2020 Feb 20.

Department of Immunology, Medical University of Bialystok, ul. Waszyngtona 15A, 15-269, Bialystok, Poland.

Neutrophils (PMN) play a key role in eliciting congenital immune response. These cells are equipped with specific receptors that are located on the surface of their cell membrane. These receptors produce various signals which in turn help in the effective functioning of PMN. The activity of these cells may be modified by factors of endo- and exogenous origin, including xenoestrogens such as bisphenol A (BPA). The aim of this study was to evaluate the effect of BPA on the expression of CD11c, CD14, CD15, CD16, CD62L and CD284 compounds on the surface of neutrophils in women and men. The study material included PMN isolated from the whole blood. The cells were incubated in the presence of BPA and/or LPS. Flow cytometry technique was used to evaluate the expression of CD antigens. Studies of these receptors indicate that BPA, at a concentration corresponding to the serum level of this compound in healthy subjects as well as at higher doses, induces changes in the immunophenotype of PMN, which may lead to immunity disorders associated with the dysfunction of these cells. Moreover, the observed effects of xenoestrogen on the expression of CD11c, CD14, CD15, CD16, CD62L and CD284 differentiation markers on these cells are sex-independent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-59753-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033170PMC
February 2020

Expression of AraC/XylS stress response regulators in two distinct carbapenem-resistant Enterobacter cloacae ST89 biotypes.

J Antimicrob Chemother 2020 05;75(5):1146-1150

Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, Bialystok, Poland.

Background: The growing incidence of MDR Gram-negative bacteria is a rapidly emerging challenge in modern medicine.

Objectives: We sought to establish the role of intrinsic drug-resistance regulators in combination with specific genetic mutations in 11 Enterobacter cloacae isolates obtained from a single patient within a 7 week period.

Methods: The molecular characterization of eight carbapenem-resistant and three carbapenem-susceptible E. cloacae ST89 isolates included expression-level analysis and WGS. Quantitative PCR included: (i) chromosomal cephalosporinase gene (ampC); (ii) membrane permeability factor genes, e.g. ompF, ompC, acrA, acrB and tolC; and (iii) intrinsic regulatory genes, e.g. ramA, ampR, rob, marA and soxS, which confer reductions in antibiotic susceptibility.

Results: In this study we describe the influence of the alterations in membrane permeability (ompF and ompC levels), intrinsic regulatory genes (ramA, marA, soxS) and intrinsic chromosomal cephalosporinase AmpC on reductions in carbapenem susceptibility of E. cloacae clinical isolates. Interestingly, only the first isolate possessed the acquired VIM-4 carbapenemase, which has been lost in subsequent isolates. The remaining XDR E. cloacae ST89 isolates presented complex carbapenem-resistance pathways, which included perturbations in permeability of bacterial membranes mediated by overexpression of ramA, encoding an AraC/XylS global regulator. Moreover, susceptible isolates differed significantly from other isolates in terms of marA down-regulation and soxS up-regulation.

Conclusions: Molecular mechanisms of resistance among carbapenem-resistant E. cloacae included production of acquired VIM-4 carbapenemase, significant alterations in membrane permeability due to increased expression of ramA, encoding an AraC/XylS global regulator, and the overproduction of chromosomal AmpC cephalosporinase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkz569DOI Listing
May 2020

Identification of a novel target for the action of endocrine disrupting chemicals: inhibitory effect of methylparaben on human neutrophil functions.

Environ Sci Pollut Res Int 2020 Feb 23;27(6):6540-6548. Epub 2019 Dec 23.

Department of Immunology, Medical University of Bialystok, Waszyngtona 15A, 15-269, Bialystok, Poland.

This study was conducted to verify a hypothesis that immune cells are a target for the action of endocrine disrupting chemicals (EDCs) by investigating whether methylparaben (MeP) modulates human neutrophil functions. Neutrophils isolated from 15 donor samples were studied. Cells were incubated in the presence of increasing MeP concentrations (0.06, 0.8, 10, and 20 μM). The cytotoxic effect of MeP on neutrophils was evaluated by the MTT test. The ability of the neutrophils for chemotaxis, phagocytosis, NADPH oxidase activity, and superoxide anion generation was assessed in Boyden's chamber, Park's method with latex, the NBT test, and the cytochrome C reduction test, respectively. The total nitric oxide (NO) concentration was measured by the Griess reaction. There was no observable cytotoxic effect of MeP on human neutrophils. MeP (10 and 20 μM) exposure decreased neutrophilic ability for the tested functions, except for NO production. In neutrophils incubated with MeP (0.8 μM as well as 0.06 and 0.8 μM, respectively), we observed a decreased activity of NADPH oxidase as well as decreased generation of superoxide anion. Our results suggest a suppressive effect of MeP on the tested functions of human neutrophils, which confirms that immune cells are vulnerable to EDC action. Therefore, the disturbance of neutrophils' oxygen-dependent phagocytic function as a result of exposure to environmental doses of MeP action could lead to impairment of innate immune responses in humans exposed to xenoestrogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-019-07388-wDOI Listing
February 2020

Endothelial Microparticles and Blood Coagulation Activation in Head and Neck Cancer Patients Undergoing Radiotherapy or Radiochemotherapy.

In Vivo 2019 Mar-Apr;33(2):627-632

Department of Oncology, Medical University of Bialystok, Bialystok, Poland.

Background/aim: Endothelial microparticles (EMP) are small vesicles which are released from the endothelium and contribute to blood coagulation activation in various clinical settings. The aim of this study was to examine whether EMP influence blood coagulation activation in cancer patients during radiotherapy/radiochemotherapy (RT/RCT).

Materials And Methods: Sixteen head and neck cancer (HNC) patients undergoing RT/RCT and 10 controls were examined. EMP and thrombin-antithrombin complex (TAT) were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Tissue factor-positive EMP (TFEMP) were defined as CD31/CD142/CD42b Results: TFEMP were significantly elevated in HNC patients before RT/RCT (T) (1299±1154/μl), one day after RT/RCT (T) (1257±603/μl) and 3 months after RT/RCT (T) (1289±372/μl) compared to controls (688±647/μl). TFEMP levels at T/T and T, as well as at T and T were not significantly different. TAT levels at T and T did not differ significantly but at T were significantly lower compared to T and T TFEMP and TAT concentrations were not significantly correlated at T (r=0.058; p=0.828), T (r=0.373, p=0.154) and T (r=-0.302, p=0.204).

Conclusion: TFEMP may not contribute to hemostatic abnormalities in HNC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/invivo.11520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506302PMC
June 2019

Endothelial Microparticles and Vascular Endothelial Growth Factor in Patients With Head and Neck Cancer Undergoing Radiotherapy or Radiochemotherapy.

In Vivo 2019 Mar-Apr;33(2):581-586

Department of Oncology, Medical University of Bialystok, Bialystok, Poland.

Background: Endothelial microparticles (EMPs) released from activated or apoptotic endothelial cells may play a role in coagulation and thrombus formation. However, there is insufficient evidence regarding the impact of EMPs on angiogenesis in patients with cancer.

Materials And Methods: Sixteen patients with head and neck cancer (HNC) undergoing radiotherapy/radiochemotherapy (RT/RCT) and 10 healthy controls were studied. Serum EMPs were counted by flow cytometry, and vascular endothelial growth factor (VEGF) was measured by enzyme-linked immunosorbent assay (ELISA).

Results: The mean EMP level was significantly higher in patients with HNC before RT/RCT (1,601±1,479 EMP/μl) compared to the control group (782±698 EMP/μl). The number of EMPs was not notably increased after RT/RCT (1,629±769 EMP/μl). There was no significant correlation between the plasma EMP number and concentration of VEGF before (r=0.131; p=0.625), 1 day after (r=-0.042, p=0.874), nor 3 months after RT/RCT (r=0.454, p=0.076).

Conclusion: Released EMPs may not influence promotion of neovascularization in patients with HNC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/invivo.11514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506281PMC
June 2019

Fatty acids and sphingolipids profile in the blood plasma of experienced divers in response to hyperbaric exposure.

Undersea Hyperb Med 2018 Sep-Oct;45:521-529

Regional Blood Transfusion Center in Bialystok, Białystok, 23 Sklodowskiej Str., 15-950 Bialystok, Poland.

Introduction: Hyperbaric exposure mimics air-breathing scuba diving, which is reaching enormous popularity around the world. The diver's body is subjected to a broad range of divergent effects exerted by, e.g.: an increased partial pressure of inert gases, microclotting, oxidative stress and/or production of gas bubbles. However, very little is known regarding the impact of hyperbaric exposure on plasma fatty acids content and composition, together with the body's sphingolipids profile.

Material And Methods: The aim of this study was to investigate the contents of major fatty acids present in the plasma as well as sphingolipids, namely: sphingosine (SPH); sphingosine-1-phosphate (S1P); sphinganine (SPA); and ceramide (CER), after hyperbaric exposure corresponding to dives conducted to the depths of 30 and 60 meters of seawater. For the plasma lipids measurements, high-performance liquid chromatography together with gas-liquid chromatography were applied.

Results: We demonstrated that hyperbaric exposure does not affect the content and composition of plasma fatty acids of experienced divers. Similarly, the amounts of major sphingolipids fractions were not influenced, as only the content of sphingosine-1-phosphate in the plasma was significantly decreased.

Conclusions: Observed lack of significant changes in plasma lipid profile after hyperbaric exposure suggests that the procedure might be considered as secure. However, decreased sphingosine-1-phosphate content in the plasma might possibly exert some adverse effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2019

Very Small Embryonic-Like Stem Cells, Endothelial Progenitor Cells, and Different Monocyte Subsets Are Effectively Mobilized in Acute Lymphoblastic Leukemia Patients after G-CSF Treatment.

Stem Cells Int 2018 21;2018:1943980. Epub 2018 Jun 21.

Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Ul. Waszyngtona 13, 15-269 Bialystok, Poland.

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease of lymphoid progenitor cells. ALL chemotherapy is associated with numerous side effects including neutropenia that is routinely prevented by the administration of growth factors such as granulocyte colony-stimulating factor (G-CSF). To date, the effects of G-CSF treatment on the level of mobilization of different stem and progenitor cells in ALL patients subjected to clinically effective chemotherapy have not been fully elucidated. Therefore, in this study we aimed to assess the effect of administration of G-CSF to ALL patients on mobilization of other than hematopoietic stem cell (HSCs) subsets, namely, very small embryonic-like stem cells (VSELs), endothelial progenitor cells (EPCs), and different monocyte subsets.

Methods: We used multicolor flow cytometry to quantitate numbers of CD34+ cells, hematopoietic stem cells (HSCs), VSELs, EPCs, and different monocyte subsets in the peripheral blood of ALL patients and normal age-matched blood donors.

Results: We showed that ALL patients following chemotherapy, when compared to healthy donors, presented with significantly lower numbers of CD34+ cells, HSCs, VSELs, and CD14+ monocytes, but not EPCs. Moreover, we found that G-CSF administration induced effective mobilization of all the abovementioned progenitor and stem cell subsets with high regenerative and proangiogenic potential.

Conclusion: These findings contribute to better understanding the beneficial clinical effect of G-CSF administration in ALL patients following successful chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/1943980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032642PMC
June 2018

High-frequency (13.56-MHz) and ultrahigh-frequency (915-MHz) radio identification systems do not affect platelet activation and functions.

Transfusion 2016 05;56(5):1148-52

Regional Centre for Transfusion Medicine and the , Medical University of Bialystok, Bialystok, Poland.

Background: In radiofrequency identification (RFID) systems used in labeling of blood components, blood cells are subjected to the direct influence of electromagnetic waves throughout the storage period. The aim of this study was to prove the safety of storage of platelet concentrates (PCs) in containers labeled with RFID tags.

Study Design And Methods: Ten pooled PCs obtained from 12 buffy coats each suspended in additive solution were divided into three separate containers that were assigned to three groups: control, PCs labeled with ultrahigh frequency (UHF) range tags and exposed to 915-MHz radio waves, and PCs labeled with high-frequency (HF) range tags and exposed to 13.56-MHz radio waves. PCs were stored at 20 to 24°C for 7 days. In vitro tests of platelet (PLT) function were performed on the first, fifth, and seventh days of storage.

Results: There were no significant differences in pH; hypotonic shock resistance; surface expression of CD62P, CD42a, or CD63; release of PLT-derived microparticles; PLT aggregation; and number of PLTs between PCs stored at a constant exposure to radio waves of two different frequencies and the control group on the first, fifth, and seventh days of storage.

Conclusion: The results of the study indicate no impact of electromagnetic radiation generated in HF and UHF RFID systems and constant contact with the tags on the quality of stored PCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.13506DOI Listing
May 2016

Surface antigen expression on peripheral blood monocytes in women with gynecologic malignancies.

BMC Cancer 2015 Mar 15;15:129. Epub 2015 Mar 15.

Regional Center for Transfusion Medicine, Białystok, Poland.

Background: Of many specialized blood cells, monocytes are gaining increasing attention for their role in neoplastic disorders. The purpose of the present investigation was to determine the expression of selected peripheral blood monocyte surface antigens in cases of cervical, endometrial, and ovarian cancers. In addition, our aim was to validate the diagnostic value of two artificial coefficients recently proposed for the diagnosis of gynecologic malignancies: Neutrophil to Lymphocyte Ratio (NLR), and Multiplication of Neutrophil and Monocyte Counts (MNM).

Methods: We studied 69 white Caucasian women with histopathologic confirmation of endometrial (N = 42), cervical (N = 13), and ovarian (N = 14) cancers. Reference Group I were women suspected of cancer but histologically nullified (N = 20), and Group II were healthy blood donors (N = 23). Expression of CD11a, CD11b, CD11c, CD16, CD54 (ICAM-1), CD62 L (L-selectin), CD64, and HLA-DR was measured with immunofluorescence in a flow cytometer.

Results: CD54 expression increased by ≥35.6% (p < 0.001) whilst HLA-DR decreased by ≥10.8% (p < 0.001) in all cancer subgroups and Group I as compared to blood donors. A correlation (p < 0.05) between CD54 and CD62 L was stronger in all cancers studied than in healthy subjects. There was no difference in the NLR values between any of these subgroups. Moreover, we observed an increase in MNM parameter in cases of cervical and endometrial cancer and in the Reference Group I.

Conclusions: In the studied gynecologic malignancies, CD54 expression on peripheral blood monocytes is enhanced, indicating a higher transmigrational potential present in such patients, and HLA-DR expression diminished, indicating a decreased readiness of the immune system to recognize foreign antigens. The more pronounced correlation for the expression of CD54 and CD62 L in cancer suggests that monocytes uptake from the bloodstream and their local adhesion increase the pool of tumor-associated macrophages. This study challenged the suggested credibility and usefulness of the artificial parameters of MNM and NLR for the differential diagnosis of gynecologic malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-015-1136-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416309PMC
March 2015

Epstein-Barr virus effect on frequency of functionally distinct T cell subsets in children with infectious mononucleosis.

Adv Med Sci 2014 Sep 11;59(2):227-31. Epub 2014 Jun 11.

Regional Center for Transfusion Medicine in Bialystok, Bialystok, Poland.

Purpose: Epstein-Barr virus is a common human pathogen which infects the great majority of population worldwide. A striking proliferation of CD8⁺ T cells is an immune response to EBV invasion of B lymphocytes during infectious mononucleosis. The aim of the study was to analyze frequencies of CD28⁺CD95⁻, CD28⁺CD95⁺, CD28⁻CD95⁺ T cell subsets putative naïve (T(N)), central (T(CM)) and effector memory (T(EM)) T cells in children with infectious mononucleosis.

Material/methods: Multiparameter flow cytometric analysis of CD4⁺ and CD8⁺ T cell subsets was performed in 19 children with acute infectious mononucleosis.

Results: The CD4⁺/CD8⁺ ratio was found to be decreased (0.53) in children with infectious mononucleosis. Median T(N), T(CM), T(EM) frequencies were estimated to be 3.7, 4.5, 15.1% of CD8⁺ and 23, 59.3, 5.5% of CD4⁺ T cells, respectively. In the present study we demonstrated negative correlations between CD8⁺CD28⁺CD95⁺ and CD8⁺CD28⁻CD95⁺ T cells and both VCA IgM antibody titers and disease duration. However, no such correlation was found when subset of CD4⁺ T cells or CD8⁺CD28⁺CD95⁻ cells was compared.

Conclusions: We conclude that there is a rapid decrease in the number of memory CD8⁺ T cells in early acute stage of infectious mononucleosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.advms.2014.04.003DOI Listing
September 2014

PI3K-Akt/PKB signaling pathway in neutrophils and mononuclear cells exposed to N-nitrosodimethylamine.

J Immunotoxicol 2014 Jul-Sep;11(3):231-7. Epub 2013 Aug 23.

Department of Immunology .

Neutrophils (PMN) play diverse regulatory and effector functions in the immune system through the release of reactive nitrogen species, including nitric oxide (NO). The enzyme responsible for NO synthesis in PMN is inducible nitric oxide synthase (iNOS) that is regulated by various signaling pathways, e.g. PI3K-Akt/PKB, and transcription factors. N-Nitrosodimethylamine (NDMA), a xenobiotic widespread in the human environment, affects immune cells. The study objective here was to examine the role of the PI3K-Akt/PKB pathway in induction of NO synthesis (with involvement of iNOS) in human PMN, as well as in autologous mononuclear cells (PBMC), exposed to NDMA. Isolated cells were incubated for 2 h with a sub-lethal dose of NDMA and then the expression of several select proteins in the cell cytoplasmic and nuclear fractions were determined by Western blot analyses. The results indicated that NDMA enhanced expression of iNOS, phospho-PI3K, and phospho-IκBα in the cytoplasmic fraction of the PMN and PBMC. The nuclear fraction of these cells also had a higher NF-κB expression. Moreover, in PMN, NDMA caused an increased expression of phospho-Akt (T308), phospho-Akt (S473), and phospho-IKKαβ in the cytoplasm, and c-Jun and FosB in the nuclear fraction. Blocking of PI3K caused a decrease in expression of all these proteins in NDMA-exposed PMN. However, inhibition of PI3K led to a drop in expression of iNOS, phospho-PI3K, and phospho-IκBα in the cytoplasm, and in NF-κB in the nuclear fraction, of PBMC. The results of these studies indicated to us that NDMA activates the PI3K-Akt/PKB pathway in human PMN and that this, in turn, contributes to the activation of transcription factors NF-κB, c-Jun, and FosB involved in NO production (through modulation of iNOS expression).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/1547691X.2013.826307DOI Listing
April 2015

Role of ERK1/2 kinase in the expression of iNOS by NDMA in human neutrophils.

Indian J Exp Biol 2013 Jan;51(1):73-80

Department of Immunology Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland.

Potential role of ERK1/2 kinase in conjunction with p38 in the regulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, and superoxide anion generation by human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA) was determined. Increased synthesis of NO due to the involvement of iNOS in neutrophils exposed to NDMA was observed. In addition, intensified activation of ERK1/2 and p38 kinases was determined in these cells. Inhibition of kinase regulated by extracellular signals (ERK1/2) pathway, in contrast to p38 pathway, led to an increased production of NO and expression of iNOS in PMNs. Moreover, as a result of inhibition of ERK1/2 pathway, a decreased activation of p38 kinase was observed in neutrophils, while inhibition of p38 kinase did not affect activation of ERK1/2 pathway in these cells. An increased ability to release superoxide anion by the studied PMNs was observed, which decreased after ERK1/2 pathway inhibition. In conclusion, in human neutrophils, ERK1/2 kinase is not directly involved in the regulation of iNOS and NO production induced by NDMA; however, the kinase participates in superoxide anion production in these cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2013

Combination of LC-MS- and GC-MS-based metabolomics to study the effect of ozonated autohemotherapy on human blood.

J Proteome Res 2012 Dec 26;11(12):6231-41. Epub 2012 Nov 26.

Department of Physical Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland.

Ozonated autohemotherapy (O3-AHT) is a medical approach during which blood obtained from the patient is ozonated and injected back into the body. Despite an increasing number of evidence that O3-AHT is safe, this type of therapy remains controversial. To extend knowledge about the changes in blood evoked by O3-AHT, LC-MS- and GC-MS-based metabolic fingerprinting was used to compare plasma samples obtained from blood before and after the treatment with potentially therapeutic concentrations of ozone. The procedure was performed in PVC bags utilized for blood storage to study also possible interactions between ozone and plastic. By use of GC-MS, an increase in lactic acid and pyruvic acid was observed, which indicated an increased rate of glycolysis. With LC-MS, changes in plasma antioxidants were observed. Moreover, concentrations of lipid oxidation products (LOP) and lysophospholipids were increased after ozone treatment. This is the first report of increased LOPs metabolites after ozonation of blood. Seven metabolites detected by LC-QTOF-MS only in ozonated samples could be considered as novel biomarkers of oxidative stress. Several plasticizers have been detected by both techniques in blood stored in PVC bags. PVC is known to be an ozone resistant material, but ozonation of blood in PVC bags stimulates leaching of plasticizers into the blood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/pr3008946DOI Listing
December 2012

Role of AP-1 family proteins in regulation of inducible nitric oxide synthase (iNOS) in human neutrophils.

J Immunotoxicol 2013 Jan-Mar;10(1):32-9. Epub 2012 Jun 26.

Department of Immunology, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland.

The aim of the study was to assess the activity of AP-1 family proteins, e.g. Fra-1, Fra-2, JunB, JunD, and FosB, engaged in the regulation of inducible nitric oxide synthase (iNOS) expression and the production of NO by neutrophils (PMN) exposed to N-nitrosodimethylamine (NDMA) xenobiotic. Isolated human PMN were incubated in the presence of NDMA. iNOS mRNA expression was then analyzed using Northern blot and the expression of other proteins in the cytoplasmic and nuclear fractions were assessed using Western blot. The obtained results indicate that NDMA increased iNOS mRNA and protein expression in human PMN. Furthermore, it increased the expression of Fra-1, Fra-2, JunB, and JunD in the cytoplasmic fraction, and FosB expression in the fractions of analyzed cells. As a consequence of inhibiting p38 pathway and JNK, reduced iNOS expression and NO production was noted in PMN exposed to NDMA. Inhibition of the p38 pathway resulted in reduced expression of all analyzed proteins in the cytoplasmic fraction of PMN exposed to NDMA. Furthermore, increased Fra-2 expression and reduced FosB expression were found in the nuclear fraction of those cells. Inhibiting ERK5 pathway resulted in increased JunB expression in both fractions of the analyzed cells. Therefore, no changes in the expression of analyzed proteins in the presence of NDMA were observed in PMN pre-incubated with JNK pathway inhibitor. In conclusion, the results here indicate a role of Fra-1, Fra-2, JunB, JunD, and FosB transcription factors in the regulation of iNOS expression and NO production by human neutrophils exposed to NDMA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/1547691X.2012.686929DOI Listing
September 2013

Evaluation of hemostatic balance in blood from patients with polycythemia vera by means of thromboelastography: the effect of isovolemic erythrocytapheresis.

Platelets 2012 18;23(6):455-62. Epub 2011 Nov 18.

Department of Physical Chemistry, Medical University of Bialystok , Bialystok , Poland.

Polycythemia vera (PV) is associated with an increased frequency of thrombotic complications. This study was undertaken to evaluate the hemostatic balance in the blood of PV patients by means of thromboelastography (TEG). The effect of isovolemic erythrocytapheresis (ECP) on the hemostasis of PV patients was also studied. We assessed the coagulation status of 76 PV patients undergoing ECP and 50 of healthy controls. TEG measurements were performed immediately before and after the ECP procedure. Coagulation was triggered by recalcification in freshly collected citrated blood. We recorded clotting time (R), alpha angle, and maximum amplitude (MA) of the clot. The results presented here show that, compared with healthy controls, PV patients demonstrated an increase in alpha angle (p<0.005) and in MA (p=0.14). In the subgroup of PV patients with high (>440 × 10(9)l(-1)) platelet (PLT) count, differences in MA (p<0.01) and alpha angle (p<0.001) were more significant. Following ECP procedure, a significant (p ≤ 0.01) reduction of R time, a rise of alpha angle, and MA were observed, indicating augmentation of a hypercoagulable state. In PV patients, the rise in alpha angle positively correlated (r=0.549) with platelet count but not with the number of erythrocytes and leukocytes. Following ECP, this correlation was reduced (r=0.382). Dilution (with saline) of blood from PV patients and of healthy controls, to a degree similar to that used during the ECP procedure, resulted in reduction of R and rise of the alpha angle. In conclusion, TEG measurements show that the majority of PV patients demonstrate abnormal hemostasis in which a major role is played by platelets rather than plasma factors. The hypercoagulable state in PV patients is significantly augmented following the ECP and may be related to the hemodilution intrinsically included in this procedure. TEG may help to assess the thrombotic risk in individual PV patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/09537104.2011.633178DOI Listing
December 2012

Improving blood safety and patient outcomes with pathogen reduction technology.

Transfus Apher Sci 2011 Dec 9;45(3):229-38. Epub 2011 Nov 9.

CardianBCT Biotechnologies, LLC, Lakewood, CO 80215, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transci.2011.10.001DOI Listing
December 2011

Effect of N-nitrosodimethylamine on inducible nitric oxide synthase expression and production of nitric oxide by neutrophils and mononuclear cells: the role of JNK signalling pathway.

APMIS 2011 Jul 25;119(7):431-41. Epub 2011 Apr 25.

Department of Immunology, Medical University of Bialystok, Poland.

In neutrophils (PMN) and mononuclear cells (PBMC), one of the enzymes responsible for nitric oxide (NO) synthesis is inducible nitric oxide synthase (iNOS). Changes in iNOS expression result from various signalling pathways including the mitogen-activated protein kinase (MAPK) pathway activated by endogenic and exogenic factors. N-nitrosodimethylamine (NDMA) is a xenobiotic with widespread occurrence in human environment and has an effect on cells of the immune system. The aim of this study was to determine the effect of NDMA on iNOS expression and NO production by human PMN and PBMC cells in the light of superoxide anion production by PMN cells. Moreover, the role of JNK and p38 pathways in NO production with involvement of iNOS was studied. Additionally, the function of JNK pathway in generation of superoxide anion was determined. Moreover, nitrotyrosine expression was studied in PMN and PBMC cells in the presence of NDMA. This work shows that NDMA increases iNOS expression and NO production by PMN and PBMC cells. In addition, elevated expression of phospho-JNK and phospho-p38, which are markers of JNK and p38 MAPK pathways activation, were observed. Lower iNOS expression and NO production by neutrophils exposed to extended action of NDMA were observed after application of inhibitor of JNK and p38 pathways. Lower phospho-p38 expression in PMN stimulated by NDMA was found as a result of arresting JNK pathway, whereas, application of inhibitor of p38 pathway resulted in enhanced phospho-JNK expression in PMN and PBMC cells. Increased ability to release superoxide anion by NDMA-stimulated PMN cells was observed. This ability was reduced after the application of inhibitor of JNK pathway. In PMN and PBMC cells exposed to NDMA, an increased expression of nitrotyrosine, which is dependant on JNK and p38 pathways that are activated by this particular xenobiotic, was observed. Generally, increased induction of iNOS related to elevated production of NO by PMN and PBMC cells exposed to NDMA may result in dysfunction of regulation of immunity responses controlled by this molecule in various conditions. Increased expression of nitrotyrosine in PMN and PBMC cells exposed to NDMA may affect their functions in an auto- and/or a paracrine way. Mutual interactions of JNK and p38 MAPK during the induction of iNOS expression in cells exposed to NDMA indicate complex mechanism of induction of iNOS synthase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0463.2011.02750.xDOI Listing
July 2011

[Quality of buffy-coat-derived platelet concentrates prepared using automated system terumo automated centrifuge and separator integration (TACSI)].

Pol Merkur Lekarski 2011 Mar;30(177):191-4

Regionale Centrum Krwiodawstwa i Krwiolecznictwa w Białymstoku.

Unlabelled: Platelet recovery, and viability, and function is strongly dependent on the method of the preparation of platelet concentrate (PC). The glucose consumption, decrease of pH, release of alpha granules during storage in platelet concentrate impair their clinical effectiveness.

The Aim Of Study: To compare of the quality of buffy-coat-derieved platelet concentrates prepared using automatic system terumo automated centrifuge and separator integration (TACSI) and stored over 7 days.

Material And Methods: PCs were prepared from buffy coats using manual method (group I), or automatic system TACSI (group II). Fifteen PCs prepared from the 5 buffy coats each were stored over 7 days in 22-24 degrees C and tested. Samples were taken from the PCs container on days 1 and 7. The following laboratory tests were performed: number of platelets, platelets derived microparticles, CD62P expression, platelet adhesion, pH, glucose, lactate dehydrogenase activity.

Results: We have observed higher expression of CD62P in PCs prepared using manual method compared to the PCs produced automatically Platelet recovery was significantly higher in PCs prepared using automatic systems compare to manual method.

Conclusion: Compared to manual methods, automatic system for preparation of buffy coats, is more efficient and enable production of platelets concentrates of higher quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2011

[The quality of platelet concentrates in dependence on storage time before pathogen inactivation].

Pol Merkur Lekarski 2011 Mar;30(177):187-90

Regionaine Centrum Krwiodawstwa i Krwiolecznictwa w Białymstoku.

Unlabelled: Pathogen inactivation procedure performed just before distribution of platelet concentrates (PCs) may decrease costs caused by loss of these components due to relatively short expiry date.

The Aim Of Study: To evaluate the quality of PCs pathogen inactivated on the first or the fifth day of storage.

Material And Methods: PCs preparated from buffy-coats were suspended in platelet additive solution (Intersol, Baxter Healthcare Corporation, Belgium). The photochemical pathogen inactivation was performed on the 1st or the 5th day of storage using amotosalen and UVA (Cerus, Europe BV). PCs were stored for 7 days.

Results: There were observed increased expression of CD62 and CD63, elevated activity of LDH and lower concentration of glucose in PCs pathogen inactivated on day 1 compare to the control group. PCs pathogen inactivated on day 5 showed decreased expression of CD62 and CD63 compare to the control group. There were no significant differences in platelet number, pH, lactate concentration, hypotonic shock response and release of platelet derived microparticles in both groups of pathogen inactivated PCs.

Conclusions: Time of storage of PCs before pathogen inactivation has no significant impact on PCs quality. Pathogen inactivation procedure performed just after having received request for PCs is more cost effective than the routine pathogen inactivation in all PCs before storage.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2011

Activation of platelets and fibrinolysis induced by saturated air dives.

Aviat Space Environ Med 2010 Jun;81(6):585-8

Military Institute of the Health, Department of Maritime and Tropical Medicine, Gdynia, Poland.

Introduction: The Doppler technique is currently the usual method for detection of bubbles in the circulation following decompression. However, cases of decompression sickness (DCS) frequently occur in the absence of detectable bubbles, so that other markers for increasing risk of DCS would be welcome. This study assessed the hemostatic effects of compressed-air saturation dives that conformed to the "safe" limits of accepted decompression tables.

Methods: We measured coagulation times, thrombin generation, platelets, and fibrinolysis in 21 male divers who were subjected to saturated hyperbaric exposures to 0.28-0.3 MPa (corresponds to 18-20 msw). Each diver did one dive.

Results: Pooled before- and after-dive data for all exposures showed after decompression, statistically significant changes included decrease of the mean platelet count after, increased induced platelet aggregation and number of platelet aggregates, increased number of P-selectin (CD62P) positive platelets and CD62P density on platelets, increase of platelet derived microparticles in the blood of the divers, decrease of factor XII, X, and fibrinogen concentrations, and marked increase of plasmin-antiplasmin complex concentration. Thrombin activation markers and coagulation times did not change significantly.

Conclusions: Saturated hyperbaric exposures followed by nominally safe decompression led to activation of platelets and the fibrinolytic system. The probable mechanism for the activation of platelets and fibrinolysis is contact with the surface of evolved bubbles in the divers' circulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3357/asem.2626.2010DOI Listing
June 2010

Metabolomic approach with LC-MS reveals significant effect of pressure on diver's plasma.

J Proteome Res 2010 Aug;9(8):4131-7

Pharmacy Faculty, Campus Monteprincipe, San Pablo-CEU University, Boadilla del Monte. Madrid, Spain.

Professional and recreational diving are growing activities in modern life. Diving has been associated with increased prevalence of stroke, hypertension, asthma, diabetes, or bone necrosis. We evaluated the effect of increased pressure equivalent to diving at 30 and 60 m for 30 min in two groups of divers using an untargeted approach with LC-MS fingerprinting of plasma. We found over 100 metabolites to be altered in plasma post exposure and after the corresponding decompression procedures. Among them, a group of lysophosphatidylcholines and lysophosphatidylethanolamines were increased, including lysoplasmalogen, a thrombosis promoter, together with changes in metabolic rate-associated molecules such as acylcarnitines and hemolysis-related compounds. Moreover, three metabolites that could be associated to bone degradation show different intensities between experimental groups. Ultimately, this nontargeted, short-term study opens the possibility of discovering markers of long-term effect of pressure that could be employed in routine health control of divers and could facilitate the development of safer decompression procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/pr100331jDOI Listing
August 2010

Evaluation of the memory CD4+ and CD8+ T cells homeostasis during chronic venous disease of lower limbs.

Folia Histochem Cytobiol 2009 Jan;47(3):471-7

Department of Microbiological Diagnostics, Medical University of Bialystok, Poland.

More and more is known about the role of venous wall abnormalities and valvular incompetence in the development of chronic venous disorders (CVD). Unfortunately detailed mechanisms of CVD pathophysiology are not well understood. Recent studies focus on involvement of the inflammatory process in the structural remodeling of venous valves and venous wall. The aim of this study is to investigate and to document the memory T cells homeostasis in CVD patients. In this study we present lymphocytic changes in blood from varicose veins in terms of total CD4+ and CD8+ T cells and their particular subsets of memory T cells: TN, TCM and TEM. Results suggest that immunological memory may be involved in the CVD development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2478/v10042-009-0081-4DOI Listing
January 2009

The inflammatory reaction during chronic venous disease of lower limbs.

Folia Histochem Cytobiol 2009 ;47(2):185-9

Department of Microbiological Diagnostics, Medical University of Białystok, Białystok, Poland.

Chronic venous disease (CVD) is an insufficiency of distal veins caused by their partial or total obstruction, endothelial distension and functional disorders. Chronic venous disease of lower limbs is common problem and affects millions of people. In this article we suggest that inflammatory process is involved in the structural remodeling in venous valves and in the venous wall, leading to valvular incompetence and the development of varicose veins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2478/v10042-009-0029-8DOI Listing
April 2010

Effector and memory CD4+ and CD8+ T cells in the chronic infection process.

Folia Histochem Cytobiol 2008 ;46(4):413-7

Department of Microbiological Diagnostics, Medical University of Bialystok, Poland.

T cell memory in comparison with B cell memory is not well understood. This review focuses on CD8+ and CD4+ memory T cells. In this article we try to define memory cells and also present models of memory T cells formation. We would also like to delineate their differentiation into distinct subsets. Long-lived memory T cells consist in two main subsets: TCM and TEM. Recent studies have shown that not all cells considered to be memory cells differentiate into TCM and TEM, but a small proportion of theses cells exhibit naive cells phenotype. Memory T cells constitute a heterogeneous population of cells. In this study we lay stress on characteristic of main memory T cells subsets and their alleged participation in immune response upon reexposure to the Ag.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2478/v10042-008-0077-5DOI Listing
February 2009

Vasopressin acts on platelets to generate procoagulant activity.

Blood Coagul Fibrinolysis 2008 Oct;19(7):615-24

Department of Physical Chemistry, Medical University of Bialystok, KIlinskiego 1, Bialystok, Poland.

The aim of our study was to examine whether arginine vasopressin (AVP) is able to evoke in human platelets a procoagulant response due to activation of an Na+/H+ exchanger. It was found that treatment of platelets with AVP (20-100 nmol/l) results in generation of a weak calcium signal, activation of Na+/H+ exchanger, aggregation, and development of a procoagulant response. The AVP-evoked procoagulant response was dose and time dependent, weaker than that produced by collagen or monensin (mimics Na+/H+ exchanger), and less pronounced following the inhibition of Na+/H+ exchanger by 5-(N-ethyl-N-isopropyl) amiloride or genistein. Flow cytometry studies reveal that in-vitro platelet treatment with AVP results in an unimodal left shift in the forward and side scatter of the entire platelet population, indicating morphological changes on the plasma membrane. The shift was dose related, weaker than that evoked by collagen, similar to that produced by monensin and strongly reduced in the presence of 5-(N-ethyl-N-isopropyl) amiloride or genistein. Using flow cytometry, we demonstrated enhanced expression of phosphatidylserine on the AVP-treated platelets. AVP-evoked phosphatidylserine exposure was dose dependent, inhibited by 5-(N-ethyl-N-isopropyl) amiloride or genistein and weaker than that produced by collagen. AVP in a dose-dependent manner produced a rise in platelet volume. The swelling was inhibited by 5-(N-ethyl-N-isopropyl) amiloride, and its kinetics was similar to that observed in the presence of monensin. We conclude that prolonged treatment of platelets with AVP results in a procoagulant response, which may occur as a consequence of Na+ influx mediated by Na+/H+ exchanger.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0b013e328309905dDOI Listing
October 2008