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1.
Platelets ; 28(7): 657-667, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28067100

ABSTRACT

Strenuous physical exercise leads to platelet activation that is normally counterbalanced by the production of endothelium-derived anti-platelet mediators, including prostacyclin (PGI2) and nitric oxide (NO). However, in the case of endothelial dysfunction, e.g. in atherosclerosis, there exists an increased risk for intravascular thrombosis during exercise that might be due to an impairment in endothelial anti-platelet mechanisms. In the present work, we evaluated platelet activation at rest and following a single bout of strenuous treadmill exercise in female ApoE/LDLR-/- mice with early (3-month-old) and advanced (7-month-old) atherosclerosis compared to female age-matched WT mice. In sedentary and post-exercise groups of animals, we analyzed TXB2 generation and the expression of platelet activation markers in the whole blood ex vivo assay. We also measured pre- and post-exercise plasma concentration of 6-keto-PGF1α, nitrite/nitrate, lipid profile, and blood cell count. Sedentary 3- and 7-month-old ApoE/LDLR-/- mice displayed significantly higher activation of platelets compared to age-matched wild-type (WT) mice, as evidenced by increased TXB2 production, expression of P-selectin, and activation of GPIIb/IIIa receptors, as well as increased fibrinogen and von Willebrand factor (vWf) binding. Interestingly, in ApoE/LDLR-/- but not in WT mice, strenuous exercise partially inhibited TXB2 production, the expression of activated GPIIb/IIIa receptors, and fibrinogen binding, with no effect on the P-selectin expression and vWf binding. Post-exercise down-regulation of the activated GPIIb/IIIa receptor expression and fibrinogen binding was not significantly different between 3- and 7-month-old ApoE/LDLR-/- mice; however, only 7-month-old ApoE/LDLR-/- mice showed lower TXB2 production after exercise. In female 4-6-month-old ApoE/LDLR-/- but not in WT mice, an elevated pre- and post-exercise plasma concentration of 6-keto-PGF1α was observed. In turn, the pre- and post-exercise plasma concentrations of nitrite (NO2-) and nitrate (NO3-) were decreased in ApoE/LDLR-/- as compared to that in age-matched WT mice. In conclusion, we demonstrated overactivation of platelets in ApoE/LDLR-/- as compared to WT mice. However, platelet activation in ApoE/LDLR-/- mice was not further increased by strenuous exercise, but was instead attenuated, a phenomenon not observed in WT mice. This phenomenon could be linked to compensatory up-regulation of PGI2-dependent anti-platelet mechanisms in ApoE/LDLR-/- mice.


Subject(s)
Aging/blood , Apolipoproteins E/deficiency , Atherosclerosis/blood , Blood Platelets/metabolism , Physical Exertion , Platelet Activation , Receptors, LDL/deficiency , 6-Ketoprostaglandin F1 alpha/blood , Aging/genetics , Aging/pathology , Animals , Apolipoproteins E/blood , Apolipoproteins E/genetics , Atherosclerosis/genetics , Atherosclerosis/pathology , Blood Platelets/pathology , Disease Models, Animal , Female , Fibrinogen/genetics , Fibrinogen/metabolism , Gene Expression Regulation , Mice , Mice, Knockout, ApoE , Nitrates/blood , Nitrites/blood , P-Selectin/blood , P-Selectin/genetics , Physical Conditioning, Animal/methods , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Receptors, LDL/blood , Receptors, LDL/genetics , Sedentary Behavior , Thromboxane B2/blood , von Willebrand Factor/genetics , von Willebrand Factor/metabolism
2.
Transpl Infect Dis ; 18(5): 690-698, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27479544

ABSTRACT

BACKGROUND: Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo-HSCT) because of delayed immune reconstitution and graft-versus-host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients. OBJECTIVE: The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012-2013. PATIENTS AND METHODS: In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02-22 years (median age: 7 years), 92 after allo-HSCT and 22 after autologous HSCT (auto-HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug-resistant organisms, and impact of underlying disease and of graft-versus-host disease on BI episodes. RESULTS: In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo-HSCT and 36 after auto-HSCT. Among allo-HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor-HSCT 0.3; matched donor-HSCT 0.4; mismatched unrelated donor [MMUD]-HSCT 0.8; P = 0.027) and after auto-HSCT 0.3 per 1 transplanted patient. In patient after allo-HSCT because of myelo- or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram-positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto-HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly. CONCLUSIONS: The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD-HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram-negative bacteria predominated in patients with myelo- and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram-positive strains were predominant.


Subject(s)
Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Enterobacteriaceae/isolation & purification , Graft vs Host Disease/epidemiology , Gram-Positive Bacteria/isolation & purification , Hematopoietic Stem Cell Transplantation/adverse effects , Unrelated Donors , Adolescent , Adult , Child , Child, Preschool , Drug Resistance, Multiple, Bacterial , Female , Graft vs Host Disease/complications , Humans , Incidence , Infant , Male , Poland/epidemiology , Retrospective Studies , Transplantation, Autologous/adverse effects , Transplantation, Homologous/adverse effects , Young Adult
3.
Clin Microbiol Infect ; 22(2): 179.e1-179.e10, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26493843

ABSTRACT

This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.


Subject(s)
Bacterial Infections/epidemiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Mycoses/epidemiology , Virus Diseases/epidemiology , Bacterial Infections/microbiology , Child , Child, Preschool , Hematologic Neoplasms/complications , Hematologic Neoplasms/mortality , Hematopoietic Stem Cell Transplantation/mortality , Humans , Incidence , Infant , Mycoses/microbiology , Poland/epidemiology , Risk Factors , Survival Rate , Transplantation, Autologous/statistics & numerical data , Transplantation, Homologous/statistics & numerical data , Virus Diseases/virology
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