Strenuous physical exercise leads to platelet activation that is normally counterbalanced by the production of endothelium-derived anti-platelet mediators, including prostacyclin (PGI
2
) 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 TXB
2
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-PGF
1α
, 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 TXB
2
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 TXB
2
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 TXB
2
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-PGF
1α
was observed. In turn, the pre- and post-exercise plasma concentrations of nitrite (NO
2
−
) and nitrate (NO
3
−
) 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 PGI
2
-dependent anti-platelet mechanisms in ApoE/LDLR
−
/−
mice.
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.
COPD represents a major global health issue, which is often accompanied by cardiovascular diseases. A considerable body of evidence suggests that cardiovascular risk is elevated by the activation of ...blood platelets, which in turn is exacerbated by inflammation. As reactive oxygen species are believed to be an important factor in platelet metabolism and functioning, the aim of our study was to perform a complex assessment of mitochondrial function in platelets in chronic smoke exposed animals with COPD-like lung lesions.
Eight-week-old, male Dunkin Hartley guinea pigs (the study group) were exposed to the cigarette smoke from commercial unfiltered cigarettes (0.9 mg/cig of nicotine content) or to the air without cigarette smoke (control group), using the Candela Constructions
exposure system. The animals were exposed for 4 hours daily, 5 days a week, with 2×70 mL puff/minute, until signs of dyspnea were observed. The animals were bled, and isolated platelets were used to monitor blood platelet respiration. The mitochondrial respiratory parameters of the platelets were monitored in vitro based on continuous recording of oxygen consumption by high-resolution respirometry.
An elevated respiration trend was observed in the LEAK-state (adjusted for number of platelets) in the smoke-exposed animals: 6.75 (5.09) vs 2.53 (1.28) (pmol O
/s ⋅ 110
platelets); bootstrap-boosted
=0.04. The study group also demonstrated lowered respiration in the ET-state (normalized for protein content): 12.31 (4.84) vs 16.48 (1.72) (pmol O
/s ⋅ mg of protein); bootstrap-boosted
=0.049.
Our results suggest increased proton and electron leak and decreased electron transfer system capacity in platelets from chronic smoke-exposed animals. These observations may also indicate that platelets play an important role in the pathobiology of COPD and its comorbidities and may serve as a background for possible therapeutic targeting. However, these preliminary outcomes should be further validated in studies based on larger samples.
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.
Leptin is an adipokine that in vitro enhances agonist-induced platelet aggregation and adipokine expression. Hyperleptinaemia represents a risk factor for cardiovascular disease. We conducted a ...prospective evaluation of the potential link between blood platelet activation and plasma leptin levels in post-stroke patients. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P, the subpopulations of monocyte-platelet aggregates and platelet-derived microparticles (PMPs) as well as the plasma leptin, soluble leptin receptor (sOb-R), leptin/sOb-R ratio, the plasma adiponectin, and leptin/adiponectin ratio were assessed in 98 stroke patients on the first (V₀), 10th (V₁ ) and 90th (V₂) day after stroke and once in 78 age-, gender- and vascular risk factor-matched disease controls. We demonstrated that at V0 leptin resistance, defined as leptin/sOb-R ratio, was higher than in the controls 1.1 (0.5-1.8 vs. 0.5 (0.2-1.1); p=0.02. After adjustment according to the factors which influence platelet activation, we confirmed the relationship between percentage of circulating PMPs and plasma leptin level (B=0.18; p=0.02) or the leptin/sOb-R ratio (B=0.23; p=0.02) in normal-weight subjects in the acute phase of stroke. No correlation could be demonstrated between the adipokine parameters and the percentage of monocyte-platelet aggregates or expression of platelet pro-inflammatory glycoproteins. In conclusion, formation of PMPs on the first day following an ischaemic stroke shows a positive correlation with leptin levels and with resistance to leptin. Leptin level does not seem to affect the expression of platelet surface proinflammatory glycoproteins.
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.
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