Anna Bodzenta-Łukaszyk

Nitric oxide synthase inhibition and platelet function

Nitric oxide (NO), synthesized and released by endothelium, contributes to the regulation of vascular tone and platelet function (1,2). Platelets themselves generate NO, which acts as a negative-feedback mechanism to inhibit platelet adhesion and aggregation (3,4). The arginine analogue, NO-monomethyl-L-arginine (L-NMMA), competitively antagonizes the synthesis of NO from L-arginine (5). The aim of this study was to determine the platelet effects of L-NMMA in healthy subjects.

Relationship between circulating endothelial progenitor cells and endothelial dysfunction in children with type 1 diabetes: a novel paradigm of early atherosclerosis in high-risk young patients.

OBJECTIVE The low number of circulating endothelial progenitor cells (EPCs) has emerged as a biomarker of cardiovascular (CV) risk in adults. Data regarding EPCs in paediatric populations with CV risk factors are limited. The aim of the study was to estimate the EPC number and its relationship with vascular function and structure in children with type 1 diabetes mellitus (T1DM). DESIGN AND METHODS We performed a comparative analysis of 52 children with T1DM (mean age 14.5 years; diabetes duration, 6.0 years; HbA1c level, 8.5%) and 36 healthy age- and gender-matched control children. EPCs were identified and analysed by flow cytometry with the use of MABs directed against CD34, CD144 (VE-cadherin) and CD309 (VEGFR-2). sICAM-1, hsCRP, thrombomodulin and adiponectin levels were also assessed. We evaluated vascular function (flow-mediated dilation (FMD)) and structure (carotid intima-media thickness (IMT)) ultrasonographically. RESULTS Frequencies of CD34+ cells were similar in both groups (P=0.30). In contrast, frequencies of CD34+VE-cadherin+ cells were significantly higher in diabetic children compared with the healthy group (P=0.003). Similarly, diabetic patients tended to present with higher frequencies of CD34+VEGFR+ cells (P=0.06). FMD was lower (6.9 vs 10.5%, P=0.002) and IMT was higher (0.50 vs 0.44 mm, P=0.0006) in diabetic children. We demonstrated a significant relationship between CD34+VEGFR-2+ cells and BMI (r=0.3, P=0.014), HDL (r=-0.27, P=0.04), sICAM-1 (r=0.47, P=0.023) and FMD (r=-0.45, P<0.001). Similarly, frequencies of CD34+VE-cadherin+ cells were significantly correlated with BMI (r=0.32, P=0.02) and FMD (r=-0.31, P=0.03). CONCLUSIONS We demonstrated here that increased frequencies of EPCs observed in diabetic children are negatively correlated with endothelial function. Further studies are warranted to assess whether this phenomenon might result from effective mobilisation of EPCs in order to repair damaged endothelium in children at increased risk for atherosclerosis.

Plasminogen activator inhibitor-1 (PAI-1) and urokinase plasminogen activator (uPA) in sputum of allergic asthma patients.

Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) have been associated with asthma. The aim of this study was to evaluate concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs). The study was performed on 19 HDM-AAs and 8 healthy nonatopic controls (HCs). Concentration of uPA and PAI-1 was evaluated in induced sputum supernatants using ELISA method. In HDM-AAs the median sputum concentration of uPA (128 pg/ml; 95% CI 99 to 183 pg/ml) and PAI-1 (4063 pg/ml; 95%CI 3319 to 4784 pg/ml) were significantly greater than in HCs (17 pg/ml; 95%CI 12 to 32 pg/ml; p<0.001 and 626 pg/ml; 95%CI 357 to 961 pg/ml; p<0.001 for uPA and PAI-1 respectively). The sputum concentration of uPA correlated with sputum total cell count (r=0.781; p=0.0001) and with logarithmically transformed exhaled nitric oxide concentration (eNO) (r=0.486; p=0.035) but not with FEV1 or bronchial reactivity to histamine. On the contrary, the sputum PAI-1 concentration correlated with FEV1 (r=-0,718; p=0.0005) and bronchial reactivity to histamine expressed as log(PC20) (r=-0.824; p<0.0001) but did not correlate with sputum total cell count or eNO. The results of this study support previous observations linking PAI-1 with airway remodeling and uPA with cellular inflammation. Moreover, the observed effect of uPA seems to be independent of its fibrynolytic activity.

Does acute experimental pancreatitis affect blood platelet function

The role of blood platelets in the disturbed haemostasis in acute pancreatitis is not fully elucidated. The aim of this study was to evaluate the blood platelet function during the first hours of acute experimental pancreatitis (AEP) in dogs. AEP was induced by the retrograde injection of bile and trypsin into the main pancreatic duct. Platelet count, platelet aggregation induced with ADP, PAF, AA as well as plasma Beta-TG and TXB2 levels were determined. At 30 min after induction of AEP a significant decrease of platelet count was noted; these changes were observed until 4 th hr. At 30 min as well as at 60 min of AEP increased sensitivity of platelet aggregation to ADP was found. After that time evident decrease of platelet aggregation to ADP was shown. Platelets sensitivity to PAF was higher at 30 min of AEP whereas 60 min, 2 and 4 hrs after AEP normalization of platelet aggregation by PAF was observed. The significant increase of plasma Beta-TG and TXB2 concentrations corresponded well to changes of platelet aggregation. These results indicate that AEP affects blood platelet function with the drop of their count.

Pharmacological Consequences of Inhaled Drug Delivery to Small Airways in the Treatment of Asthma

Small peripheral airways are an important target for the anti-inflammatory treatment of asthma. To make anti-inflammatory drugs (inhaled corticosteroids [ICS]) effectively reach small airways, they should be delivered using inhalation techniques containing high proportions of fine or super-fine particles. Higher proportions of fine particles are associated with higher systemic absorption of ICS leading to an increased risk of endogenous cortisol suppression. Ciclesonide, despite the highest proportion of fine and super-fine particle fractions, is the only ICS not associated with an increased risk of systemic adverse effects, including cortisol suppression. In contrary to ICS, bronchodilators should not be administered to peripheral airways. This does not improve their efficacy and may increase their risk of cardiotoxicity. Thus, from a pharmacological point of view and the theory of aerosols’ deposition, fixed combinations of ICS and long-acting beta agonists are always suboptimal. In many cases, the best solution may be to use fine-particle ciclesonide and a non-fine particle beta agonist administered from separate inhalers.

Blood platelet function in canine acute pancreatitis with reference to treatment with Nafamostat mesilate (FUT - 175)

The aim of this study was to investigate the effect of Nafamostat mesilate (FUT-175) on some blood platelet properties during the first hours of acute experimental pancreatitis (AEP) in dogs. A significant decrease in platelet count, hyperaggregability of platelets by ADP and PAF as well as an increased level of TXB2, were found in the early stage of AEP. No changes in platelet aggregation induced with AA were demonstrated. FUT-175 prevented a decrease in platelet number and inhibited platelet aggregation induced with ADP, PAF and AA when it was given immediately after induction of AEP. No evident changes in TXB2 levels in dogs treated with FUT-175 were found. Our results indicate that the positive effect of FUT-175 in AEP in part depends on its antiaggregatory action.

Enhanced pretreatment CD25 expression on peripheral blood CD4+ T cell predicts shortened survival in acute myeloid leukemia patients receiving induction chemotherapy

BACKGROUND Recently, identification of CD25 (interleukin-2 receptor alpha) expression on leukemic blasts was correlated to early treatment failure and unfavorable outcome in acute myeloid leukemia (AML) patients. Here we wished to determine whether quantification of CD25 on peripheral blood CD4+ T cells could improve prognostication in newly diagnosed AML patients. METHODS The mean fluorescence intensity (MFI) of CD25 expression and frequencies of peripheral blood CD4+ T cells with varying levels of CD25 and CD127 expression were assessed by flow cytometry in all studied individuals. RESULTS Using univariate (unadjusted) and multivariate (adjusted) analyses we demonstrated that detection of high pretreatment CD25 expression on circulating CD4+ T cells was associated with significantly decreased survival rate of AML patients subjected to standard induction chemotherapy. These associations held true for both entire group of analyzed AML patients and different subgroups of patients identified by presence or absence of favorable and adverse molecular prognostic factors. CONCLUSIONS Our data indicate that quantification of CD25 expression on peripheral blood CD4+ T cells could become a novel, easily accessible method of shortened survival prognostication of AML patients subjected to standard cytotoxic therapy.

Markers of anaphylaxis – a systematic review

Anaphylaxis is defined as severe, life-threatening, systemic or general, immediate reaction of hypersensitivity, with repeatable symptoms caused by the dose of stimulus which is well tolerated by healthy persons. The proper diagnosis, immediate treatment and differential diagnosis are crucial for saving patients life. However, anaphylaxis is relatively frequently misdiagnosed or confused with other clinical entities. Thus, there is a continuous need for identifying detectable markers improving the proper diagnosis of anaphylaxis. Here we presented currently known markers of anaphylaxis and discussed in more detail the most clinically valuable ones: tryptase, platelet activacting factor (PAF), PAF-acethylhydrolase, histamine and its metabolites.

Management of suspected drug hypersensitivity reactions. Guidelines of the Section of Drug Hypersensitivity of the Polish Society of Allergology

1Klinika Immunologii, Reumatologii i Alergii, Uniwersytet Medyczny w Łodzi 2 Klinika Pulmonologii, II Katedra Chorób Wewnętrznych im. Prof. Andrzeja Szczeklika, Uniwersytet Jagielloński Collegium Medicum w Krakowie 3Klinika Alergologii i Chorób Wewnętrznych, Uniwersytet Medyczny w Białymstoku 4 Katedra i Klinika Chorób Wewnętrznych, Alergologii i Immunologii Klinicznej, Wydział Lekarski z Oddziałem Lekarsko-Dentystycznym w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach 5Zakład Alergologii Klinicznej, Pomorski Uniwersytet Medyczny w Szczecinie 6Katedra i Klinika Chorób Wewnętrznych i Alergologii, Uniwersytet Medyczny we Wrocławiu 7Zakład Alergologii Klinicznej i Środowiskowej, Uniwersytet Jagielloński Collegium Medicum w Krakowie 8Poradnia Alergologiczna i Poradnia Alergologiczna dla Dzieci w Starachowicach 9 Poradnia Alergologiczna, Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego w Szczecinie 10Klinika Reumatologii, Uniwersytet Medyczny w Łodzi

Introduction to management of drug hypersensitivity. Guidelines of the Section of Drug Hypersensitivity of the Polish Society of Allergology

1Klinika Immunologii, Reumatologii i Alergii, Uniwersytet Medyczny w Łodzi 2 Klinika Pulmonologii, II Katedra Chorób Wewnętrznych im. Prof. Andrzeja Szczeklika, Uniwersytet Jagielloński Collegium Medicum w Krakowie 3Klinika Alergologii i Chorób Wewnętrznych, Uniwersytet Medyczny w Białymstoku 4 Katedra i Klinika Chorób Wewnętrznych, Alergologii i Immunologii Klinicznej, Wydział Lekarski z Oddziałem Lekarsko-Dentystycznym w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach 5Zakład Alergologii Klinicznej, Pomorski Uniwersytet Medyczny w Szczecinie 6Katedra i Klinika Chorób Wewnętrznych i Alergologii, Uniwersytet Medyczny we Wrocławiu 7Zakład Alergologii Klinicznej i Środowiskowej, Uniwersytet Jagielloński Collegium Medicum w Krakowie 8Poradnia Alergologiczna i Poradnia Alergologiczna dla Dzieci w Starachowicach 9 Poradnia Alergologiczna, Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego w Szczecinie 10Klinika Reumatologii, Uniwersytet Medyczny w Łodzi