Persistent imbalance, anti-apoptotic, and anti-inflammatory signature of circulating C-C chemokines and cytokines in patients with paroxysmal nocturnal hemoglobinuria.

OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal non-malignant disease in which hematopoietic cell apoptosis may play an important pathophysiological role. Previous studies of the content of phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) indicated the possibility of remote transmission of anti-apoptotic signals between pathological and normal hematopoietic progenitors. METHODS: The study determined the plasma levels of beta chemokines and cytokines in N = 19 patients with PNH and 31 healthy controls. The research material was peripheral blood plasma (EDTA) stored at -80 °C until the test. Beta chemokine and cytokine concentrations were tested in duplicate with Bio-Plex Pro Human Cytokine Assay (Bio-Rad, Hercules, CA, USA) using a Luminex 200 flow cytometer and xPONENT software (Luminex Corporation, Austin, TX, USA). In peripheral blood CD34+ cells we tested the proportions of PI(3,4,5)P3+ and Annexin binding apoptotic phenotype using FC and phosflow. RESULTS: Compared to the control group, the PNH group showed a significant increase in the plasma concentration of some beta chemokines and cytokines, including MIP-1alpha/CCL3, eotaxin/CCL11, MCP1/CCL2, IL4 and G-CSF. In the group of PNH patients, a significant decrease in the concentration of some cytokines was also observed: RANTES/CCL5, MIP-1beta/CCL4, PDGF-BB and IL9. At the same time, the plasma concentrations of the chemokine IP-10/CXCL10 and the cytokines IFN-gamma, TNF, IL6 and IL10 showed no significant deviations from the values for the control group. Anti-apoptotic phenotype and phosphatidylinositol (3,4,5)-trisphosphate content in PNH clone of CD34+ cells were associated with the level of CCL3 and negatively associated with CCL5, CCL4, PDGF-BB and IL9. CONCLUSIONS: This data suggest the existence of apoptotic and PI(3,4,5)P3 imbalance in PNH CD34+ cells driven by anti-apoptotic cytokine biosignature in PNH. Plasma cytokines and intracellular enzymes that regulate the phosphoinositide pathways may become a therapeutic target in PNH.

Antiplatelet effect of statins is augmented in diabetic rabbits.

The effects of various statins on platelet aggregation in blood samples from normal and diabetic rabbits were measured. All of the statins used in our study inhibited platelet aggregation by about 20% at 1 microM. Our results show that diabetes increased the rate of platelet aggregation from 48 +/- 5% to 72 +/- 8%, however, statins inhibited the rate of platelet aggregation by about 60% (p < 0.01). The addition of leptin (125 ng/ml) to blood samples from healthy rabbits increased the aggregation rate to about 64%, but statins decreased this rate to about 26%. Our results indicate that diabetes increases the rate of platelet aggregation in rabbits and increases antiplatelet efficacy of statins due to interactions with leptin.

[Safety and efficacy of varicella vaccine in healthy children--one year follow-up]. / Bezpieczenstwo i skutecznosc szczepionki przeciwko ospie wietrznej u dzieci zdrowych--obserwacje jednoroczne.

BACKGROUND AND AIMS: to assess the safety and efficacy of varicella virus vaccine after administration of one dose. MATERIAL AND METHODS: 106 healthy children (59 girls, 47 boys), with no history of varicella, were vaccinated between March and April 2004. The subjects were aged 9 months to 12 years (median 47 months). Antibody concentrations were determined twice: after 46 days (test 1) and after 13 months (test 2). The concentration of IgG-antibody against VZV was measured using the ELISA IgG Test kit (Genzyme Virotech, Germany). RESULTS: no local and/or general symptoms were observed after vaccination. Effectiveness of vaccination was 98.1%. Two vaccinated children with borderline values (antibody concentrations were 9-11 VE) developed a mild form of varicella 13 months after vaccination. Protective levels of antibody concentrations were found in 95 out of 106 children (89.6%) 46 days after vaccination and in 72 out of 104 children (69.2%) 13 months after vaccination. The mean antibody concentration 46 days after vaccination (test 1) was 21.3VE (6.7-43.8 VE), and 13 months after vaccination (test 2) was 17.2VE (4.9-38.4) i.e. significantly lower (p<0.001). In both tests no significant statistical differences were noted between the post-vaccination concentrations in girls (VE1-20.6 and VE2-22.2) and boys ( VE2-17.3 and VE2-17.0). Neither the subjects' age nor sex at the time of vaccination correlated with the decreased antibody concentrations 13 months after vaccination. In 27.4% of children statistically significant lowering of antibody concentration was detected 13 months after vaccination (lp < 0.0001). CONCLUSIONS: the varicella vaccine (Varilrix) was found to be safe and its effectiveness was 98.1% after 13 months. Only in 2 children mild clinical sings of varicella occurred. However, because of a statistically significant lowering of antibody concentration 13 months after the vaccination, a two dose regimen of varicella vaccination should be recommended.

[Usefulness of determining the blood levels of B-type natriuretic peptide in the evaluation of cardiotoxicity in children treated with anthracyclines]. / Przydatnosc oznaczania stezenia peptydu natriuretycznego typu B w surowicy krwi w ocenie kardiotoksycznosci poantracyclinowej u dzieci.

Cardiotoxicity of anthracydines is a serious clinical problem, and it is the main factor limiting their wide use, despite the recognized antineoplastic properties of anthracyclines. Early detection of adverse effects of anthracyclines is therefore very important for proper prevention of congestive heart failure. Current methods of detection of cardiotoxic activity of anthracyclines (ECG, ECHO) are suitable only for fully symptomatic cases. In subclinical damage of the heart these methods are insufficient. Measurement of NT-proBNP has been shown to be a sensitive indicator of cardiac abnormalities. Concentration of NT-proBNP in blood increases very early in response to volume overload of the ventricles of the heart seen in congestive heart failure. Chemical and physical features of NT-proBNP: long half-time in blood, low requirements for sample collection and storage conditions and easy availability of kits for its measurements make NT-proBNP a very good marker of subclinical postanthracycline congestive heart failure.