Cardiovascular complications among hematopoietic cell transplantation survivors - the role of cardiomarkers.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for numerous malignant and nonmalignant diseases. The number of survivors and length of follow-up after successful HSCT is continually increasing. HSCT can induce damage of various organs and tissues - from minimal potentially progressive subclinical changes to life-threatening conditions. The aim of this thesis was to assess the prognostic value of high sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing and early identification of patients at high risk of a cardiac event after allogeneic HSCT. PATIENTS AND METHODS: Sixty-three patients with the median age of 37 years at the time of allogeneic HSCT for hematologic diseases were studied. Cardiac bio-markers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before the conditioning regimen and 1 month after HSCT by echocardiography. RESULTS: The differences in plasma NT-proBNP and hs-cTnT concentrations during the 30 days following HSCT were statistically significant (P < 0.001 vs. P = 0.02). Seven of 63 patients (11.1 %) developed a cardiac event defined as cardiovascular dys-rhythmias, pericarditis with cardiac tamponade and heart failure. By multivariate analysis, the strongest prognostic factor of cardiac event was an increased level of hs-cTnT and NT-proBNP persisted for a period of 14 days after HSCT (P < 0.0001). The area under the curve from hs-cTnT testing plus NT-proBNP testing together (AUC = 0.95) was superior to each dia-gnostic modality alone. CONCLUSION: Measurements of plasma NT-proBNP and hs-cTnT concentrations might be a useful tool for identification of high-risk patients requiring further cardiological follow up. Measurement of hs-cTnT plus NT-proBNP together was superior to hs-cTnT and NT-proBNP measurements alone.

Novel biomarkers for prediction of acute kidney injury in acute heart failure.

BJECTIVES: Acute kidney injury (AKI) is a frequent event in patients with an acute heart failure (AHF) and is associated with a poor short and long-term outcome. The aim of this study was to describe diagnostic yield of selected novel biomarkers in prediction of AKI in patients admitted for AHF. METHODS: We performed a prospective cohort study of 72 consecutive patients (46/26 M/F) aged 69±10,3 years admitted for AHF. Renal damage was defined according to KDIGO guidelines. Patients were divided into the two groups: AKI- (without renal injury, n=52) and AKI+ (with renal injury, n=20). Urine samples for AKI biomarkers measurements (NGAL, TIMP2, IGFBP7) were collected at the admission. The ROC and linear logistic regression of new biomarkers and selected clinical variables was performed for the evaluation of the AKI prediction. RESULTS: The patients with AKI+ were older (median age: 75 vs 64 years, p=0.01), had lower BMI (median: 28 vs 29.5 kg/m2, p=0.04), were with a higher proportion of patients with HF with a reduced ejection fraction (55 % vs 23.1 %, p=0.01) and a higher level of serum NTproBNP. Urinary NGAL at admission was significantly higher in the AKI+ compared to the AKI - group (152 vs 19.5 ng/mL, p<0.0001); also median of u-TIMP-2 and u-IGFBP-7 in the AKI+ patients was significantly higher: 194.1 versus 42.5 ng/mL (p<0.0001) and 379 versus 92.4 pg/mL (p<0.0001) resp. Age, u-NGAL, u-TIMP2, u-IGFBP7, s-haemoglobin, NTproBNP and LVEF were associated with the development of AKI. Urine concentration of IGFBP-7 was measured, which is the best marker for the prediction of AKI (AUC 0.94). CONCLUSION: Urine concentrations of NGAL, TIMP2, IGFBP7 at the time of admission for AHF predicted a development of AKI. Age, NTproBNP, LVEF and s-haemoglobin were also associated with AKI in AHF patients (Tab. 3, Fig. 3, Ref. 22). Text in PDF www.elis.sk Keywords: biomarkers, cardiorenal syndrome, acute heart failure.

Identification of amino acids in the N-terminal SH2 domain of phospholipase C gamma 1 important in the interaction with epidermal growth factor receptor.

Photoaffinity labeling and site-directed mutagenesis have been used to identify amino acid residues of the phospholipase C gamma 1 (PLC gamma 1) N-terminal SH2 domain involved in recognition of the activated epidermal growth factor receptor (EGFR). The photoactive amino acid p-benzoylphenylalanine (Bpa) was incorporated into phosphotyrosine-containing peptides derived from EGFR autophosphorylation sites Tyr992 and Tyr1068. Irradiation of these labels in the presence of SH2 domains showed cross-linking which was time-dependent and specific; labeling was inhibited with non-Bpa-containing peptides from EGFR in molar excess. The phosphotyrosine residue on the peptides was important for SH2 recognition, as dephosphorylated peptides did not cross-link. Radiolabeled peptides were used to identify sites of cross-linking to the N-terminal SH2 of PLC gamma 1. Bpa peptide-SH2 complexes were digested with trypsin, and radioactive fragments were purified by HPLC and analyzed by Edman sequencing. These experiments showed Arg562 and an additional site in the alpha A-beta B region of the SH2 domain, most likely Glu587, to be labeled by the Tyr992-derived peptide. Similar analysis of the reaction with the Tyr1068-derived photoaffinity label identified Leu653 as the cross-linked site. Mutation of the neighboring residues of Glu587 decreased photo-cross-linking, emphasizing the importance of this region of the molecule for recognition. These results are consistent with evidence from the v-Src crystal structure and implicate the loop spanning residues Gln640-Ser654 of PLC gamma 1 in specific recognition of phosphopeptides.

IgM-Fc receptor-mediated phagocytosis of rat macrophages.

The features and function of IgM-FcR of rat peritoneal macrophages were studied. Macrophages specifically bind and phagocytose ox red blood cells coated with rat IgM (EA-IgM) through a specific receptor. This receptor is trypsin sensitive and its activity requires Ca++ ions. Both sodium azide and low temperature (4 degrees) inhibit the bindings as well as ingestion of EA-IgM by macrophages, suggesting the metabolically dependent character of the interaction between EA-IgM and macrophages. Colchicine inhibits the binding of EA-IgM by macrophages. Similarly, the ingestion of EA-IgM was also inhibited when peritoneal exudate cells (PEC) were pre-treated with colchicine or vinblastine or cytochalasin B. It is suggested that cytoskeletal elements of macrophages play an important role both in the binding of EA-IgM to their receptors and in the subsequent internalization of the receptor-ligand complexes. Ingestion of soluble IgM antibodies containing immune complexes (IC) resulted in a release of beta-glucuronidase from macrophages.

Assay of serum free fatty acids by extraction-photometric procedure.

Reaction conditions for extraction-photometric determination of free fatty acids in serum were studied. The results were found to be influenced by (a) sodium chloride concentration in the copper reagent, (b) the kind of standard solution used, (c) centrifugation of the reaction mixture and (d) serum phospholipids. A micromethod based on the formation of free fatty acids-copper soaps with a stable copper reagent and sensitive indicator for copper, 2-(2-thiazolylazo)-4-methoxyphenol, is described.