Repolarization disparity as a predictor of response to Head up Tilt-table Test in pediatric syncope.

BACKGROUND: Head up Tilt-table Test (HUTT) is a practical examination of the most common type of pediatrics syncope. The electrocardiographic (ECG) changes during this test, show the autonomic defects that cause neuraly-mediated syncope in response to tilting process. METHODS: All pediatric syncope patients referred to our center in a 1-year period, were included in the study. HUTT was performed and patients were classified into two groups of Negative and Positive HUTT results, and the latter group was subclassified as three subgroups of "vasodepressor", "cardioinhibitory" and "mixed type" responses to HUTT. QT and corrected QT (QTc) dispersion was measured by the baseline standard 12-lead ECG obtained before HUTT. RESULTS: Eighty-six patients with a mean age of 12.19 ± 5.34 were included. Patients with positive HUTT were significantly younger and male gender was more prevalent in this group. Mean QT dispersion was significantly higher in patients with positive HUTT result and also in patients with mixed response to HUTT compared to isolated vasodepressor response. Duration of QTc interval did not change between different study groups. Reciever-Operating-Characteristic (ROC) analysis showed that QT dispersion higher than 32 ms is a significant predictor of positive HUTT result (with 92% sensitivity and 98% specificity) and values higher than 40 ms can predict the mixed type of response to HUTT (with 84% sensitivity and 63% specificity). CONCLUSIONS: Baseline myocardial repolarization disparity significantly correlates with susceptibility to symptomatic vasovagal syncope. This pathology seems to play its role mainly via excessive vagotonic response to sympathetic activation during HUTT process (known as cardioinhibitory response).

Changes in endothelial progenitor cell subsets in normal pregnancy compared with preeclampsia.

BACKGROUND: The results of studies measuring the number of endothelial progenitor cells (EPCs) in normal pregnancies and in preeclampsia have been highly controversial or even contradictory because of cross-sectional designs and different methodologies enumerating three distinct subsets of EPCs: circulating angiogenic cells (CAC), colony-forming unit endothelial cell (CFU-ECs), and endothelial colony forming cells (ECFCs). To provide a clear explanation for these underlying controversies, we designed a prospective study to compare the number of all EPC subsets between three trimesters of normal gestation and a case-control study to compare these values as preeclampsia occurs with those from gestational age (GA) matched normal pregnancy. METHODS: Samples from peripheral blood of nine women were taken during their three consecutive trimesters of normal pregnancy, and from eight women with preeclampsia. To cover most of the reported phenotypes for CACs and ECFCs in the literature, we enumerated 13 cell populations by quantitative flow cytometry using various combinations of the markers CD34, CD133, CD309, and CD45. We used routine culturing techniques to enumerate CFU-ECs. RESULTS: The numbers of CACs and ECFCs were higher in women with preeclampsia (p = 0.014). By contrast, preeclampsia was associated with a reduced number of CFU-ECs (p = 0.039). The CAC number rose with the increase in GA (p = 0.016) during normal pregnancy, while the number of CFU-ECs and ECFCs did not differ during the trimesters. CONCLUSION: Although we did demonstrate an increase in absolute counts of CACs and ECFCs in preeclampsia, fewer colony formation capacities indicated a loss in their functional capabilities. By contrast, the number of CACs increased without alterations in colony formation ability in normal pregnancy with the growth of the fetus. Here, by comparing different methodologies to calculate the number of EPC subsets, we could imitate the existing controversy in the literature for such calculations, which may help to elucidate clearer explanations.

Colony forming unit endothelial cells do not exhibit telomerase alternative splicing variants and activity.

INTRODUCTION: Endothelial progenitor colony forming unit-endothelial cells (CFU-EC) were first believed to be the progenitors of endothelial cells, named endothelial progenitor cells. Further studies revealed that they are monocytes regulating vasculogenesis. The main hindrance of these cells for therapeutic purposes is their low frequency and limited replicative potentials. This study was undertaken to determine telomerase activity and alternative splicing variants in CFU-EC as a potential cause of limited replicative capacity in these cells. METHODS: CFU-EC were isolated from peripheral blood using a standard cell culture assay. Colonies were detached mechanically and alternative splicing variant mRNA were evaluated using real-time PCR. Telomerase enzyme activity was assessed using telomerase repeat amplification protocol. The same procedures were done on the cancer cell line Calu6 as the positive control. RESULTS: The cultured peripheral blood mononuclear cells formed colonies with spindle-shaped monocytic cells sprouted from the clusters. These morphological characteristics fulfill the definition of CFU-EC. Telomere length amplification protocol assay revealed no telomerase activity and real-time PCR showed no expression of telomerase enzyme mRNA in CFU-EC. Both parameters were significantly higher in the cancer cell line Calu6 taken as the positive control. CONCLUSION: The absence of telomerase activity in the CFU-EC is a result of pre-transcriptional regulation of gene expression rather than other mechanisms for controlling telomerase activity such as post-transcriptional modifications. This finding can explain the limited proliferative activity of CFU-EC cells. We propose that absence of telomerase activity in CFU-EC can be attributable to their more mature monocytic nature that needs further investigations.