Spatial Repolarization Heterogeneity Detected by Magnetocardiography Correlates with Cardiac Iron Overload and Adverse Cardiac Events in Beta-Thalassemia Major

Background

Patients with transfusion-dependent beta-thalassemia major (TM) are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events.

Methods and Results

Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG) to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QT_c (SI-QT_c), a standard deviation of QT_c (SD-QT_c), and a QT_c dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QT_c, SD-QT_c, and QT_c dispersion compared to the control subjects (all p values<0.001). Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20) compared to those with normal T2* (all p values<0.001). Log_e cardiac T2* correlated with SI-QT_c (r = −0.609, p<0.001), SD-QT_c (r = −0.572, p<0.001), and QT_c dispersion (r = −0.622, p<0.001), while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86), similar to that of cardiac T2*.

Conclusions

Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events.     

A highly conserved nuclear gene for low-level phylogenetics: elongation factor-1 alpha recovers morphology-based tree for heliothine moths

Molecular systematists need increased access to nuclear genes. Highly conserved, low copy number protein-encoding nuclear genes have attractive features for phylogenetic inference but have heretofore been applied mostly to very ancient divergences. By virtue of their synonymous substitutions, such genes should contain a wealth of information about lower-level taxonomic relationships as well, with the advantage that amino acid conservatism makes both alignment and primer definition straightforward. We tested this postulate for the elongation factor-1 alpha (EF-1 alpha) gene in the noctuid moth subfamily Heliothinae, which has probably diversified since the middle Tertiary. We sequenced 1,240 bp in 18 taxa representing heliothine groupings strongly supported by previous morphological and allozyme studies. The single most parsimonious gene tree and the neighbor-joining tree for all nucleotides show almost complete concordance with the morphological tree. Homoplasy and pairwise divergence levels are low, transition/transversion ratios are high, and phylogenetic information is spread evenly across gene regions. The EF-1 alpha gene and presumably other highly conserved genes hold much promise for phylogenetics of Tertiary age eukaryote groups.      

Phylogenetic studies of the genus <Emphasis Type="Italic">Cebus</Emphasis>(Cebidae-Primates) using chromosome painting and G-banding

Background  

Chromosomal painting, using whole chromosome probes from humans and Saguinus oedipus, was used to establish karyotypic divergence among species of the genus Cebus, including C. olivaceus, C. albifrons, C. apella robustus and C. apella paraguayanus. Cytogenetic studies suggested that the species of this genus have conservative karyotypes, with diploid numbers ranging from 2n = 52 to 2n = 54.     

Cigarette smoke extract induces HO‐1 expression in mouse cerebral vascular endothelial cells: Involvement of c‐Src/NADPH oxidase/PDGFR/JAK2/STAT3 pathway

Several chemicals present in cigarette smoke (CS) have been reported to induce heme oxygenase‐1 (HO‐1) expression, which represents a prime defense mechanism in protecting the cells from stress‐dependent adverse effects on peripheral vascular system. However, the effects of cigarette smoke extract (CSE) on HO‐1 induction and the mechanisms underlying CSE‐induced HO‐1 expression in brain vessels are not completely understood. Here, we used a mouse brain endothelial cell culture (bEnd.3) to investigate the effect of CSE on HO‐1 induction and the mechanisms underlying CSE‐induced HO‐1 expression in cerebral vessels. We demonstrated that sublethal concentrations of CSE (30 µg/ml) induced submaximal HO‐1 expression in bEnd.3 cells. NADPH oxidase‐dependent ROS generation played a key role in CSE‐induced HO‐1 expression. CSE‐induced HO‐1 expression was mediated through PDGFR/JAK2/STAT3 cascade, which was observed by pretreatment with the respective pharmacological inhibitors or transfection with PDGFR shRNA. CSE activated NADPH oxidase through c‐Src in bEnd.3 cells. Taken together, these results suggested that, in bEnd.3 cells, CSE‐induced HO‐1 expression was mediated through PDGFR/JAK2/STAT3 cascade, which was regulated by c‐Src or c‐Src activated‐NADPH oxidase/ROS. J. Cell. Physiol. 225: 741–750, 2010. © 2010 Wiley‐Liss, Inc.     

Biological Evaluation of Secondary Metabolites from the Root of Machilus obovatifolia

Bioassay‐guided fractionation of the root of Machilus obovatifolia led to the isolation of four new lignans, epihenricine B ( 1 ), threo‐(7′R,8′R) and threo‐(7′S,8′S)‐methylmachilusol D ( 2 and 3 ), and isofragransol A ( 4 ), along with 23 known compounds. The compounds were obtained as isomeric mixtures (i.e., 2 / 3 and 4 / 20 , resp.). The structures were elucidated by spectral analyses. Among the isolates, 1 , licarin A ( 12 ), guaiacin ( 14 ), (±)‐syringaresinol ( 21 ), and (?)‐epicatechin ( 23 ) showed ABTS (=2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) cation radical‐scavenging activity, with SC₅₀ values of 11.7±0.5, 12.3±1.1, 11.0±0.1, 10.6±0.3, and 9.5±0.2 μM in 20 min, respectively. In addition, kachirachirol B ( 17 ) showed cytotoxicity against the NCI‐H460 cell line with an IC₅₀ value of 3.1 μg/ml.     

Risk of Tuberculosis in Children with Juvenile Idiopathic Arthritis: A Nationwide Population-Based Study in Taiwan

Objective

We aimed to determine the risk of tuberculosis in children with juvenile idiopathic arthritis (JIA) in Taiwan.

Methods

We used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a nested case-control study. We identified a JIA cohort and matched each JIA child with non-JIA children for comparison. Methotrexate (MTX), tumor necrosis factor (TNF) inhibitor administration, and new tuberculosis cases were determined during our study period. To compare tuberculosis (TB) risk among our study groups, Cox proportional regression models were used to determine adjusted hazard ratios (aHRs).

Results

We identified 1495 children with JIA and 11592 non-JIA children. Majority (68.7%) children with JIA had not received MTX or TNF inhibitors; 23.9% used MTX without TNF inhibitors, and 7.4% received TNF inhibitors, irrespective of MTX administration. In total, 43 children developed tuberculosis. The overall tuberculosis infection rate for children with JIA was two times higher than that for non-JIA children. Compared with non-JIA children, children with JIA who used MTX without TNF inhibitors revealed a significantly increased of tuberculosis infection rate (aHR = 4.67; 95% CI: 1.65–13.17; P = 0.004). Children with JIA who either received TNF inhibitors or never used MTX and TNF inhibitors revealed a tuberculosis infection rate comparable to that of non-JIA children.

Conclusions

Analysis of nationwide data of Taiwan suggested that children with JIA were at higher risk of tuberculosis compared with those without JIA.     

A new model for fish ion regulation: identification of ionocytes in freshwater- and seawater-acclimated medaka (Oryzias latipes)

The ion regulation mechanisms of fishes have been recently studied in zebrafish (Danio rerio), a stenohaline species. However, recent advances using this organism are not necessarily applicable to euryhaline fishes. The euryhaline species medaka (Oryzias latipes), which, like zebrafish, is genetically well categorized and amenable to molecular manipulation, was proposed as an alternative model for studying osmoregulation during acclimation to different salinities. To establish its suitability as an alternative, the present study was conducted to (1) identify different types of ionocytes in the embryonic skin and (2) analyze gene expressions of the transporters during seawater acclimation. Double/triple in situ hybridization and/or immunocytochemistry revealed that freshwater (FW) medaka contain three types of ionocyte: (1) Na⁺/H⁺ exchanger 3 (NHE3) cells with apical NHE3 and basolateral Na⁺-K⁺-2Cl^? cotransporter (NKCC), Na⁺-K⁺-ATPase (NKA) and anion exchanger (AE); (2) Na⁺-Cl^? cotransporter (NCC) cells with apical NCC and basolateral H⁺-ATPase; and (3) epithelial Ca²⁺ channel (ECaC) cells [presumed accessory (AC) cells] with apical ECaC. On the other hand, seawater (SW) medaka has a single predominant ionocyte type, which possesses apical cystic fibrosis transmembrane conductance regulator (CFTR) and NHE3 and basolateral NKCC and NKA and is accompanied by smaller AC cells that express lower levels of basolateral NKA. Reciprocal gene expressions of decreased NHE3, AE, NCC and ECaC and increased CFTR and NKCC in medaka gills during SW were revealed by quantative PCR analysis.