Electrochemistry of photochromic [2.2]paracyclophane-bridged imidazole dimers: rational understanding of the electronic structures.

[2.2]Paracyclophane-bridged imidazole dimers, which show unique fast photochromism, have various practical applications in industry. To put them to practical use, it is necessary to prepare various types of the imidazole dimers which have different color, reaction rate, sensitivity, etc. One of the simple methods for modulating the optical properties is to add substituents and sensitizers. However, it is difficult to estimate the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels of the imidazole dimers by optical spectroscopy because the LUMO of the imidazole dimers are optically inactive. In the present study, we applied electrochemistry and density functional theory to reveal the effect of substituents on the electronic states of the imidazole dimers. We revealed that the HOMO and LUMO of the imidazole dimers are localized over only one of the imidazole rings of the imidazole dimer. By comparing the measured LUMO energies of the imidazole dimers and calculated LUMO energies of several visible sensitizers, we found which visible sensitizers work in the imidazole dimer systems. These fundamental insights provide useful information for understanding the electronic structures of the imidazole dimers and give a strategy for designing novel fast photochromic molecules whose photochromism is triggered by visible light.

Identification of unusual reentry circuit sites of nonischemic ventricular outflow tract tachycardia.

BACKGROUND: Reentrant ventricular outflow tract (OT) tachycardia is rare in patients with nonischemic heart disease. The mechanism of ventricular tachycardia (VT) arising from the region of the aortic sinus of Valsalva (ASOV) is usually focal, rather than reentrant. Consequently, less is known about reentrant circuits in the OT and the aortic sinuses. The purpose of this study was to evaluate existence of reentry circuits in these areas using entrainment mapping techniques. METHODS: We performed electrophysiological study in 51 consecutive patients with idiopathic or nonischemic symptomatic VT arising from the OT. Six of these patients were found to have VT of reentrant mechanism with 8 VT morphologies. Entrainment mapping, electroanatomical mapping (in 2 patients), and radiofrequency catheter ablation were performed. RESULTS: Pacing entrained the VT at 93 sites, 52 of which were determined to be in the reentry circuit based on matching of the postpacing interval and VT cycle length. Of the reentry circuit sites, 6 were in the aortic sinus, 43 were below the aortic valve, and 3 were in the right OT below the pulmonary valve. Classification of reentry circuit sites identified 7 as exit, 1 as central-proximal, 19 as inner loop, and 25 as outer loop sites. Catheter ablation terminated VT at 4 of the 6 aortic sinus sites and 4 of the 46 OT sites (P = 0.0006). CONCLUSIONS: We definitively demonstrated involvement of the ASOV in OT reentrant tachycardia using entrainment mapping. It may be useful for successful VT ablation to identify reentry circuit localization.

Prevalence and influence of hyperthyroidism on the long-term outcome of catheter ablation for drug-refractory atrial fibrillation.

BACKGROUND: Hyperthyroidism is usually regarded as a reversible cause of atrial fibrillation (AF); however, one-third of patients remain in AF despite euthyroid restoration. We hypothesized that a significant number of AF patients with hyperthyroidism (Hyperthyroid-AF) as well as those without (Non-thyroid-AF) would benefit from catheter ablation of AF (AF ablation). This study aimed to clarify the prevalence of hyperthyroidism in candidates for AF ablation and to compare the long-term outcome of AF ablation between the Hyperthyroid-AF and Non-thyroid-AF groups. METHODS AND RESULTS: This study enrolled 337 consecutive patients with AF who underwent a first AF ablation that mainly involved extensive encircling pulmonary vein isolation. Sixteen (4.7%) patients had hyperthyroidism; the remaining 321 (95.3%) did not. In the Hyperthyroid-AF patients, a euthyroid state had been restored for at least 3 months before the ablation. During a mean follow-up period of 4±1 years after ablation, AF recurred in 7 patients (44%) with Hyperthyroid-AF and in 139 patients (43%) with Non-thyroid-AF (P=0.91 by the log-rank test). In the multivariate Cox regression models, the presence of hyperthyroidism was not associated with a higher risk of AF recurrence (hazard ratio, 0.87; 95% confidence interval, 0.40-1.88; P=0.73). CONCLUSIONS: In the AF ablation candidates without structural heart disease, hyperthyroidism was not rare. After euthyroid restoration on pharmacological treatment, hyperthyroidism was not associated with a higher risk of AF recurrence.

Spectroelectrochemistry of a photochromic [2.2]paracyclophane-bridged imidazole dimer: clarification of the electrochemical behavior of HABI.

The photochromic behavior of the imidazole dimers can be attributable to the photoinduced homolytic cleavage of the C-N bond between the two imidazole rings. On the other hand, although the simultaneous formation of the imidazolyl radical and imidazole anion by the one-electron reduction of an imidazole dimer was reported, no definitive evidence for this electrochemical reaction has been demonstrated. We report the first direct evidence for the electrochemical generation of the imidazolyl radical from the radical anion of the imidazole dimer by conducting the UV-vis-NIR spectroelectrochemical analysis of the [2.2]paracyclophane-bridged imidazole dimer.

Riboflavin depletion impairs cell proliferation in adult human duodenum: identification of potential effectors.

BACKGROUND AND AIMS: Riboflavin (vitamin B2) is an essential dietary component with a known function in oxidative metabolism. Our previous data using a rat model of riboflavin deficiency suggested that riboflavin also functions as a luminal signaling molecule regulating crypt development and cell turnover. Riboflavin deficiency is prevalent in both high- and low-income countries across the globe. This study aims to establish whether riboflavin deficiency has consequences for gastrointestinal (GI) morphology in adults and what the effects and effectors of any such alteration may be. METHODS: Duodenal biopsies and blood samples were collected from a cross-section of gastroscopy patients. Crypt morphology and cell division were studied by immunohistochemistry, and biochemical riboflavin status was determined. Additionally a cell culture model of riboflavin deficiency was developed and analyzed using a combination of flow cytometry, and microarray and clonogenic assays. RESULT: Duodenal crypts from subjects in the lowest quartile of riboflavin status were significantly shorter (P=0.023), less cellular (P=0.007), and had fewer cell divisions (P=0.034) than the crypts of subjects in the top quartile of riboflavin status. Following riboflavin depletion of colon cells in culture, cell cycle slowed. Microscopy revealed impaired mitosis and accumulation of aneuploid cells. Alterations in gene expression profiles reflected this alteration, with several mitosis-related genes altered, including AspM, cyclin B1, and Birc5 downregulated and Kif23 upregulated. Riboflavin depletion in vitro caused irreversible loss of proliferative potential of cells. CONCLUSIONS: Riboflavin depletion in adult humans impairs proliferation and proliferative potential of intestinal cells, which may have implications for gastrointestinal function.

Prevalence of electrocardiographic abnormalities in young, elite Japanese athletes.

BACKGROUND: The question as to whether or not electrocardiogram (ECG) evaluations should be performed in all athletes is still controversial. So, in this study, the prevalence of electrocardiographic abnormalities was evaluated in young, elite Japanese athletes. METHODS: Subjects included 174 male and 101 female Japanese athletes (mean age, 21.5 years). Sports activities included baseball, basketball, diving, fencing, gymnastics, judo, rhythmic gymnastics, soccer, swimming, tennis, track and field, volleyball, and water polo. A 12-lead resting ECG was recorded and evaluated. We used the criteria for distinctly abnormal ECG patterns as defined by Pelliccia et al. Subjects were divided into 2 groups on the basis of their exercise training type: an endurance training group and a static training group. RESULTS: Twenty six of 174 male subjects (14.9%) and 11 of 101 (10.9%) female subjects presented with abnormal ECG results. ECG abnormalities were observed much more frequently in track athletes compared to athletes of other sporting events. Field players did not present with any ECG abnormalities. Overall, the incidences of ECG abnormalities were statistically lower in the static exercise training group than in the endurance training group both in male and female. High voltage of left ventricle was observed in 114 of 175 male subjects (65.1%), and 27 of 101 female subjects (26.7%). CONCLUSIONS: The prevalence of ECG abnormalities in young, elite, Japanese athletes was comparable to that previously reported by both Western and Asian investigators.

Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake.

We recently reported that methionine-loaded human umbilical vein endothelial cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl radical generation and oxidation of lipids in LDL. Herein we have analysed the Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with cardiovascular disease (CVD). While reagent Hcy (< 50 microM) promoted copper-catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs promoted LDL protein nitration. In addition, LDL nitration was associated with enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein nitration and uptake by monocytes, but not carbonyl formation, was elevated in both RA and OA patients with CVD compared with disease-matched patients that had no evidence of CVD. Moreover, a direct correlation between plasma total Hcy (tHcy) and LDL uptake was observed. The present studies suggest that elevated plasma tHcy may promote LDL nitration and increased scavenger receptor uptake, providing a molecular mechanism that may contribute to the clinical link between CVD and elevated plasma tHcy.

Copper-mediated LDL oxidation by homocysteine and related compounds depends largely on copper ligation.

Oxidation of low-density lipoprotein (LDL) is thought to be a major factor in the pathophysiology of atherosclerosis. Elevated plasma homocysteine is an accepted risk factor for atherosclerosis, and may act through LDL oxidation, although this is controversial. In this study, homocysteine at physiological concentrations is shown to act as a pro-oxidant for three stages of copper-mediated LDL oxidation (initiation, conjugated diene formation and aldehyde formation), whereas at high concentration, it acts as an antioxidant. The affinity for copper of homocysteine and related copper ligands homocysteine, cystathionine and djenkolate was measured, showing that at high concentrations (100 microM) under our assay conditions, they bind essentially all of the copper present. This is used to rationalise the behaviour of these ligands, which stimulate LDL oxidation at low concentration but generally inhibit it at high concentration. Albumin strongly reduced the effect of homocystine on lag time for LDL oxidation, suggesting that the effects of homocystine are due to copper binding. In contrast, copper binding does not fully explain the pro-oxidant behaviour of low concentrations of homocysteine towards LDL, which appears in part at least to be due to stimulation of free radical production. The likely role of homocysteine in LDL oxidation in vivo is discussed in the light of these results.

Reentrant ventricular tachycardia originating in the right ventricular outflow tract: slow conduction identified by right coronary artery ostium pacing.

A case of reentrant ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT) is described. An electrophysiological study revealed that programmed stimulation from the right ventricle apex induced 2 types of VT with similar left bundle branch block configuration and inferior axis. Yet, VT cycle length (CL) was different; one was stable, sustained VT with a CL of 360 ms and the other was hemodynamically intolerable VT with a CL of 330 ms. Similarly for both VTs, perfect pace mapping was obtained at the anterior septum beneath the pulmonary valve in the RVOT, and exits of both VTs were very close. Entrainment mapping during stable VT was performed and the anterior septum RVOT was designated as the exit for the stable VT. Intriguingly, entrainment pacing from the ostium of the right coronary artery showed that the post-pacing interval was identical to VTCL. The stimulus to QRS interval was very long (340 ms) during entrainment with concealed fusion, and the right coronary artery ostium was therefore consistent with the VT reentry circuit inner loop or the upper portion of the VT reentry circuit exit. These findings suggest that the stable VT reentry circuit had a slow conduction zone from the ostium of the right coronary artery to the exit in the anterior septum RVOT. When radiofrequency catheter ablation was performed at the 2 exits of the anterior septum RVOT, both VTs then could not be induced.

Hyperhomocystinemia in children with inflammatory bowel disease.

OBJECTIVES: Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Plasma total homocysteine (tHcy) is a risk factor for vascular disease and has been implicated as a mediator of thromboembolic events in adults with IBD. The authors studied the link between tHcy and IBD in children, in whom associations may be clearer, and investigated associations with plasma von Willebrand factor antigen, a marker of vascular damage. METHODS: This cross-sectional study included 43 patients with IBD (27 Crohn disease, 9 ulcerative colitis, and 7 indeterminate colitis) and 46 control subjects from a pediatric gastroenterology clinic. Plasma tHcy, plasma 5-methyl tetrahydrofolate, red cell folate, plasma vitamin B12, plasma von Willebrand factor antigen, and methylene tetrahydrofolate reductase (MTHFR) genotype (for the C677T mutation) were measured. RESULTS: Plasma tHcy concentrations were higher in children with IBD than in control subjects, when corrected for age (P < 0.05), and plasma tHcy was negatively correlated with plasma 5 methyl tetrahydrofolate (P < 0.0005). Plasma 5 methyl tetrahydrofolate and age were the main predictors of plasma tHcy. Neither MTHFR genotype nor von Willebrand factor showed any association with any other measure, and there were no differences between children with IBD and control subjects. CONCLUSIONS: Elevated plasma tHcy is a consequence of IBD in children, probably mediated by poor folate status associated with diet or the pathophysiology of the disease.