Clinical Application of Intracoronary Ultrasound (IVUS) and Quantitative Coronary Angiography (QCA) to Assess Coronary Intervention and Atherosclerosis

Ischemic heart disease remains a major cause of mortality and morbidity in Europe, the United States and Japan. It has been proposed that coronary atherosclerosis is the consequence of the vascular response to injurious effects of exposure to the classical cardiovascular risk factors including smoking, diabetes, hypertension and hyperlipidemia. However, the relationship between such coronary risk factors and atherosclerotic coronary plaque burden has not yet been fully elucidated. The epidemic of cardiovascular disease demands further efforts to elucidate the mechanisms of atherosclerosis and further research to develop and guide treatments. Since Andreas R. Grüntzig performed the first percutaneous transluminal coronary angioplasty on September 16th 1977, coronary intervention has become accepted as an effective therapy for patients with coronary artery disease all over the world. The initial success achieved with percutaneous coronary intervention continues to be limited by restenosis. Intracoronary ultrasound (IVUS) studies reveal that late vessel remodeling and plaque growth plays an important role in the restenosis process. Coronary stenting, by supporting the vessel wall, limits early and late vessel remodeling and subsequently decreases restenosis. More recently short- to medium-term restenosis appears to have been further ameliorated by the advent of drug-eluting stent (DES) technologies. However, several limitations still restrict the widespread application of this technique including concerns about subacute or late stent thrombosis, the limited success rates of PCI for complex lesion morphology (e.g. chronic total occlusion (CTO)) and interventional cost. The ultimate goal of interventional cardiology is to disclose the mechanism of progression and regression of coronary atherosclerosis, and to provide less invasive and more effective treatments for the patients suffering from ischemic heart disease. Each interventional device should be carefully sized and deployed using reliable techniques such as intracoronary ultrasound (IVUS) and quantitative coronary angiography (QCA)

Fluctuation of spastic location in patients with vasospastic angina: A quantitative angiographic study

Objectives.: This study sought to determine whether the location of coronary spastic activity may change over time in patients with persistent variant angina. Background.: Although electrocardiographic studies have provided indirect evidence to indicate that the location of ischemia may change in patients with variant angina, it has not been tested by quantitative angiography whether the location of vasospastic activity may change over time. Methods.: Paired ergonovine provocation tests and coronary angiography were performed at a mean (±SD) interval of 43 ± 13 months apart in patients with persistent symptoms of vasospastic angina in the absence of significant atherosclerosis. A total of 87 spastic and nonspastic segments of 87 major vessels in 29 patients were analyzed by quantitative angiography at baseline, after the administration of ergonovine and after isosorbide dinitrate at the initial and follow-up tests. Results.: In 13 patients (group 1), coronary spasm was observed in the same 16 coronary segments at both the initial and follow-up ergonovine provocation tests. In 16 patients (group 2), the following angiographic changes occurred between the initial and follow-up tests in 48 major vessels: Of the 23 segments that developed spasm at the initial test, 10 did not have spasm at the follow-up test; of the 25 vessels that did not demonstrate spasm on the initial test, 12 demonstrated spasm on the follow-up test (a new site of spasm). Thus, in 22 (46%) of 48 vessels, fluctuation of spastic location was observed at follow-up. Conclusions.: Quantitative coronary angiography and repeated ergonovine tests revealed that some patients with persistent vasospastic angina demonstrate fluctuation of vasospastic location, whereas others exhibit a fixed location of vasospasm. Vasospastic angina may not only be a transient disease restricted in location, but may also be a persistent and variable condition involving multiple vessels over many years

Identification of lysophospholipid receptors in human platelets: the relation of two agonists, lysophosphatidic acid and sphingosine 1-phosphate

AbstractLysophosphatidic acid (LPA) and sphingosine 1-phosphate (Sph-1-P) are known as structurally related bio-active lipids activating platelets through their respective receptors. Although the receptors for LPA and Sph-1-P have been recently identified in various cells, the identification and characterization of ones in platelets have been reported only preliminarily. In this report, we first investigated the distinct modes of LPA and Sph-1-P actions in platelet activation and found that LPA functioned as a much stronger agonist than Sph-1-P, and high concentrations of Sph-1-P specifically desensitized LPA-induced intracellular Ca2+ mobilization. In order to identify the responsible receptors underlying these observations, we analyzed the LPA and Sph-1-P receptors which might be expressed in human platelets, by RT-PCR. We found for the first time that Edg2, 4, 6 and 7 mRNA are expressed in human platelets

IMPACT OF CORONARY ATHEROSCLEROSIS IN JAPANESE WOMEN WITH CHRONIC KIDNEY DISEASE

How do our brains transform the "blooming buzzing confusion" of daily experience into a coherent sense of self that can learn and selectively attend to important information? How do local signals at multiple processing stages, none of which has a global view of brain dynamics or behavioral outcomes, trigger learning at multiple synaptic sites when appropriate, and prevent learning when inappropriate, to achieve useful behavioral goals in a continually changing world? How does the brain allow synaptic plasticity at a remarkably rapid rate, as anyone who has gone to an exciting movie is readily aware, yet also protect useful memories from catastrophic forgetting? A neural model provides a unified answer by explaining and quantitatively simulating data about single cell biophysics and neurophysiology, laminar neuroanatomy, aggregate cell recordings (current-source densities, local field potentials), large-scale oscillations (beta, gamma), and spike-timing dependent plasticity, and functionally linking them all to cognitive information processing requirements.Air Force Office of Scientific Research (F49620-01-1-0397); National Science Foundation (SBE-0354378); Office of Naval Research (N00014-01-1-0624

Anomalous Surface Impedance in a Normal-metal/Superconductor Junction with a Spin-active Interface

We discuss the surface impedance (Z=R-iX) of a normal-metal/superconductor proximity structure taking into account the spin-dependent potential at the junction interface. Because of the spin mixing transport at the interface, odd-frequency spin-triplet s-wave Cooper pairs penetrate into the normal metal and cause the anomalous response to electromagnetic fields. At low temperature, the local impedance at a surface of the normal metal shows the nonmonotonic temperature dependence and the anomalous relation R>X. We also discuss a possibility of observing such anomalous impedance in experiments.Comment: 7pages, 7 figure

Daily intake of β-cryptoxanthin prevents bone loss by preferential disturbance of osteoclastic activation in ovariectomized mice

AbstractAlthough β-cryptoxanthin, a xanthophyll carotenoid, has been shown to exert an anabolic effect on bone calcification, little attention has been paid thus far to the precise mechanism of bone remodeling. Daily oral administration of β-cryptoxanthin significantly inhibited osteoclastic activation as well as reduction of bone volume in ovariectomized mice. In vitro studies revealed that β-cryptoxanthin inhibited differentiation and maturation of osteoclasts by repression of the nuclear factor-κB-dependent transcriptional pathway. Our results suggest that supplementation with β-cryptoxanthin would be beneficial for prophylaxis and for therapy of metabolic bone diseases associated with abnormal osteoclast activation

Association between the quality of life and asymptomatic episodes of paroxysmal atrial fibrillation in the J-RHYTHM II study

AbstractBackgroundParoxysmal atrial fibrillation (AF) patients have a reduced quality-of-life (QoL) despite the fact that the majority of AF episodes are asymptomatic. Asymptomatic AF is likely to be associated with substantial morbidity and mortality rates similar to those with symptomatic AF, whereas its effect on the QoL has not yet been clarified.PurposeWe studied the specific contribution of asymptomatic AF episodes to reducing the QoL.MethodsWe assessed the QoL in 233 patients with paroxysmal AF and hypertension (age 64.9±9.7 years, 71% male) enrolled in the Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) using an AF-specific QoL questionnaire (AFQLQ). The AFQLQ comprised 3 components: AFQLQ1, the frequency and duration of symptoms; AFQLQ2, severity of symptoms; and AFQLQ3, limitations in daily activities and mental anxiety. Higher scores indicated a better QoL. Each patient transmitted electrocardiograms for 30s daily at a predetermined time as well as whenever arrhythmia-related symptoms were experienced. We examined the relationship between the 3 AFQLQ components and frequency of symptomatic and asymptomatic AF episodes (days/month) during 12 months of follow-up.ResultsThe symptomatic and asymptomatic AF frequencies were 0.9±3.1 days/month and 1.5±3.5 days/month, respectively. AFQLQ1 negatively correlated with the symptomatic AF frequency (Spearman's correlation coefficient: r=−0.332, p<0.001). AFQLQ2 and AFQLQ3 correlated with both the symptomatic AF frequency (r=−0.27, p<0.001 and r=−0.265, p<0.001, respectively) and asymptomatic AF frequency (r=−0.197, p<0.01 and r=−0.229, p<0.005, respectively).ConclusionThe asymptomatic AF episode frequency correlates with a reduced QoL in patients with paroxysmal AF, suggesting that there would be psychological benefits to its reduction

Coronary lumen at six-month follow-up of a new radiopaque Cordis tantalum stent using quantitative angiography and intracoronary ultrasound.

To determine the reliability of geometric (edge-detection) quantitative coronary angiographic analysis (QCA) of restenosis within a new Cordis tantalum stent, QCA and intracoronary ultrasound (ICUS) measurements were compared in both an experimental restenosis model and in the clinical follow-up of patients. In the experimental series, Plexiglas phantom vessels with concentric stenosis channels ranging from 0.75 to 3.0 mm in diameter and with a reference diameter of 3.0 mm were imaged both before and after their insertion in tantalum stents. In the clinical series, the agreement of QCA and ICUS measurements were studied in 23 patients who had undergone coronary implantation of the new tantalum stent and in 23 patients who had undergone balloon angioplasty 6 months previously. The reliability of QCA declined in the presence of the radiopaque stent (accuracy of QCA decreased from -0.07 to -0.12 mm), whereas the reliability of lumen measurements by ICUS was independent of the presence of the radiopaque stent (-0.12 and -0.13 mm). Without the stent, the average minimal luminal diameter (MLD) obtained by QCA of the 1.00 mm Plexiglas vessel was 1.00 +/- 0.01 mm, and the 3.00 mm reference vessel diameter was 2.81 +/- 0.05 mm, providing a 64 +/- 1% diameter stenosis. After introduction of the stent, the average MLD and reference vessel diameter were 0.99 +/- 0.06 and 3.36 +/- 0.17 mm, respectively, providing a diameter stenosis of 71 +/- 2%. ICUS measurements (2.77 mm) of the reference vessel diameter (3.00 mm) were unaffected by the presence of the stent. (ABSTRACT TRUNCATED AT 250 WORDS

Initial periodontal treatment affects nucleotide-binding domain leucine-rich repeat-containing protein 3 inflammasome priming in peripheral blood mononuclear cells

Objective: Accumulating evidence suggests an association between periodontitis and several systemic diseases, such as atherosclerosis. In the lesions of these diseases, nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and caspase-1 form inflammasome complex, which leads to the functional maturation of interleukin (IL)-1β via cleavage of caspase-1 in macrophages. IL-1β plays a critical role in the etiology of these diseases; however, inflammasome priming?specifically, IL-1β and NLRP3 upregulation?is necessary for effective IL-1β production. We investigated the effect of initial periodontal treatment on the inflammasome priming of peripheral blood mononuclear cells (PBMCs). Methods: Twenty-two patients with chronic periodontitis were enrolled in this study and given initial periodontal treatment. Peripheral blood samples were collected at baseline and re-evaluation (41.1 ± 29.1 d after the treatment), and the relative expression of IL-1β, and three inflammasome components, ASC, NLRP3 and Caspase-1, mRNA was determined using quantitative reverse transcription PCR. PBMCs were stimulated with silica crystals, and the IL-1β secretion was measured via enzyme-linked immunosorbent assay. Results: Probing pocket depth and bleeding on probing (BOP) were significantly improved after the treatment. Expression of IL-1β and ASC in the PBMCs decreased after the treatment. PBMCs stimulated with silica crystals secreted IL-1β. The treatment attenuated IL-1β secretion by PBMCs in low BOP percentages group whereas IL-1β secretion was increased in high BOP percentages group. Conclusion: Periodontal treatment altered the inflammasome priming status of the PBMCs, however, the effects on systemic diseases need to be further investigated

Deficiency of the basic helix‐loop‐helix transcription factor DEC1 prevents obesity induced by a high‐fat diet in mice

Obesity is a major public health problem in developed countries resulting from increased food intake and decreased energy consumption and usually associated with abnormal lipid metabolism. Here, we show that DEC1, a basic helix‐loop‐helix transcription factor, plays an important role in the regulation of lipid consumption in mouse brown adipose tissue (BAT), which is the major site of thermogenesis. Homozygous Dec1 deletion attenuated high‐fat‐diet‐induced obesity, adipocyte hypertrophy, fat volume and hepatic steatosis. Furthermore, DEC1 deficiency increased body temperature during daytime and enhanced the expression of uncoupler protein 1, a key factor of thermogenesis, and various lipolysis‐related genes in interscapular BAT. In vitro experiments suggested that DEC1 suppresses the expression of various lipolysis‐related genes induced by the heterodimer of peroxisome proliferator‐activated receptor γ and retinoid X receptor α (RXRα) through direct binding to RXRα. These observations suggest that enhanced lipolysis in BAT caused by DEC1 deficiency leads to an increase in lipid consumption, thereby decreasing lipid accumulation in adipose tissues and the liver. Thus, DEC1 may serve as an energy‐saving factor that suppresses lipid consumption, which may be relevant to managing obesity.This work was supported by Grants‐in‐Aid for Science from the Japan Society for the Promotion of Science (grant numbers 22590223 and 2339042351)