Coronary Artery Spasm and Perivascular Adipose Tissue Inflammation: Insights From Translational Imaging Research

Perivascular adipose tissue, which constitutes perivascular components along with the adventitial vasa vasorum, plays an important role as a source of various inflammatory mediators in cardiovascular disease. Inflammatory changes in the coronary adventitia are thought to be involved in the pathogenesis of coronary artery spasm and vasospastic angina. Recent advances in translational research using non- invasive imaging modalities, including 18F-fluorodeoxyglucose PET and cardiac CT, have enabled us to visualise perivascular inflammation in the pathogenesis of coronary artery spasm. These modality approaches appear to be clinically useful as a non-invasive tool for examining the presence and severity of vasospastic angina

Use of a Caco-2 permeability assay to evaluate the effects of several Kampo medicines on the drug transporter P-glycoprotein

In modern medical care in which Kampo and Western drugs are often combined, it is extremely important to clarify drug–drug interaction (DDI) to ensure safety and efficacy. However, there is little evidence of DDI in Kampo medicines. Therefore, as part of our studies to clarify the DDI risk for Kampo medicines, we evaluated the effects of five Kampo medicines [yokukansan (YKS), rikkunshito (RKT), shakuyakukanzoto (SKT), hangeshashinto (HST), and goshajinkigan (GJG)] that are widely used in Japan, on drug transporter P-glycoprotein (P-gp) using a Caco-2 permeability assay. These Kampo medicines inhibited the P-gp transport of digoxin through a Caco-2 cell monolayer. The IC50 values were 1.94–10.80 mg/ml. Of the five Kampo medicines, YKS showed the strongest inhibition (IC50 = 1.94 mg/ml), which was attributed to Uncariae Uncis Cum Ramulus. Unfortunately, we could not find the active ingredients responsible for its action. Finally, the Igut/IC50 values for the five Kampo medicines were calculated, and the DDI risk was objectively evaluated according to the criteria in the DDI guidance issued by the Japanese Ministry of Health, Labor, and Welfare and the US Food and Drug Administration. The Igut/IC50 values for the five Kampo medicines were ≤3.4. As these values were <10, they were evaluated as having a weak P-gp inhibitory effect that does not require further verification in humans, suggesting that the DDI risk due to P-gp inhibition for these Kampo medicines is low. The results should provide useful clinical information on the safety and efficacy of the combined use of Kampo and Western medicines

A Biased Bayesian Inference for Decision-Making and Cognitive Control

Although classical decision-making studies have assumed that subjects behave in a Bayes-optimal way, the sub-optimality that causes biases in decision-making is currently under debate. Here, we propose a synthesis based on exponentially-biased Bayesian inference, including various decision-making and probability judgments with different bias levels. We arrange three major parameter estimation methods in a two-dimensional bias parameter space (prior and likelihood), of the biased Bayesian inference. Then, we discuss a neural implementation of the biased Bayesian inference on the basis of changes in weights in neural connections, which we regarded as a combination of leaky/unstable neural integrator and probabilistic population coding. Finally, we discuss mechanisms of cognitive control which may regulate the bias levels

A Decision-Theoretic Model of Behavior Change

Undesirable habitual or addictive behaviors are often difficult to change. The issue of “behavior change” has long been studied in various research fields. Several models for behavior change have converged to the hypothesis that attitudes, norms, and self-efficacy are important determinants of intentions and behavior. To improve the accuracy of behavior-change models, some researchers have tried to combine behavioral economics models with existing models for behavior change. However, these attempts have failed because the existing models [e.g., Theory of Planned Behavior (TPB)] are not consistent with Expected Utility Theory (EUT), which underlies various behavioral economics models. In the present paper, we clarify the corresponding components between existing models for behavior change and EUT, and propose a new model, the Decision-Theoretic Model of behavior change (DTM), which is a natural extension of ordinary EUT

Right-sided infective endocarditis as a potentially fatal complication in patients with long-term refractory severe bradyarrhythmia after cervical spinal cord injury: A case report

AbstractBradyarrhythmia is usually a spontaneously subsiding complication of cervical spinal cord injury. However, in severe cases, it can lead to cardiac arrest. We report a case of cervical spinal cord injury, complicated by right-sided infective endocarditis after the placement of a temporary pacing catheter in the right ventricle for severe bradyarrhythmia that led to cardiac arrest. Although the patient׳s condition was successfully treated by pacing catheter removal and pharmacological therapy, right-sided infective endocarditis would be a fatal complication in cases of cervical spinal cord injury where cardiac pacing is required for long-term refractory severe bradyarrhythmia

Mechanisms of Coronary Artery Spasm

Recent clinical trials have highlighted that percutaneous coronary intervention in patients with stable angina provides limited additional benefits on top of optimal medical therapy. This has led to much more attention being paid to coronary vasomotion abnormalities regardless of obstructive or non-obstructive arterial segments. Coronary vasomotion is regulated by multiple mechanisms that include the endothelium, vascular smooth muscle cells (VSMCs), myocardial metabolic demand, autonomic nervous system and inflammation. Over the years, several animal models have been developed to explore the central mechanism of coronary artery spasm. This review summarises the landmark studies on the mechanisms of coronary vasospasm demonstrating the central role of Rho-kinase as a molecular switch of VSMC hypercontraction and the important role of coronary adventitial inflammation for Rho-kinase upregulation in VSMCs

Macrophage centripetal migration drives spontaneous healing process after spinal cord injury.

Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury

Burn-associated delayed dilated cardiomyopathy evaluated by cardiac PET and SPECT: Report of a case

AbstractDilated cardiomyopathy is a delayed-onset and rarely reported cardiac complication of burn injury although the mechanism remains unclear. We thus report a case of dilated cardiomyopathy following severe burn injury, in which technetium 99m sestamibi single-photon emission computed tomography (SPECT), iodine-123 beta-methyl-iodophenylpentadecanoic acid SPECT and 18F-fluorodeoxyglucose positron emission tomography (PET) were performed to evaluate the pathophysiologic condition in combination with cardiac catheterization and myocardial biopsy. The cardiac PET and SPECT images showed reduced myocardial blood flow, decreased fatty acid metabolism, and increased glucose utilization in the left ventricular lateral wall in spite of normal coronary angiography, no significant cardiac fibrosis, and inflammatory cell infiltration, which suggests that myocardial ischemia due to microcirculatory disturbance in hypermetabolic state associated with burn injury might be a causative mechanism of dilated cardiomyopathy in this case. A beta blocker, bisoprolol, was successfully introduced in this patient in combination with oral inotropic agents, pimobendan and digitalis after the prolonged use of intravenous dobutamine infusion, which might have been beneficial for this patient with burn-associated dilated cardiomyopathy not only to reduce regional myocardial ischemia but also to attenuate hypermetabolic state after severe burn injury.<Learning objective: Dilated cardiomyopathy complicated with burn injury has been reported to cause a sudden attack of dyspnea and death. This case report suggests that burn-associated dilated cardiomyopathy may be caused by relative myocardial ischemia due to microvascular disturbance in hypermetabolic state associated with burn injuries and can be treated effectively with beta blockers with or without oral inotropic agents.

Which Side-Bending X-ray Position is Better to Evaluate the Preoperative Curve Flexibility in Adolescent Idiopathic Scoliosis Patients, Supine or Prone?

Study Design Prospective cohort study. Purpose The present study aimed to evaluate the difference in the preoperative curve flexibility between the supine and prone positions in patients with adolescent idiopathic scoliosis (AIS). Overview of Literature In AIS, a side-bending view is necessary to differentiate a structural curve from a nonstructural curve using the Lenke classification system. However, there are no published studies about which position, supine or prone, is more effective when evaluating preoperative curve flexibility using side-bending X-ray images in AIS patients. Methods Radiographs were analyzed for 32 AIS patients (26 females, six males) who underwent posterior correction and fusion of their main thoracic (MT) curves. Cobb angles of MT, proximal thoracic (PT), and thoracolumbar/lumbar (TL/L) curves were measured preoperatively using upright, supine (anteroposterior and side-bending), and prone (posteroanterior and side-bending) X-rays. Results The average Cobb angles of PT, MT, and TL/L curves on preoperative upright/supine/prone X-rays were 29.1°/26.7°/26.6°, 60.7°/48.5°/48.2°, and 41.0°/32.6°/33.1°, respectively. The average Cobb angles of PT, MT, and TL/L curves on supine/prone sidebending X-rays were 19.2°/20.3°, 36.3°/36.4°, and 13.9°/15.7°, respectively. The flexibility rates of PT, MT, and TL/L curves in supine/prone positions were 35.3%/32.5%, 40.6%/40.2%, and 71.7%/68.2%, respectively. Comparing flexibility rates in the prone position with those in the supine position in each case, the average ratios of PT, MT, and TL/L curves were found to be 1.0, 1.0, and 0.9, respectively. There were no statistically significant differences between supine and prone side-bending X-ray measurements. However, the Lenke classification in six of 32 patients (18.8%) differed between supine and prone positions because the TL/L curve in the supine position was slightly more flexible than in the prone position. Conclusions Supine side-bending films may be suitable for the evaluation of preoperative curve flexibility in AIS, especially for lumbar modifier C