Shuji Yakubo

Prolonged Survival of Fully Mismatched Cardiac Allografts and Generation of Regulatory Cells by Sairei-to, a Japanese Herbal Medicine

Sairei-to (TJ114), a 12-component Japanese herbal medicine, is used to treat immune-related diseases. We investigated the effects of oral administration of TJ114 in a murine model of cardiac transplantation with fully mismatched allografts. Untreated CBA mice rejected C57BL/6 hearts acutely (median survival time [MST], 7 days), whereas survival of allografts from mice given TJ114 was significantly prolonged (MST >100 days). Secondary CBA recipients of C57BL/6 hearts also had prolonged allograft survival (MST >100 days) after adoptive transfer of whole or CD4+ splenocytes from primary CBA allograft recipients given TJ114. None of the individual components of TJ114 prolonged allograft survival, suggesting that its effects require administration of the combination agent. In mixed leukocyte cultures, proliferation of splenocytes from TJ114-treated CBA recipients was markedly suppressed compared with that of splenocytes from untreated mice, and interferon-&ggr; production was significantly reduced. Thus, in our model, TJ114 treatment induced hyporesponsiveness to cardiac allografts and generated CD4+ regulatory cells.

Intra-QRS high-frequency ECG changes with ischemia: Is it possible to evaluate these changes using the signal-averaged holter ECG in dogs?

The purpose of this experiment is to study the possibility of intra-QRS high-frequency electrocardiographic (HFECG) changes for the evaluation of and recovery from myocardial ischemia in both the time-domain and spectral-turbulence analyses on the signal-averaged ECG using the Holter ECG monitoring (Holter SAECG) system. A balloon catheter was inserted into the left anterior descending coronary artery (LAD of 8 mongrel dogs and was maintained inflated for 2 hours to occlude the LAD and then was deflated to allow for reperfusion. The cardiac signal from the three orthogonal leads of the surface ECG (X, Y, and Z) was recorded and analyzed with a Del Mar Avionics (model 459, Irvine, CA) recorder and analyzer (model 563). The Holter SAECG was assessed before the LAD occlusion phase (control), during the coronary occlusion phase (ischemia), after the reperfusion phase (recovery). To evaluate intra-QRS ECG changes in the time-domain analysis, root-mean-square (RMS) voltage of the entire QRS in 40-250 HZ (40 RMS), 100-250 Hz (100 RMS), and 150-250 Hz (150 RMS) were studied and the vector magnitude of the QRS was depicted. In the spectral-turbulence analysis and spectrocardiogram to study the discordance of the ECG wave front velocity by fast Fourier transformation analysis, the interslice correlation mean (IC mean) and interslice correlation standard deviation (IC SD), which were calculated as the mean and standard deviation of the Pearson correlation coefficient of each time slice with its neighbor, were investigated. In the time-domain analysis, the LAD occlusion by balloon catheter at ischemia produced a reduction in 40 RMS, 100 RMS, and 150 RMS, while a restoration was seen at recovery in 40 RMS and 100 RMS. In the spectral-turbulence analysis, LAD occlusion at ischemia caused a decrease in IC mean and an increase in IC SD. The waveform of the vector magnitude and the spectrocardiogram seen at control showed changes with ischemia and was restored at recovery with the coronary reperfusion. It was thought possible to capture the intra-QRS HFECG changes that occur during myocardial ischemia and recovery from it in the time-domain analysis and spectral-turbulence analysis on the Holter SAECG system in spite of the limitation of this methodology. To evaluate myocardial ischemia and recovery, this method should be useful clinically.

Detection of late potentials. Comparison of two commercial high-resolution ECG systems.

Signal-averaged electrocardiogram (SAECG) is used for detection of ventricular late potentials (LPs) in cardiac patients. As many commercial SAECG systems become available, it is essential to determine if they provide equivalent diagnostic information. Two high-resolution (Hi-Res) ECG systems (MAC-12, Marquette Electronics, Inc (MEI), Milwaukee, WI and LVP101, Arrhythmia Research Technology (ART), Austin, TX) were tested on 143 subjects (13 controls and 130 cardiac patients, 21 of whom were tested for inducible ventricular tachycardia [VT]). Late potential measurements (total QRS duration, high-frequency low-amplitude signal duration, and root-mean-square voltage) obtained from the two systems were in good agreement in most of the controls and patients. Application of Multicenter criteria for the MEI system and Gomes criteria for the ART system yielded very good agreement in LP diagnosis (at least 2 parameters abnormal). The two Hi-Res systems predicted inducible VT with good accuracy. The MEI system gave slightly higher sensitivity (90% vs 70%) and specificity (91% vs 82%) than the ART system in patients tested for inducible VT. In controls, both systems gave the same specificity (92%) and the LP diagnosis agreed in all controls (100%). Although the number of patients was small, neither sensitivity nor specificity were significantly different between the two systems at p < 0.05. To conclude, MEI and ART Hi-Res systems gave very similar LP diagnoses when appropriate criteria were applied.

Effects of the herbal medicine composition “Saiko-ka-ryukotsu-borei-To” on the function of endothelial progenitor cells in hypertensive rats

Endothelial progenitor cells (EPCs) are known to repair vascular injuries. Recent studies suggest that Saiko-ka-ryukotsu-borei-To (SKRBT), a traditional herbal medicine that has been used to treat stress-related neuropsychiatric disorders, has protective effects on cardiovascular diseases such as hypertension and arteriosclerosis. Spontaneously hypertensive rats (SHRs) were fed diets containing lyophilized SKRBT extract for 6 weeks. Peripheral blood mononuclear cells (MNCs) were isolated and cultured to assay EPC colony formation. Oxidative stress in MNCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay and flowcytometric analyses. Treatment with SKRBT increased EPC colony numbers significantly (p<0.05) with decrease in oxidative stress and without affecting blood pressure in SHRs. Treatment with SKRBT did not reduce the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in cardiovascular organs. Serum IL-6 level was significantly reduced. SKRBT is a feasible herbal medicine that protects against cardiovascular diseases through an increase in EPC function along with anti-oxidative effects, and may affect the link between chronic inflammation and cardiovascular disease.

Modification of an abdominal diagnosis teaching simulator to reproduce patterns of resistance to pressure

Within the Kampo medical system, there exists a system specific to Japan of abdominal diagnosis called abdominal palpation, or Fukushin, which is used to obtain a holistic picture, called an abdominal pattern, of the physical indications in the abdominal area. In order to educate students in this system, we have devised and continued to develop a Fukushin simulator, incorporating various improvements as appropriate. The present study describes some recent additions to the model with the aim of increasing its applicability across a broad range of abdominal patterns.

Systematic Review: Effects of the Kampo Formula Yokukan-San-Ka-Chimpi-Hange on Behavioral and Psychological Symptoms of Dementia

Introduction: Randomized usual-case controlled studies on Japanese dementia patients with behavioral and psychological symptoms were conducted to examine the effects of Kampo medicine Yokukan-San (YKS) on the behavioral and psychological symptoms of dementia (BPSD). These studies showed that YKS is effective in treating BPSD. Yokukan-San-Ka-Chimpi-Hange is a Kampo medicine made by adding dried citrus peel and pinellia tuber to YKS. In Japan, we usually administer Yokukan-San-Ka-Chimpi-Hange as Kracie Yokukan-San-Ka-Chimpi-Hange extract granules (KB-83), produced by Kracie Pharma, Ltd. (Tokyo, Japan). Methods: We investigated 3 trials carried out on the use of KB-83 for the treatment of severe dementia in elderly. Results: KB-83 showed no change in core symptoms after administration in cases of dementia, but significant improvements in BPSD were reported. KB-83 was particularly effective in treating aggressive symptoms such as restlessness or abusive language. Conclusion: In the treatment of dementia, we think that the administration of KB-83 is effective in mitigating the BPSD, and that further studies are need to investigate the effects of EK-83.

Kampo Medical Education for University Students of Health Education

学校や一般社会で健康教育活動を将来担う大学生を対象として，漢方医学についての講義を行う機会があった。このような学生に対する漢方医学教育の目標の設定は検討されていない。我々は漢方医学の必要性を理解し，将来これに関する適切な助言ができることを目標として講義を行った。講義の前後のアンケート調査を検討すると，漢方医学に関する我々の考えている望ましい認識は講義前の58.0 ± 15.4％から講義には88.5 ± 10.2％と増加した。現在行われている漢方医学の有用性に関しては，極めて有用，あるいは有用という認識に関して，講義前は58.4％であったが，講義後には95.9％となった。講義により漢方医学に関する充分な認識にもとづいて，将来，彼らが学校や社会において，漢方医学に関しても適切な健康教育活動を行うことが期待される。