Protective Effects of Japanese Soybean Paste (Miso) on Stroke in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP)

[BACKGROUND AND HYPOTHESIS] Soybean isoflavones have been shown to reduce the risk of cerebral infarction in humans according to epidemiological studies. However, whether intake of miso can reduce the incidence of stroke in animal models remains unknown. In this study, we investigated the effects of soybean paste (miso) in an animal model of stroke. [METHODS] Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a miso diet (normal diet 90%, miso 10%; final NaCl content 2.8%), a high salt diet (normal diet and NaCl 2.5%; final NaCl content 2.8%), or a low salt diet (normal diet; final NaCl content 0.3%). [RESULTS] Kaplan–Meier survival curves revealed a significantly lower survival rate in the high salt group compared to the miso group (P = 0.002) and the low salt group (P ≤ 0.001). Large hemorrhagic macules were found in the cerebrum in the high salt group, whereas none were found in the other 2 groups. There were also fewer histological and immunohistochemical changes in the brain and kidneys in the miso group compared to the high salt group. [CONCLUSION] Our results suggest that miso may have protective effects against stroke despite its high salt content.This work was supported by a grant-in-aid from the Central Miso Institute, Tokyo, Japa

Estimation of Arterial Viscosity Based on an Oscillometric Method and Its Application in Evaluating the Vascular Endothelial Function

This paper proposes an algorithm for estimating the arterial viscosity using cuff pressures and pulse waves measured by an automatic oscillometric sphygmomanometer. A change in the arterial viscosity during the enclosed-zone flow-mediated dilation test is calculated as an index for evaluating the vascular endothelial function %η. In all, 43 individuals participated in this study. After the index %η was calculated, the accuracy of the index %η in distinguishing healthy subjects and subjects at a high risk of arteriosclerosis was tested via a receiving operating characteristic (ROC) analysis. The calculated %η for the healthy participants and those at a high risk of arteriosclerosis was 13.4 ± 55.1% and −32.7 ± 34.0% (mean ± S.D.), respectively. The area under the ROC curve was 0.77. Thus, it was concluded that the proposed method can be used to evaluate the vascular endothelial function.This research was partly supported by the Transportation Technology Development Promotion Competitive Funding Program from Ministry of Land, Infrastructure, Transport and Tourism, and the Center of Innovation Program from Japan Science and Technology Agency

Low body mass index is a risk factor forimpaired endothelium-dependent vasodilation in humans: role of nitric oxide and oxidative stress

AbstractObjectivesThe purpose of this study was to evaluate the relationship between body mass index (BMI), including low BMIs, and endothelial function.BackgroundEpidemiologic study has demonstrated that not only obesity but also a low BMI may be a risk factor for cardiovascular disease.MethodsThe forearm blood flow (FBF) response to acetylcholine (ACh) and isosorbide dinitrate (ISDN) was measured in 87 healthy young men (15 low BMI, 51 normal, 14 obese, and 7 extremely obese).ResultsPlasma concentrations of 8-hydroxy-2′-deoxyguanosine and serum concentrations of malondialdehyde-modified low-density lipoprotein were higher in low BMI, obese, and extremely obese subjects than in normal subjects and were similar among the low BMI, obese, and extremely obese groups. The FBF response to ACh was greater in the normal group than in the other groups (p < 0.001), and was lower in the extremely obese group as compared with the other groups (p < 0.001). The ACh-stimulated vasodilation was similar between the low BMI group and the obese group. The ISDN-stimulated vasodilation was similar in all four groups. There were no significant differences in ACh-stimulated vasodilation between the four groups after the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine infusion. Co-infusion of vitamin C augmented the FBF response to ACh in low BMI, obese, and extremely obese groups—but not in normal BMI group.ConclusionsThese findings suggest that not only obesity but also a low BMI may be a risk factor for impaired endothelium-dependent vasodilation through the increased oxidative stress, leading to the reduced bioavailability of NO

Quantitative Evaluation of Pain during Electrocutaneous Stimulation using a Log-Linearized Peripheral Arterial Viscoelastic Model

In clinical practice, subjective pain evaluations, e.g., the visual analogue scale and the numeric rating scale, are generally employed, but these are limited in terms of their ability to detect inaccurate reports, and are unsuitable for use in anesthetized patients or those with dementia. We focused on the peripheral sympathetic nerve activity that responds to pain, and propose a method for evaluating pain sensation, including intensity, sharpness, and dullness, using the arterial stiffness index. In the experiment, electrocardiogram, blood pressure, and photoplethysmograms were obtained, and an arterial viscoelastic model was applied to estimate arterial stiffness. The relationships among the stiffness index, self-reported pain sensation, and electrocutaneous stimuli were examined and modelled. The relationship between the stiffness index and pain sensation could be modelled using a sigmoid function with high determination coefficients, where R2 ≥ 0.88, p < 0.01 for intensity, R2 ≥ 0.89, p < 0.01 for sharpness, and R2 ≥ 0.84, p < 0.01 for dullness when the stimuli could appropriately evoke dull pain.This work was supported by the Center of Innovation Program from Japan Science and Technology Agency.Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-21223-1

Age, gender, insulin and blood glucose control status alter the risk of ischemic heart disease and stroke among elderly diabetic patients

<p>Abstract</p> <p>Background</p> <p>We analyzed the effects of insulin therapy, age and gender on the risk of ischemic heart disease (IHD) and cerebrovascular accident (CVA) according to glycemic control.</p> <p>Methods and Results</p> <p>We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) of type 2 diabetes patients (n = 4014) for 2 years. The primary endpoint was the onset of fatal/non-fatal IHD and/or CVA, which occurred at rates of 7.9 and 7.2 per 1000 person-years, respectively. We divided diabetic patients into four groups based on age (≤ 70 and > 70) and hemoglobin A1C levels (≤ 7.0 and > 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure and low HDL-C in patients under 70 years of age with fair glycemic control and was associated with low diastolic blood pressure in the older/fair group. Interestingly, insulin use was associated with IHD in the older/poor group (OR = 2.27, 95% CI = 1.11-5.89; p = 0.026) and was associated with CVA in the older/fair group (OR = 2.09, 95% CI = 1.06-4.25; p = 0.028). CVA was associated with lower HDL-C and longer duration of diabetes in younger/poor glycemic control group. Results by stepwise analysis were similar. Next, patients were divided into four groups based on gender and diabetic control(hemoglobinA1C < or > 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure in male/fair glycemic control group, age in male/poor control group, and short duration of diabetic history in females in both glycemic control groups. Interestingly, insulin use was associated with IHD in the male/poor group(OR = 4.11, 95% CI = 1.22-8.12; p = 0.018) and with CVA in the female/poor group(OR = 3.26, 95% CI = 1.12-6.24; p = 0.02). CVA was associated with short duration of diabetes in both female groups.</p> <p>Conclusions</p> <p>IHD and CVA risks are affected by specific factors in diabetics, such as treatment, gender and age. Specifically, insulin use has a potential role in preventing IHD but may also be a risk factor for CVA among the diabetic elderly, thus revealing a need to develop improved treatment strategies for diabetes in elderly patients. The Japan Cholesterol and Diabetes Mellitus Study was formulated to evaluate them(Umin Clinical Trials Registry, clinical trial reg. no. UMIN00000516; <url>http://www.umin.ac.jp/ctr/index.htm</url>).</p

Effect of evodiamine on catecholamine secretion from bovine adrenal medulla

The effect of evodiamine on catecholamine secretion from bovine adrenal medulla was investigated. Evodiamine, a bioactive component isolated from dry unripened fruit of Evodia rutaecarpa Bentham, was found to stimulate the secretion of catecholamine from perfused bovine adrenal medulla at a concentration of 10 μM and its effect persisted for at least 30 min. This stimulatory effect of evodiamine was abolished by omission of Ca2+ from the perfusion fluid. Evodiamine (0.1-10 μM) markedly enhanced the secretion of catecholamine from the adrenal medulla induced by acetylcholine (100 μM) or high K+(56 mM). The secretion of catecholamine was promptly enhanced by acetylcholine or high K+, but returned to the control level on treatment for 20 min. However, when evodiamine was added to the perfusion fluid after acetylcholine or high K+ stimulation for 10 min, the secretion of catecholamine again increased greatly. These results indicate that evodiamine not only stimulated the secretion of catecholamine from bovine adrenal medulla but also reversed insensitivity of these cells to acetylcholine or high K+ stimulation

Novel Oral Derivative UD-017, a Highly Selective CDK7 Inhibitor, Exhibits Anticancer Activity by Inducing Cell-Cycle Arrest and Apoptosis in Human Colorectal Cancer

Objective: This study aimed to investigate the anticancer profile of a new cyclin-dependent kinase 7 (CDK7) inhibitor, UD-017, by examining its mechanism of action using HCT-116 colorectal cancer cells. Methods: The anticancer properties of UD-017 were assessed using several assays, including in vitro kinase, proliferation, and apoptosis assays, western blot analysis, and an in vivo xenograft mouse model. Results: UD-017 significantly inhibited CDK7 activity (IC50 = 16 nM) with high selectivity in an in vitro kinase assay testing a panel of over 300 proteins and lipid kinases. UD-017 also inhibited the growth of HCT-116 cells (GI50 = 19 nM) and inhibited the phosphorylation of various downstream mediators of CDK7 signaling. In cell cycle and apoptosis assays using HCT-116 cells, UD-017 increased the number of cells in both G1 and G2/M phases and induced apoptosis. In vivo, UD-017 inhibited tumor growth in an HCT-116 xenograft mouse model by 33%, 64%, and 88% at doses of 25, 50, and 100 mg/kg, respectively, with clear dose-dependency. Co-administration of 5-FU and 50 mg/kg UD-017 had a strong synergistic effect, as reflected in the complete inhibition of tumor growth. Conclusion: CDK7 may play a major role in colorectal cancer growth by regulating the cell cycle and apoptosis. UD-017 is a promising candidate therapeutic agent for the treatment of cancer involving CDK7 signaling

Response of Arterial Mechanical Impedance to Different Concentrations of Remifentanil during Abdominal Laparoscopic Colectomy

A specific and reliable method for monitoring analgesia during general anesthesia is urgently required. Previously, we introduced a method that indicates arterial mechanical properties for estimating arterial wall stiffness (K). However, whether the response of K actually indicates changes in remifentanil target concentrations under continuous surgical stress, is unclear. Thus, we aimed to evaluate how K responds to different remifentanil target concentrations. This prospective study enrolled 30 patients who underwent laparoscopic colectomy. The patients received 3 different effect-site concentrations (2, 4, and 6 ng/ml) of remifentanil 3 times during the study period. The K values at 4-ng/ml administration were used as control values (Kcontrol). K values at 6-ng/ml administration (K6ng) and those at 2-ng/ml administration (K2ng) were normalized by dividing them by the control values. The results showed that K responded to the changes in remifentanil concentration, significantly decreasing at 6-ng/ml remifentanil effect-site concentration and increasing at 2-ng/ml concentration. The stress response at low analgesia was higher than that at high analgesia, and, as predicted, normalized K2ng was significantly greater than normalized K6ng. In conclusion, we found that K is a sensitive stress response monitor and dynamically responds to changes in remifentanil concentration in invasive stimulation during laparoscopic colectomy

Assessment of Lower-limb Vascular Endothelial Function Based on Enclosed Zone Flow-mediated Dilation

This paper proposes a novel non-invasive method for assessing the vascular endothelial function of lower-limb arteries based on the dilation rate of air-cuff plethysmograms measured using the oscillometric approach. The principle of evaluating vascular endothelial function involves flow-mediated dilation. In the study conducted, blood flow in the dorsal pedis artery was first monitored while lower-limb cuff pressure was applied using the proposed system. The results showed blood flow was interrupted when the level of pressure was at least 50 mmHg higher than the subject’s lower-limb systolic arterial pressure and that blood flow velocity increased after cuff release. Next, values of the proposed index, %ezFMDL, for assessing the vascular endothelial function of lower-limb arteries were determined from 327 adult subjects: 87 healthy subjects, 150 subjects at high risk of arteriosclerosis and 90 patients with cardiovascular disease (CAD). The mean values and standard deviations calculated using %ezFMDL were 30.5 ± 12.0% for the healthy subjects, 23.6 ± 12.7% for subjects at high risk of arteriosclerosis and 14.5 ± 15.4% for patients with CAD. The %ezFMDL values for the subjects at high risk of arteriosclerosis and the patients with CAD were significantly lower than those for the healthy subjects (p < 0.01). The proposed method may have potential for clinical application.This work was supported by JSPS KAKENHI Grant Number 16K21076

A Logical Method of Selecting an Approach for Amplatzer Septal Occluder Implantation : Using Transesophageal Echocardiography to Reduce Procedure Durations and Avoid Complications

Percutaneous closure of atrial septal defects using an Amplatzer Septal Occluder (ASO) has recently become the procedure of first choice. However, when ASO deployment is difficult, procedures may be prolonged and complications may occur. We investigated a method for identifying cases in which ASO deployment would be difficult. After retrospectively identifying 70 patients (age: 4.1-70.4 years; body weight: 15.6-77.3 kg) who underwent atrial septal defect closure using an ASO in 2007 or later, we classified them into three groups: Group A, implantation by a conventional approach; Group B, implantation by a right upper pulmonary vein approach, and Group C, change from a conventional to a right upper pulmonary vein approach. Characteristics of the groups were compared. Individually, none of the investigated characteristics was suitable for identifying difficult cases. Furthermore, we observed no consistent trends between aortic rim deficiency and ASO diameter, or between SG/IAS angle, which is the angle formed by the super stiff guidewire (SG) and the intra-atrial septum (IAS). However, the ASO diameter divided by the diameter of the left atrium (ASO/LA) correlated with the SG/IAS angle in Group C. Using this correlation, ASO implantation is predicted to be difficult in patients with an ASO/LA (%) ratio exceeding the (SG/IAS angle) × 1.44 + 48.1, which represents the 95th percentile of Group C. Graphing the SG/IAS angle and the ASO/LA ratio can identify cases in which ASO implantation may be difficult. We consider this method of selecting an approach to be extremely useful for avoiding various risks