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BACKGROUND: Whole-body cryotherapy (WBC) is used as a conditioning method for athletes. However, the scientific evidence for its effects is still insufficient. OBJECTIVE: To elucidate the effects of transient WBC on the expression of heat shock protein (HSP) 70 and the secretion of related hormones in humans. MATERIALS AND METHODS: The participants in this study were six healthy adult men. WBC was performed for 3 min in a booth at a temperature in the range of -150 to -120°C, and measurements were taken immediately before (Pre), immediately after (Post), and 60 min after WBC (Post60). For measurement of core body temperature (gastrointestinal temperature), participants ingested a capsule-type wireless temperature sensor. The body surface temperature was measured using a noncontact thermometer, and measurements were taken at four sites on the body surface (chest, abdomen, front of the thigh, and front of the lower thigh). Leukocyte count, lactate dehydrogenase, creatine kinase, hemoglobin, hematocrit, adrenaline, noradrenaline, cortisol, adrenocorticotropic hormone (ACTH), erythropoietin, and HSP70 in the collected blood were measured. RESULTS: The results showed a decrease in body surface temperature and an increase in noradrenaline and ACTH immediately after WBC. In addition, the core body temperature decreased 60 min after WBC, accompanied by an increase in HSP70 expression. CONCLUSION: WBC may increase HSP70 expression via noradrenaline and ACTH. The results of this study suggest the usefulness of WBC in triggering protein synthesis and the maintenance of immune function after training.

Aim: Stroke is well known to lead to hypertension; nevertheless, the role of vascular function in hypertension remains unclear. In this study, we aimed to clarify the mechanism underlying increased arterial stiffness following stroke. Methods: The cardio-ankle vascular index (CAVI) was measured in five New Zealand White rabbits. Under general anesthesia, intracranial pressure (ICP) was increased by injecting saline (15 mL) into the cisterna magna. ICP was monitored using a catheter inserted into the subarachnoid space via right frontal bone craniotomy. Blood pressure (BP), CAVI, and common carotid flow (CCF) were evaluated, and the responses of these parameters to increased ICP were analyzed. Results: Saline injection into the cisterna magna increased the ICP by over 20 mmHg. Both BP and CAVI increased from 63.2±4.84 to 128.8±14.68 mmHg and from 4.02±0.28 to 4.9±0.53, respectively. Similarly, BP and CCF increased. When hexamethonium was administered before the increase in ICP, the increase in BP (132.2±9.41 mmHg with 10 mg/kg hexamethonium vs. 105.6±11.01 mmHg with 100 mg/kg hexamethonium) and CAVI (5.02±0.64 with 10 mg/kg hexamethonium vs. 4.82±0.42 with 100 mg/kg hexamethonium) were suppressed in a dose-dependent manner. Conclusion: Increased ICP causes an increase in BP and CAVI, suggesting that enhanced stiffness of the muscular arteries contributes to high BP. Blocking the autonomic nervous system with hexamethonium suppresses the increase in BP and CAVI, indicating that these increases are mediated by activation of the autonomic nervous system.

Aim: In the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), a multicenter randomized controlled trial, pitavastatin significantly reduced cardiovascular (CV) events compared to atorvastatin in patients with hypercholesterolemia. To investigate the mechanism by which pitavastatin preferentially prevents CV events, we investigated the relationship between CV events and cardio-ankle vascular index (CAVI) using the TOHO-LIP database. Methods: For the subgroup analysis, we selected patients from a single center, Toho University Sakura Medical Center. After excluding those who had CV events at baseline or during the first year, 254 patients were enrolled. The primary end point was the same as that of TOHO-LIP, and three-point major cardiac adverse events (3P-MACE) was added as secondary end point. Results: The cumulative 5-year incidence of 3P-MACE (pitavastatin 1.6%, atorvastatin 6.1%, P =0.038) was significantly lower in pitavastatin group (2 mg/day) than in atorvastatin group (10 mg/day). CAVI significantly decreased only in pitavastatin group during the first year (9.50–9.34, P =0.042), while the change in low-density lipoprotein cholesterol (LDL-C) did not differ between the two groups. The change in CAVI during the first year positively correlated with 3P-MACE and tended to be an independent predictor of 3P-MACE in Cox proportional hazards model (hazard ratio, 1.736; P =0.079). The annual change in CAVI throughout the observation period was significantly higher in subjects with CV events compared to those without. Conclusions: In this subgroup analysis, the reduction in CV events tended to be associated with the CAVI-lowering effect of pitavastatin, which was independent of the LDL-C-lowering effect.

Kazuhiro Shimizu,1 Mao Takahashi,1 Shuji Sato,1 Atsuhito Saiki,1 Daiji Nagayama,1,2 Takashi Hitsumoto,3 Akira Takahara,4 Kohji Shirai1,5 1Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba, Japan; 2Department of Internal Medicine, Nagayama Clinic, Oyama, Tochigi, Japan; 3Hitsumoto Medical Clinic, Shimonoseki, Yamaguchi, Japan; 4Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan; 5Department of Internal Medicine, Seijinkai Mihama Hospital, Chiba, Chiba, JapanCorrespondence: Kazuhiro Shimizu, Department of Internal Medicine, Toho University Sakura Medical Center, 561-4 Shimoshizu, Sakura, Chiba, 285-8741, Japan, Tel +81-43-462-8811, Fax +81-43-462-8820, Email k432@sakura.med.toho-u.ac.jpAbstract: Predictive factors for vascular events have not been established. The vasculature of the atheroma is supplied by penetration of the vasa vasorum through the smooth muscle cell layer from the adventitia. Smooth muscle cell contraction induces compression of the vasa vasorum, resulting in ischemia in intimal atheromatous lesions. Cardio-ankle vascular index (CAVI) has become known as an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle. CAVI reflects the progress of arteriosclerosis, and a rapid rise in CAVI indicates arterial smooth muscle cell contraction. We hypothesized that rapidly increased arterial stiffness evaluated by CAVI may be a predictor of impending cardiovascular events.Keywords: arterial stiffness, stress, plaque rupture, CAVI

Waon therapy is a form of thermal treatment in a dry sauna developed by Tei. Although Waon therapy is reportedly effective for chronic heart failure (CHF) patients, not all patients respond to the therapy. The reason for this ineffectiveness has not been fully clarified. The cardio-ankle vascular index (CAVI) is an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle, and it is thought to reflect some of the afterload of the left ventricle. We investigated the effects of Waon therapy on CAVI and plasma brain natriuretic peptide (BNP) level to clarify the usefulness of CAVI during Waon therapy.CHF patients (n = 21) treated with Waon therapy (2 weeks of 10 sessions) were divided into two groups: responders with an improved BNP level (n = 11) and nonresponders with no improvement in BNP (n = 10). CAVI was measured using Vasela 1500.A significant decrease in CAVI (median and interquartile range) was observed in the responder group (from 10.3 [9.6, 11.6] to 9.6 [8.6, 10.3], P = 0.021), whereas no change was observed in the nonresponder group (from 9.6 [8.6, 10.5] to 9.5 [9.1, 11.2], P = 0.919). The incidence of rehospitalization or cardiac death due to heart failure was significantly higher in patients in whom Waon therapy was ineffective at 12 months of follow-up (log-rank P = 0.001).The effectiveness of Waon therapy in CHF patients may be reflected by the improvement in CAVI.

Hypertension increases arterial stiffness, leading to dysfunction and structural changes in the left atrium (LA) and left ventricle (LV). However, the effects of hypertension on the right atrium (RA) and the right ventricle are still not fully understood. The purpose of this study was to clarify whether there is an interaction not only in the left ventricular system but also in the right ventricular system in hypertensive patients with preserved LV ejection fraction. The current retrospective observational study included patients (n = 858) with some risk of metabolic abnormalities (hypertension, diabetes, and dyslipidemia) who had visited our hospital and undergone echocardiography between 2015 and 2018. Among them, we retrospectively studied 165 consecutive hypertensive patients with preserved LV ejection fraction who had echocardiography performed on the same day as a cardio-ankle vascular index (CAVI) in our hospital. The phasic function of both atria was evaluated by two-dimensional speckle-tracking echocardiography. CAVI was measured using Vasela 1500 (Fukuda Denshi®). In the univariate analysis, CAVI was significantly correlated with LA and RA conduit function (LA conduit function, r = −0.448, p = 0.0001; RA conduit function, r = −0.231, p = 0.003). A multivariate regression analysis revealed that LA and RA conduit function was independently associated with CAVI (LA, t = −5.418, p = 0.0001; RA, t = −2.113, p = 0.036). CAVI showed a possibility that the association between heart and vessels are contained from not only LA phasic function but also RA phasic function in hypertensive patients.

An animal study demonstrated that 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), a major bioactive compound in Japanese pungent spice wasabi, has an action of inhibiting the activation of calpain-1 (a protease). Increases in calpain activity can cause continual strength loss after eccentric exercise. It remains to be determined in humans whether 6-MSITC intake would modulate calpain and/or muscle damage responses after eccentric exercise. We performed a randomized, double-blind, crossover design study wherein eight healthy young males were randomly assigned to ingest 9 mg/day of 6-MSITC or placebo from 1 day before exercise to 4 days after exercise (30 maximal isokinetic eccentric contractions of the elbow flexors using an isokinetic dynamometer). Calpain-1 concentration, inflammatory and muscle damage markers (creatine kinase activity, urinary titin concentration, muscle strength, range of motion, muscle soreness and transverse relaxation time) were assessed. Plasma calpain-1 concentration after eccentric exercise was similar between the placebo- and 6-MSITC-treated conditions. All muscle damage and inflammatory markers were not affected by 6-MSITC relative to those in the placebo-treated condition. Our results suggest that 6-MSITC has no effect on plasma calpain-1 concentration and muscle damage and inflammatory markers measured after eccentric exercise.

We aimed to evaluate whether changes in the noninvasively assessed urinary N-terminal fragment of titin (U-titin) concentration may be associated with those of serum creatine kinase (CK) activity, transverse relaxation time (T

Background The role of arterial stiffness in the pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is unclear. The cardio-ankle vascular index (CAVI) is a novel arterial stiffness index reflecting stiffness of the arterial tree from the origin of the aorta to the ankle, independent from blood pressure at the time of measurement. CAVI reflects functional stiffness, due to smooth muscle cell contraction or relaxation, and organic stiffness, due to atherosclerosis. Here, we report the case of a patient with an increased CAVI due to CTEPH and the improvement after riociguat administration and balloon pulmonary angioplasty (BPA). Case presentation A 65-year-old man suffered from dyspnea on exertion, and he was diagnosed with distal CTEPH. The mean pulmonary artery pressure (mPAP) was 51 mmHg, and the initial CAVI was 10.0, which is high for patient's age. In addition to right ventricular dysfunction, left ventricular dysfunction was observed as reduced global longitudinal strain (GLS-LV). After riociguat administration, CAVI decreased to 9.1 and GLS-LV improved from -10.3% to -17.3%, although pulmonary hypertension remained (mPAP 41 mmHg). Subsequently, a total of five BPA sessions were performed. Six months after the final BPA, mPAP decreased to 19 mmHg and GLS-LV improved to 19.3%. The patient was symptom free and his 6-minute walk distance improved from 322 m to 510 m. CAVI markedly decreased to 5.8, which is extremely low for his age. Conclusion These observations suggested that arterial stiffness as measured by CAVI was increased in CTEPH, potentially deteriorating cardiac function because of enhanced afterload. The mechanism of the increase of CAVI in this case of CTEPH was obscure; however, riociguat administration and BPA might improve the pathophysiology of CTEPH partly by decreasing CAVI.

Background Venous thromboembolism (VTE) may present acutely as pulmonary embolism (PE), and its late complications include chronic thromboembolic pulmonary hypertension (CTEPH). PEs may arise from thrombi originating in a venous aneurysm, in rare cases of the popliteal vein. Case presentation A 77-year-old woman was referred to our hospital due to respiratory distress. Computed tomography revealed pulmonary thrombi and a thrombus in a popliteal vein aneurysm (PVA); PE was diagnosed. After 3 months of anticoagulant therapy (rivaroxaban), her pulmonary hypertension showed little improvement. She underwent perfusion scintigraphy, which showed multiple perfusion defects, and Swan-Ganz catheterization. Mean pulmonary artery pressure was 26 mmHg. Pulmonary angiography revealed organized distal thrombi. Based on these findings, we diagnosed CTEPH due to recurrent formation of thrombi in the PVA. Conclusion Asymptomatic PVA can lead silently to PE and CTEPH. The possibility of asymptomatic recurrent VTE should be considered in patients with pulmonary hypertension and PVA.

Kazuhiro Shimizu,1 Mao Takahashi,1 Shuji Sato,1 Atsuhito Saiki,1 Daiji Nagayama,1 Masashi Harada,2 Chikao Miyazaki,2 Akira Takahara,3 Kohji Shirai1 1Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Chiba, Japan; 2Department of Neurosurgery, Toho University Omori Medical Center, Omori, Tokyo, Japan; 3Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, JapanCorrespondence: Kohji ShiraiDepartment of Internal Medicine, Toho University Sakura Medical Center, 561-4 Shimoshizu, Sakura City, Chiba, 285-8741, JapanTel +81-43-462-8811Fax +81-43-462-8820Email kshirai@kb3.so-net.ne.jpAbstract: Cardiovascular diseases have been recognized as the main cause of death all over the world. Recently, the established cardio-ankle vascular index (CAVI) has become known as an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle. CAVI reflects the progress of arteriosclerosis, and a rapid rise in CAVI indicates arterial smooth muscle cell contraction. Considering the vasculature of the atheroma where vasa vasorum penetrates the smooth muscle cell layer and supplies blood to the intimal atheromatous lesion, a rapid rise of CAVI means “choked” atheroma. Thus, we proposed a “smooth muscle cell contraction” hypothesis of plaque rupture.Keywords: arterial stiffness, atherosclerosis, smooth muscle cell contraction, CAVI

Myocardial injury is a problem associated with percutaneous coronary intervention (PCI). This study aimed to clarify the role of nicorandil administration in preventing myocardial injury. This study included patients with stable angina who underwent PCI from November 2013 to June 2016. Of 58 consecutive patients, the first 20 patients received only saline infusion after PCI (control group); the other 38 patients received a continuous intravenous infusion of nicorandil and saline after PCI (nicorandil group). Troponin I and brain natriuretic peptide (BNP) levels were measured. Vascular parameters, such as blood pressure (BP), cardiac output, cardio-ankle vascular index (CAVI), and estimated systemic vascular resistance (eSVR), were measured. Troponin I of both groups increased 12 h after PCI. Changes in BNP levels between immediately after PCI and 12 h after PCI were significantly higher in the control than in the nicorandil group (10.8 ± 44.2 vs. − 2.6 ± 14.6 pg/ml, p = 0.04). In the nicorandil group, BP, eSVR, and CAVI decreased significantly at 12 h after PCI compared with those immediately after PCI (p r = 0.36, p r = − 0.47, p

The relative usefulness of arterial stiffness parameters on renal function remains controversial. This study aimed to compare the predictive ability of three arterial stiffness parameters at baseline; cardio-ankle vascular index (CAVI), heart-ankle pulse wave velocity (haPWV) and CAVI 0 , a variant of CAVI that theoretically excludes dependence on blood pressure, for renal function decline in Japanese general population.A total of 27 864 Japanese urban residents without renal impairment at baseline who participated in two to eight consecutive (mean 3.5 ± 1.7 times) annual health examinations were studied.During the study period, 6.6% of participants developed renal function decline (estimated glomerular filtration rate60 ml/min per 1.73 m 2 ), all of whom had relatively high values in all arterial stiffness parameters. In receiver-operating characteristic curve analysis, the discriminatory power for renal function decline showed a decreasing trend of CAVI to haPWV to CAVI 0 (C-statistic: 0.740 vs. 0.734 vs. 0.726). The cut-offs were CAVI 8.0, haPWV 7.23 and CAVI 0 11.6. In Cox-proportional hazards analysis for increase of each parameter above cut-off or by 1 standard deviation (SD) adjusted for two models of confounders, only CAVI always contributed significantly to renal function decline. Restricted cubic spline regression analysis suggested that CAVI most accurately reflected the risk of renal function decline.Increase in arterial stiffness parameters, especially CAVI, may represent a major modifiable risk factor for renal function decline in the general population. Further research is needed to examine whether CAVI-lowering interventions contribute to the prevention of chronic kidney disease.

BACKGROUND Excessive training stress can result in decreased performance and deep fatigue due to hormonal changes. There are few available data on recovery methods for mood disturbance, especially fatigue, after high-intensity training. This study, therefore, aimed to examine the effects of mild hyperbaric oxygen at 1.3 atmospheres absolute with 31% oxygen on mood disturbance induced by high-intensity exercises. METHODS Ten healthy adult men participated in and completed 2 trials: the control (CON) trial and the mild hyperbaric oxygen (MHO) trial. In a randomized crossover design, each subject cycled for 60 min at the physical work capacity at 75% of their maximal heart rate and were subsequently exposed to the CON and MHO conditions for 60 min as the recovery period. RESULTS During the 20 to 40 min recovery time points, the average change ratio of heart rates was lower in the MHO trial than in CON (p < 0.05). We observed that the fatigue-inertia, tension-anxiety, and total mood disturbance Profile of Mood States (POMS) scores decreased 60 min post-exercise in the MHO trial, but no differences of these score were observed in the CON trial. There were no differences in oxidative stress, derived-reactive oxygen metabolites, and biological antioxidant potential between both trials. These results suggest that impaired mood states induced by high-intensity exercise can be improved early by MHO without any changes in oxidative stress. This improvement may be associated with decreased heart rate secondary to MHO exposure after the high intensity exercise. CONCLUSIONS We conclude that MHO can improve mood disturbances, especially in the fatigue-inertia and tension-anxiety domains, after high-intensity exercise. This study suggest that MHO is potentially an effective recovery method for mood states after high-intensity training.

Fencing is suggested as one of the most dangerous sporting events in terms of dehydration because of the uniform and gear covering the entire body. We aimed to elucidate the change in hydration status before and after training in elite fencing athletes in winter along with the assessment of sex and fencing style differences.Twenty-seven elite fencing athletes (14 males and 13 females) belonging to the Japanese National Team participated in this clinical survey. Dehydration status before and after winter training was assessed using body mass change, fluid intake, urine osmolarity, urine specific gravity (USG), and sodium, potassium, chlorine, and creatinine levels.More than half of the participants (59.3%) drank water and tea during training. The change rate of body mass (males vs. females, 1.61±0.82% vs. 0.45±0.68%, P0.01; foil vs. epee, 2.25±0.45% vs. 1.16±0.72%, P0.05) and sweating rate (males vs. females, 938±251 g/h vs. 506±92 g/h, P0.01; foil vs. epee, 1136±156 g/h vs. 796±207 g/h, P0.05) during training showed significant differences between sexes and fencing styles. Of all participants, 66.7% were dehydrated (USG≥1.020), and 37.0% were seriously dehydrated (USG≥1.030) before training.Fencing athletes may be susceptible to severe dehydration before training, even in winter. Additionally, males and foil fencers appear to be at a greater risk than females and epee fencers of developing dehydration during exercise.

Although elasticity of the conduit arteries is known to be contribute effective peripheral circulation via Windkessel effects, the relationship between changes in intra-aortic blood volume and conduit artery elasticity remains unknown. Here we assessed the effects of change in intra-aortic blood volume induced by blood removal and subsequent blood transfusion on arterial stiffness and the involvement of autonomic nervous activity using our established rabbit model in the presence or absence of the ganglion blocker hexamethonium (100 mg/kg). Blood removal at a rate of 1 mL/min gradually decreased the blood pressure and blood flow of the common carotid artery but increased a stiffness indicator the cardio-ankle vascular index, which was equally observed in the presence of hexamethonium. These results suggest that arterial stiffness acutely responds to changes in intra-aortic blood volume independent of autonomic nervous system modification.

We report a case of idiopathic orbital inflammation with a shallow anterior chamber and choroidal detachments. This study involved an 87-year-old female patient who presented at our department after becoming aware of the progression of diplopia. Examination of the patient’s right eye revealed proptosis, as well as conjunctival edema with dilated and tortuous blood vessels. The right-eye anterior chamber was shallow, and fundus examination revealed marked choroidal detachments. Magnetic resonance imaging revealed enlargement of the right-orbit extraocular muscles and a suspected compression of the right-orbit superior and inferior ophthalmic veins, yet no expansion of the cavernous sinus. We diagnosed the patient as having idiopathic orbital inflammation in her right orbit, and subsequently started corticosteroid therapy. One week after initiating treatment, the anterior chamber was found to be nearing a normal depth, and the choroidal detachments were found to have disappeared. Our findings revealed that the inflammatory swelling of the extraocular muscle due to idiopathic orbital inflammation resulted in compression of the right-orbit superior and inferior ophthalmic veins, thus leading to an apparent choroidal circulation disorder that presented with a shallow anterior chamber and marked choroidal detachments.

Background: This study aims to investigate the health condition of university judo athletes during a period of weight loss before a competition, using secretory immunoglobulin A (SIgA) in saliva. Methods: The subjects were 30 university judo athletes, who were divided into three groups: control group (n = 10), under 5% weight loss group (n = 10), and over 5% weight loss group (n = 10). The items evaluated were body weight measurements, salivary SIgA level and its secretion rates, incidences of symptoms of upper respiratory tract infections, and mental state. Results: The over 5% body weight loss group had significantly lower SIgA secretion rates on the first day and third day before the real competition compared to those of the control group. Furthermore, the over 5% body weight loss group had an increased number of symptoms of upper respiratory tract infections. Alterations in mental statuses were also seen, such as decreased vitality and increased fatigue on the day before the competition in the over 5% weight loss group. Conclusions: This study shows that over 5% body weight loss in judo athletes induces a decrease in the salivary SIgA secretion rate and causes health condition of the body and the mind to deteriorate. J Clin Med Res. 2019;11(12):798-806 doi: https://doi.org/10.14740/jocmr3998

Aim: The cardio-ankle vascular index (CAVI) represents the blood pressure-independent arterial stiffness from the origin of the aorta to the ankle. CAVI0 has been proposed as a variant index. We aimed to clarify the difference between CAVI and CAVI0 among large populations, and to explore reasons of the difference. Methods: The subjects were 5,293 Japanese healthy and 3,338 hypertensive people. Simple and multiple regression analyses were performed using age, sex, body mass index, systolic, and diastolic blood pressure (Pd) as variables. Sub-group analysis was performed by sex and age. The CAVI values with and without adjustment by reference pressure were also compared. Results: CAVI had a positive correlation with Pd, while CAVI0 had a negative correlation with Pd in the healthy population. The CAVI values of the hypertensive group were higher than those of healthy group in both men and women, but the CAVI0 values in women of the hypertensive group in the 30–39 age group was significantly lower than that of the corresponding healthy group. Differences of CAVI values with or without modification using the reference pressure were 1.09% ± 1.38% for the healthy group and 3.68% ± 1.66% for the hypertensive group. Conclusion: CAVI showed the expected values, but CAVI0 showed inexplicable results in the healthy and hypertensive populations. The differences were due to the strong dependency of CAVI0 on Pd. Differences of CAVI values with or without reference pressure were negligible. These results indicate that CAVI obtained by the VaSera system is appropriate, but CAVI0 is not.

The α-actinin-3 proteins regulate muscle function and are located in the Z-line of the fast skeletal muscle. A common null polymorphism of R577X in α-actinin-3 gene (