Health benefits of interval walking training.

Interval walking training (IWT) is a free-living training intervention involving alternating fast and slow walking cycles. IWT is efficacious in improving physical fitness and muscle strength, and reducing factors associated with lifestyle-related diseases. In individuals with type 2 diabetes, IWT improves glycemic control directly through enhanced glucose effectiveness, challenging conventional views on mechanisms behind training-induced improvements in glycemic control. Whereas adherence to IWT in short-term studies is high, ensuring long-term adherence remains a challenge, particularly in populations with chronic diseases and/or overweight/obesity. Long-term studies in real-world settings are imperative to ascertain the widespread effectiveness of IWT and elucidate its impact on hard endpoints.

Interval walking training in type 2 diabetes: A pilot study to evaluate the applicability as exercise therapy.

There are few established easy-to-perform exercise protocols with evidence-based effects for individuals with type 2 diabetes (T2D). A unique exercise regimen, interval walking training (IWT), has been reported to be beneficial for improving metabolic function, physical fitness and muscle strength in adults of overall health. This pilot study aims to demonstrate descriptive statistics of IWT adherence and changes in various data before and after the intervention of IWT in adults with T2D, perform statistical hypothesis testing, and calculate effect sizes. We performed a single-arm interventional pilot study with IWT for 20 weeks. We enrolled 51 participants with T2D aged 20-80 years with glycohemoglobin (HbA1c) levels of 6.5-10.0% (48-86 mmol/mol) and a body mass index of 20-34 kg/m2, respectively. The target was 60 min/week of fast walking for 20 weeks. The participants visited the hospital and were examined at 4-week intervals during this period. Between the start of IWT and after 20 weeks, we measured and evaluated changes in glucose and lipid metabolism data, body composition, physical fitness, muscle strength, dietary calorie intake, and daily exercise calories. All included participants completed IWT, with 39% of them reaching the target length of fast walking over 1,200 minutes in 20 weeks. In the primary outcome, HbA1c levels, and in the secondary, lipid metabolism and body composition, no significant changes were observed except for high-density lipoprotein cholesterol (HDL-C) (from 1.4 mmol/L to 1.5 mmol/L, p = 0.0093, t-test). However, in the target achievement group, a significant increase in VO2 peak by 10% (from 1,682 mL/min to 1,827 mL/min, p = 0.037, t-test) was observed. Effect sizes were Cohen's d = 0.25 of HDL-C, -0.55 of triglyceride, and 0.24 of VO2 peak in the target achievement group, which were considered to be of small to medium clinical significance. These results could be solely attributed to IWT since there were no significant differences in dietary intake and daily life energy consumption before and after the study. IWT could be highly versatile and was suggested to have a positive effect on lipid metabolism and physical fitness. In future randomized controlled trial (RCT) studies, the detailed effects of IWT, focusing on these parameters, will be examined. Trial registration: This trial was registered with the Japanese University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR: Usefulness on interval walking training in patients with type 2 diabetes. 000037303).

Effects of Interval Walking Training on Oral Health Status in Middle-Aged and Older Adults: A Case-Control Study.

The purpose of this study was to determine the effect of walking training "Interval Walking Training (IWT)" on oral health status. Participants were divided into two groups: an exercise intervention group and a non-intervention group (control). The intervention group consisted of 59 subjects (20 males, 39 females) aged 50 years or older who participated in the IWT program in Matsumoto from 2019 to April 2022. The control group consisted of 33 subjects (14 males and 19 females) aged 50 years or older who have visited Niigata University Medical and Dental Hospital and agreed to participate in the study. The intervention group underwent walking training (interval walking training) for at least 5-6 months. The walking training consisted of five sets of fast walking above 70% peak aerobic capacity for walking (VO2peak) for 3 min, followed by 3 min of slow walking at ~40% VO2 peak per day for more than four days/week. The oral health status was evaluated for the number of teeth, occlusal force, salivary occult blood, masticatory performance, and tongue pressure. A total of 57 participants were analyzed in the intervention group (18 males and 39 females, age: 66.7 ± 0.8 (mean ± S.E.) years) and 33 participants in the control group (14 males and 19 females, age: 74.5 ± 1.1 (mean ± S.E.) years). There were no significant differences in gender, salivary occult blood, tongue pressure, masticatory performance, or occlusal force between the two groups at the start of the intervention (p = 0.36, p = 0.48, p = 0.42, p = 0.58, and p = 0.08, respectively by unpaired t-test or χ2 test). On the other hand, there were significant differences in age and BMI, with a trend toward lower age and higher BMI in the intervention group (p < 0.001 and p < 0.001, respectively, by unpaired t-test). In terms of rate of change, the intervention group showed a significant increase in occlusal force (F = 4.5, p = 0.04, ANCOVA) and a significant decrease in BMI (F = 7.3, p = 0.009, ANCOVA). No significant differences were observed in the other measured items. It was found that walking training in both middle-aged and older people does not only affect the physical aspect of weight loss but may help maintain and improve the occlusal force.

Effects of Yogurt Intake on Cardiovascular Strain during Outdoor Interval Walking Training by Older People in Midsummer: A Randomized Controlled Study.

We examined whether post-exercise yogurt intake reduced cardiovascular strain during outdoor interval walking training (IWT) in older people during midsummer. The IWT is a training regimen repeating slow and fast walking at ~40% and ≥70% peak aerobic capacity, respectively, for 3 min each per set, ≥5 sets per day, and ≥4 days/wk. We randomly divided 28 male and 75 female older people (~73 yr), who had performed IWT ≥12 months, into a carbohydrate group (CHO-G) consuming jelly (45 g CHO, 180 kcal) and a yogurt group (YGT-G) consuming a yogurt drink (9.3 g protein, 39 g CHO, 192 kcal) immediately after daily IWT for 56 days while monitoring exercise intensity and heart rate (HR) with portable devices. We analyzed the results in 39 subjects for the CHO-G and 37 subjects for the YGT-G who performed IWT ≥ 4 days/wk, ≥60 min total fast walking/wk, and ≥4 sets of each walk/day. We found that the mean HR for fast walking decreased significantly from the baseline after the 30th day in the YGT-G (p < 0.03), but not in the CHO-G (p = 1.00). There were no significant differences in training achievements between the groups. Thus, post-exercise yogurt intake might reduce cardiovascular strain during outdoor walking training in older people.

New portable device for continuous measurement of sweat rate under heat stress during field tests.

We have developed a portable method to measure sweat rate (SR) under heat stress during field tests. We randomly divided 15 males and 17 females (23-78 yr) into a group, equation group (EG) to determine an equation to convert a unit of SR (mmHg) by the portable method to that (mg·min-1·cm-2) by the ventilation method, and another group, validation group (VG) to validate the equation. Since we repeated measurements twice in three subjects, we randomly assigned the two measurements to one of the two groups and analyzed the results in 18 and 17 subjects for EG and VG, respectively. Subjects cycled for 20 min at moderate intensity in a warm environment while chest SR was simultaneously measured with a capsule installed with 4.8 g of silica gel and two microfans (8.4 cm3 volume) and with another capsule (12.6 cm2 area) ventilated with dry air at 1.5 L·min-1. Since the esophageal temperature (Tes) threshold for increasing SR and the slope of SR at a given increase in Tes by the portable method (x) were in high agreement with those values obtained by the ventilation method (y) in both groups (all r > 0.88, P < 0.001), we determined regression equations for all subjects after pooling data from both groups: y = 1.11x - 3.99 and y = 1.05x + 0.01 when the 95% prediction limits were ±0.12°C and ±0.43 mg·min-1·cm-2·°C-1 with minimum mean differences over the range of 36.2°C-37.2°C and 0.2-2.4 mg·min-1·cm-2·°C-1, respectively, using Bland-Altman analysis. Based on these findings, we consider the portable device to be reliable enough to evaluate individual sweating capacity during field tests.NEW & NOTEWORTHY We developed a portable device to measure sweat rate continuously under heat stress during field tests, with precision similar to that obtained by the ventilation method, which has been used to evaluate individual sweat rate responses in laboratory tests. This new, portable device will provide more opportunities to determine factors influencing sweat rate in larger populations of subjects during field tests.

Role of linkage between cerebral activity and baroreflex control of heart rate via central vasopressin V1a receptors in food-deprived mice.

We previously reported that cerebral activation at the onset of voluntary locomotion suppressed baroreflex control of heart rate (HR) and increased arterial pressure via vasopressin V1a receptors in the brain. Here, we examined whether these responses were associated with food seeking, a motivated behavior, using free-moving wild type (WT, n = 10), V1a receptor knockout (KO, n = 9), and wild-type mice locally infused with a V1a receptor antagonist into the nucleus tractus solitarii (BLK, n = 10). For three consecutive days, mice were fed ad libitum (Fed), food deprived (FD), and refed (RF) under a dark/light cycle (1900/0700). Food was removed on day 2 and restored on day 3 at 1800. Throughout the protocol, cerebral activity was determined from the power density ratio of θ- to δ-wave band (θ/δ) by electroencephalogram every 4 s. Baroreflex was evaluated by the cross-correlation function [R(t)] between changes in HR and arterial pressure every 4 s. The cerebro-baroreflex linkage was then evaluated by the cross-correlation function between θ/δ and R(t). Behavior was recorded with CCD camera. We found that cerebro-baroreflex linkage, enhanced in WT at night after FD (P = 0.006), returned to Fed level after RF (P = 0.68). Similarly, food-seeking behavior increased after FD to a level twofold higher than during Fed (P < 0.001) and returned to Fed level after RF (P = 0.54). However, none of these changes occurred in KO or BLK (P > 0.11). Thus, the suppression of baroreflex control of HR linked with cerebral activation via central V1a receptors might play an important role at the onset of motivated behaviors, such as food seeking induced by FD.NEW & NOTEWORTHY Motivated behaviors, characterized by goal-directed and persistent movements, are indispensable for living. However, how cerebro-cardiovascular adjustment occurs during such behaviors remains unknown. By focusing on food-seeking behavior in a food-deprived condition using free-moving mice, we found that this condition enhanced the linkage between cerebral activation and suppression of baroreflex control of heart rate through central vasopressin V1a receptors, making it easier to start motivated behaviors by enhancing pressor response.

Effects of 5-aminolevulinic acid with iron supplementation on respiratory responses to graded cycling and interval walking training achievement in older women over 75 yrs.

BACKGROUND: Exercise training above a given intensity is necessary to prevent age-associated physical disability and diseases; however, the physical and psychological barriers posed by deteriorated physical fitness due to aging may hinder older people from performing daily exercise training. Because 5-aminolevulinic acid (ALA), a precursor of heme, reportedly improves mitochondrial function, we examined whether ALA, combined with sodium ferrous citrate (SFC) for enhancement, improved aerobic capacity and voluntary exercise training achievement in older women aged over 75 yrs. METHODS: The study was conducted using a placebo-controlled, double-blind crossover design. Fifteen women aged ~78 yrs. with no exercise habits underwent two trials for 7 days each where they performed interval walking training (IWT), repeating fast and slow speeds of walking for 3 min each, at >70% and at ~40% of peak aerobic capacity for walking, respectively, with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), with a 12-day washout period. Before and after each trial, subjects underwent a graded cycling test while having their oxygen consumption rate (V·O2), carbon dioxide production rate (V·CO2), and plasma lactate concentration ([Lac-]p) measured. Furthermore, during the supplement intake period, exercise intensity for IWT was measured by accelerometry. RESULTS: In ALA+SFC, the increases in V·O2 and V·CO2 during the graded cycling test were attenuated (both, P < 0.01) with a 13% reduction in [Lac-]p (P = 0.012) while none of these attenuated responses occurred in CNT (all, P > 0.46). Furthermore, energy expenditure and time during fast walking for IWT were 25% (P = 0.032) and 21% (P = 0.022) higher in ALA+SFC than in CNT. CONCLUSION: Thus, ALA+SFC supplementation improved aerobic capacity and thus increased fast-walking training achievement in older women.

Effect of Carbohydrate-Electrolyte Solution Including Bicarbonate Ion Ad Libitum Ingestion on Urine Bicarbonate Retention during Mountain Trekking: A Randomized, Controlled Pilot Study.

We investigated whether bicarbonate ion (HCO3-) in a carbohydrate-electrolyte solution (CE+HCO3) ingested during climbing to 3000 m on Mount Fuji could increase urine HCO3- retention. This study was a randomized, controlled pilot study. Sixteen healthy lowlander adults were divided into two groups (six males and two females for each): a tap water (TW) group (0 kcal with no energy) and a CE+HCO3 group. The allocation to TW or CE+HCO3 was double blind. The CE solution contains 10 kcal energy, including Na+ (115 mg), K+ (78 mg), HCO3- (51 mg) per 100 mL. After collecting baseline urine and measuring body weight, participants started climbing while energy expenditure (EE) and heart rate (HR) were recorded every min with a portable calorimeter. After reaching a hut at approximately 3000 m, we collected urine and measured body weight again. The HCO3- balance during climbing, measured by subtracting the amount of urine excreted from the amount of fluid ingested, was -0.37 ± 0.77 mmol in the CE+HCO3, which was significantly higher than in the TW (-2.23 ± 0.96 mmol, p < 0.001). These results indicate that CE containing HCO3- supplementation may increase the bicarbonate buffering system during mountain trekking up to ~3000 m, suggesting a useful solution, at least, in the population of the present study on Mount Fuji.

Internet of Things (IoT) System and Field Sensors for Exercise Intensity Measurements.

Although exercise training according to individual peak aerobic capacity ( V ˙ o2peak ) has been recommended at all ages, sensors available in the field are limited. The most popular sensors in the field are pedometers, but they cannot be used to monitor exercise intensity. Instead, although heart rate (HR) monitors are broadly available in the field to estimate exercise intensity, HR responses to exercise vary by individual according to physical fitness and environmental conditions, which hinders the precise measurement of energy expenditure. These issues make it difficult for exercise physiologists to collaborate with geneticists, nutritionists, and clinicians using the internet of things (IoT). To conquer these problems, we have developed a device that is equipped with a triaxial accelerometer and a barometer to measure energy expenditure during interval walking training (IWT) in the field with inclines. IWT is a training regimen to repeat fast and slow walking for 3 min each, equivalent to greater than 70% and approximately 40% of individual V ˙ o2peak , respectively. Additionally, we developed an IoT system that enables users to receive instructions from trainers according to their walking records even if they live far away. Since the system is available at low cost with minimum personnel, we can investigate any factors affecting the adherence to and effects of IWT in a large population for a long period. This system was also used to verify any effects of nutritional supplements during IWT and to examine the value of applying IWT to clinical medicine. © 2020 American Physiological Society. Compr Physiol 10:1207-1240, 2020.

Countdown before voluntary exercise induces muscle vasodilation with baroreflex-mediated decrease in muscle sympathetic nerve activity in humans.

We examined whether a countdown (CD) before voluntary cycling exercise induced prospective vascular adjustment for the exercise and, if so, whether and how muscle sympathetic nerve activity (MSNA) was involved in the responses. Young men performed voluntary cycling in a semirecumbent position (n = 14) while middle cerebral artery blood flow velocity (VMCA; Doppler ultrasonography), heart rate (HR), arterial pressure (AP; finger photoplethysmography), oxygen consumption rate (V̇o2), oxygen saturation in the thigh muscle (StO2; near-infrared spectrometry), cardiac output (CO; Modelflow method), and total peripheral resistance (TPR) were measured (experiment 1). Another group underwent the same exercise protocol but used only the right leg (n = 10) while MSNA (microneurography) was measured in the peroneal nerve of the left leg (experiment 2). All subjects performed eight trials with a ≥5-min rest between trials. In four trials randomly selected from the eight trials, exercise onset was signaled by a 30-s CD, whereas in the remaining four trials, exercise was started without CD. We found that CD first increased VMCA, HR, CO, and mean AP, and then decreased TPR and increased StO2 and V̇o2 (experiment 1; all P < 0.021). Furthermore, the CD-induced increase in mean AP decreased total MSNA and burst frequency (experiment 2; both P < 0.048) through the baroreflex, with decreased TPR and increased StO2 (experiment 2; both P < 0.001). The vasodilation and increased V̇o2 continued after the start of exercise. Thus CD before starting exercise induced the muscle vasodilatory response with a concomitant reduction in MSNA through the baroreflex to accelerate aerobic energy production after the start of exercise.NEW & NOTEWORTHY Prospective cardiovascular adjustment occurs before starting voluntary exercise, increasing heart rate and arterial pressure followed by muscle vasodilation; however, the precise mechanisms and significance for this vasodilation remain unknown. We found that during the countdown before starting exercise cerebral blood flow velocity increased, followed by increases in heart rate and arterial pressure, which suppressed MSNA through baroreflex, resulting in thigh muscle vasodilation to increase oxygen consumption rate, which might make it easier to start exercise.

Mathematical model to estimate the increase in firefighters' core temperature during firefighting activity with a portable calorimeter.

We developed a mathematical model to estimate the increase in firefighters' core body temperature from energy expenditure (EE) measured by accelerometry to prevent heat illness during firefighting. Wearing firefighter personal protective equipment, seven male subjects aged 23-42 years underwent a graded walking test on a treadmill while esophageal temperature (Tes) and skin temperature were measured with thermocouples and EE was measured with a tri-axial accelerometer. To estimate the increase in Tes from EE, we proposed a mathematical model composed of the heat capacity of active muscles (C1, kcal·°C-1), the heat capacity of the sum of resting muscles and skin (C2), the resistance to heat flux from C1 to C2 (R1, °C·min·kcal-1), and the resistance from C2 to the skin surface (R2). We determined the parameters while minimizing the differences between the estimated and measured changes in Tes profiles during graded walking. We found that C1 and C2 in individuals were highly correlated with their body weight (kg) and body surface area (m2), respectively, whereas R1 and R2 were similar across subjects. When the profiles of measured Tes (y) and estimated Tes (x) were pooled in all subjects, they were almost identical and were described by a regression equation without an intercept, y = 0.96x (r = 0.96, P < 0.0001), with a mean difference of - 0.01 ± 0.12 °C (mean ± SD) ranging from - 0.18 to 1.56 °C of the increase in Tes by Bland-Altman analysis. Thus, the model can be used for firefighters to prevent heat illness during firefighting.

High-Intensity Walking Time Is a Key Determinant to Increase Physical Fitness and Improve Health Outcomes After Interval Walking Training in Middle-Aged and Older People.

OBJECTIVE: To examine the effects of interval walking training (IWT) on the estimated peak aerobic capacity (eV˙O2peak) and lifestyle-related disease (LSD) score while focusing on exercise intensity and volume in middle-aged and older people. PARTICIPANTS AND METHODS: Men and women (N=679; mean age, 65±7 SD years) completed 5-month IWT. Participants were instructed to repeat 5 or more sets of fast and slow walking for 3 minutes each at 70% or more and 40% eV˙O2peak for walking, respectively, per day for 4 or more d/wk. This study was conducted from April 1, 2005, through February 29, 2008. RESULTS: Interval walking training increased eV˙O2peak by 14% and decreased LSD score by 17% on average (P<.001). During 5-month IWT, fast and slow walking times were 88±65 SD and 100±86 min/wk, respectively, but varied among participants. We divided participants into approximately 10 bins for 6 minutes each of fast and slow walking times per week up to 60 min/wk, and above this time, approximately 8 bins for 30 or 60 minutes each of fast and slow walking up to the maximal time. We found that both eV˙O2peak and LSD score improved as fast walking time per week increased up to 50 min/wk (R2=0.94; P<.001 for eV˙O2peak; R2=0.51; P=.03 for LSDS) but plateaued above this time. In contrast, improvement in neither eV˙O2peak nor LSDS was positively correlated with slow or total walking time per week. Multiple regression analyses confirmed that fast walking time per week was the major determinant of improvements in eV˙O2peak (P<.001) and LSD score (P=.001). CONCLUSION: High-intensity walking time during IWT is a key factor to increase eV˙O2peak and decrease LSD score in middle-aged and older people.

Development of a collagen-like peptide polymer via end-to-end disulfide cross-linking and its application as a biomaterial.

Collagen is the most abundant protein in the animal kingdom and has a unique triple-helical structure. It not only provides mechanical strength to tissues, but also performs specific biological functions as a multifaceted signaling molecule. Animal-derived collagen is therefore widely used as a biocompatible material in vitro and in vivo. In this study, we developed a novel peptide-based material that mimicked both the polymeric properties and a selected biological function of native collagen. This material was prepared by end-to-end multiple disulfide cross-linking of chemically synthesized triple-helical peptides. The peptide polymer showed a gel-forming property, and receptor-specific cell binding was observed in vitro by incorporating a peptide harboring an integrin α2ß1-binding sequence. Furthermore, cell signaling activity and biodegradability were tunable according to the polymer contents. The results demonstrated the potential of this material as a designer collagen. STATEMENT OF SIGNIFICANCE: Collagen is a useful biomaterial with the gel-forming property. It also exhibits various biological activities through the interaction of specific amino acid sequences displayed on the triple helix with functional biomacromolecules. Here we report a novel synthetic material, artificial collagen, by end-to-end cross-linking of chemically synthesized collagen-like triple-helical peptides. The material allows independent regulation of polymer properties, i.e. gel stiffness, and sequence-specific bioactivities by altering peptide compositions. This material can also be variously shaped, for example, thin films with high transparency. In addition, it has low inflamatogenic properties and tunable biodegradability in vivo.

Interactions between body fluid homeostasis and thermoregulation in humans.

Humans are unique in their ability to control body temperature with a large amount of skin blood flow and sweat rate while exercising in an upright position. However, cutaneous vasodilation in the body reduces total peripheral resistance and blood pooling in cutaneous veins decreases venous return to the heart and cardiac filling pressure. In addition, hypovolemia by sweating accelerates the reduction in cardiac filling pressure. These may threaten the maintenance of blood pressure if they are not compensated for. To prevent this, cutaneous vasodilation and sweat rate are suppressed by baroreflexes or hyperosmolality with dehydration. These mechanisms suppress heat dissipation, accelerate the increase in body temperature, and sometimes cause heat stroke. As a countermeasure to prevent this, we have recommended glucose electrolyte solutions but recently found that aerobic training with carbohydrate + whey protein supplementation markedly improves heat dissipation mechanisms by plasma volume expansion. In this article, we will discuss the importance of improving body fluid homeostasis for thermoregulation under heat stress in humans and the strategy to attain this.

Rapid saline infusion and/or drinking enhance skin sympathetic nerve activity components reduced by hypovolaemia and hyperosmolality in hyperthermia.

KEY POINTS: In hyperthermia, plasma hyperosmolality suppresses both cutaneous vasodilatation and sweating responses and this suppression is removed by oropharyngeal stimulation such as drinking. Hypovolaemia suppresses only cutaneous vasodilatation, which is enhanced by rapid infusion in hyperthermia. Our recent studies suggested that skin sympathetic nerve activity (SSNA) involves components synchronized and non-synchronized with the cardiac cycle, which are associated with an active vasodilator and a sudomotor, respectively. In the present study, plasma hyperosmolality suppressed both components; drinking removed the hyperosmolality-induced suppressions, simultaneously with increases in cutaneous vasodilatation and sweating, while not altering plasma volume and osmolality. Furthermore, a rapid saline infusion increased the synchronized component and cutaneous vasodilatation in hypovolaemic and hyperthermic humans. The results support our idea that SSNA involves an active cutaneous vasodilator and a sudomotor, and that a site where osmolality signals are projected to control thermoregulation is located more superior than the medulla where signals from baroreceptors are projected. ABSTRACT: We reported that skin sympathetic nerve activity (SSNA) involved components synchronized and non-synchronized with the cardiac cycle; both components increased in hyperthermia and our results suggested that the components are associated with an active vasodilator and a sudomotor, respectively. In the present study, we examined whether the increases in the components in hyperthermia would be suppressed by plasma hyperosmolality simultaneously with suppression of cutaneous vasodilatation and sweating and whether this suppression was released by oropharyngeal stimulation (drinking). Also, effects of a rapid saline infusion on both components and responses of cutaneous vasodilatation and sweating were tested in hypovolaemic and hyperthermic subjects. We found that (1) plasma hyperosmolality suppressed both components in hyperthermia, (2) the suppression was released by drinking 200 mL of water simultaneously with enhanced cutaneous vasodilatation and sweating responses, and (3) a rapid infusion at 1.0 and 0.2 ml min-1  kg-1 for the first 10 min and the following 20 min, respectively, increased the synchronized component and cutaneous vasodilatation in diuretic-induced hypovolaemia greater than those in a time control; at 0.1 ml min-1  kg-1 for 30 min no greater increases in the non-synchronized component and sweating responses were observed during rapid infusion than in the time control. The results support the idea that SSNA involves components synchronized and non-synchronized with the cardiac cycle, associated with the active cutaneous vasodilator and sudomotor, and a site of osmolality-induced modulation for thermoregulation is located superior to the medulla where signals from baroreceptors are projected.

Effects of 5-aminolevulinic acid supplementation on home-based walking training achievement in middle-aged depressive women: randomized, double-blind, crossover pilot study.

Depressive patients often experience difficulty in performing exercise due to physical and psychological barriers. We examined the effects of 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) supplementation during home-based walking training in middle-aged depressive women. Nine outpatients [53 ± 8 (SD) yr] with major depressive disorder participated in the pilot study with randomized, placebo-controlled, double-blind crossover design. They underwent two trials for 7 days, each performing interval walking training (IWT) with ALA + SFC (ALA + SFC) or placebo supplement intake (PLC) intermittently with >a 10-day washout period. For the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. Before and after each trial, subjects underwent a graded cycling test, and lactate concentration in plasma ([Lac-]p), oxygen consumption rate ([Formula: see text]), and carbon dioxide production rate ([Formula: see text]) were measured with depression severity by the Montgomery-Åsberg Depression Rating Scale (MADRS). We found that the increases in [Lac-]p, [Formula: see text] and [Formula: see text] during the test were attenuated only in ALA + SFC ([before vs. after] × workload; all, P < 0.01), accompanied by increased training days, impulse, and time at fast walking during IWT (all, P < 0.05) with decreased MADRS-score (P = 0.001). Thus, ALA + SFC supplementation increased IWT achievement to improve depressive symptoms in middle-aged women.

Development of a carboplatin derivative conjugated with a collagen-like triple-helical peptide.

AIM: The development of a platinum anticancer agent that has improved efficacy by efficient delivery to a tumor and that suppresses side effects has been investigated. Arginine-rich triple-helical peptides are promising drug carriers because of their stability in body fluids and cell-penetrating activity. RESULTS: We synthesized a carboplatin derivative conjugated with an arginine-rich triple-helical peptide. This derivative released platinum under acidic conditions or in the presence Cl- ions. Administration of this derivative to P388 tumor-bearing mice showed comparable survival rates to twice the dose of carboplatin, which was attributed to a longer mean residence time by pharmacokinetics analysis. CONCLUSION: The collagen-like triple-helical peptide was an efficient carrier of a platinum anticancer agent because of a modification to its pharmacokinetic profile.

Interval Walking Training and Nutritional Intake to Increase Plasma Volume in Elderly.

PURPOSE: Aerobic training-induced plasma volume (PV) expansion improves thermoregulation, and carbohydrate (CHO) + whey protein supplementation enhanced the effects in older people; however, these were suggested by studies on gym-based cycling training but not on home-based interval walking training (IWT). Moreover, long-term walking training effects on PV remain unknown. METHODS: Seventeen male and 10 female subjects (~69 yr), having performed IWT for ≥24 months before the study, were used. After pre-intervention measurement (PRE) of PV, plasma albumin content (Albcont), fasting glucose concentration ([Glc]f), and HbA1c, the subjects were randomly divided into two groups: CHO and Pro-CHO, either consuming CHO (22.5 g) alone or CHO (15 g) + whey protein (10 g), respectively, during additional 5-month IWT from May to November, 2009. After the additional IWT, we measured the same variables again (postintervention measurement). RESULTS: The baseline PV and Albcont were significantly correlated with the number of IWT days for the 12 months preceding PRE (r = 0.716, P < 0.001 and r = 0.671, P < 0.001, respectively). In postintervention, PV and Albcont marginally decreased in CHO from the baselines (P = 0.081 and P = 0.130, respectively) with increased HbA1c (P < 0.001) after correction for the baseline [Glc]f by ANCOVA, but these values remained unchanged in Pro-CHO (both, P > 0.74), with significant differences in the changes between groups (P = 0.020, P = 0.041, and P = 0.018 respectively). CONCLUSIONS: PV was proportional to the number of IWT days for 12 months and a CHO + whey protein supplementation during the 5-month IWT prevented PV reduction for the period of no supplementation, which might be partially linked with blood glucose control mechanisms.

Barometric pressure change and heart rate response during sleeping at ~ 3000 m altitude.

We investigated effects of change in barometric pressure (P B) with climate change on heart rate (HR) during sleep at 3000 m altitude. Nineteen healthy adults (15 males and four females; mean age 32 years) participated in this study. We measured P B (barometry) and HR (electrocardiography) every minute during their overnight stay in a mountain lodge at ~ 3000 m. We also measured resting arterial oxygen saturation (SpO2) and evaluated symptoms of acute mountain sickness (AMS) by using the Lake Louise Questionnaire at 2305 and 3000 m, respectively. P B gradually decreased during the night at the speed of approximately - 0.5 hPa/h. We found that HR during sleep decreased linearly as P B decreased in all subjects, with significance (r = 0.492-0.893; all, P < 0.001). Moreover, cross correlation analysis revealed that HR started to decrease after ~ 15 min following the decrease in P B, on average. SpO2 was 93.8 ± 1.7% at 2305 m before climbing, then decreased significantly to 90.2 ± 2.2% at the lodge before going to bed, and further decreased to 87.5 ± 2.7% after waking (all, P < 0.05). Four of the 19 subjects showed a symptom of AMS after waking (21%). Further, the decrease in HR in response to a given decrease in P B (ΔHR/ΔPB) was negatively related with a decrease in SpO2 from before going to bed to after waking at 3000 m (r = - 0.579, P = 0.009) and with total AMS scores after waking (r = 0.489, P = 0.033).

Effects of dried tofu supplementation during interval walking training on the methylation of the NFKB2 gene in the whole blood of older women.

Muscle atrophy with aging is closely associated with chronic systemic inflammation and lifestyle-related diseases. Here, we assessed whether dried tofu intake during 5-month interval walking training (IWT) enhanced increases in thigh muscle mass and strength and ameliorated susceptibility to inflammation in older women. Subjects (n = 32, ~ 65 years) who performed IWT for > 6 months participated in this study. They were randomly divided into 2 groups: IWT + placebo intake (PLG, n = 16; 108 kcal, 0.2 g protein, 5.5 g fat, and 14.4 g carbohydrate) and IWT + dried tofu intake (DTG, n = 16; 111 kcal, 9.6 g protein, 6.0 g fat, and 4.6 g carbohydrate). They were instructed to repeat ≥ 5 sets of fast and slow walking for 3 min each at ≥ 70 and 40% peak aerobic capacity for walking, respectively, per day for ≥ 4 days/week. Immediately after daily exercise, subjects were instructed to consume the supplements assigned to each group. In the DTG, after IWT, the methylation increased at 4/6 sites in the promoter region of the NFKB2 gene in the whole blood (all, P < 0.04), with an 18% increase in the average methylation of the 6 sites (P = 0.035). On the other hand, in the PLG, the increase occurred at only 2/6 sites, with no significant increase in the average methylation of the 6 sites. No significant differences were observed in increases in thigh muscle strength or cross-sectional area between the groups (all, P > 0.2). Altogether, dried tofu supplementation during IWT likely enhanced the methylation of the NFKB2 gene more than IWT alone, without detectably enhanced increases in thigh muscle strength or cross-sectional area.