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Tryptophan (TRP), a precursor of serotonin is believed to have an antidepressant effect. The pathway for brain uptake of TRP is shared by other large neutral amino acids; therefore, the best time to take TRP may be between meals. No previous study has, however, designated the time of TRP dosing to improve mood. Further, the effects of TRP on autonomic nervous system (ANS) activity are unclear. This study investigated the effects of TRP, vitamin B6, and nicotinamide-containing supplements loading between meals on mood and ANS activity in depressive young adults. Thirty depressive young adults were randomly allocated to receive TRP, vitamin B6, and nicotinamide-containing supplements or a placebo supplements twice daily between meals for 7 d. Mood was measured using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Profile of Mood States (POMS). ANS activities were analyzed by heart rate variability power spectral analysis. Blood samples were assayed for plasma total TRP concentration. For analysis, TRP and placebo groups were further classified into two subgroups according to CES-D score (mild to moderate vs. severe depressive symptoms). The CES-D score significantly improved following both treatments in the severe depression subgroups, while the POMS depression score was significantly improved only in the TRP severe depression subgroup. There was no significant change in ANS activity or plasma total TRP in any group. TRP, vitamin B6, and nicotinamide-containing supplements loading between meals can quickly improve depressed mood in quite low dose in young adults with severe subclinical depression.

A 3-month-old male infant appeared on multiple clinical examinations to have acutely developed bilateral retrogeniculate blindness. Electroencephalography showed focal status epilepticus confined to the left posterior cerebral hemisphere. MRI demonstrated restricted diffusion in the domain of the left posterior cerebral artery consistent with acute stroke. Notably, the restricted diffusion extended across the midline in the splenium of the corpus callosum. This splenial sign may be the imaging correlate of cerebral diaschisis, a well-described phenomenon in which patients with new brain lesions develop acutely impaired neurologic function in related but nonlesioned brain regions. Diaschisis has been posited as the explanation for the temporary bilateral blindness in adult patients suffering from unilateral occipital infarctions.

Background Patients with schizophrenia have a higher mortality risk than the general population. Additionally, the autonomic nervous system (ANS) activity of patients with schizophrenia is lower and more dysfunctional than that of the general population. Nonetheless, the association between ANS dysfunction and mortality in schizophrenia is unclear. The aim of this study was to investigate the association between ANS activity and mortality in schizophrenia and to evaluate the predictive values of heart rate variability for long-term survival. Methods This study involves the 10-year follow-up of a sample population consisting of 59 Japanese inpatients with schizophrenia between 60 and 70 years of age from 2007 to 2016. The ANS activity of all patients was evaluated using heart rate variability in 2007. Results Fifty-three participants could be followed up because they stayed in the hospital during the follow-up period. Of these patients, 11 died during follow-up. Their mean age at death was 70.55 ± 3.45 years. The parasympathetic activity of nonsurvivors was significantly lower than that of survivors, and multiple logistic regression analysis showed a significant association between death and parasympathetic activity. Conclusion We suggest that decreased parasympathetic activity could be associated with 10-year all-cause mortality in older schizophrenic patients.

Background There are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction. Accordingly, to clarify the interindividual differences in the adverse effects of specific atypical antipsychotics in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in patients with schizophrenia. Methods In total, 233 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 89 participants received risperidone, 69 olanzapine, 48 aripiprazole, and 27 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. Four single nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs1128503, rs2032582, and rs2235048) were genotyped using the TaqMan method. Results For aripiprazole, sympathetic and total autonomic nervous activities were significantly lower in the rs1045642 T allele carrier–rs2235048 C allele carrier group than in the rs1045642 non-T allele carrier–rs2235048 non-C allele carrier group. In addition, in the aripiprazole group, the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582) was associated with decreased ANS activity. However, there were no significant associations between ANS activity and ABCB1 gene polymorphisms in the risperidone, olanzapine, and quetiapine groups. Multiple regression analysis revealed that sympathetic and total nervous activities were significantly associated with the ABCB1 rs1045642–rs2235048 genotype and the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582). Conclusion We suggest that ABCB1 genetic polymorphisms affect aripiprazole-related ANS dysfunction but do not affect risperidone-, olanzapine-, or quetiapine-related ANS dysfunction.

Background Since age-related muscle strength loss cannot be explained solely by muscle atrophy, other determinants would also contribute to muscle strength in elderly. The present study aimed to clarify contribution of neuromuscular activation pattern to muscle strength in elderly group. From 88 elderlies (age: 61~ 83 years), multi-channel surface electromyography (EMG) of the vastus lateralis muscle was recorded with two-dimensional 64 electrodes during isometric submaximal ramp-up knee extension to assess neuromuscular activation pattern. Correlation analysis and stepwise regression analysis were performed between muscle strength and the parameters for signal amplitude and spatial distribution pattern, i.e., root mean square (RMS), correlation coefficient, and modified entropy of multi-channel surface EMG. Results There was a significant correlation between muscle strength and RMS (r = 0.361, p = 0.001) in the elderly. Muscle thickness (r = 0.519, p

Purpose: It is clinically important to elucidate the precise mechanism of exercise intolerance in patients with type 2 diabetes (T2DM). The aim of this study was to examine whether there is a difference in the time course change of the oxygenation in the vastus lateralis (VL) muscle during submaximal incremental cycling exercise between patients with T2DM and age-matched healthy subjects. Methods: Nine elderly men with T2DM and 10 age-matched healthy men (CON) participated in this study. All participants performed an incremental cycling exercise.Total, deoxygenated and oxygenated hemoglobin/myoglobin in the VL muscle were assessed using near-infrared spectroscopy, and cardiorespiratory response was also evaluated during the exercise. Results: There were no significant differences in the time course changes of deoxygenated hemoglobin/myoglobin between groups ( p > 0.05). However, the oxygenated hemoglobin/myoglobin in T2DM was significantly higher than that in CON at an intensity above ventilatory threshold during the incremental cycling exercise ( p< 0.05). Conclusion: This study suggests that patients with T2DM had early limitation of oxygen extraction and lower capacity of oxygenated myoglobin dissociation in the VL muscle. The fact that patients with T2DM showed different oxygen kinetics in a peripheral tissue from healthy subjects may partly explain the potential mechanisms of exercise intolerance in T2DM.

Background: Patients with schizophrenia have abnormal autonomic nervous system (ANS) activity compared with the general population. One reason for this difference is the muscarinic affinity for antipsychotic drugs; therefore, single nucleotide polymorphisms (SNPs) of the muscarinic receptor gene influence this ANS dysfunction. This study sought to determine the effect of SNPs of the cholinergic muscarinic receptor (CHRM) gene on ANS activity in patients with schizophrenia receiving antipsychotic drugs. Methods: A total of 173 Japanese patients with schizophrenia were included in this study. Heart rate variability (HRV) was measured as an index of ANS activity. SNPs in CHRM1 (rs542269 and rs2075748), CHRM2 (rs324640, rs8191992, rs1824024, and rs7810473), and CHRM3 (rs3738435, rs4620530, and rs6429157) were genotyped using the TaqMan® method. Patients were grouped according to standard equivalent conversions of chlorpromazine (CP) into a high-CP group (HG; ≥1,000 mg) and a low-CP group (LG; p value was Results: The A allele of the CHRM2 rs8191992 polymorphism in HG was associated with decreased ANS activity. Conclusion: Our results show reduced ANS activity in association with the CHRM2 rs8191992 polymorphism in patients with schizophrenia on high-dose antipsychotics. CHRM2 polymorphisms may play an important role in ANS activity in patients with schizophrenia.

Physical exercise exerts favourable effects on brain health and quality of life of the elderly; some of these positive health effects are induced by the modulation of microbiota composition. We therefore conducted a randomised, double blind, placebo-controlled trial that assessed whether a combination of Bifidobacterium spp. supplementation and moderate resistance training improved the cognitive function and other health-related parameters in healthy elderly subjects. Over a 12-week period, 38 participants (66-78 years) underwent resistance training and were assigned to the probiotic Bifidobacterium supplementation (n=20; 1.25×1010 cfu each of Bifidobacterium longum subsp. longum BB536, B. longum subsp. infantis M-63, Bifidobacterium breve M-16V and B. breve B-3) or the placebo (n=18) group. At baseline and at 12 weeks, we assessed the cognitive function, using the Japanese version of the Montreal Cognitive Assessment instrument (MoCA-J); modified flanker task scores; depression-anxiety scores; body composition; and bowel habits. At 12 weeks, the MoCA-J scores showed a significant increase in both the groups, while the flanker task scores of the probiotic group increased more significantly than those of the placebo group (0.35±0.9 vs -0.29±1.1, P=0.056). Only the probiotic group showed a significant decrease in the depression-anxiety scores (5.2±6.3 to 3.4±5.5, P=0.012) and body mass index (24.0±2.8 to 23.5±2.8 kg/m2, P

This study aimed to examine the effect of prolonged neuromuscular electrical stimulation (NMES) on the metabolic profile and cognition-related blood parameters in patients with type 2 diabetes mellitus (T2DM).Fourteen patients with T2DM (63.2 ± 3.0 years, 76.1 ± 3.5 kg) participated in a randomized controlled cross-over study, in which 8-week-long NMES interventions were performed on both legs. The NMES training protocol consisted of 40-min sessions, 5 days per week, for 8 weeks. The relative changes in glucose and lipid profiles, and cognition-related blood parameters were evaluated.NMES training induced significant changes in the fasting glucose concentration (p 0.05) and percent body fat (p 0.05), although there were no significant changes in HbA1c and blood lipid levels (p ≥ 0.05). The change in plasma brain-derived neurotrophic factor (BDNF) levels was significantly higher in the NMES period than in the control period (p 0.05).This study showed that an 8-week NMES training program could induce greater changes in the blood glucose concentration, percent body fat, and plasma BDNF levels than the control intervention in patients with T2DM. NMES training might prove to be an alternative exercise method for patients who might have difficulties in performing adequate voluntary exercise.

The 3111T/C single nucleotide polymorphism (SNP) of Circadian Locomotor Output Cycles Kaput (CLOCK) gene reportedly affects gastric motility before breakfast. It is of interest to know whether this SNP can affect the motility during the daytime. We investigated the association between the CLOCK 3111T/C SNP and several gastric motility parameters during the time period from 8:00 to 20:00 in 34 young women with scheduled meals. There were similar daytime fluctuations in gastric motility before and after the meals between the major (T/T) and minor (T/C) allele carriers. The CLOCK SNP may affect daytime gastric motility less than food stimulation.

The aim of this study is examining the effects of multiple sets of high-velocity resistance exercise (HVRE) on cardiovascular responses. Fifteen healthy adult men participated in two experimental sessions: one comprised three sets of resistance exercise performed against high-intensity resistance exercise (HIRE) at low velocity and the other three sets of HVRE performed against reduced load at high velocity. Blood pressure (BP), heart rate (HR), stroke volume (SV) and cardiac output (CO) during both sessions were evaluated using impedance electrocardiography. The increases in BP, HR and CO were significantly lowered during HVRE compared with HIRE (p0.05). In contrast, there was no significant difference in SV between sessions (p0.05). This study suggested that the increases in BP and CO during HVRE were lower than those during HIRE although HVRE required performing fast movement. HVRE might be applied to patients for whom HIRE is contraindicated because of cardiovascular diseases.

We previously reported that carbonated water ingestion induced fullness and gastric motility. In order to determine whether such satiating effects occur through oral carbonic stimulation alone, we conducted modified sham-feeding (SF) tests (carbonated water ingestion (CW), water ingestion (W), carbonated water sham-feeding (CW-SF), and water sham-feeding (W-SF)), employing an equivalent volume and standardized temperature of carbonated and plain water, in a randomized crossover design. Thirteen young women began fasting at 10 p.m. on the previous night and were loaded with each sample (15oC, 250 mL) at 9 a.m. on separate days. Electrogastrography (EGG) recordings were obtained from 20 min before to 45 min after the loading to determine the power and frequency of the gastric myoelectrical activity. Appetite was assessed using visual analog scales. After ingestion, significantly increased fullness and decreased hunger ratings were observed in the CW group. After the load, transiently but significantly increased fullness as well as decreased hunger ratings were observed in the CW-SF group. The powers of normogastria (2-4 cpm) and tachygastria (4-9 cpm) showed significant increases in the CW and W groups, but not in the CW-SF and W-SF groups. The peak frequency of normogastria tended to shift toward a higher band in the CW group, whereas it shifted toward a lower band in the CW-SF group, indicating a different EGG rhythm. Our results suggest that CO2-induced oral stimulation is solely responsible for the feeling of satiety. Moreover, different gastric-contraction rhythms (slow or fast) were induced by oral carbonic stimulation alone and carbonated water ingestion.

We aimed to test the effect of additional electrical muscle stimulation (EMS) during moderate-intensity voluntary pedaling exercise on metabolic and cardiovascular responses. Eleven healthy male subjects performed moderate-intensity pedaling exercise at a constant workload (80 % of ventilatory threshold) for 20 min while EMS was applied to thigh muscles from 5 to 10 min and from 15 to 20 min during the exercise. A significantly higher oxygen uptake (VO2), heart rate, and respiratory gas exchange ratio were observed during the exercise periods with EMS despite the constant workload. These changes were accompanied by an elevated blood lactate concentration, suggesting the existence of additional fast-twitch motor unit (MU) recruitment during the exercise with EMS. Our data suggest that the use of intermittent EMS during a constant load exercise mimics the high-intensity interval training, possibly due to additional fast-twitch MU recruitment and co-contractions of the quadriceps and hamstrings muscles, leading to higher anaerobic metabolism and a lower mechanical efficiency.

[Purpose] We investigated the effect exercise training has on cardiac autonomic nervous system (ANS) and cardiovascular risk profiles in children with type 1 diabetes mellitus (DM). [Subjects] Fifteen type 1 DM children (all boys; 13.0±1.0 years of age) were enrolled in the study. [Methods] The subjects received exercise training three times a week in a 12-week program. Each child was asked to walk on a treadmill to achieve an exercise intensity of VO2max 60%. ANS activity was measured by power spectral analysis of the electrocardiogram (ECG). Blood samples were obtained for serum lipid profiles. To evaluate Doppler-shifted Fourier pulsatility index (PI) analysis, a 5-MHz continuous wave Doppler (VASCULAB D10) set was used to measure forward blood flow velocity (FLOW) in the radial artery. [Results] Total and low-frequency (LF) power of heart rate variability increased significantly after exercise intervention. Total cholesterol (TC) levels were significant lower after exercise intervention. Total and high-frequency (HF) power were significantly correlated with higher TC levels, but diastolic blood pressure and HF was significantly correlated with lower TC levels. [Conclusion] Regular exercise intervention should be prescribed for children with type 1 DM.

Introduction: We investigated the motor unit (MU) firing pattern in type 2 diabetes mellitus (T2DM) patients by means of multichannel surface electromyography (SEMG). Methods: Eight T2DM patients and 8 age-matched, healthy men performed a ramp-up contraction to 20% of maximal voluntary contraction (MVC). They also performed a sustained contraction at 10% of MVC during isometric knee extension. Multichannel SEMG signals recorded from the vastus lateralis muscle were decomposed with the convolution kernel compensation technique to extract individual MU firing patterns. Results: During the ramp contraction, the extent of MU firing modulation was significantly attenuated in T2DM. Variability of MU firing rate was significantly higher in T2DM at later periods during the sustained contraction. Conclusions: Our findings suggest that T2DM patients manifest characteristic MU activity patterns due possibly to some degree of neuromuscular impairment affecting the integrity of MU firing modulation. Muscle Nerve 48:806–813, 2013

Background Many women become obese during pregnancy and the postpartum period. Weight gain and obesity in the general population are often attributed to abnormalities of autonomic nervous system (ANS) activity. The aim of this study was to clarify change in ANS activity, body weight, percentage fat mass (%FM), and body mass index (BMI) and the factors regulating the return to the pre-pregnancy weight in the first year postpartum. Methods This study was conducted from 2012 to 2016 at the University Hospital of the Kyoto Prefectural University of Medicine and a nearby obstetrics and gynecology clinic in Japan. Body weight and %FM were measured in 51 women using a dual-frequency body composition measuring device. Heart rate variability and R–R spectral transformation were used as indicators of ANS activity. All parameters were calculated at three postpartum time points. Repeated measure analysis of variance was used for comparisons between measurement times. A multivariable Cox proportional hazards model was conducted to determine factors associated with the return to pre-pregnancy weight. Results Mean body weight, %FM, and BMI decreased significantly over time after delivery (P

The aim of this study was to examine whether percutaneous electrical muscle stimulation (EMS) attenuates postprandial hyperglycemia in type 2 diabetes.Eleven patients with type 2 diabetes participated in two experimental sessions; one was a 30-min EMS 30 min after a breakfast (EMS trial) and the other was a complete rest after a breakfast (Control trial). In each trial, blood was sampled before and at 30, 60, 90, and 120 min after the meal.Postprandial glucose level was significantly attenuated in EMS trial at 60, 90, and 120 min after a meal (p0.05). The C-peptide concentration was also significantly lowered in EMS trial (p0.01). On the other hand, there was no significant increase in creatine phosphokinase (CPK) concentration in each trial.The present results provide first evidence indicating that EMS is a new exercise method for treating postprandial hyperglycemia in individuals with type 2 diabetes, especially who cannot perform adequate voluntary exercise because of excessive obesity, orthopedic diseases, or severe diabetic complications.

Exercise is a useful modality to ameliorate postprandial hyperglycemia. Here we show that a short bout (∼6 min) of stair climbing–descending exercise (STAIR) starting at 90 min after meal accelerates the decrease in blood glucose concentrations in middle-aged sedentary men with impaired glucose tolerance, although STAIR is easy to perform and keeps the exercise intensity at a moderate level.

【目的】我々はこれまでに，腹壁電極から胃の活動電位（胃電図）を導出・解析する方法により胃運動を測定し，飲水（冷水・温水）が胃運動を一過性に増大させることや，胃運動の強さと食欲には関連がみられたことを報告している。本研究では，刺激味を有する液体が胃運動や食欲感覚へ及ぼす影響を検討することを目的として，香辛料（カレーパウダーとコンソメ）を含むスープ（Spice）と等エネルギー・等Na量で風味がないプラセボスープ（Control）を用いて比較試験を行った。【方法】若年女性12名に異なる2日間の朝9時に，SpiceまたはControlをランダムな順序で負荷した。ベッド上で胃電図，鼓膜温，心拍数をスープ負荷20分前から負荷40分後まで測定し，食欲感覚（空腹感，満腹感，予想食事量，満足感）は，負荷20分前，負荷直後，40分後の3回測定した。胃運動の強さは，胃電図から徐波，正常波，速波の各パワー値を計算し負荷前を基準としたパワー比を評価に用いた。【結果】Spice負荷後の胃運動は，徐波，正常波，速波パワー比ともにControlと比較して高い傾向が示された。Spice負荷後の食欲感覚は，満腹感と満足感でControlと比較して有意に高値を示した。鼓膜温，心拍数は両スープとも負荷後に上昇したが，鼓膜温（増加量）はSpiceでControlよりも有意に高値を示した。【結論】香辛料を含むスープ摂取後には，胃運動が増大する傾向があること，満腹感と満足感が高まること，負荷直後の体温が上昇することが等エネルギー・等ナトリウムのプラセボスープとの比較により示唆された。

Genetic polymorphisms of the renin-angiotensin system have been implicated in cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 3123C/A polymorphism of the angiotensin II type 2 receptor (AT(2)R) gene affect blood pressure and other obesity-related metabolic changes in response to low-energy diets using meal replacement shakes for weight loss.Clinical, metabolic, and biochemical profiles were measured before and after a 2-mo intervention in 32 obese women (age 49.9 ± 8.4 [SD] y; BMI 28.4 ± 3.3 kg/m²) restricted to 1200 kcal/d (5021 kJ/d). The polymorphisms were determined with an intercalater-mediated FRET probe assay system.Although weight loss and nutrient intake levels did not differ among the genotypes, the reduction in body fat after weight loss was significantly less in the ACE deletion/deletion (D/D) genotype than insertion/insertion (I/I) plus I/D genotype (-2.25 ± 1.40% versus -0.80 ± 1.57%, P0.05). The AT₂R A/A group had significantly less improved levels of systolic blood pressure (-7.23 ± 8.50 versus 2.50 ± 12.6 mmHg, P0.05), low-density lipoprotein-cholesterol (-0.36 ± 0.29 versus -0.09 ± 0.25 mmol/L, P0.05), carbohydrate (-54.4 ± 27.2 versus -31.8 ± 16.3 mg/min, P0.05) and fat oxidation (8.31 ± 11.86 versus 0.05 ± 9.99 mg/min, P0.05) than the C/C plus C/A genotypes.The present findings suggest that the homozygous form of the ACE gene may hinder the improvement of body fat and that the homozygous form of the AT₂R gene may make improving systolic blood pressure and some obesity-related metabolic parameters through a dietary intervention difficult among obese women.

Recent findings regarding the existence of functional brown adipose tissue (BAT) in adult humans suggest a physiological role of BAT and uncoupling protein 1 (UCP1)-linked thermogenesis in energy balance.To investigate whether UCP1 polymorphism was associated with resting energy expenditure (REE) and thermoregulatory sympathetic nervous system (SNS) activity in humans.A total of 82 healthy females (20-22 years) were genotyped for the -3826 A/G polymorphism of the UCP1 gene using a fluorescent allele-specific DNA primer assay system. REE was measured by indirect calorimetry. The thermoregulatory SNS activity was assessed by heart rate variability power spectral analysis according to our previously reported method. Each subject was studied in the morning, after an overnight fast. Nutritional values were calculated on the basis of 2-day food records.The frequencies of A/A, A/G and G/G genotypes were 0.27, 0.45 and 0.28, respectively. No significant difference was found in anthropometric indexes among the three groups. However, in the G/G group, the percentage of energy consumed as fat was lower (A/A: 30.7 ± 1.1%, A/G: 31.3 ± 1.0%, G/G: 26.0 ± 1.2%, P0.01), and energy intake tended to be lower (A/A: 7209 ± 310 kJ d(-1), A/G: 7075 ± 280 kJ d(-1), G/G: 6414 ± 264 kJ d(-1), P=0.16). With regard to metabolic parameters, group differences were observed in REE (A/A: 5599 ± 170 kJ d(-1), A/G: 5054 ± 115 kJ d(-1), G/G: 4919 ± 182 kJ d(-1), P0.01) and in thermoregulatory SNS activity (A/A: 313 ± 47 ms(2), A/G: 333 ± 42 ms(2), G/G: 185 ± 23 ms(2), P0.05).Diminished REE in G-allele carriers as well as reduced thermoregulatory SNS activity for the G/G genotype, suggest that attenuated UCP1-linked thermogenesis has an adverse effect on the regulation of energy balance.

Percutaneous low-frequency electrical muscle stimulation (LF-ES) is a new alternative exercise prescription for individuals who cannot adequately perform voluntary exercise. However, substantial undesirable elevation of both systolic blood pressure (SBP) and cardiac afterload occurs during LF-ES and must be resolved. Therefore, this study examined whether or not the synchrony between cardiac systole and skeletal muscle contraction affects instantaneous blood pressure and cardiac afterload during intermittent evoked muscle contractions. In eight subjects, the quadriceps and biceps femoris muscles of each limb were simultaneously stimulated at 20Hz with a duty cycle of 0.3s stimulation and 0.7s pause for 15min. The phase difference between the ECG R-peak and the onset of muscle contraction ( τ c–s ) was measured for all heartbeats. Then, instantaneous SBP, tension-time index (TTI), and peripheral vascular resistance (PVR) associated with each heartbeat were plotted as functions of τ c–s . The results showed that SBP, TTI, and PVR were significantly lowered at positive τ c–s (i.e., the moment at which a muscle contraction started during the cardiac recovery phase). These results suggest that a well-designed stimulator, one that induces muscle contractions coupled with heartbeats with appropriate phase difference, would effectively attenuate the elevation of SBP and cardiac afterload during LF-ES.

Early sub-clinical assessment of severity of cardiac autonomic neuropathy (CAN) and intervention are of prime importance for risk stratification and early treatment in preventing sudden death due to silent myocardial infarction. The Ewing battery is currently the diagnostic tool of choice but is unable to detect sub-clinical disease and requires patient cooperation. Time and frequency domain analysis have several shortcomings including sensitivity to recording length, respiratory activity and non-stationarities in the ECG signal. An important step forward is to have a non-invasive method of detecting CAN that is robust against these shortcomings and has a higher sensitivity for the presence of both sub-clinical and overt clinical disease. This study presents a novel parameter, tone-entropy (T-E) that analyses heart rate variability (HRV) of 20 min lead II ECG recordings. Tone (T) represents sympatho-vagal balance and entropy (E) the autonomic regularity activity. Thirteen normal subjects without (CAN-) and 21 with CAN (CAN+) participated in this study. Among 21 CAN+ subjects, 13 are early CAN+ (eCAN+), eight are definite CAN+ (dCAN+) according to autonomic nervous system function tests as described by Ewing. The results showed that tone was higher and the entropy was lower in the dCAN+ group (T=-0.033 to -0.010 and E=1.73-2.24) compared with the eCAN+ (T=-0.0927 to -0.0311 and E=2.0-2.65) and normal (T=-0.128 to -0.0635 and E=2.64-3.15) group. The research verified that T-E is a suitable method to determine the presence of CAN that correctly identifies experimentally induced changes in cardiac function akin to parasympathetic and sympathetic dysfunction and differentiates between stages in CAN disease progression identified using the Ewing battery.

本研究の目的は, スープ摂取後の安堵感（心がほっと安らぐ感覚）の定量的評価を行い, スープの種類による安堵感の違い, および安堵感に影響を及ぼす心理的, 生理的要因を検討することである。予備試験では, 訓練された6名のパネルによる官能検査を4種類のサンプル（コーンポタージュ[90 kcal], チキンコンソメ[43 kcal], および等エネルギーで風味に乏しいコーン・プラセボ, チキン・プラセボ）について行い, 各サンプルの特性を位置づけた。本試験では, 前夜から絶食した11名の女性（22.6±0.3歳）に, スープサンプルを朝食として, 異なる4日間にランダムな順序で負荷した。安堵感スコア, 満腹感スコア, 心拍数, 交感・副交感神経活動（心拍変動解析による), エネルギー消費量（呼気ガス分析による）を, スープ摂取前および摂取1時間後まで経時的に測定した。サンプルへの嗜好スコアは, コーンポタージュ, チキンコンソメの順に高く, 両プラセボで最も低かった。スープ摂取後の安堵感は, コーンポタージュでは他のスープサンプルより有意に高値を示した。安堵感は, 嗜好スコア, 満腹感スコア, 心拍数と正相関し, 副交感神経活動と負の相関を示した。本結果から, コーンポタージュ摂取後の高い安堵感には, スープへの嗜好性, および摂取後の満腹感と心拍数の上昇が関連していることが示唆された。

The present study aimed to examine whether a single bout of percutaneous low-frequency electrical muscle stimulation (EMS) can attenuate postprandial hyperglycemia in human subjects. Ten obese and 4 pre-obese Japanese men participated in two experimental sessions, one involved 20 min of EMS just after a breakfast (EMS trial) and the other involved complete rest after a breakfast (Control trial). In each trial, blood samples were taken before and at 30, 60, 90, and 120 minutes after the meal. Blood lactate concentration and respiratory gas exchange were measured during EMS and at complete rest after a meal in the EMS and Control trials, respectively. The results showed that the postprandial hyperglycemia was significantly attenuated in the EMS trial (P

Background: In the adiponectin gene polymorphisms, single-nucleotide polymorphism (SNP)−45 and SNP276 have reportedly been associated with obesity, Type 2 diabetes, and other features of metabolic syndrome. Aim: Whether these adiponectin SNP affect obesity-related parameters during caloric restriction in obese subjects. Subjects and methods: Thirty-two obese Japanese women were treated by meal replacement with a low calorie diet for 8 weeks and asked to maintain their habitual lifestyle. Obesity-related parameters were measured before and after the treatment period. We determined four SNP (T45G, I164T, G276T, and C-11377G) using a fluorescent allele-specific DNA primer assay system and FRET probe assay system. Results: After the treatment, the extent of decrease in waist circumference was greater in the subjects with the G/G or G/T genotype of SNP276 than in those with the T/T genotype (p=0.026). As for SNP45, the extent of decrease in triglyceride levels was greater in the subjects with the T/T genotype than in those with the T/G genotype (p=0.003). For SNP-11377, the extent of decrease in systolic blood pressure and fasting plasma glucose was greater in the subjects with the C/G or G/G genotype than in those with the C/C genotype (p=0.044). Conclusion: Our findings indicate that each SNP in the adiponectin gene might modify the change in obesity-related parameters during meal replacement with a low calorie diet.

Objectives The mitochondrial uncoupling proteins UCP2 and UCP3 are implicated in energy metabolism and regulation of reactive oxygen species, which are closely involved in autonomic nervous system function. Heart rate variability (HRV) reflects cardiac autonomic regulation and has been used to evaluate dysfunction of the autonomic nervous system in hypertension and cardiovascular diseases. We examined the association between polymorphisms in the UCP2 and UCP3 genes and HRV in healthy young Japanese men. Methods The 45 bp insertion/deletion polymorphism in exon8 of UCP2 and the -55C/T polymorphism in the UCP3 promoter region were genotyped (n = 255). Cardiac autonomic function was evaluated by power spectral analysis of HRV during supine rest and in a standing position. Low-frequency ( 0.15 Hz) components of HRV were quantified by frequency domain analysis. Results The I/I genotype of the UCP2 45 bp insertion/ deletion polymorphism was associated with relatively higher blood pressure and HRV sympathetic indices (low frequency percentage and low frequency:high frequency ratio) at supine rest. For the -55C/T polymorphism of UCP3, individuals carrying the -55T allele had significantly lower HRV sympathetic indices, but higher HRV parasympathetic indices (high frequency and high frequency percentage), than carriers of the C/C genotype at standing. Both UCP2 and UCP3 polymorphisms were significantly associated with a third-degree family history of hypertension, diabetes, and obesity. Additionally, carriers of the UCP2 45 bp I allele -UCP3 -55C/C combined genotype had the lowest HRV sympathetic and the highest HRV parasympathetic indices at standing among the combined genotypes. Conclusion UCP2 and UCP3 polymorphisms were associated with HRV in young and healthy states, suggesting a significant relationship between autonomic cardiovascular regulation and UCP2/UCP3 polymorphisms.

胃電図は, 腹部に装着した表面電極から経皮的に胃筋電活動を記録する非侵襲的な胃運動評価法である。本研究では, 胃電図を指標として朝食欠食と朝の胃運動の関連を検討するために, 朝食摂取習慣のある女性11名 (21.5±0.2歳) に, 1週間の朝食欠食および1週間の再摂食試験を連続して行った。各試験の前後に検査日を設け, 前夜から絶食した被験者の体組成, 空腹感と食欲 (Visual analog scaleによる) を測定し, 午前9時より胃電図と心電図を同時に記録した。得られた胃の電気信号を解析し, 1分間に約3回生じる正常波パワー (Normal power), 正常波パワー含有率 (% Normal power) およびその出現頻度 (Dominant frequency; DF) を定量した。心電図からは心臓自律神経活動を定量した。1週間の朝食欠食は, 有意ではないが% Normal powerとDFを低下させた。DFは欠食後から再摂食後にさらに低下した (p=0.074 versus baseline) 。朝食欠食後の空腹感スコア (r=0.55, p=0.077), 食欲スコア (r=0.60, p=0.051) と % Normal powerの相関には有意傾向が認められた。以上の結果より, 1週間の朝食欠食が習慣的に朝食を摂取している若年女性の胃運動を減弱させる傾向が認められたこと, および, 胃収縮運動の強さが空腹感や食欲の強さと関連している可能性が示唆された。

The uncoupling protein-1 (UCP1) gene is of major importance for regulation of body weight and lipid/lipoprotein metabolism. Our cross-sectional study has shown that subjects with the G/G genotype of the -3826 A/G polymorphism in the UCP-1 gene have higher levels of serum high-density lipoprotein cholesterol (HDL-C) than those with other genotypes. Low circulating HDL-C level has been regarded as a major atherosclerotic risk factor. We therefore investigated whether the -3826 A/G polymorphism affects the obesity- and lipid-related parameters during a low-calorie diet (LCD) intervention. In 32 obese women (49.9 ± 8.4 years of age), anthropometric, physiological and biochemical characteristics were measured before and after a 2-month LCD treatment, which restricted each subject to the same energy intakes, such as 5,120 kJ/day. The -3826 A/G polymorphism was detected using a PCR-restriction fragment-length polymorphism method. There were 6 subjects with the A/A genotype, 15 with the A/G genotype and 11 with the G/G genotype. The LCD intervention decreased weight (P < 0.001) and serum HDL-C levels (P < 0.05) in all subjects. There was no difference in the levels of change in weight, nutrient intake, physiological measurements in energy expenditure, and fat oxidation between subjects with and without the G allele. In contrast, the degree of the reduction in the HDL-C levels was significantly smaller in subjects with the G allele than those without the G allele. These results suggest that the G allele at -3826 in the UCP1 gene may ameliorate the reduction in serum HDL-C levels in obese women during LCD.

現代人の多忙な生活の中で，簡便で即効性のある栄養補助食品が求められている。本研究では，GABAを30 mg含有したカプセルの経口摂取によるリラクセーション効果を，自律神経活動の観点から評価することを試みた。12名の健康な若年男性（21.7±0.8歳）を対象に，GABAとプラセボカプセルを摂取させ，摂取前（安静時），摂取30分および60分後の心電図を胸部CM5 誘導より測定した。自律神経活動は，心拍のゆらぎ（心電図R-R間隔）をパワースペクトル解析し，非観血的に交感神経活動と副交感神経活動を弁別定量化した。その結果，GABA摂取前と比較して，総自律神経活動は摂取30分後 (p

Summary Uncoupling protein-1 (UCP1) activity in brown adipose tissue increases energy expenditure, and contributes to diet-induced or cold-induced thermogenesis. We previously reported that children with −3826 A → G nucleotide variant of the UCP1 gene had lowered postprandial thermogenesis in response to a high-fat meal. In this study, we investigated whether the UCP1 polymorphism was associated with cold-induced thermogenesis in healthy children. Resting energy expenditure was measured in 19 children (6–10 years) by indirect calorimetry for 30 min under thermoneutral (25 °C) or cold conditions (10 °C) in an environmental chamber. The activity of autonomic nervous system (ANS) was assessed by power spectral analysis of heart rate variability (HRV). Samples of saliva were collected for cortisol determination at the end of the experimental session. Each experiment was performed on 2 consecutive days. Children were genotyped for the UCP1 polymorphism with a PCR-restriction fragment length analysis using buccal samples. During cold exposure, total power of the HRV, an index of the overall ANS activity, as well as the salivary cortisol concentration significantly increased in the children with homozygous (GG) for the UCP1 polymorphism while only cortisol response was found in the carriers of the wild-type (AA) and heterozygous (AG) alleles; however, the GG allele group showed a lower cold-induced thermogenesis compared to the AA + AG group. In conclusion, despite cold-induced autonomic stimulation, the GG allele carriers have a reduced capacity for thermogenesis in response to acute cold exposure, suggesting that such reduced UCP1-linked thermogenesis may have adverse effects on the regulation of body weight.

We investigated whether capsaicin ingestion (150 mg) enhances substrate oxidation associated with thermogenic sympathetic activity as an energy metabolic modulator without causing prolongation of the cardiac OT interval during aerobic exercise in humans. Ten healthy males [24.4 (4.3) y] volunteered for this study. The cardiac autonomic nervous activities evaluated by means of heart rate variability of power spectral analysis, energy metabolism, and ECG QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilatory threshold (50% VT(max)) on a stationary ergometer with placebo or capsaicin oral administration chosen at random. The results indicated that there were no significant differences in heart rate during rest or exercise between the two trials. Autonomic nervous activity increased in the capsaicin tablet trial during exercise, but the difference did not reach statistical significance. Capsaicin, however, significantly induced a lower respiratory gas exchange ratio [0.92 (0.02) vs. 0.94 (0.02), means (SE), p0.05] and higher fat oxidation [0.17 (0.04) vs. 0.12 (0.04) g/min, means (SE), p0.05] during exercise. On the other hand, the data on the cardiac OT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, it may be considered that capsaicin consumption 1 h before low intensity exercise (50% VT(max)) is a valuable supplement for the treatment of individuals with hyperlipidemia and/or obesity because it improves lipolysis without any adverse effects on the cardiac depolarization and repolarization process.

L-カルニチンがヒトの空腹感に及ぼす影響を明らかにするために, 若年健常女性12名 (21.3±0.3歳) を対象として, L-カルニチン300mgを含有するフォーミュラ食と通常のフォーミュラ食を用いた二重盲検プラセボ対照試験による検証を行った (ウォッシュアウト : 1週間)。前夜からの絶食の後, フォーミュラ食を朝食として摂取させ, 食前および食後6時間まで満腹感スコア (ビジュアルアナログスケールズ ; VASs), 唾液コルチゾール, 血清カルニチン濃度, 血糖値, および心拍変動パワースペクトル解析を用いた自律神経活動指標を経時的に測定した。実験結果から, L-カルニチン摂取により主観的空腹感が軽減される可能性があること, および, 空腹感の軽減には血清総カルニチン濃度が関連していることが示唆された。さらに, 唾液コルチゾールはL-カルニチン摂取30分後, 2時間後には低値を示したが, 空腹感軽減との明確な関連は明らかではなかった。

Bray has proposed the "MONA LISA" hypothesis, an acronym for Most Obesities kNown Are Low In Sympathetic Activity indicating that obesity is associated with a relative or absolute reduction in the activity of the thermogenic component of the sympathetic nervous system. Our series of studies have suggested a potential reversibility in ANS activity regulating fat metabolism and appetite control by regular exercise training in middle aged individuals and obese children with depressed ANS activity. In other words habitual exercise plays a vital role in enhancing not only fat and glucose metabolism, but also ANS activities in the prevention of obesity and appetite control. There are growing expectations that too much sitting is a real and substantial risk to health. One of the intriguing findings from these accelerometer measurement studies is that breaks in sedentary time were shown to have beneficial associations with metabolic biomarkers, due possibly to challenging and enhancing autonomic nervous system that regulates body weight and appetite. Recent findings of brain-derived neurotrophic factors (BDNF) seem to have shed some light upon age-related neurodegenerative diseases and appear to influence energy metabolism, appetite and aspects of neuro-cognitive function. These data strongly suggest that a lack of exercise as characterized by a sedentary lifestyle and an unhealthy diet may lead to accelerated ageing, diseases of the body and brain, and an overall decline in the quality of life.

Background Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or PER35/5 genotypes). Conclusions These results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut.

alpha(1A)-adrenergic receptor (alpha(1A)-AR) regulates the cardiac and peripheral vascular system through sympathetic activation, and alpha(2A)-AR and alpha(2C)-AR subtypes are essential for presynaptic feedback regulation of catecholamine release from the central and peripheral sympathetic nerve. Genetic variations in each human alpha-AR subtype gene have been identified and have been implicated in hypertension and cardiovascular disease. It is not yet clear whether these genetic variations actually have an effect on sympatho-vagal modulation. The aim of the present study was to evaluate the relation between the five representative genetic polymorphisms of alpha-AR subtypes (Arg347Cys of alpha(1A)-AR; C-1291G, Asn251Lys, and DraI RFLP of alpha(2A)-AR; and Del322-325 of alpha(2C)-AR) and autonomic nervous system (ANS) function in young and healthy Japanese males. One hundred forty-nine subjects were genotyped for each alpha-AR polymorphism, and underwent evaluation of ANS function by power spectral analysis of heart rate variability (HRV) during supine rest and in a standing position. In a supine position, the alpha(1A)-AR 347Cys allele was significantly associated with lower HRV sympathetic index (normalized low frequency power [LF(%)] and LF:HF ratio) and higher HRV parasympathetic index [HF(%)]. Meanwhile, subjects with the alpha(2C)-AR Del322-325 allele had markedly higher LF(%) and LF:HF ratio and lower HF(%) than noncarriers. Thus, the alpha(1A)-AR and alpha(2C)-AR genetic variations influence sympatho-vagal balance even in young and healthy normotensive states, which could be postulated to constitute an intermediate phenotype for future pathological episodes of various ANS dysfunction-related diseases.

Tremendous numbers of heart rate variability studies have aimed to elucidate age-associated alterations of autonomic function in the past decades. However, the studies, far from clarifying ageing mechanisms, fell into confusion by a lack of common scales. The purpose of this study is to show a possibility to establish a comparative scale of autonomic function through a method, tone-entropy (T-E) analysis on heart period variation, whose validity has been already examined on typical physiological cases (Oida et al. in J Appl Physiol 82:1794-1801, 1997; Oida et al. in J Gerontol 54A:M219-M224, 1999a; Oida et al. in Acta Physiol Scand 165:129-134, 1999b; Oida et al. in Acta Physiol Scand 165:421-422, 1999c; Amano et al. in Eur J Appl Physiol 94:602-610, 2005). In this study, 276 subjects from teens to seventies were examined at rest by T-E analysis together with conventional time and frequency domain analyses. The tone (negativity represents vagal predominance) became significantly high [-0.174 +/- 0.026 (teens) to -0.024 +/- 0.004 (seventies), P0.05 for one-way ANOVA], and the entropy (total autonomic activity), significantly low [4.40 +/- 0.12 (teens) to 2.90 +/- 0.09 bit (seventies), P0.05] with advancing age. The result, plotted in 2-D T-E space, showed that the ageing traced a curvi-linear relation from right-bottom to left-top, and was consistent with previously studied typical physiological cases. The conventional analyses showed almost the same autonomic reduction as T-E did, but failed in detecting delicate alteration of autonomic balance. The results, showing that autonomic activity reduced in both pathways impairing vagal predominance significantly with ageing, suggested a possibility to assess autonomic function in 2-D T-E space in a comparative way.

The majority of women of reproductive age experience a regular recurrence of various symptoms in the premenstrual phase. The etiopathogenesis of premenstrual symptomatology, however, remains inconclusive. The present study was proposed to evaluate whether the activity of the autonomic nervous system (ANS), which largely contributes to the relative stability of a human's internal environment, is altered during the menstrual cycle of women with premenstrual symptomatology. Thirty eumenorrheic young women participated in this study. All subjects were investigated during the follicular and late luteal phases. The ANS activity was assessed by means of heart rate variability power spectral analysis during supine rest. No intramenstrual cycle differences in the ANS activity were found in women experiencing no or small increases in premenstrual symptoms. In contrast, the sympathetic nervous system (SNS) activity significantly increased and the parasympathetic nervous system (PNS) activity apparently decreased in the late luteal phase in subjects whose premenstrual symptomatology was not unbearable, but substantially increased (> 20%) compared to the symptom-free follicular phase. The women with greater degrees of premenstrual distress possessed higher SNS activity and lower PNS activity in the late luteal phase than the women with less symptomatology. The ANS activity in the follicular phase did not differ among the subjects regardless of their premenstrual symptoms. Although causes and consequences continue to elude, the present study provides additional intriguing evidence that the altered functioning of ANS in the late luteal phase could be associated with diverse psychosomatic or behavioral symptoms appearing premenstrually.

Background The T allele of the C825T polymorphism of the G protein β3 subunit gene ( GNB3 ) is reported to be associated with increased intracellular signal transduction and the prevalence of essential hypertension. Because the two major receptors in the autonomic nervous system (ANS), the adrenergic and muscarinic acetylcholine receptors, are G protein-coupled receptors, it was expected that the GNB3 C825T polymorphism was associated with ANS function. In the present study, we have investigated the association of this polymorphism with ANS in young, healthy Japanese male individuals. Methods A total of 94 young, healthy subjects underwent the genotyping for the GNB3 C825T polymorphism and electrocardiogram R-R interval power spectral analysis in supine rest and standing positions. Results There were no significant differences among genotypes in any of the characteristics investigated (body mass index, blood pressure, plasma glucose, insulin, lipids, and family history of hypertension, diabetes, or obesity). However, in power spectral analysis of heart rate variability, the very-low-frequency component when standing was higher in TT carriers than in CC carriers, and TT and CT carriers had a significantly higher sympathetic nervous system (SNS) index and lower parasympathetic nervous system (PNS) index when standing than CC carriers. In addition, we found that TT carriers showed no chronological variations in either SNS or PNS index after postural change. Conclusions These observations suggested that GNB3 C825T polymorphism is associated with ANS in youth. These findings raise the possibility that individuals who are T allele carriers are at increased risk for developing hypertension in relation to ANS function.

Our objective was to investigate the effect of a long-term moderate exercise program on cardiac autonomic nervous system (ANS) activity in healthy children. Three hundred and five children aged 6–11 years participated in a 12-month school-based exercise training program (130–140 bpm, 20 min/day, 5 days/week). Cardiac ANS activities were measured using heart rate variability (HRV) power spectral analysis in resting conditions. Following the first measurement, 100 children from the lowest total power (TP) HRV were chosen as experimental samples and the same number of age-, height-, and weight-matched controls (CG) was randomly selected from the remaining children. In the low group (LG), all the frequency components of the HRV were significantly increased after the training period, whereas only low-frequency power was augmented in the control group (CG). Our data suggest that the 12-month moderate exercise training has a positive effect on cardiac ANS activity in the children who initially had low HRV.

There is considerable evidence to suggest that electrical stimulation (ES) activates glucose uptake in rodent skeletal muscle. It is, however, unknown whether ES can lead to similar metabolic enhancement in humans. We employed low-frequency ES through surface electrodes placed over motor points of quadriceps femoris muscles. In male subjects lying in the supine position, the highest oxygen uptake was obtained by a stimulation pattern with 0.2-ms biphasic square pulses at 20 Hz and a 1-s on-off duty cycle. Oxygen uptake was increased by approximately twofold throughout the 20-min stimulation period and returned to baseline immediately after stimulation. Concurrent elevation of the respiratory exchange ratio and blood lactate concentration indicated anaerobic glycogen breakdown and utilization during ES. Whole body glucose uptake determined by the glucose disposal rate during euglycemic clamp was acutely increased by 2.5 mg · kg−1 · min−1in response to ES and, moreover, remained elevated by 3–4 mg · kg−1 · min−1for at least 90 min after cessation of stimulation. Thus the stimulatory effect of ES on whole body glucose uptake persisted not only during, but also after, stimulation. Low-frequency ES may become a useful therapeutic approach to activate energy and glucose metabolism in humans.

Reductions in tonic vagal controls of the heart and depressed baroreflex sensitivity (BRS) have been associated with a postural fall in blood pressure (BP) and the incidence of cardiac events among older people. We examined the hypothesis that BP regulation during orthostatic challenge as well as heart rate variability (HRV) at rest can be better maintained in long-term exercise-trained, healthy, older men (aged 60-70 years). Subjects were classified into two groups; long-term exercise-trained (LTET, n=14) and sedentary (SED, n=10) according to their history of physical activity. Prior to the dynamic BRS assessment, supine resting autonomic cardiac modulation was assessed by means of time domain HRV [standard deviation of ECG R-R interval (RRISD) and the coefficient of variation (CV)]. The BRS was assessed during 60 degrees head-up tilting by simultaneously measuring beat-by-beat systolic blood pressure (SBP) and ECG R-R interval changes. The BRS gain was determined by the regression slope coefficient based on the extent of the SBP fall and the corresponding ECG R-R shortening during the orthostatic challenge. The results indicated that the LTET group manifested greater ECG R-R interval fluctuations with significantly higher resting RRISD and CV, compared with the SED group [59.5 (10.4) versus 27.7 (7.8) ms, p0.05; 5.5 (0.8) versus 2.8 (0.7)%, p0.05], respectively. Using dynamic BRS testing during the acute orthostatic challenge, the LTET group showed a significantly higher BRS gain than the SED [6.4 (0.8) versus 3.8 (0.6) ms x mmHg(-1), p0.017] group. These results indicate that CV and BRS are well maintained in healthy, LTET older individuals when compared with their sedentary peers. Our data suggest that this augmented autonomic cardiac modulation reflects better parasympathetic responsiveness in LTET individuals. Data provide further support for long-term exercise training as another possible cardioprotective factor that might decrease susceptibility to ventricular fibrillation as well as assist arterial BP at the onset of an orthostatic challenge in older men.

Several polymorphisms of genes involved in autonomic nervous system (ANS) function have been reported to affect metabolic regulation. We have investigated the association of an alpha(2B)-adrenergic receptor (alpha(2B)AR) three-amino acid deletion polymorphism with ANS activity in young healthy subjects by means of electrocardiogram R-R interval power spectral analysis. Three hundred eighty-one young healthy Japanese males (mean +/- SE, 20.6 +/- 0.1 yr) were studied. One hundred sixty-eight (44.1%) were homozygotes of Long allele (Long/Long), 162 (42.5%) were heterozygotes (Long/Short), and 51 (13.4%) were homozygotes of Short allele (Short/Short). The allele frequency of Short allele was 0.35. No significant differences were observed in any of the characteristics investigated: body mass index, plasma glucose, plasma insulin, or family history of diabetes and obesity. In R-R spectral analysis of heart rate variability, carriers of Short/Short had significantly greater low frequency and very low frequency than Long/Long, as well as a higher sympathetic nervous system index. These findings suggest that the alpha(2B)AR deletion polymorphism might result in metabolic disorder by altering ANS function.

NAGAI, NARUMI, TAMAKI MATSUMOTO, HIROKO KITA, AND TOSHIO MORITANI. Autonomic nervous system activity and the state and development of obesity in Japanese school children. Obes Res. 2003;11:25–32. Objective: The autonomic nervous system (ANS) plays an important role in regulating energy expenditure and body fat content; however, the extent to which the ANS contributes to pediatric obesity remains inconclusive. The aim of this study was to evaluate whether sympathetic and/or the parasympathetic nerve activities were altered in an obese pediatric population. We further examined a physiological association between the duration of obesity and the sympatho-vagal activities to scrutinize the nature of ANS alteration as a possible etiologic factor of childhood obesity. Research Methods and Procedures: Forty-two obese and 42 non-obese healthy sedentary school children were carefully selected from 1080 participants initially recruited to this study. The two groups were matched in age, gender, and height. The clinical records of physical characteristics and development of the obese children were retrospectively reviewed to investigate the onset and progression of obesity. The ANS activities were assessed during a resting condition by means of heart rate variability power spectral analysis, which enables us to identify separate frequency components, i.e., total power (TP), low-frequency (LF) power, and high-frequency (HF) power. The spectral powers were then logarithmically transformed for statistical testing. Results: The obese children demonstrated a significantly lower TP (6.77 0.12 vs. 7.11 0.04 ln ms 2 , p 0.05), LF power (6.16 0.12 vs. 6.42 0.05 ln ms 2 , p 0.05), and HF power (5.84 0.15 vs. 6.34 0.07 ln ms 2 , p 0.01) compared with the non-obese children. A partial correlation analysis revealed that the LF and HF powers among 42 obese children were negatively associated with the duration of obesity independent of age (LF: partial r 0.55, p 0.001; HF: partial r 0.40, p 0.01). The obese children were further subdivided into two groups based on the length of their obesity. All three spectral powers were significantly reduced in the obese group with obesity of 3 years (n 18) compared to the group with obesity of 3 years. Discussion: Our data indicate that obese children possess reduced sympathetic as well as parasympathetic nerve activities. Such autonomic depression, which is associated with the duration of obesity, could be a physiological factor promoting the state and development of obesity. These findings further imply that preventing and treating obesity beginning in the childhood years could be an urgent and crucial pediatric public health issue.

Leptin is an adipocyte-derived hormone that decreases food intake and increases energy expenditure through the activation of the sympathetic nervous system (SNS). Notwithstanding recent intensive research, the underlying physiological mechanism of leptin as well as the etiology of obesity in humans remains elusive. The present study attempted to investigate the potential association between endogenous circulating leptin and sympatho-vagal activities in age- and height-matched obese and nonobese healthy young women. Plasma leptin concentrations were measured by radioimmunoassay. The autonomic nervous system activity was assessed during the resting condition by means of a recently devised power spectral analysis of heart rate variability, which serves to identify three separate frequency components, very low (VLO), low (LO), and high (HI). Plasma leptin concentrations were greater in the obese than in the control group (45.7 +/- 5.89 vs. 11.2 +/- 1.10 ng. ml(-1), P < 0.01). As to the contribution of endogenous leptin to SNS activity, both the ratios of the VLO frequency component reflecting thermoregulatory sympathetic function and the global SNS index [(VLO + LO)/HI] to plasma leptin concentration were markedly reduced in the obese compared to the control group (VLO per leptin: 5.9 +/- 1.39 vs. 37.8 +/- 8.1 ms(2). ml. ng(-1), P < 0.01; SNS index per leptin: 0.04 +/- 0.008 vs. 0.33 +/- 0.01 ml c. ng(-1), P < 0.01). Additionally, a nonlinear regression analysis revealed that these ratios exponentially decreased as a function of body fat content (VLO per leptin r(2) = 0.57, P < 0.01; SNS index per leptin r(2) = 0.53, P < 0.01). Our data suggest that reduced sympathetic responsiveness to endogenous leptin production, implying peripheral leptin resistance, might be a pathophysiological feature of obesity in otherwise healthy young women. The findings regarding the association of leptin, body fat content, and SNS activity further indicate that the 30% of total body fat, which has been used as a criterion of obesity, might be a critical point at which leptin resistance is induced.

The effects of caffeine ingestion on the activities of the autonomic nervous system (ANS) during endurance exercise at low intensity were investigated using a power spectrum analysis of heart rate variability. Placebo or caffeine (300 mg) capsules were randomly administered to the subjects. Each subject ingested the samples 2 h before cycling on an ergometer for 30 min at an intensity corresponding to 40%-50% of his ventilatory threshold. The electrocardiogram, blood pressure (BP) and gas exchange parameters were monitored during rest and exercise. The results indicated that there were no significant differences in heart rate and systolic blood pressure between the trials. The spectrum integrated values of the low frequency power and total power components in the caffeine trial were significantly greater than in the placebo trial during exercise, which implied that activities of the ANS were augmented by caffeine. Caffeine also induced enhanced lipid oxidation as shown by the significantly lower respiratory gas exchange ratio and increases in diastolic blood pressure during exercise. The results shed some light upon the relationship between the activity of the ANS, energy metabolism and BP. In conclusion, the results suggest that caffeinated beverages have a potential to be useful supplements to the prescription of exercise for individuals who experience a depressed activity of the ANS. The results also suggest that the experiment protocol used in this study is a sensitive and noninvasive method for evaluating the effects of various foods and nutrients on the activity of the ANS.

Background The lower limb muscle may play an important role in decreasing the heart’s pumping workload. Aging and inactivity cause atrophy and weakness of the muscle, leading to a loss of the heart-assisting role. An electrical lower limb muscle stimulator can prevent atrophy and weakness more effectively than conventional resistance training; however, it has been reported to increase the heart’s pumping workload in some situations. Therefore, more effective tools should be developed. Methods We newly developed a cardiac cycle-synchronized electrical lower limb muscle stimulator by combining a commercially available electrocardiogram monitor and belt electrode skeletal muscle electrical stimulator, making it possible to achieve strong and wide but not painful muscle contractions. Then, we tested the stimulator in 11 healthy volunteers to determine whether the special equipment enabled lower limb muscle training without harming the hemodynamics using plethysmography and a percutaneous cardiac output analyzer. Results In 9 of 11 subjects, the stimulator generated diastolic augmentation waves on the dicrotic notches and end-diastolic pressure reduction waves on the plethysmogram waveforms of the brachial artery, showing analogous waveforms in the intra-aortic balloon pumping heart-assisting therapy. The heart rate, stroke volume, and cardiac output significantly increased during the stimulation. There was no change in the systolic or diastolic blood pressure during the stimulation. Conclusion Cardiac cycle-synchronized electrical muscle stimulation for the lower limbs may enable muscle training without harmfully influencing the hemodynamics and with a potential to reduce the heart’s pumping workload, suggesting a promising tool for effectively treating both locomotor and cardiovascular disorders.

Objective: Sympathetic nervous system abnormality in humans is still a matter of debate. The present study was designed to examine diet-induced autonomic nervous system activity and metabolic change in obese and non-obese young women. Research Methods and Procedures: Sixteen age- and height-matched obese and non-obese young women participated in this study. Sympathovagal activities were assessed by means of our newly developed spectral analysis procedure of heart-rate variability during the resting condition and after mixed-food ingestion (480 kcal). Energy expenditure was also measured under these two conditions. Results: There was no significant difference in any of the parameters of the heart-rate variability between the obese group and control group during the resting condition. In the control group, both absolute values (221.5 ± 54.5 vs. 363.8 ± 43.7 ms2, p < 0.05) and relative values (0.23 ± 0.03 to 0.36 ± 0.02, p < 0.05) of a very-low-frequency component and global sympathetic nervous system index (1.46 ± 0.19 vs. 3.26 ± 0.61, p < 0.05) were significantly increased after mixed-food ingestion compared with the values obtained after resting condition. However, no such sympathetic response was found in the obese group. Energy expenditure increased in the two groups after the meal, but the magnitude of the increase above the preprandial resting condition was significantly greater in the control group than in the obese group (11.2 ± 2.3 vs. 6.7 ± 0.8%, p < 0.05). Discussion: Our data suggest that despite identical sympathovagal activities at the resting condition, obese young women may possess a reduced sympathetic response to physiological perturbation such as mixed food intake, which might be related to lowered capacity of thermogenesis and the state of obesity.