Influence of Ambient Temperature on Autonomic Nerve Function and Peripheral Sensation from Moderate-Intensity Treadmill Exercise.

Objective: The main objective was to ascertain the acute responses in autonomic nervous activity and peripheral sensation induced by moderate-intensity treadmill exercise performed under different ambient temperatures. Methods: Twelve young healthy subjects underwent three sessions of moderate-intensity treadmill exercise (warming, 5 min and running, 25 min), on different days under 10°C, 20°C and 30°C room temperatures. Pre- and post-intervention, heart rate variability (HRV) and plantar vibrotactile perception threshold (VPT) were measured. Additionally, rate of perceived exertion (RPE) was recorded after intervention. Results: In comparison with the corresponding baseline values, after intervention, low frequency power (LF) and LF/high frequency power (HF) of HRV increased significantly and HF decreased significantly under the condition of 10°C only (p < .005). Following intervention, VPT increased significantly at the hallux for 31.5 Hz test frequency under 30°C and at the heel for 31.5 Hz test frequency under 10°C (both p < .05). In contrast, VPT decreased significantly at the hallux for 125 Hz test frequency under 10°C (p < .005). Exposure under the temperature of 20°C did not result in any significant change in VPT. After intervention, RPE under 30°C showed significantly higher values than those under 20°C (p < .01) and 10°C (p < .005) conditions with no difference between the latter two conditions. Conclusions: Treadmill exercise under 20°C ambient temperature did not exert any negative impacts on autonomic and peripheral nerve function and resulted in a perceived exertion of moderate intensity among the study participants. Therefore, an ambient temperature around 20°C might be recommended for the mentioned purpose.

Effects of Heat-Killed Lacticaseibacillus paracasei MCC1849 on the Maintenance of Physical Condition in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

We previously reported that the intake of heat-killed Lacticaseibacillus paracasei MCC1849 suppressed the onset of cold-like symptoms in healthy young women who were susceptible to colds. This study aimed to investigate the effects of MCC1849 on subjective symptoms of physical condition in healthy adults of a wide age range. In this randomized, double-blind, placebo-controlled, parallel-group study, 200 healthy adults were randomly divided into the MCC1849 group or placebo group. The participants received test powder with 50 billion MCC1849 cells or placebo powder without MCC1849 for 24 weeks. Subjective symptoms were assessed by diary scores. Analysis was performed on 183 participants (MCC1849 group; n = 91, placebo group; n = 92) in the per-protocol set. The number of days of stuffy nose and cold-like symptoms was significantly reduced in the MCC1849 group compared with the placebo group. In addition, the duration of stuffy nose, sore throat and cold-like symptoms was significantly lower in the MCC1849 group. No side effects were observed. Therefore, oral intake of MCC1849 suppressed subjective symptoms in healthy adults of a wide age range. These data suggest that MCC1849 may help maintain physical condition.

Association of Plasma Branched-Chain and Aromatic Amino Acids with Reduction in Kidney Function Evaluated in Apparently Healthy Adults.

The published literature on the association of circulatory branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) with reduced kidney function is inconsistent or conflicting. Clarification of it might help to better understand the underlying pathophysiology and to determine potential biomarkers for early detection and evaluation of kidney function decline. Our main purpose was to explore and clarify the potential relationships of individual BCAAs and AAAs with estimated glomerular filtration rate (eGFR) decline. We included the data from 2804 healthy subjects and categorized them into three groups based on eGFR tertiles. The associations between individual amino acids and eGFR were explored by covariate-adjusted logistic regression models. There was a progressive increase in the concentrations of BCAAs and AAAs from the upper to the lower tertiles. We revealed significant positive associations of isoleucine, leucine, and phenylalanine with lower tertiles of eGFR in the adjusted models (p < 0.01-0.001). The findings hold a promising potential of using plasma isoleucine, leucine, and phenylalanine levels for evaluation of kidney function decline. Future longitudinal studies should investigate the causal association between altered levels of these amino acids and impaired kidney function and also the utility of the former as potential biomarkers for evaluating the risk and early detection of the latter.

Analysis of Relationships between Immune Checkpoint and Methylase Gene Polymorphisms and Outcomes after Unrelated Bone Marrow Transplantation.

Unrelated bone marrow transplantation (uBMT) is performed to treat blood disorders, and it uses bone marrow from an unrelated donor as the transplant source. Although the importance of HLA matching in uBMT has been established, that of other genetic factors, such as single-nucleotide polymorphisms (SNPs), remains unclear. The application of immunoinhibitory receptors as anticancer drugs has recently been attracting attention. This prompted us to examine the importance of immunoinhibitory receptor SNPs in uBMT. We retrospectively genotyped five single-nucleotide polymorphisms (SNPs) in the immune checkpoint genes, BTLA, PD-1, LAG3, and CTLA4, and two SNPs in the methylase genes, DNMT1 and EZH2, in 999 uBMT donor-recipient pairs coordinated through the Japan Marrow Donor Program matched at least at HLA-A, -B, and -DRB1. No correlations were observed between these SNPs and post-uBMT outcomes (p > 0.005). This result questions the usefulness of these immune checkpoint gene polymorphisms for predicting post-BMT outcomes. However, the recipient EZH2 histone methyltransferase gene SNP, which encodes the D185H substitution, exhibited a low p-value in regression analysis of grade 2-4 acute graft-versus-host disease (p = 0.010). Due to a low minor allele frequency, this SNP warrants further investigation in a larger-scale study.

Plasma Branched-Chain and Aromatic Amino Acids in Relation to Hypertension.

Findings of the available studies regarding the roles of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in hypertension are inconsistent, conflicting and inconclusive. The purpose of this study was to explore and clarify the existence of any relationships of individual BCAAs and AAAs with hypertension with adjustments for potential relevant confounders. A total of 2805 healthy controls and 2736 hypertensive patients were included in the current analysis. The associations between individual amino acids and hypertension were explored by logistic regression analyses adjusted for potential confounding variables. Among the investigated amino acids, only the BCAAs showed consistently significant positive associations with hypertension in the adjusted models (p-trend < 0.05 to 0.001). However, compared with the corresponding lowest quartile of individual BCAAs, the positive association with hypertension remained significant only in the highest quartile (p < 0.01 to 0.001). We confirmed in a relatively large cohort of subjects that BCAAs, not AAAs, demonstrated consistent positive associations with hypertension. The results display the promising potential for the use of BCAAs as relevant and accessible biomarkers, and provide perspectives on interventions directed towards the reduction in plasma BCAA levels in the prevention and management of hypertension.

Acute Effects of Whole-Body Vibration on Peripheral Blood Flow, Vibrotactile Perception and Balance in Older Adults.

BACKGROUND: Non-invasive application of whole-body vibration (WBV) has the potential for inducing improvements in impaired peripheral circulation, cutaneous sensation and balance among older adults. However, relevant studies have frequently applied high magnitudes of vibration and show conflicting and inconclusive results. Therefore, we attempted to ascertain the acute responses in those parameters from exposure of thirty older subjects to WBV of three different magnitudes, defined according to ISO 2631-1 (1997). METHODS: Each subject randomly underwent four sessions of intervention (three bouts of 1 min exposure with 1 min between-bout rests): WBV at 15, 20, or 25 Hz with a peak-to-peak displacement of 4 mm, or control condition. RESULTS: Both during and after intervention, dorsal foot skin blood flow increased significantly under 20 and 25 Hz exposure conditions with greater responses under the latter condition, the magnitude of which slightly exceeded the recommended value. Plantar vibrotactile perception showed significant increases after WBV exposure with overall greater responses under higher frequencies of vibration. In contrast, no WBV-induced change in balance was observed. CONCLUSIONS: WBV at 20 Hz with a magnitude within the recommended limit can be effective in inducing enhancements in peripheral blood flow; however, the same magnitude of vibration seems insufficient in improving balance among older adults.

A systematic review of studies investigating the effects of controlled whole-body vibration intervention on peripheral circulation.

The findings of the published studies investigating the changes in peripheral circulation induced by exposure to whole-body vibration (WBV) are not consensual or conclusive. Also, those studies did not consider the role of vibration magnitude on the peripheral circulatory responses making the interpretation of the observed findings difficult. We aimed to review the published literature investigating the effects of controlled WBV intervention on peripheral circulation by characterizing the relevant exposure conditions including vibration magnitudes, and ascertain the specific patterns of responses in peripheral circulation of the lower extremity from such exposure. A computerized search was performed in PubMed and Scopus using selected key search terms, and the relevant data were extracted. The vibration magnitude in the included studies frequently exceeded the limit specified in the International Standard ISO 2631-1 (1997) for such exposure. As observed, exposure to WBV with frequencies ≤30 Hz caused an improvement in peripheral blood flow (BF) and/or skin temperature (ST) of the lower extremity. In contrast, the responses in BF and ST from exposure to WBV of higher frequencies (31 Hz-50 Hz) produced conflicting results. The findings of this review indicate that WBV exposure with relatively lower frequency and magnitude can be safely and effectively used to induce improvements in peripheral circulation. For this purpose, the limits recommended by the ISO 2631-1 (1997) should be considered till safe and effective vibration-related parameters are established.

Relationship of reduced glomerular filtration rate with alterations in plasma free amino acids and uric acid evaluated in healthy control and hypertensive subjects.

The potential association between altered levels of plasma free amino acids (PFAAs) and uric acid (UA) with estimated glomerular filtration rate (eGFR) remains unknown among patients with hypertension. A total of 2804 healthy controls and 2455 hypertensive patients were included in the current analysis. eGFR was defined as reduced when it was <60 ml/min/1.73 m2. The associations between reduced eGFR and individual PFAAs and UA in the healthy control and hypertension groups were explored by logistic regression analyses adjusted for potential confounding variables. Results show that UA had a significant positive association with reduced eGFR in both healthy control and hypertension groups (P < 0.001). Among the PFAAs, citrulline, glycine and phenylalanine showed significant positive associations with reduced eGFR in both healthy control (P < 0.01 to 0.001) and hypertension (P < 0.001) groups. Moreover, alanine, asparagine and methionine achieved significant positive associations with reduced eGFR only in the hypertension group (P < 0.01 to 0.001). Conversely, serine showed significant inverse associations with reduced eGFR in the hypertension group only (P < 0.001). Our findings provide first evidence for a strong relationship between distinct patterns of PFAAs and elevated UA with reduced eGFR in hypertension. The findings may appear useful in developing effective strategies for the prevention or early detection and treatment of declined kidney function in hypertension.

Association of plasma free amino acids with hyperuricemia in relation to diabetes mellitus, dyslipidemia, hypertension and metabolic syndrome.

Previous studies demonstrated independent contributions of plasma free amino acids (PFAAs) and high uric acid (UA) concentrations to increased risks of lifestyle-related diseases (LSRDs), but the important associations between these factors and LSRDs remain unknown. We quantified PFAAs and UA amongst Japanese subjects without LSRDs (no-LSRD, n = 2805), and with diabetes mellitus (DM, n = 415), dyslipidemia (n = 3207), hypertension (n = 2736) and metabolic syndrome (MetS, n = 717). The concentrations of most amino acids differed significantly between the subjects with and without hyperuricemia (HU) and also between the no-LSRD and LSRD groups (p < 0.05 to 0.001). After adjustment, the logistic regression analyses revealed that lysine in DM, alanine, proline and tyrosine in dyslipidemia, histidine, lysine and ornithine in hypertension, and lysine and tyrosine in MetS demonstrated significant positive associations with HU among the patients with LSRDs only (p < 0.05 to 0.005). By contrast, arginine, asparagine and threonine showed significant inverse associations with HU in the no-LSRD group only (p < 0.05 to 0.01). For the first time, we provide evidence for distinct patterns of association between PFAAs and HU in LSRDs, and postulate the possibility of interplay between PFAAs and UA in their pathophysiology.

Alteration in plasma free amino acid levels and its association with gout.

BACKGROUND: Studies on the association of plasma-free amino acids with gout are very limited and produced conflicting results. Therefore, we sought to explore and characterize the plasma-free amino acid (PFAA) profile in patients with gout and evaluate its association with the latter. METHODS: Data from a total of 819 subjects (including 34 patients with gout) undergoing an annual health examination program in Shimane, Japan were considered for this study. Venous blood samples were collected from the subjects and concentrations of 19 plasma amino acids were determined by high-performance liquid chromatography-electrospray ionization-mass spectrometry. Student's t-test was applied for comparison of variables between patient and control groups. The relationships between the presence or absence of gout and individual amino acids were investigated by logistic regression analysis controlling for the effects of potential demographic confounders. RESULTS: Among 19 amino acids, the levels of 10 amino acids (alanine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, serine, tryptophan, valine) differed significantly (P < .001 to .05) between the patient and control groups. Univariate logistic regression analysis revealed that plasma levels of alanine, isoleucine, leucine, phenylalanine, tryptophan and valine had significant positive associations (P < .005 to .05) whereas glycine and serine had significant inverse association (P < .05) with gout. CONCLUSIONS: The observed significant changes in PFAA profiles may have important implications for improving our understanding of pathophysiology, diagnosis and prevention of gout. The findings of this study need further confirmation in future large-scale studies involving a larger number of patients with gout.

Plasma free amino acid profiles evaluate risk of metabolic syndrome, diabetes, dyslipidemia, and hypertension in a large Asian population.

BACKGROUND: Recently, the association of plasma free amino acid (PFAA) profile and lifestyle-related diseases has been reported. However, few studies have been reported in large Asian populations, about the usefulness of PFAAs for evaluating disease risks. We examined the ability of PFAA profiles to evaluate lifestyle-related diseases in so far the largest Asian population. METHODS: We examined plasma concentrations of 19 amino acids in 8589 Japanese subjects, and determined the association with variables associated with obesity, blood glucose, lipid, and blood pressure. We also evaluated the PFAA indexes that reflect visceral fat obesity and insulin resistance. The contribution of single PFAA level and relevant PFAA indexes was also examined in the risk assessment of lifestyle-related diseases. RESULTS: Of the 19 amino acids, branched-chain amino acids and aromatic amino acids showed association with obesity and lipid variables. The PFAA index related to visceral fat obesity showed relatively higher correlation with variables than that of any PFAA. In the evaluation of lifestyle-related disease risks, the odds ratios of the PFAA index related to visceral fat obesity or insulin resistance with the diseases were higher than most of those of individual amino acid levels even after adjusting for potential confounding factors. The association pattern of the indexes and PFAA with each lifestyle-related disease was distinct. CONCLUSIONS: We confirmed the usefulness of PFAA profiles and indexes as markers for evaluating the risks of lifestyle-related diseases, including diabetes mellitus, metabolic syndrome, dyslipidemia, and hypertension in a large Asian population.

The different roles of innate immune receptors in inflammation and carcinogenesis between races.

Innate immune factors exert widespread effects on cytokine secretion, cell survival, autophagy, and apoptosis. Nucleotide-binding and oligomerization domain-like receptors (NLRs) are members of the innate immune system in the cytosol that sense pathogens, endogenous danger molecules such as uric acid, and pollutants. Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1 and NOD2) are components of NLR family, and ligands of these factors are γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and muramyl dipeptide (MDP), respectively. Upon recognition of ligands, NOD1 and NOD2 induce the production of inflammatory cytokines and transcription factors including interleukin-6 (IL-6) and nuclear factor-κB (NF-κB). We examined the function of NOD1 and NOD2 in innate immunity, with a focus on their differing roles in disease pathogenesis between Japanese and Caucasian populations. Susceptibility to several immune-related diseases, including Crohn's disease, colorectal and breast cancers, and graft-versus-host-disease (GVHD) showed a correlation with genetic variants of NOD2 in Caucasian, but not in Japanese, populations. This difference may be primarily due to the fact that three major NOD2 SNPs (R702W, G908R, L1007insC) prevalent in Caucasians are rare or absent in Japanese populations. Because NLR has diverse effects on immune function, it is possible that many as yet uncharacterized immune-related diseases will also show different susceptibilities between races due to the different ratio of genetic variants in innate immune genes.

Analysis of long-term stored plasma samples for investigation into the pathophysiology of vibration-induced white finger: preliminary results.

Blood samples were collected 25 yr ago from hand-arm vibration syndrome patients with vibration-induced white finge/VWF (VWF+ group) and without it (VWF- group), and healthy controls (n=12 in each group), and stored at -80 °C. The subjects provided venous blood twice: at baseline, and after cold exposure at 7 °C for 25 min. Blood specimens were analyzed for plasma endothelin-1 (ET-1) by an enzyme-linked immunosorbent assay. Baseline concentration of plasma ET-1 was found to be significantly larger in the VWF- group than the control group, whereas no such difference was observed for the VWF+ group. However, the %change was larger in the VWF+ group (107.73 ± 30.49%) than the other two groups, and more subjects in the VWF+ group showed the maximum increase in ET-1 than the other two groups. In conclusion, ET-1 appears to have a role in the pathophysiology of VWF.