Diurnal repeated exercise promotes slow-wave activity and fast-sigma power during sleep with increase in body temperature: a human crossover trial.

The effects of exercise on sleep have been explored from various perspectives, but little is known about how the effects of acute exercise on sleep are produced through physiological functions. We used a protocol of multiple daytime sessions of moderate-intensity aerobic exercise and examined the subsequent effects on sleep structure, core body temperature (CBT), distal-proximal skin temperature gradient (DPG), and subjective parameters. Fourteen healthy men who did not exercise regularly were evaluated under the baseline (no exercise) and exercise conditions on a within-subject crossover basis. Under the exercise condition, each participant performed a 40-min aerobic workout at 40% of maximal oxygen intake, four times between morning and early evening. We observed a 33% increase in slow-wave sleep (SWS; P = 0.005), as well as increases in slow-wave activity (SWA; P = 0.026), the fast-sigma power/SWA ratio (P = 0.005), and subjective sleep depth and restorativeness the following morning. Moreover, both CBT and the DPG increased during sleep after exercise (P = 0.021 and P = 0.047, respectively). Regression analysis identified an increased nocturnal DPG during sleep after exercise as a factor in the increase in SWA. The fast-sigma/SWA ratio correlated with CBT. The performance of acute exercise promotes SWS with nocturnal elevation in the DPG. Both CBT and fast-sigma power may play a role in the specific physiological status of the body after exercise. NEW & NOTEWORTHY We used multiple daytime sessions of moderate-intensity aerobic exercise to examine the effects on the sleep structure, core body temperature (CBT), distal-proximal skin temperature gradient (DPG), and subjective parameters. Significant increases in slow-wave activity (SWA), CBT, DPG, fast-sigma power, and subjective parameters were observed during the night and the following morning. Nocturnal DPG is a factor in the increased SWA.

Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health 2017 guidelines for hormone replacement therapy.

Hormone replacement therapy (HRT) plays a large part in maintaining and improving the quality of life (QOL) of postmenopausal women. Despite this obvious role, the use of HRT has stagnated in Japan as well as the United States, since the interim report of the HRT trial of Women's Health Initiative study was published in 2002. The Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health formulated the Guidelines for Hormone Replacement Therapy in 2009, which was subsequently revised in 2012, with the aim of organizing perceptions about HRT and allowing people to provide or receive HRT with a sense of security. Later on, in light of changes in indications for HRT and attitudes toward its impact on cancer risks, amendments were made again in 2017. With the establishment of the 2017 guidelines, practitioners in Japan are able to address various issues related to HRT with more appropriate judgment. Moreover, the practice of reliable, safe and effective HRT is expected to promote further efforts toward improvement or maintenance of QOL in patients.

Levonorgestrel-releasing intrauterine system placement for severe uterine cervical stenosis after conization: two case reports.

BACKGROUND: Several approaches for treating severe uterine cervical stenosis after conization for cervical intraepithelial neoplasia have been reported; yet, the condition can still be difficult to treat successfully. CASE PRESENTATION: We performed uterine cervical dilation surgery in two patients with severe stenosis, followed by insertion of the levonorgestrel-releasing intrauterine system, which is used for dysmenorrhea or endometriosis-related pain because of its strong progesterone activity. Patient 1 was a 34-year-old Japanese woman who was diagnosed with dysmenorrhea caused by recurrent uterine cervical stenosis and hematometra after laser conization. Patient 2 was a 44-year-old Japanese woman who developed dysmenorrhea and prolonged menstruation caused by uterine cervical stenosis without hematometra. After providing informed consent, they underwent cervical dilation surgery followed by insertion of the levonorgestrel-releasing intrauterine system. After treatment, their symptoms immediately improved, and after removal of their devices, they remained asymptomatic. CONCLUSIONS: To the best of our knowledge, this is the first report to confirm the usefulness and easy applicability of the levonorgestrel-releasing intrauterine system for uterine cervical stenosis. Although we had success with the method, this study of two patients is preliminary. Further study with larger numbers of patients is necessary to confirm the usefulness of our technique.

Effect of a home-based simple yoga program in child-care workers: a randomized controlled trial.

OBJECTIVES: This study investigated the effect of a brief, simple, home-based yoga program on body pain and health status in child-care workers. DESIGN: This was a randomized, controlled trial comparing a home-based yoga group and a control group. PARTICIPANTS: The trial comprised 98 healthy female nursery school and kindergarten teachers. INTERVENTIONS: A DVD of a simple home-based yoga program was provided for a period of 2 weeks. OUTCOME MEASURES: The primary outcome measure was the reported change in body pain at 2 weeks (after intervention) and 4 weeks (follow-up). The secondary outcome measure was the 30-item General Health Questionnaire (GHQ30) score and physical function. RESULTS: The 67 yoga group participants reported improved menstrual pain at 4 weeks; menstrual pain was reduced from 57.0 ± 27.8 to 37.8 ± 26.7 in the yoga group, versus 52.4 ± 36.5 to 46.9 ± 32.1 in the control group (change from baseline in the yoga group versus change from baseline in the control group, -15.3 points; p=0.044). The total GHQ30 score and the GHQ subscale scores ("sleep disturbance" and "anxiety and dysphoria") improved significantly at 4 weeks in the yoga group, but not in the control group. In the good-adherence group, low back pain improved during the intervention (p=0.006) and follow-up (p=0.001) periods. Menstrual pain was also improved (p=0.044). No adverse events were observed. CONCLUSIONS: A home-based simple yoga program may improve the health status of child-care workers.

Effect of regular gum chewing on levels of anxiety, mood, and fatigue in healthy young adults.

INTRODUCTION: The effect of regular gum chewing on psychological status is unknown. The purpose of this study was to examine the effect of gum chewing for fourteen days on psychological status and physical and mental fatigue in healthy young adults. METHODS: We assigned 50 volunteers randomly to an intervention group (n = 26) and a control group (n = 24). Participants in the intervention group were requested to chew the gum twice per a day for fourteen days. The volunteers were required to complete a questionnaire related to lifestyle for baseline assessment. The State-Trait Anxiety Inventory (STAI), the Profile of Mood State (POMS), the World Health Organization Quality of Life 26, and assessment of physical and mental fatigue by visual analog scale were used at baseline, 2 weeks (after intervention), and 4 weeks (follow-up). RESULTS: At 2 weeks, the score of state anxiety was significantly lower in the intervention group than the control group. The intervention participants' scores of depression-dejection, fatigue and confusion in POMS were better than the control group scores. Mental fatigue were also relieved after the intervention. At 4 weeks, there were no significant differences between both groups. CONCLUSION: Fourteen days' gum chewing may improve the levels of anxiety, mood and fatigue.

Role of glucocorticoid receptor in the inhibitory effect of medroxyprogesterone acetate on the estrogen-induced endothelial nitric oxide synthase phosphorylation in human umbilical vein endothelial cells.

We aimed to clarify which steroid receptor is involved in the inhibitory effect of medroxyprogesterone acetate (MPA) on estrogen-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVEC). The progesterone/glucocorticoid receptor (GR) antagonist RU-486 and introduction of GR siRNA caused attenuation of the inhibitory effect of MPA on the estrogen-induced eNOS phosphorylation and eNOS activity in HUVEC.

Reference intervals of serum tartrate-resistant acid phosphatase type 5b activity measured with a novel assay in Japanese subjects.

Among the isotypes of serum tartrate-resistant acid phosphatase (TRACP), only type 5b (TRACP-5b) is derived from osteoclasts, and it is necessary to develop an assay specific for this TRACP-5b for evaluation of osteoclastic activity. Recently, a novel assay system for TRACP-5b called the fragments absorbed immunocapture enzymatic assay (FAICEA) has been developed. With two unique monoclonal antibodies, one that is highly specific for TRACP-5b and another which absorbs inactive TRACP-5b fragments that interfere with measuring active TRACP-5b, this assay provides correct measurement of TRACP-5b activity in the serum without interference by the inactive fragments of TRACP-5b and other isotypes of TRACP, especially TRACP-5a. To study the reference data of Japanese subjects, we measured TRACP-5b activity in the serum of 320 men (age, 20-82 years) and 466 women [315 premenopausal (age, 18-55 years) and 151 postmenopausal (age, 45-77 years)] with this novel assay. In men, serum TRACP-5b activity did not vary significantly with age. The postmenopausal women had significantly higher serum TRACP-5b activity than the premenopausal women. The reference intervals (logarithmic mean +/-1.96 SD) for men, premenopausal women, and postmenopausal women were 1.7-5.9 U/l, 1.2-4.4 U/l, and 2.5-7.6 U/l, respectively.

Pilot study of fluvoxamine treatment for climacteric symptoms in Japanese women.

BACKGROUND: Selective serotonin-reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of depression and can be used as nonhormonal alternatives to manage hot flashes for women with a history of breast cancer and unable to take hormone replacement therapy. There are, however, few reports on the efficacy of SSRIs for the treatment of natural postmenopausal climacteric symptoms. In this pilot study, we evaluate the SSRI, fluvoxamine, for controlling climacteric symptoms and vasomotor symptoms, in particular. METHODS: Twenty-two patients were enrolled from our hospital. All were orally administered fluvoxamine (50 mg daily). Climacteric and depressive symptoms were assessed using simple menopausal index (SMI) and self-rating questionnaire for depression (SRQ-D), respectively, at baseline, and at 2 and 6 weeks post-treatment. RESULTS: Six weeks following drug administration, neither the SRQ-D nor SMI scores significantly decreased compared to baseline. The mean levels of vasomotor symptoms and mental symptoms decreased significantly following fluvoxamine administration, while skeletal muscle symptom scores did not. CONCLUSION: We were able to demonstrate that fluvoxamine was effective in treating not only depressive moods in climacteric symptoms but also the associated vasomotor symptoms. There are several limitations to this preliminary study. Future controlled studies are needed to further evaluate the efficacy of fluvoxamine for climacteric disturbances.

[The mechanism of TRACP 5b maturation].

Serum tartrate resistant acid phosphatase 5b (TRACP 5b) is an isozyme of osteoclast origin. Indeed, measurement of TRACP 5b activity is used as an index of osteoclast activity. However, the precise mechanism of TRACP 5b maturation is unclear. This study aimed to clarify the mechanism of generation of TRACP 5b. We used a highly sensitive fiber-type DNA chip to investigate the mechanism of generation of TRACP 5b at the genetic level. Genes derived from three related cell types (monocytes, macrophages and osteoclasts) were compared. In addition, at the protein level, posttranscriptional modification was tested by Western blotting using an antiserum specific for the flexible loop region of TRACP 5. Our DNA chip study shows that genes implicated in oligosaccharide construction do not show significant differences in expression levels between the cell types under investigation. Strongly expressed Cathepsin K was observed in osteoclasts. Western blotting demonstrated that TRACP undergoes unique partial degradation during bone resorption, such that serum TRACP 5b lacks the flexible loop found in TRACP 5a. In conclusion, TRACP 5b generated by a specific posttranscriptional modification pathway undergoes partial digestion in resorption lacunae or inside osteoclasts. Serum TRACP 5b lacking the flexible loop differs from TRACP 5a in terms of optimum pH, isoelectric point, sugar chain and antigenicity. The measurement of TRACP 5b could therefore be of great use for monitoring of osteoporosis, rheumatoid arthritis and bone metastasis.

Development of a novel fragments absorbed immunocapture enzyme assay system for tartrate-resistant acid phosphatase 5b.

BACKGROUND: Osteoclastic activity is mainly assessed by measuring urinary markers. To correct for differences in renal clearance, the levels of urinary markers are usually corrected by the urine creatinine concentration. Therefore, alternative serum markers to evaluate osteoclastic activity are required. We developed a novel system for the determination of serum tartrate-resistant acid phosphatase 5b (TRACP5b) activity to evaluate osteoclastic activity. METHODS: Two unique monoclonal antibodies were generated and the specificity was tested using a surface enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI TOF-MS). A novel fragments absorbed immunocapture enzymatic assay (FAICEA) method was developed using 2 monoclonal antibodies. RESULTS: FAICEA gave a sensitivity 0.1 U/l, linearity of 0.1-28 U/l, recovery 92-103%, inter-assay CV 2.95% and intra-assay CV 2.15%. Unlike other TRACP5b assay systems, FAICEA avoided interference from TRACP 5a. CONCLUSIONS: According to the FAICEA, postmenopausal women had higher TRACP5b concentrations than younger women. The results show that TRACP5b is a novel bone resorption marker in serum.

[Bone and bone related biochemical examinations. Bone and collagen related metabolites. Tartrate-resistant acid phosphatase (TRACP)].

Tartrate-resistant acid phosphatase (TRACP) is a well-known marker for bone resorption, but it is not enough for clinical use in specificity of bone and instability in serum. Tartrate-resistant acid phosphatase type 5b (TRACP-5b) is an osteoclast-produced enzyme and was reported the clinical performance of a novel fragments absorbed immunocapture enzyme assay. TRACP-5b have smaller day-to-day and diurnal variation than those of urinary bone resorption markers and show the usefulness as promising markers in monitoring the treatment for osteoporosis.

Randomized trial comparing low-dose hormone replacement therapy and HRT plus 1alpha-OH-vitamin D3 (alfacalcidol) for treatment of postmenopausal bone loss.

We conducted a prospective, randomized, multicenter, open-label 2-year trial with 76 postmenopausal women aged > or =60 years with low (T-score less than -1) lumbar bone mineral density (BMD). The hormone replacement therapy (HRT) group received a low dose of conjugated estrogen (CEE) at a dose of 0.31 mg/day +/- medroxyprogesterone acetate (MPA) 2.5 mg/day. Group HRT/D received the same dose of HRT together with alfacalcidol in a daily dose of 1.0 microg/day. Changes in lumbar BMD measured by dual energy X-ray absorptiometry (DXA) were followed every 6 months for 2 years. The lumbar BMD of group HRT increased 3.37% [95% confidence interval (CI) 1.6%-5.2%], 4.00% (95%CI 1.6%-6.4%), and 2.32% (95%CI -0.7% to 5.3%) at 12, 18, and 24 months, respectively, when the baseline value was taken as 0%. Lumbar BMD of group HRT/D showed a significant increase beyond 6 months. The percent increases for this group at 6, 12, 18, and 24 months were 6.18 (95%CI 1.3%-6.6%), 6.18% (95%CI 3.9%-8.5%), 7.17% (95%CI 4.3%-10.0%), and 8.75% (95%CI 6.0%-11.5%), respectively. In addition, there was a significant difference in the changes of the lumbar BMD between the two groups at 24 months, suggesting that the combination of HRT and alfacalcidol is more effective than HRT alone in terms of the BMD effect. This study is the first prospective trial demonstrating an additive effect of alfacalcidol on lumbar BMD in postmenopausal women receiving low-dose HRT. It suggests that the combination therapy can be considered to be a promising mode of treatment for bone loss after menopause.

Development and characterization of novel monoclonal antibodies against tartrate-resistant acid phosphatase 5.

Serum band 5 tartrate-resistant acid phosphatase (TRACP 5; EC 3.1.3.2) is a glycoprotein that exists as two very similar isoforms, TRACP 5a and TRACP 5b. The similarity of these two isoforms has made it difficult to establish monoclonal antibodies specific for either isoform. We report here the development of a monoclonal antibody with high specificity for TRACP 5b. We prepared TRACP 5b antigens from four sources: TRACP 5b purified from human bone, recombinant TRACP 5 from Escherichia coli, recombinant TRACP 5 from insect cells, and a synthetic TRACP 5b peptide. Thirty-seven mice were each immunized with 1 of the 4 different TRACP antigens to generate 473 antibody-producing clones. Three of these clones, Trk27, Trk49, and Trk62, reacted with TRACP 5b. These three clones were all established from mice exposed to native bone TRACP 5b antigen. In fact, none of the other antigens were able to generate anti-TRACP 5b monoclonal antibodies in mice. Furthermore, Trk62 interacted more strongly with TRACP 5b than with TRACP 5a. These results suggested that although recombinant proteins can be effective antigens, the native TRACP 5 protein might be more effective at generating monoclonal antibodies of greater specificity due to its more faithful representation of the native three-dimensional structure of the protein.

[A study of attentional resource of discrete and gradational allocation strategy using error-related negativity (ERN)].

The error-related negativity (ERN) is a component of the event-related brain potential (ERP) that is associated with action monitoring and error detection. The ERN amplitude reflects attentional resource allocated to error detection. The present study examined whether discrete or gradational allocation strategy of attentional resource in error detection using the ERN amplitude. Only Eriksen flanker task was used in the single task condition. Eriksen flanker task was used as a primary task and Sternberg memory search task was used as a secondary task in the dual task conditions. The task difficulty of the secondary task manipulated in the present study included the memory load. Memory set sizes of 2, 4 and 6 were used in the Sternberg memory search task (M2, M4 and M6 conditions). The results indicated that reaction time was gradually delayed in the primary task as the task difficulty of the secondary task gradually increased. However the ERN amplitude of the primary task decreased in M6 condition alone. In conclusion, discrete allocation strategy of attentional resource was adopted in the error detection.

Medroxyprogesterone acetate attenuates estrogen-induced nitric oxide production in human umbilical vein endothelial cells.

We report the novel observation that medroxyprogesterone acetate (MPA) attenuates the induction by 17beta estradiol (E2) of both nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) activity in human umbilical vein endothelial cells. Although MPA had no effect on basal NO production or basal eNOS phosphorylation or activity, it attenuated the E2-induced NO production and eNOS phosphorylation and activity. Moreover, we examined the mechanism by which MPA attenuated the E2-induced NO production and eNOS phosphorylation. MPA attenuated the E2-induced phosphorylation of Akt, a kinase that phosphorylates eNOS. Treatment with pure progesterone receptor (PR) antagonist RU486 completely abolished the inhibitory effect of MPA on E2-induced Akt phosphorylation and eNOS phosphorylation. In addition, the effects of actinomycin D were tested to rule out the influence of genomic events mediated by nuclear PRs. Actinomycin D did not affect the inhibitory effect of MPA on E2-induced Akt phosphorylation. Furthermore, the potential roles of PRA and PRB were evaluated. In COS cells transfected with either PRA or PRB, MPA attenuated E2-induced Akt phosphorylation. These results indicate that MPA attenuated E2-induced NO production via an Akt cascade through PRA or PRB in a non-genomic manner.