Core body temperature changes in school-age children with circadian rhythm sleep-wake disorder.

OBJECTIVE/BACKGROUND: Core body temperature (CBT) is considered a valuable marker for circadian rhythm. This study aimed to investigate the changes in CBT that are associated with the symptoms of circadian rhythm sleep-wake disorder (CRSWD) post-treatment in children. PATIENTS/METHODS: Twenty-eight school-age children [10 boys and 18 girls; mean age (±standard deviation), 13.68 ± 0.93 years] who were admitted to our hospital with CRSWD underwent treatment for 6-8 weeks according to the following protocol: lights-out for sleep at 21:00; phototherapy for waking at 6:00 or 7:00; light exercise everyday (eg, a 20- to 30-min walk). CBT was continuously measured for 24 h on the first day of admission and on the first day after treatment. RESULTS: The mean time of sleep onset/offset (±standard deviation; in hours:minutes) 1 week before admission and 1 week after treatment were 23:53 ± 2:26/9:58 ± 2:15 and 21:17 ± 0:19/6:46 ± 0:32, respectively. The mean times of sleep onset and offset measured post-treatment were significantly earlier than those measured pre-treatment (p < 0.001). The mean CBT and mean minimum CBT during sleep were significantly lower on the first day post-treatment than on the first day of admission (p = 0.011 and p < 0.001, respectively). CONCLUSIONS: Symptom improvements in patients with CRSWD were associated with a decrease in CBT during sleep, suggesting that CBT may be a biomarker for improvements in CRSWD. These results help elucidate the cause of this sleep disorder.

Serum concentrations of insulin-like growth factor-1 as a biomarker of improved circadian rhythm sleep-wake disorder in school-aged children.

STUDY OBJECTIVES: We aimed to investigate whether improvements in the symptoms of circadian rhythm sleep-wake disorder after treatment were associated with an increase in serum insulin-like growth factor-1 (IGF-1) concentration. METHODS: Eighty-seven school-aged children (32 males, 55 females), aged 14.31 ± 1.50 years (mean ± standard deviation), who were admitted to our hospital with circadian rhythm sleep-wake disorder received treatment for 6-8 weeks consisting of the following protocol: (1) lights-out for sleep occurred at 21:00, (2) phototherapy for waking started at 06:00 or 07:00, and (3) light exercise was required every day (eg, a 20- to 30-minute walk). Blood samples were collected at 08:00 am to measure the serum concentrations of IGF-1, pre- and posttreatment. RESULTS: The mean times of day of sleep onset and offset at the pre- and posttreatment timepoints were 23:32 ± 4.21 and 10:27 ± 2.98, and 21:26 ± 0.55 and 06:50 ± 0.70, respectively. The mean times of day of sleep onset and offset measured at the posttreatment timepoint were significantly earlier compared with the pretreatment baselines (P < .01). The mean serum levels of IGF-1 significantly increased from 315.59 ± 68.26 ng/mL at pretreatment to 335.09 ± 69.78 ng/mL at posttreatment (P < .01). CONCLUSIONS: Improvements in the symptoms of patients with circadian rhythm sleep-wake disorders were associated with increased serum concentrations of IGF-1, suggesting that serum IGF-1 may be a biomarker of improvements in school-aged children with circadian rhythm sleep-wake disorder.

Efficacy of femtosecond lasers for application of acupuncture therapy.

Acupuncture treatment utilizes the stimulation of metal acupuncture needles that are manually inserted into a living body. In the last decades, laser light has been used as an alternative to needles to stimulate acupuncture points. We previously reported suppression of myostatin (Mstn) gene expression in skeletal muscle by means of femtosecond laser (FL) irradiation, after electroacupuncture, in which acupuncture needles are stimulated with a low-frequency microcurrent. The purpose of the study here was to investigate the efficacy of FL irradiation in mouse skeletal muscle with regard to protein synthesis. After irradiation of the hindlimbs, we first analyzed Mstn gene expression and Mstn protein level in the skeletal muscle. We then evaluated phosphorylation of the mammalian target of rapamycin (mTOR) and its downstream target 70-kDa ribosomal protein S6 kinase (p70S6K). The results showed that FL irradiation significantly reduced the amount of Mstn protein and enhanced the phosphorylation of p70S6K in of the mTOR/S6K signaling pathway. We suggest that FL irradiation activated the protein synthetic pathway in the skeletal muscle. In conclusion, we determined that FL irradiation can serve as an alternative for acupuncture needles and has the potential of being a new non-invasive acupuncture treatment of skeletal muscle.

Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as Treatment of Painful Muscle Cramps in Patients with Lumbar Spinal Stenosis and Its Minimum Effective Dose.

Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) is a Kampo medicine, which is known to be effective against muscle cramps as well as crampy pain in the gastrointestinal smooth muscle and skeletal muscle. However, glycyrrhizin in this medicine also causes adverse drug reactions such as hypokalemia, hypertension, and edema. We analyzed the therapeutic efficacy of Shakuyaku-kanzo-to for painful muscle cramps associated with lumbar spinal stenosis and clarified its minimum effective dose. 58 patients with lumbar spinal stenosis and painful muscle cramps were included. We evaluated the therapeutic efficacy of Shakuyaku-kanzo-to (n=16) comparing with eperisone hydrochloride (n=14). We then examined the minimum effective dose of Shakuyaku-kanzo-to in the remaining 28 patients. Shakuyaku-kanzo-to reduced the frequency of painful muscle cramps to less than 50% in 13 of 16 patients. However, eperisone hydrochloride reduced it to the same level in 4 of 14 patients. The onset of the maximum therapeutic effect of Shakuyaku-kanzo-to was less than 3 days from the start of treatment in 11 of 15 patients. Regarding the minimum effective dose for painful muscle cramps, 2.5 g of Shakuyaku-kanzo-to used as needed had a therapeutic effect that was equivalent to the regular use of 7.5 g/day (given in divided doses three times daily). Our data show that Shakuyaku-kanzo-to is effective for painful muscle cramps associated with lumbar spinal stenosis. The dosage of 2.5 g of Shakuyaku-kanzo-to as needed had a therapeutic effect that was equal to the regular use of 7.5 g/day.

Full-length sequence of mouse acupuncture-induced 1-L (aig1l) gene including its transcriptional start site.

We have been investigating the molecular efficacy of electroacupuncture (EA), which is one type of acupuncture therapy. In our previous molecular biological study of acupuncture, we found an EA-induced gene, named acupuncture-induced 1-L (Aig1l), in mouse skeletal muscle. The aims of this study consisted of identification of the full-length cDNA sequence of Aig1l including the transcriptional start site, determination of the tissue distribution of Aig1l and analysis of the effect of EA on Aig1l gene expression. We determined the complete cDNA sequence including the transcriptional start site via cDNA cloning with the cap site hunting method. We then analyzed the tissue distribution of Aig1l by means of northern blot analysis and real-time quantitative polymerase chain reaction. We used the semiquantitative reverse transcriptase-polymerase chain reaction to examine the effect of EA on Aig1l gene expression. Our results showed that the complete cDNA sequence of Aig1l was 6073 bp long, and the putative protein consisted of 962 amino acids. All seven tissues that we analyzed expressed the Aig1l gene. In skeletal muscle, EA induced expression of the Aig1l gene, with high expression observed after 3 hours of EA. Our findings thus suggest that the Aig1l gene may play a key role in the molecular mechanisms of EA efficacy.

Herbal Medicine Containing Licorice May Be Contraindicated for a Patient with an HSD11B2 Mutation.

Licorice ingestion, as well as mutations in the HSD11B2 gene, inhibits 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2) enzyme activity, causing the syndrome of apparent mineral corticoid excess (AME). However, the combined effect of licorice ingestion and an HSD11B2 mutation has never been reported, until now. In this study, we demonstrated that licorice ingestion can produce overt hypertension in an individual without medical history of hypertension who is heterozygous for wild-type and mutant HSD11B2 genes. Our patient was a 51-year-old female with serious hypertension who had been taking herbal medicine containing licorice for more than one year. She was clinically diagnosed as having licorice intoxication, because she did not present with hypertension after ceasing the herbal medicine. Molecular analysis showed that she carried a missense mutation, c.40C>T, in HSD11B2. In conclusion, licorice ingestion is an environmental risk factor for hypertension or AME state in patients with a mutation in HSD11B2. Carrying a mutation in HSD11B2 is, conversely, a genetic risk factor for licorice-induced hypertension or AME state. Herbal medicine containing licorice may, therefore, be contraindicated in patients with an HSD11B2 mutation.

[The origin of pediatric acupuncture technique: beginnings and historical background of pediatric acupuncture practitioners].

Pediatric acupuncture for infants in Japan has its own special method. There is no specialized literature about it that was published before the 20th century and it has not been investigated systematically. To elucidate the history of pediatric acupuncture, we investigated fragmented information on pediatric acupuncture written in the medical literature published before the Meiji Restoration and articles on traditional Japanese medicine (Kampo) and acupuncture published after the Meiji Restoration. We analyzed the history of Japanese pediatric acupuncture from the viewpoints of the acupuncture needles and the methods. As a result, we found that pediatricians used fragments of broken pottery for the treatment in the 1650's. This finding suggests that the present pediatric acupuncture needles originated from "ho-shin" which was used for the treatment of "oketsu" for infants (in ancient China) and that the present pediatric acupressure technique was derived from the pediatric acupressure by using friction with small stones. In addition, our analysis suggests that the integration of the edged pediatric acupuncture needles and the acupressure-like technique correlates with the "Regulations for Acupuncture and Moxibustion clinics" published by the Ministry of Home Affairs in Japan and enforced in 1912.

Electroacupuncture suppresses myostatin gene expression: cell proliferative reaction in mouse skeletal muscle.

Complementary and alternative medicine (CAM) may provide patients with an alternative to traditional medicine, but an assessment of its efficacy is required. One CAM method, electroacupuncture (EA) treatment, is a maneuver that utilizes stimulation of acupuncture needles with a low-frequency microcurrent. To study the effect of short-term EA, we evaluated the differential expression of genes induced by EA in mouse skeletal muscle for up to 24 h. We then used RT-PCR to confirm the expression patterns of six differentially expressed genes. Bioinformatics analysis of their transcription control regions showed that EA-inducible genes have numerous common binding motifs that are related to cell differentiation, cell proliferation, muscle repair, and hyperplasia. These results suggested that EA treatment may induce cell proliferation in skeletal muscle. To verify this possibility, we used EA to stimulate mouse skeletal muscle daily for up to 1 mo and examined the long-term effects. Immunohistochemical analysis showed that nuclei of muscle cells treated with EA for 1 mo, especially nuclei of satellite cells, reacted with anti-human PCNA. Also, expression of the gene encoding myostatin, which is a growth repressor in muscle satellite cells, was suppressed by daily EA treatment for 1 wk; EA treatment for 1 mo resulted in more marked suppression of the gene. These molecular findings constitute strong evidence that EA treatment suppresses myostatin expression, which leads to a satellite cell-related proliferative reaction and repair in skeletal muscle.