Quality assessment of Japanese clinical practice guidelines including recommendations for acupuncture.

Background: The quality of clinical practice guidelines (CPGs) should be extensively evaluated. This study aimed to evaluate Japanese CPGs that include recommendations for acupuncture. Methods: In a literature search, CPGs including recommendations for acupuncture published in Japan until October 2021 were sought. We assessed (1) whether the CPGs were developed in accordance with the Grading Recommendations Assessment, Development and Evaluation (GRADE) system, (2) the quality of the CPGs using the Appraisal of Guidelines for Research and Evaluation (AGREE) II, and (3) whether the strength of the recommendations for acupuncture was consistent with each CPG's predefined procedure. Results: Seventeen CPGs including 23 recommendations in total were identified and assessed. (1) Three CPGs were in accordance with the GRADE system. (2) The mean score of overall assessment using AGREE II was 4.5 on a 7-point Likert scale. The mean domain scores were 77% for domain 1 (scope and purpose), 54% for domain 2 (stakeholder involvement), 48% for domain 3 (rigor of development), 78% for domain 4 (clarity of presentation), 20% for domain 5 (applicability), and 51% for domain 6 (editorial independence). (3) The strength of the recommendations for acupuncture in two CPGs was judged to be underestimated. Some of the CPGs contained elementary problems that were not considered in AGREE II. Conclusion: The methodological quality of Japanese CPGs including recommendations for acupuncture was not necessarily high. Since technical issues exist in each field of therapy, the respective experts should be involved in developing and reviewing CPGs to disseminate accurate health information.

Lifestyle Changes and Oxidative Stress in a High-incidence Area of Amyotrophic Lateral Sclerosis in the Southwestern Kii Peninsula, Japan.

Objective Lifestyle changes may play an important role in the incidence reduction and delay of onset age of amyotrophic lateral sclerosis (ALS) in the Koza/Kozagawa/Kushimoto (K) area. The aim of this study was to evaluate recent lifestyle changes in the K area and to investigate the relationships between lifestyle and oxidative stress among the residents. Methods We conducted a medical checkup for elderly residents in the K area and the control area and evaluated the urinary 8-OHdG levels, cognitive function test scores and metal contents in serum and scalp hair, coupled with a lifestyle questionnaire survey between 2010 and 2015. Results Recent lifestyle changes among the K residents, including a decrease in the Japanese pickle consumption, increase in fresh vegetable consumption and decrease in farm work, were evaluated in this study. Low consumption of Japanese pickles, high consumption of fresh vegetables, rare farm work and low levels of 8-OHdG/creatinine were all associated with high scores in the cognitive function tests. Frequent farm work and consumption of Japanese pickles was associated with high contents of transition metals, such as Mn, Al and V, in the scalp hair. Conclusion These lifestyle changes among residents in the K area may be associated with their oxidative stress.

The effect of electroacupuncture with different frequencies on muscle oxygenation in humans.

The aim of the present study was to investigate the effect of electroacupuncture (EA) with different frequencies on muscle oxygenation in humans. The subjects were 8 healthy male volunteers. Muscle oxygenation was measured using near-infrared spectroscopy (NIRS). Blood pressure (BP) and heart rate (HR) were monitored simultaneously. After baseline recording, EA was given for 15 min and recovery was measured for 20 minutes. The procedure of EA at 1 Hz, at 20 Hz, and at control followed in the same subjects. Tissue oxygenation index (TOI) decreased during EA at 20 Hz (P < 0.05) and increased during the recovery period. Normalized tissue hemoglobin index (nTHI) also decreased during EA at 20 Hz and increased during the recovery period (P < 0.05), whereas TOI and nTHI in the EA at 1 Hz did not change significantly throughout the experiment. The peak TOI and nTHI values at 20 Hz during the recovery period were higher than the values at 1 Hz and in the control (P < 0.05). BP and HR remained constant. These data suggest that the supply of oxygen to muscle decreased during EA at 20 Hz and increased after EA at 20 Hz, without any changes in HR and BP.

Neutron activation analysis of scalp hair from ALS patients and residents in the Kii Peninsula, Japan.

The aim of this study was to evaluate the accumulation of transition metals in the scalp hair of amyotrophic lateral sclerosis (ALS) patients in the Koza/Kozagawa/Kushimoto (K) area (K-ALS) in the Kii Peninsula, Japan. Metal contents were measured in the unpermed, undyed hair samples of 88 K-residents, 20 controls, 7 K-ALS patients, and 10 sporadic ALS patients using neutron activation analysis at the Research Reactor Institute, Kyoto University. A human hair standard and elemental standards were used as comparative standards. The contents of Zn, Mn, and V were higher, while that of S was lower in K-ALS patients than in the controls. The content of Mn in K-ALS patients negatively correlated with clinical durations. The content of Al was significantly higher in K-residents than in the controls, with 15.9 % of K-residents having high Mn contents over the 75th percentile of the controls. The contents of Zn, Mn, and V were high in the scalp hair of K-ALS patients and correlated with the content of Al. The accumulation of these transition metals may chronically increase metal-induced oxidative stress, which may, in turn, trigger the neuronal degeneration associated with K-ALS.

Effects of nitric oxide synthase inhibition on cutaneous vasodilation in response to acupuncture stimulation in humans.

OBJECTIVES: The aim of the present study was to elucidate the mechanism of cutaneous vasodilation following acupuncture stimulation by investigating the roles of nitric oxide (NO) and axon reflex vasodilation. METHODS: The subjects were 17 healthy male volunteers. The role of NO was investigated by administering N(G)-nitro-l-arginine methyl ester hydrochloride (L-NAME, 20 mM), an NO synthase inhibitor or Ringer's solution (control site), via intradermal microdialysis (protocol 1; n=7). The role of axon reflex vasodilation by local sensory neurones was investigated by comparing vasodilation at sites treated with 'eutectic mixture of local anaesthetics' (EMLA) cream (2.5% lidocaine and 2.5% prilocaine) with untreated sites (control site) (protocol 2; n=10). After 5 min of baseline recording, acupuncture was applied to PC4 and a control site in proximity to PC4 for 10 min and scanning was performed for 60 min after acupuncture stimulation. Skin blood flow (SkBF) was evaluated by laser Doppler perfusion imaging. Cutaneous vascular conductance (CVC) was calculated from the ratio of SkBF to mean arterial blood pressure. RESULTS: In the first protocol, sites administered L-NAME showed significant reductions in CVC responses following acupuncture stimulation compared to control sites (administered Ringer's solution) (p<0.05). In the second protocol, changes in CVC responses after acupuncture stimulation did not differ significantly between treated sites with EMLA cream and untreated sites (p>0.05). CONCLUSIONS: These data suggest that cutaneous vasodilation in response to acupuncture stimulation may not occur through an axon reflex as previously reported. Rather, NO mechanisms appear to contribute to the vasodilator response.

Inhibition of nitric oxide synthase attenuates cutaneous vasodilation during warm moxibustion-like thermal stimulation in humans.

OBJECTIVES: This study investigated if nitric oxide (NO) and/or prostaglandin (PG) are responsible for cutaneous vasodilation during warm moxibustion-like thermal stimulation (WMTS). DESIGN: For two protocols, two microdialysis membranes were placed in the medial forearm skin. In the first protocol (n=8), the sites were randomly assigned and perfused with N(G)-nitro-l-arginine methyl ester hydrochloride (l-NAME), an NO synthase inhibitor or Ringer's solution (control site). Similarly, two microdialysis membranes were placed in the medial forearm skin in the second protocol (n=6). One site was perfused with ketorolac (Keto), the cyclo-oxygenase (COX) pathway inhibitor, and the other site was perfused with Ringer's solution (control site). In both protocols, cutaneous vasodilation was induced using WMTS with an electronic warm moxibustion treatment appliance. After 10 minutes of baseline recording, WMTS was applied to the forearm skin for 20 minutes and recovery was monitored over a period of 20 minutes. Skin blood flow (SkBF) at each site was measured using laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial blood pressure (BP). SETTINGS/LOCATION: The study was conducted in a laboratory at the Kansai University of Health Sciences. SUBJECTS: The subjects were 14 healthy male volunteers. INTERVENTIONS: WMTS was applied to the medial forearm skin using an electronic warm moxibustion treatment appliance. OUTCOME MEASURES: SkBF, skin temperature (Tsk), core body temperature (Tc), heart rate (HR), and BP were outcome measures. RESULTS: In the first protocol, peak CVC values during WMTS at the site perfused with l-NAME were significantly decreased, compared to those at the control site (p<0.05). In the second protocol, peak CVC values during WMTS did not differ between the control site and the Keto site (p>0.05). CONCLUSIONS: These data demonstrate that NO is involved in the mechanism of cutaneous vasodilation induced by WMTS. Furthermore, increases in CVC despite inhibition of the COX pathway suggest that PG does not contribute to cutaneous vasodilation during WMTS.

Immunohistochemical expression of IGF-I and GSK in the spinal cord of Kii and Guamanian ALS patients.

Insulin-like growth factor-I (IGF-I) is a potent survival factor for motor neurons in animals, and glycogen synthase kinase-3beta (GSK-3beta) is suspected to play roles in apoptosis and tau phosphorylation. Here we report the immunological expression of IGF-I, GSK-3beta, phosphorylated-GSK-3alpha/beta (p-GSK-3alpha/beta) and phosphorylated-tau in the spinal cord and hippocampus of Kii and Guam amyotrophic lateral sclerosis (ALS) patients. Sixteen ALS patients (10 Japanese sporadic, 3 Kii and 3 Guam ALS) and 14 neurological controls (10 Japanese and 4 Guamanian) were examined. The immunoreactivity for each antibody was rated by the percentages of positive neurons to total anterior horn neurons in each patient and was analyzed statistically. Many normal-looking neurons from Japanese sporadic ALS, Kii ALS and Guam ALS patients, as well as from Japanese and Guam controls, were positive for anti-IGF-I antibody. A positive correlation between IR scores for anti-IGF-I antibody and clinical durations of Japanese sporadic ALS patients was found in this study (P < 0.0001). This suggested that IGF-I might have a protective effect against ALS degeneration. In Japanese sporadic ALS patients, abnormal as well as normal-looking neurons showed significant high IR scores for anti-GSK-3beta antibody than those of controls. Anterior horn neurons from Guam and Kii ALS patients characteristically showed weak staining for anti-GSK-3beta antibody but were markedly positive for anti-pGSK-3alpha/beta antibody compared to those from both Japanese controls and Japanese sporadic ALS patients, and showed the co-localization of IGF-I and p-GSK-3alpha/beta. This suggested that the IGF-I signaling pathway in Guam and Kii ALS patients might function to phosphorylate GSK-3beta to protect neurons from ALS degeneration. Neurofibrillary tangles (NFTs) in the hippocampus and spinal cord from Kii and Guam ALS patients showed the co-localization of PHF-tau and p-GSK-3alpha/beta by a confocal laser scanning technique. The predominant expression of p-GSK-3alpha/beta compared to GSK-3beta in spinal motor neurons and the co-localization of p-GSK-3alpha/beta and PHF-tau in NFT-laden neurons in the hippocampus and spinal cord were characteristic findings of Kii and Guam ALS patients.

Changes in skin blood flow and skin sympathetic nerve activity in response to manual acupuncture stimulation in humans.

To determine the effects of manual acupuncture stimulation (MAS) on skin sympathetic nerve activity (SSNA), SSNA and skin blood flow (SBF) were measured during a resting period and during MAS. Twelve healthy male subjects were divided into an acupuncture group (n = 7) and a control group (n = 5). SSNA was recorded from the left median nerve at the elbow using microneurography, while SBF was recorded using laser Doppler flowmeter. In the acupuncture group, MAS was delivered to LI 4 point in the right thenar muscle. The acupuncture needle was retained for 2 minutes before being removed. SSNA and SBF recordings were performed for a total of 12 minutes, from 5 minutes prior to MAS until the end of the trial. In the control group, the 2-minute period of acupuncture was replaced by 2 minutes of rest. During the first minute of MAS, we observed an increase in SSNA accompanied by a reduction in SBF. In the acupuncture group, these parameters returned to baseline values in the second minute of MAS. Parameters in the control group were unchanged throughout the experimental procedure. A significant negative correlation was observed between changes in SSNA and SBF during the first minute of MAS. In addition, a negative correlation was demonstrated between the basal value of SSNA and the change in SSNA in response to MAS. These results suggest that MAS elicited a transient increase in SSNA and that this increase is dependent on the baseline of SSNA.