A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer’s disease

정현석,Im Jooyeon Jamie,Park Jong-Sik,Na Seunghee,Lee Wonhye,Yoo Seung-Schik,송인욱,Chung Yong-An 대한초음파의학회 2021 ULTRASONOGRAPHY Vol.40 No.4

Purpose: Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD. Methods: After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS. Results: The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported. Conclusion: These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD. Purpose: Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD.Methods: After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS.Results: The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported.Conclusion: These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.

Low-Volume 고강도 인터벌 트레이닝이 비만 성인의 혈중 아디포넥틴, 대사증후군 위험요인 및 심폐 체력에 미치는 영향

김은숙(Kim, Eun-Sook),김도현(Kim, Do-Hyun),김지웅(Kim, Ji-Woong),윤성진(Yoon, Sung-Jin) 한국사회체육학회 2021 한국사회체육학회지 Vol.- No.86

Purpose: The purpose of this study is to investigate the effects of low-volume high-intensity interval training on adiponectin, metabolic syndrome risk factors and aerobic capacity in obese adults. Method: Twenty-one obese men participated in the group of low-volume high-intensity interval training (LV-HIIT; n=7), moderate-intensity continuous training (MICT; n=7) and control (CON; n=7), respectively. All subjects measured body composition, blood test (adiponectin, HDL-C, glucose, and triglyceride) and maximal graded exercise test before the intervention and after six weeks. A two-way repeated measures ANOVA demonstrated a significant difference (p<.05). Bonferroni’s method was used for post-hoc analysis when there is a significant. Results: The results of this study are as follows. 1) Body composition was significantly improved in the low-volume high-intensity interval training group and the moderate-intensity continuous training group. 2) Adiponectin concentration was significantly increased in the low-volume high-intensity interval training group and moderate-intensity continuous training group. 3) The waist circumference, triglyceride, and glucose of metabolic syndrome risk factors significantly decreased in the low-volume high-intensity interval training group and moderate-intensity continuous training group. There was no significant difference in blood pressure and HDLC 4) Aerobic capacity was significantly improved in the low-volume high-intensity interval training group and moderate- intensity continuous training group. Conclusion: In summary, the findings in this study are that despite conducting low volume, Low-Volume high intensity interval training is efficient training compared to moderate intensity continuous training for improving adiponectin, metabolic syndrome risk factors and aerobic capacity.

운동 강도가 수면장애 모델 쥐의 혈 중 멜라토닌 농도에 미치는 영향

김희정 ( Hee Jung Kim ),김동현 ( Dong Hyun Kim ) 대한물리의학회 2014 대한물리의학회지 Vol.9 No.1

PURPOSE:In this study, we tried to find out what kind of exercise was more effective in sleep disorder by comparing melatonin in blood after applying low intensity with high intensity exercise to sleep disordered rats induced by experiment. METHODS:We used male Sprague-Dawley rats which were 8weeks old and weighted 300g. They were supplied with water and food without any restriction. We kept the room temperature at 25℃ and controld the length of day and night in 12 hours blocks, respectively. We divided the rats 60 into 2 groups. To one group we applied low intensity exercise, and to the other we applied high intensity exercise for 15minutes per day over a period of 4 weeks. We extracted the blood from abdominal aorta before, after exercise, moved into EDTA tube, performed centrifugation. We decanted the serum 200㎕ from the blood into microcentrifuge tube by samples and moved into polypropylene culture tubes with micro pipette. We split enzyme solution 50㎕ into the tubes with melatonin direct kits and make them react at 37℃ for 2 hours. We split assay buffer 50㎕ into each tube and mixed melatonin tracer 50㎕ and melatonin antiserum 50㎕, respectively. After we made them react in room temperature, we decanted the superficial layer with a centrifuge and measured the activity for 1 minute by competitive method with γ-counter equipment. We draw a standard curve through logit-log graph with CPM(counts per minute) and counted the melatonin by B/B0. We conducted independent t-test to examine the homogeneous of melatonin value of before low-intensity and high-intensity exercise. We performed paired t-test to compare before and after low-intensity and high-intensity exercise, respectively. We carried out independent t-test to compare melatonin value after low-intensity and high-intensity exercise. Significance level was .05. RESULTS:The RESULTS were as follows; firstly melatonin was more increased in the group who was exposed to high intensity exercise when we compared before to after high and low intensity exercise, respectively. Secondly, high intensity exercise was more effective than low intensity exercise when we compared the two. CONCLUSION:In CONCLUSION, secretion of melatonin which is the material of sleep improvement could be promoted by high intensity exercise. Low intensity exercise acted as a stress rather than improving sleep and had a negative effect on the secretion of melatonin because the melatonin was affected by stress..

치조골 줄기세포 증식에 저강도 초음파 자극의 효과

이응태 ( Eung Tae Lee ),임기택 ( Ki Taek Lim ),김장호 ( Jang Ho Kim ),임애리 ( Ae Li Im ),손현목 ( Hyun Mok Son ),조종수 ( Chong Su Cho ),정필훈 ( Pill Hoon Choung ),정종훈 ( Jong Hoon Chung ) 한국조직공학·재생의학회 2008 조직공학과 재생의학 Vol.5 No.4

Low-intensity ultrasound stimulation produces significant multi-functional effects that are directly relevant to bone formation. It was previously found that low-intensity ultrasound stimulation enhanced bone regeneration although the exact cellular mechanism is not clear. The aim of the present study is to investigate the effect of low-intensity ultrasound stimulation on proliferation of alveolar bone marrow stem cells. Before low-intensity ultrasound stimulation, alveolar bone marrow stem cells were cultured for 24h to facilitate their attachment. The cells were cultured in medium with or without low-intensity ultrasound stimulation. The ultrasound frequency was 1 MHz. Cell cultures stimulated with ultrasound were conducted by three treatment groups - group 1: intensity(100, 200, 300, 400 and 500 mW/cm2), group 2: duty cycle(5, 10, 30 and 50%) and group 3: duration time(1, 3, 5, 10, 20 and 30 min). The effect of low-intensity ultrasound stimulation were evaluated by cell number and morphological changes. The proliferation rates of alveolar bone marrow stem cells for the particular stimulated groups were larger than those of control groups. After low-intensity ultrasound stimulation(intensity: 100 mW/cm2, duty cycle: 30% and duration time: 10 min), the alveolar bone marrow stem cell counts were significantly increased(p < 0.05). This study suggested that the cell growth could be enhanced by appropriate low-intensity ultrasound stimulation.

일시적 혈류 제한과 함께 수행한 저강도 운동 후 알파운동신경원의 변화

김종순 ( Jong Soon Kim ) 대한물리의학회 2015 대한물리의학회지 Vol.10 No.1

PURPOSE: Low-intensity exercise with transient restriction of blood flow to muscle could be an alternative rehabilitation method which avoids the problems associated with conventional high-intensity exercise. However, the mechanism of low-intensity exercise with transient restriction of blood flow is not clearly known. Thus, the purpose of this study was to investigate the mechanism of improvement of muscular function after low-intensity exercise with transient restriction of blood flow using H-reflex analysis. METHODS: Twenty one healthy young adults with no medical history of neurological or musculoskeletal disorder voluntarily participated in this study. The α-motor neuron excitability of the triceps surae was assessed using the H-reflex. The amplitude of the M-wave and H-reflex were measured across three conditions: rest, after low-intensity exercise without restriction of blood flow and after low-intensity exercise with restriction of blood flow. The subjects performed low-intensity ankle plantar flexion exercise at their own pace for one minute without or with transient restriction of blood flow achieved by a sphygmomanometer cuff on popliteal fossa at a pressure of 120㎜of mercury(120 ㎜Hg). RESULTS: No significant changes of the excitability of the α-motor neuron were obtained across three different conditions. CONCLUSION: This study found that low-intensity exercise with transient restriction of blood flow did not influence to α-motor neuron excitability of the triceps surae. From the results, I could come to the conclusion that further study will be required.

장기간 저강도 복합운동이 여성 노인의 기능체력, 보행속도 및 신체조성에 미치는 영향

장윤호(Jang, Yoon-Ho),신상근(Shin, Sang-Keun) 한국체육과학회 2017 한국체육과학회지 Vol.26 No.3

This research aimed to verify the effects of a long term low-intensity combined exercise program as an exercise intervention on functional fitness, gait speed, and body composition in elderly women. A total of 24 subjects were assigned to low-intensity exercise group(n=12) and control group(n=12) randomly. A 60 minute Otago exercise was applied to them as the intervention 3 times a week for 32 weeks by RPE 9-12. Functional fitness was measured by Senior Fitness Test. Gait speed was measured by 10m distance divided by the second. Items for body composition consisted of height, weight, BMI, WHR, skinfold thickness(triceps, subscapular), %fat, %LBM, Fat, LBM, Fat/height, and LBM/height. Mean and standard deviations were calculated by using SPSS Version 22.0. A two-way repeated measures ANOVA was conducted to verify interactions between pre-post measurement and groups. Statistical significance was set at p<.05. This research showed that there were significant interactions between time and groups in 30- second chair stand(p<.01), 30-second arm curl(p<.05), back scratch(p<.01) and 8-foot up-and-go(p<.05), gait speed(p<.001) for low-intensity combined exercise group. Significant increases appeared between groups in 30-second chair stand(p<.05), and 30-second arm curl(p<.001) for low- intensity combined exercise group. Significant increase appeared between time in 30-second chair stand(p<.05), and back scratch(p<.05), gait speed(p<.05) for low-intensity combined exercise group. It showed significant changes between pre-mid measurements in triceps(p<.01) for low-intensity combined exercise group. With low -intensity RPE 9-12 for a long term, this combined exercise program can be used as an effective and safe exercise intervention to reduce triceps skinfold thickness and improve lower body strength, upper body strength, dynamic balance, agility, gait speed and prevent falls for elderly women living in a community.

토끼모델에서 저강도 맥동초음파가 골절치유에 미치는 영향

김종만(Kim Jong man),이충휘(Yi Chung Hwi),조상현(Cho Sang Hyun),박정미(Park Jung mi),권혁철(Kwon Hyuk cheol),황태선(Hwang Tae sun) 한국전문물리치료학회 2002 한국전문물리치료학회지 Vol.9 No.1

The purpose of this research was to determine the effects on the healing of fibular fractures in rabbits of low-intensity pulsed ultrasound (50 mW/㎠ and 500 mW/㎠) applied for periods of 4, 14 and 24 days following fibular osteotomy. Thirty-six male Japanese white rabbits were randomly randomly divided into three groups of twelve for three treatment protocols: (1) ultrasound treatment at intensities of mW/㎠ and 500 mW/㎠ until the 4th following fibular osteotomy, (2) ultrasound treatment at intensities of 50 mW/㎠ and 500 mW/㎠ until the 14th day following fibular osteotomy, and (3) ultrasound treatment at intensities of 50mW/㎠ and 500mW/㎠ until the 24th day following fibular osteotomy. The low-intensity pulsed ultrasound was applied to only one fibular of each rabbit (these served as the experimental group). The other fibular of each rabbit served as the control group. The selection of which fibular was to be treated was made randomly. The animals were sacrificed on the 4th, 14th and 24th day after the start of ultrasound treatments. Percent of trabecular bone area and fibular radiography were carried out to compare the degree of fibular bone healing. A microscope was also used to determine any histologic changes. For statistical differences in radiological changes due to length of treatment period (4, 14 and 24 days respectively), the wilcoxon signed-ranks test was used to compare the experimental and control groups. For statistical differences in fracture healing due to differences in ultrasound intensity, radiological studies were compared using the Mann-Whitney Test. And, to compute percentage differences in areas of trabecular bone, Two-way analysis of variance (ultrasound intensity x each group) was used. Experiment results were as follows: 1. In animals sacrificed in the experimental and control groups (p>.05). However, experimental groups showed more rapid bone repair than control group. 2. Both radiographic and percent of trabecular bone area studies showed significant differences in rabbits sacrificed after 14 days. Fracture healing was significantly increased in the experimental group(p<.05) 3. In the animals sacrificed on the 24th day, histologic study showed rapid bone repair but fibular radiologic studies did not show statistical differences between the two groups(p>.05). 4. On the 14th day, bone union on radiograph was significantly more rapid in the treatment group with pulsed ultrasound of 50mW/㎠ than the group with 500mW/㎠ (p<.05). Histologic studies showed that both the 14 and 24 days groups had more rapid bone repair in animals treated with 50mW/㎠ ultrasound intensity than those treated with 500 mW/㎠ intensity. In conclusion, it has been shown that the low-intensity pulsed ultrasound has a positive effect on bone fracture healing in the early stage and the range of pulse ultrasound from 50mW/㎠ to 500mW/㎠ is effective for fracture healing. Further study is needed to investigate the influence of pulsed ultrasound on delayed union and non-union in bone fractures and also for the clinical use of low-intensity pulsed ultrasound for bone healing in humans.

형태와 빈도에 따른 저강도 운동이 근감소증 비만 고령여성의 신체조성 변화에 관한 연구

천성욱,신상근 한국발육발달학회 2022 한국발육발달학회지 Vol.30 No.3

The purpose of this study is to investigate any changes in body composition, such as muscle mass, %fat, and bone density, in exercise intervention according to the frequency of low-intensity aerobic exercise and resistance exercise for 16 weeks. The subjects of the study were women aged over 75 yrs older living in Jin-gu, Busan, who were selected for sarcopenia by diagnosis of sarcopenia (ASM/weight, % ; 25.6% or less) and obesity (% fat, % ; 30% or over), Through drawing lots, a total of 104 people participated in the experiment, 29 people were eliminated from the pre-test measurement. And 29 people were excluded from the exercise intervention. The participants were randomly assigned into 5 groups; low intensity aerobic exercise 3 times per week group (n=10, 75.6±3.5 yrs), low intensity aerobic exercise 5 times per week group (n=8, 74.2±3.9 yrs), low intensity resistance exercise 3 times per week group (n=10, 75.4±3.7 yrs), low intensity resistance exercise 5 times per week group(n=8, 75.6±4.1 yrs) and a control group (n=10, 77.7±3.8 years). For the statistical analysis, such as One-Way ANOVA, t-test, and Two-Way Repeated measures ANOVA was calculated using SPSS Version 22.0. To verify mean differences between the 5 groups, two-way repeated measures ANOVA was used. As a result of the study, the interaction effect of the group and time period of %fat was shown (p<.05), As a result of post-verification, A5-G and R5-G were higher than CG. In the change in the main effect of the time period within the group, there was a significant decrease in A5-G (p<.001) and R5-G (p<.01). And in the change in LBM, there were no interaction effects and main effects. And the interaction effect was not shown in the change in Total BMD, but a significant decrease was shown in R3-G (p<.01) and CG (p<.05) in the change in the main effect. Based on the research results, The interaction effect of aerobic exercise and resistance exercise 5 times a week was shown in the body fat rate change according to the low intensity form and frequency of exercise for 16 weeks in elderly women with muscle fat and bone density. However, through this study, there is a significant decrease in bone density in older women in the control group and aerobic exercise and resistance exercise group conducted three times a week, so it seems to play a role in suppressing fat and bone density due to aging.

유산소 운동이 장내미생물 비율 및 선천면역 구성인자에 미치는 영향

신정엽(Shin, Jung-Yeop),전용균(Jeon, Yong-Kyun),하창호(Ha, Chang-Ho) 한국체육과학회 2015 한국체육과학회지 Vol.24 No.4

This study was conducted to investigate the effects of low-intensity aerobic exercise on body weight, Bacteriodetes and TLR5, and the relationships between them. Obesity was induced in C57BL/6 male mice (n=40) by high-fat diet, which were divided into two experimental groups, control group (CG), low-intensity aerobic exercise group (EG). And after a 12-week treatment of low-intensity aerobic exercise the effects in two test groups were compared by one-way ANOVA, and Pearson Correlation was employed to verify the relationships among each factors, which led to the conclusions as follows. A 12-week treatment of concurrent low-intensity aerobic exercise was effective for weight-loss, exhibited a positive effect on intestinal microorganisms, and the positive effect was greater in the combined treatment in particular than in the low-intensity aerobic exercise group. Concurrent low-intensity aerobic exercise showed more positive effects on TLR5 than control group, and relationships of body weight, Bacteriodetes and TLR5 weren’t confirmed. Therefore, it is thought that this study can be the preliminary data to provide information to help develop various exercise programs for effective weight control based on new forms of factors causing obesity.

요통 및 좌골신경통 환자의 자각적 통증 및 장애정도와 수면장애 및 피로감의 관계

이경석,도재원,배학근,윤일규 대한신경외과학회 1999 Journal of Korean neurosurgical society Vol.28 No.4