High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and easily tolerated method of altering cortical physiology. To date, numerous open and sham controlled clinical trials have explored the antidepressant potential of rTMS. In the present study, we investigated clinical trials of high-frequency rTMS (20 Hz) for treatment of refractory depression, and also examined the effect of rTMS on plasma levels of catecholamine metabolites and brain-derived neurotropic factor (BDNF). METHODS: Twenty-six depressed inpatients who met the DSM-IV criteria for major depressive disorder and had failed to respond to treatment with at least two antidepressant drugs given at adequate doses (above 150 mg/day in an equivalent dose of imipramine) and durations (at least 4 weeks for each drug) were enrolled in this study. Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78 years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography. The plasma levels of BDNF were also measured with the sandwich ELISA method. RESULTS: The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of 20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS. Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by rTMS. The levels of plasma MHPG, but not those of HVA, were significantly reduced after rTMS treatment, and a negative correlation was observed between the change in plasma MHPG levels and the change in scores of agitation. In addition, the plasma levels of BDNF were significantly increased by 23 % in responders and partial responders, but not in nonresponders, after rTMS treatment, and a trend for association was found between the changes in Ham-D scores and changes in plasma BDNF levels in all patients after rTMS treatment. CONCLUSION: These results suggest that rTMS treatment brings about some improvement in refractory depression, especially for symptoms such as agitation, by influencing MHPG and BDNF, which is in accordance with previous reports showing that BDNF was increased by various antidepressants treatments.

Motor hand representation in cortical area 44.

OBJECTIVE: To elucidate whether area 44 of human frontal cortex is essential for the organization of voluntary hand movements or not, the authors examined effects of single transcranial magnetic stimulation (TMS) of human area 44 on voluntary hand movement and electromyography (EMG) activities in hand muscles. METHOD: Surface EMG responses were recorded from the thenar muscles of 10 normal subjects following TMS over area 44. Stimuli were applied 2 cm anterior to the primary tongue motor area. RESULTS: Single TMS over area 44 could easily interrupt target-oriented hand movements. Human area 44 has facilitatory and inhibitory effects over both tonic and phasic finger movements. It is shown that single TMS of area 44 produces motor evoked potential from hand muscles. CONCLUSION: Human area 44 is involved in voluntary hand movements and has direct fast-conducting corticospinal projections.

Effects of exercise training on home blood pressure values in older adults: a randomized controlled trial.

OBJECTIVE: To determine the effects of exercise training on the blood pressure (BP) values of older adults, using home blood pressure measurement. DESIGN: Randomized controlled trial. PARTICIPANTS: A total of thirty-nine free-living older adults (including 19 men) aged from 60-81 years with home systolic blood pressure > 120 mmHg and without significant cardiopulmonary-musculoskeletal disease, were randomly allocated to either 25 weeks of exercise training (exercise group) or to a control program (control group). MAIN OUTCOME MEASUREMENTS: Change in the 2-week averages of home systolic and diastolic blood pressure values measured with a validated automatic device before, during and after the intervention period. RESULTS: Compared with the control group, the exercise group showed a significant decrease in values for home systolic blood pressure (maximum between-group difference = 7.7 mmHg, P = 0.003) and home diastolic blood pressure (4.2 mmHg, P = 0.001). These changes were observed for both genders. CONCLUSIONS: Exercise training was effective for older adults in lowering home blood pressure values. This is the first trial to demonstrate the usefulness of home blood pressure measurement in examining the effect of exercise training on blood pressure values.

Adjuvant-induced improvement of glucose intolerance in type 2 diabetic KK-Ay mice through interleukin-1 and tumor necrosis factor-alpha.

We reported that administration of complete Freund's adjuvant (CFA) improved glucose tolerance test (GTT) results in obese diabetic KK-Ay mice. In this study, we investigated its mechanism. An injection with CFA remarkably improved GTT for more than a week in KK-Ay mice, although insulin response was not changed compared with saline controls. The hypoglycemic effect of insulin was significantly, but partially, potentiated in the CFA-treated mice compared with the controls, suggesting that CFA stimulated insulin-mediated and non-insulin-mediated glucose disposal. Improvement in the GTT with CFA was partially transferable to nontreated mice by peritoneal exudative cells, but not spleen or lymph node cells. Pretreatment with anti-interleukin (IL)-1 alpha and -1 beta antibodies or anti-tumor necrosis factor (TNF)-alpha antibody significantly abrogated the improvement in the GTT with CFA. The results indicate that CFA-induced improvement in glucose intolerance in KK-Ay mice was mediated at least by IL-1 and TNF-alpha.

Randomized controlled trial of exercise training for older people (Sendai Silver Center Trial; SSCT): study design and primary outcome.

Physical exercise is expected to improve and maintain physical function in older people, thus promoting health and preventing or postponing the onset of disability in later life. The Sendai Silver Center Trial (SSCT) was a randomized controlled trial designed to evaluate the efficacy of exercise training among healthy free-living older people. Sixty-five eligible participants, aged from 60 to 81 years, were randomly allocated to an exercise group or a control group. The subjects in the exercise group were asked to attend training classes at the Sendai Silver Center, a municipal health and welfare facility in the center of Sendai City, at least twice a week for 25 weeks. Each training class, lasting two hours, started with a warm-up session, followed by an endurance session with a bicycle ergometer, and a resistance exercise training session using rubber films, and ended with a cool-down session. The subjects in the control group were asked to attend recreational classes at the Center twice a month. There were no drop-outs or accidents during the intervention. Comparison of maximum oxygen consumption (VO2max) before and after the 25-week intervention revealed a significant increase in the exercise group (2.1 ml/kg/min) but no significant change in the control group. Our result is equivalent to the participants becoming younger in aerobic capacity by five years after six months of exercise training.

A single optical fiber fluorometric device for measurement of intracellular Ca2+ concentration: its application to hippocampal neurons in vitro and in vivo.

We developed a new system to measure the intracellular Ca2+ concentration in the deep region of the central nervous system with a single optical fiber (300 microns in diameter), used for both excitation and detection of the fluorescence of previously loaded fura-2. With this system, a brain region loaded with fura-2 was illuminated by a rotating disc bearing three different interference filters of 340, 360 and 380 nm at a rate of 600 rpm. The emitted fluorescence was collected by the same fiber connected to a photomultiplier whose output was fed into a computer which regulates the timing of illumination and detection. The time course of the change in the fluorescence due to 340, 360 or 380 nm excitation was measured simultaneously at the maximum sampling rate of 10 points/s. Ratios of fluorescence intensities were obtained after the experiment. After confirming that this system was sensitive enough to detect the change of intracellular Ca2+ concentration in cultured hippocampal neurons and hippocampal slices during depolarization by high potassium medium (50 mM), we applied this system to anesthetized rats. In the hippocampus preloaded with fura-2, characteristic changes in fluorescence intensities ascribed to an increase in intracellular Ca2+ concentration were detected after asphyxia. The system is potentially useful for investigating the physiological and pathological roles of Ca2+ in the brain.

Peritoneal washing cytology at second-look laparotomy in cisplatin-treated ovarian cancer patients.

The use of peritoneal washing cytology during second-look laparotomy in 58 cisplatin-treated ovarian cancer patients was evaluated. Washing was performed for the 41 patients who showed no gross evidence of persistent disease. Peritoneal washing cytology was positive in 8 of 18 cases with histologically identified residual disease and in 4 of 23 cases without residual disease. However, three of the four cytologically positive patients without other evidence of disease later died of recurrences. The five-year survival rate of the 23 patients who showed no residual carcinomas macroscopically was 60.9%; when their washing cytologies were negative, there was a 73.7% five-year survival rate. These findings indicate that, despite its limitations, a peritoneal washing cytology at the time of second-look laparotomy is important to assess the response to treatment and to evaluate the prognosis of patients with ovarian cancer.