Makoto Sohmiya

Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson's disease.

Oxidative stress is suggested to play an important role in the pathogenesis of Parkinsons disease (PD). However, no elevation of plasma oxidative stress marker has been reported. We measured percent content of the oxidized form of coenzyme Q10 in total coenzyme Q10 (%CoQ-10) because %CoQ-10 has been shown to be a sensitive marker of oxidative stress. A slight but significant elevation in %CoQ-10 was observed in PD patients when compared with age/gender-matched normal subjects, suggesting elevated systemic oxidative stress in PD patients.

An increase of oxidized coenzyme Q-10 occurs in the plasma of sporadic ALS patients

We have compared plasma redox status of coenzyme Q-10 in 20 sporadic amyotrophic lateral sclerosis (sALS) patients with those in 20 healthy age/sex-matched controls. A significant increase in the oxidized form of coenzyme Q-10 (sALS=109.3+/-95.2 nM; controls=23.3+/-7.5 nM, P=0.0002) and in the ratio of oxidized form of coenzyme Q-10 to total coenzyme Q-10 (%CoQ-10) (sALS=12.0+/-9.3%; controls=3.2+/-0.9%, P<0.0001) were observed. Moreover, %CoQ-10 correlated significantly with the duration of illness (rho=0.494, P=0.0315). Our finding suggests systemic oxidative stress in the pathogenesis of sALS.

Structural changes in the midbrain with aging and Parkinson's disease: an MRI study.

We measured midbrain structures of 59 subjects with Parkinsons disease (PD) and 140 age- and gender-matched normal subjects without neurological disorders by using T2-weighted MR imaging. There is a significant increase in the maximum distance of the substantia nigra (SND) and a significant decrease in the average distance from the substantia nigra to the red nucleus (SNRND) in patients with PD compared with normal subjects in the 70 years old or less group. These findings may reflect the pathologic increase of iron concentration and the neuronal loss in the region. However, it is difficult to find differences between normal subjects and patients with PD in the greater than 70 years old group in the midbrain structures. These findings based on a large-scale morphometric study provide essential information to evaluate conventional MR images of PD.

Antioxidant properties of carvedilol: inhibition of lipid peroxidation, protein oxidation and superoxide generation.

Abstract Oxidative stress has been suggested to be an etiological factor in cerebro- and cardiovascular disorders. We examined antioxidant activities of carvedilol, a β- and α-adrenoreceptor blocker. Carvedilol suppressed lipid auto-oxidation and protein carbonyl formation in brain homogenate in a dose-dependent manner. Carvedilol also suppressed superoxide generation of human neutrophils. These properties of carvedilol should be suitable for treating hypertension resulting in cerebro- and cardiovascular diseases.

Age-related structural changes in the human midbrain: an MR image study.

We measured midbrain structures of 194 subjects without neurological disorders, using T2-weighted MR imaging. Age was negatively correlated with the maximum anteroposterior distance of the midbrain through the substantia nigra (MD), and the average distance from the substantia nigra to the red nucleus (SNRND), while a positive correlation was found between aging and the maximum distance of the substantia nigra (SND). Significant left-right differences were revealed in MD, SND, SNRND and the area of the red nucleus (RNA), which was possibly responsible for cerebral hemispheric dominance or handedness. There were gender differences in MD and the maximum interpeduncular distance (IPD) in age-matched groups. Age-related structural changes of the midbrain may have a close relation to a decline in motor performance with aging. These findings provide essential information to evaluate the MR images of neurodegenerative disorders.

Antioxidant properties of cabergoline: inhibition of brain auto-oxidation and superoxide anion production of microglial cells in rats

We evaluated the effect of cabergoline on superoxide anion production by rat microglial cells using a 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1, 2-a]pyrazin-3-one-dependent chemiluminescence assay. Cabergoline dose-dependently inhibited superoxide anion production by microglial cells stimulated with phorbol myristate acetate or opsonized zymosan, while it had no superoxide dismutase-like activity. We also studied the effects of cabergoline and alpha-tocopherol on thiobarbituric acid reactive substances formation in homogenized brain-tissue in rats. Cabergoline was stronger than alpha-tocopherol in inhibiting auto-oxidation. While cabergoline is commonly used to treat the motor dysfunction of Parkinsons disease, it may also be effective in inhibiting oxidative stress, a possible mechanism of dopaminergic neuronal degeneration in Parkinsons disease.

Identification of nitrated proteins in the normal rat brain using a proteomics approach

Abstract Background: The nitration of tyrosine has been suggested to play a role in the pathogenesis of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Parkinsons disease (PD) and Alzheimers disease (AD). Methods: In the present study, we identified four targets of protein nitration, T-complex polypeptide 1α subunit (TCP-1), neurofilament L (NFL), glial fibrillary acidic protein (GFAP) and clathrin heavy chain (CHC), in the normal rat cortex using a proteomics approach. Conclusions: There have been no reports on these proteins being identified by proteomics as nitrated forms in the brain. For further study, we have to investigate alterations in these nitrated proteins during aging and in neurodegenerative disorders.

Alternation of trunk movement after arthroplasty in patients with osteoarthritis of the knee

ObjectiveTrunk movement is important but still little understood after total knee arthroplasty. The alternation of trunk movement was analyzed for use in a postoperative rehabilitation program in the short-term after arthroplasty.Materials and methodsThe subjects were 25 patients with knee osteoarthritis (4 males, 21 females). The femorotibial angle was evaluated on standing anteriorposterior radiographs and recorded at pre- and post-arthroplasty. Using three-dimensional motion capture, the gait parameters (cadence, walking speed, stride length, step length, step width), range of motion of lower extremity joints (hip, knee, and ankle), and trunk movement parameters (angle, speed, and displacement) were measured and compared between the pre- and 4th post-arthroplasty week.ResultsThe femorotibial angles of the arthroplasty side were improved from an average of 189° to 175° after arthroplasty. At the 4th post-arthroplasty week, the range of motion of the hip and knee flexion, hip adduction on the arthroplasty side, and ankle dorsiflexion on the non-arthroplasty side were significantly increased compared to pre-arthroplasty. Among gait parameters, only the stride length increased significantly. Regarding the trunk movement in the coronal plane, the maximal trunk speed to the non-arthroplasty side and maximal trunk displacement to the arthroplasty side were both reduced in a medio-lateral direction; the upward maximal trunk speed on the arthroplasty side increased and the maximal trunk displacement on the non-arthroplasty side decreased significantly in an up-down direction.ConclusionThe recovery of hip adduction during the standing phase caused by improvement of knee alignment contributed the reduction of trunk movement to the operated side. In the early post-arthroplasty period, the reduction of trunk movement in the coronal plane is beneficial to maintain trunk balance and prevent falls. Functional recovery of the lower extremities is a long-term process, and sustained functional training is necessary.

Immediate effects of physical therapy on gait disturbance and frontal assessment battery in Parkinson's disease

Aim:  To examine whether the Frontal Assessment Battery is associated with the immediate effects of physical therapy on gait disturbance in patients with Parkinsons disease.

A clinical study of the efficacy of a single session of individual exercise for depressive patients, assessed by the change in saliva free cortisol level

BackgroundThe efficacy of physical exercise as an augmentation to pharmacotherapy with antidepressants for depressive patients has been documented. However, to clarify the effectiveness of exercise in the treatment of depression, it is necessary to distinguish the effect of the exercise itself from the effect of group dynamics. Furthermore, an objective measurement for estimation of the effect is needed. Previous reports adopted a series of group exercises as the exercise intervention and mainly psychometric instruments for the measurement of effectiveness. Therefore, this clinical study was done to examine the effectiveness of a single session of individual exercise on depressive symptoms by assessing the change in saliva free cortisol level, which reflects hypothalamic-pituitary-adrenocortical axis function that is disturbed in depressive patients.MethodEighteen medicated patients, who met the DSM-IV-TR criteria for major depressive disorder, were examined for the change in saliva free cortisol levels and the change in subjective depressive symptoms before and after pedaling a bicycle ergometer for fifteen minutes. Within a month after the exercise session, participants conducted a non-exercise control session, which was sitting quietly at the same time of day as the exercise session.ResultsDepressed patients who participated in this study were in remission or in mild depressive state. However, they suffered chronic depression and had disturbed quality of life. The saliva free cortisol level and subjective depressive symptoms significantly decreased after the exercise session. Moreover, the changes in these variables were significantly, positively correlated. On the other hand, although the subjective depressive symptoms improved in the control session, the saliva free cortisol level did not change.ConclusionFor the first time in depressive patients, we were able to show a decrease in the saliva free cortisol level due to physical exercise, accompanied by the improvement of subjective depressive symptoms. This identified a possible influence of exercise on the hypothalamic-pituitary-adrenal axis in depression.These results suggest the utility of assessing the effect of physical exercise by saliva free cortisol level in depressive patients who suffer from bio-psycho-social disability.