Hochuekkito Combined with Pulmonary Rehabilitation in Apathetic Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Pilot Trial.

The main treatment goals for chronic obstructive pulmonary disease (COPD) are the reduction of its symptoms and future risks. The addition of the traditional herbal medicine Hochuekkito (TJ-41) treatment to pulmonary rehabilitation (PR) has been reported to improve dyspnea and health-related quality of life (HRQOL) in patients with COPD. However, the reason for this improvement is not sufficiently understood. The purpose of the present study was to investigate whether the addition of TJ-41 treatment to PR improves symptoms of apathy, dyspnea, and HRQOL and increases physical activity among apathetic patients with COPD. Apathetic patients with COPD were randomly assigned to receive low-intensity exercise with (TJ-41 group) or without (control group) TJ-41 treatment for 12 weeks. A total of 29.9% of COPD patients had apathetic symptoms without severe depression. After the 12-week treatment, Apathy Scale, Patient Health Questionnaire-9, visual analog scale for dyspnea, and COPD assessment test energy scores decreased significantly in the TJ-41 group (p < 0.05), but not in the control group. Additionally, the total number of steps taken was significantly higher in the TJ-41 group than in the control group. TJ-41 combined with PR may benefit apathetic patients with COPD with respect to apathy, dyspnea, HRQOL, and physical activity, but larger randomized placebo-controlled trials are required to validate the findings because of the small sample size and lack of placebo controls in this study.

Increased oxygenation in the non-contracting forearm muscle during contralateral skilful hand movement.

NEW FINDINGS: What is the central question of this study? When performing skilful hand movement, motor command descends especially towards distal arm muscles. Does central command evoke a vascular response selectively in the distal arm muscles during skilful hand movement? What is the main finding and its importance? We found, using near-infrared spectroscopy, that unilateral skilful hand movement evoked a greater increase in oxygenation of the contralateral forearm muscle compared with that of the upper arm muscles. Mental imagery of the hand movement also increased oxygenation of the forearm muscle. These findings suggest that central command might contribute to the vasodilator response in the non-contracting forearm muscle during contralateral skilful hand movement. ABSTRACT: The human hand is a special organ to perform skilful movement in daily life. To meet metabolic demands of the working distal arm muscles, central command might evoke neurogenic vasodilatation in the muscles. Based on our previous demonstration that a centrally generated vasodilator signal is transmitted bilaterally to skeletal muscles during exercise, centrally induced vasodilatation might occur in the non-contracting distal arm muscles during contralateral skilful hand movement. To examine this possibility, we used near-infrared spectroscopy to measure the relative concentrations of oxygenated haemoglobin (Oxy-Hb; as an index of regional blood flow) in the non-contracting arm muscles during skilful hand movement (two-ball rotation) in 22 subjects. Two-ball rotation increased Oxy-Hb of both forearm and upper arm muscles, with little changes in perfusion pressure and cardiac output. The increased Oxy-Hb was greater in the forearm muscle than in the upper arm muscles. The increased Oxy-Hb of the forearm muscle during two-ball rotation was greater than that during one-armed cranking performed with no load. Mental imagery of two-ball rotation increased Oxy-Hb of the forearm and biceps muscles. The increases in Oxy-Hb of both forearm and upper arm muscles during two-ball rotation were reduced by decreasing the level of task difficulty. Intravenous administration of atropine attenuated the increases in Oxy-Hb of the arm muscles during two-ball rotation. It is likely that contralateral skilful hand movement evokes a selective increase in Oxy-Hb of the non-contracting forearm muscle via a sympathetic cholinergic mechanism and that the increase in oxygenation might be mediated, at least in part, by central command.

Effects of Hochuekkito combined with pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) has significant systemic effects, such as weight loss, which affects exercise capacity, health-related quality of life (HRQOL) and survival. The traditional herbal medicine, Hochuekkito (TJ-41), improves the nutritional status and decreases systemic inflammation in patients with COPD. However, to date, the additive effect of TJ-41 on pulmonary rehabilitation (PR) in patients with COPD has not been researched comprehensively. The purpose of the present study was to investigate the efficacy and safety of adding TJ-41 to PR for patients with COPD. Thirty-three malnourished patients with COPD were randomly assigned to receive low-intensity exercise with (TJ-41 group) or without (control group) TJ-41 treatment for 12 weeks. The primary outcome was the change in the 6-min walk distance (6MWD). Secondary outcomes included changes in the body composition, peripheral muscle strength, modified Medical Research Council dyspnea score, visual analog scale (VAS) score for dyspnea, VAS score for fatigue and COPD assessment test (CAT) score. After the 12-week treatment, body weight and percent ideal body weight were significantly increased in the TJ-41 group (P<0.05), but not in the control group. After the 12-week treatment, the modified Medical Research Council dyspnea score, VAS score for dyspnea, VAS score for fatigue and total CAT score decreased significantly in the TJ-41 group (all P<0.05), but not in the control group. There were no significant differences in the 6MWD and peripheral muscle strength between baseline and after 12 weeks of treatment in either group. No adverse effects were noted with the use of TJ-41. It was concluded that the addition of TJ-41 to PR may benefit malnourished patients with COPD with respect to dyspnea and HRQOL.

Central command increases muscular oxygenation of the non-exercising arm at the early period of voluntary one-armed cranking.

This study aimed to examine whether central command increases oxygenation in non-contracting arm muscles during contralateral one-armed cranking and whether the oxygenation response caused by central command differs among skeletal muscles of the non-exercising upper limb. In 13 male subjects, the relative changes in oxygenated-hemoglobin concentration (Oxy-Hb) of the non-contracting arm muscles [the anterior deltoid, triceps brachii, biceps brachii, and extensor carpi radialis (ECR)] were measured during voluntary one-armed cranking (intensity, 35-40% of maximal voluntary effort) and mental imagery of the one-armed exercise for 1 min. Voluntary one-armed cranking increased (P < 0.05) the Oxy-Hb of the triceps, biceps, and ECR muscles to the same extent (15 ± 4% of the baseline level, 17 ± 5%, and 16 ± 4%, respectively). The greatest increase in the Oxy-Hb was observed in the deltoid muscle. Intravenous injection of atropine (10-15 µg/kg) and/or propranolol (0.1 mg/kg) revealed that the increased Oxy-Hb of the arm muscles consisted of the rapid atropine-sensitive and delayed propranolol-sensitive components. Mental imagery of the exercise increased the Oxy-Hb of the arm muscles. Motor-driven passive one-armed cranking had little influence on the Oxy-Hb of the arm muscles. It is likely that central command plays a role in the initial increase in oxygenation in the non-contracting arm muscles via sympathetic cholinergic vasodilatation at the early period of one-armed cranking. The centrally induced increase in oxygenation may not be different among the distal arm muscles but may augment in the deltoid muscle.

Differential contribution of ACh-muscarinic and ß-adrenergic receptors to vasodilatation in noncontracting muscle during voluntary one-legged exercise.

We have demonstrated the centrally induced cholinergic vasodilatation in skeletal muscle at the early period of voluntary one-legged exercise and during motor imagery in humans. The purpose of this study was to examine whether central command may also cause ß-adrenergic vasodilatation during the exercise and motor imagery. Relative changes in oxygenated hemoglobin concentration (Oxy-Hb) of bilateral vastus lateralis (VL) muscles, as index of tissue blood flow, and femoral blood flow to nonexercising limb were measured during one-legged cycling and mental imagery of the exercise for 1 min before and after propranolol (0.1 mg/kg iv). The Oxy-Hb of noncontracting muscle increased (P < 0.05) at the early period of exercise and the increase was sustained throughout exercise, whereas the Oxy-Hb of contracting muscle increased at the early period but thereafter decreased. We subtracted the Oxy-Hb response with propranolol from the control response in individual subjects to identify the propranolol-sensitive component of the Oxy-Hb response during exercise. In both noncontracting and contracting VL muscles, the increase in Oxy-Hb at the early period of one-legged exercise did not involve a significant propranolol-sensitive component. However, as the exercise proceeded, the propranolol-sensitive component of the Oxy-Hb response was developed during the later period of exercise. Propranolol also failed to affect the initial increases in femoral blood flow and vascular conductance of nonexercising leg but significantly attenuated (P < 0.05) their later increases during exercise. Subsequent atropine (10-15 µg/kg iv) abolished the initial increases in Oxy-Hb of both VL muscles. Mental imagery of the one-legged exercise caused the bilateral increases in Oxy-Hb, which were not altered by propranolol but abolished by subsequent atropine. It is likely that the rapid cholinergic and delayed ß-adrenergic vasodilator mechanisms cooperate to increase muscle blood flow during exercise.

Evidence for centrally induced cholinergic vasodilatation in skeletal muscle during voluntary one-legged cycling and motor imagery in humans.

We have recently reported that central command contributes to increased blood flow in both noncontracting and contracting vastus lateralis (VL) muscles at the early period of voluntary one-legged cycling. The purpose of this study was to examine whether sympathetic cholinergic vasodilatation mediates the increases in blood flows of both muscles during one-legged exercise. Following intravenous administration of atropine (10 µg/kg), eight subjects performed voluntary 1-min one-legged cycling (at 35% of maximal voluntary effort) and mental imagery of the exercise. The relative concentrations of oxygenated- and deoxygenated-hemoglobin (Oxy- and Deoxy-Hb) in the bilateral VL were measured as an index of muscle tissue blood flow with near-infrared spectroscopy (NIRS). The Oxy-Hb in both noncontracting and contracting VL increased at the early period of one-legged cycling, whereas the Deoxy-Hb did not alter at that period. Atropine blunted (P < 0.05) the Oxy-Hb responses of both VL muscles but did not affect the Deoxy-Hb responses. The time course and magnitude of the atropine-sensitive component in the Oxy-Hb response were quite similar between the noncontracting and contracting VL muscles. With no changes in the Deoxy-Hb and hemodynamics, imagery of one-legged cycling induced the bilateral increases in the Oxy-Hb, which were completely abolished by atropine. In contrast, imagery of a circle (with no relation to exercise) did not alter the NIRS signals, irrespective of the presence or absence of atropine. It is concluded that central command evokes cholinergic vasodilatation equally in bilateral VL muscles during voluntary one-legged cycling and motor imagery.

Antitussive effect of bakumondoto a fixed kampo medicine (six herbal components) for treatment of post-infectious prolonged cough: controlled clinical pilot study with 19 patients.

Bakumondoto (TJ-29) is a traditional herbal medicine that has been used in Japan for the treatment of bronchitis, bronchial asthma, and cough. This study investigated the effect of TJ-29 for the treatment of post-infectious prolonged cough. We performed a multicenter randomized controlled trial treating patients without (group A, n=11) or with TJ-29 (group B, n=8) for a total of 2 weeks using a beta 2 stimulant as the basal agent. Efficacy and safety were compared by a cough diary, VAS and sleeping questionnaire. At 4 and 5 days after treatment, the cough score of group B showed significant improvement compared with group A, demonstrating an early antitussive effect. At the assessment 2 weeks after treatment start, both groups showed similar levels of improvement in the cough score. No significant difference was observed in the VAS and the sleeping questionnaire items. In conclusion, oral TJ-29 administration could be useful and safe for the treatment of post-infectious prolonged cough.

High dose of ascorbic acid induces cell death in mesothelioma cells.

Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

[A case of interstitial pneumonia caused by gosha-jinki-gan].

A 74-year-old woman was admitted to the hospital of Ehime University School of Medicine because of slight fever, dry cough and dyspnea on exertion. Chest X-ray films on admission showed diffuse infiltrations in both lungs. Drug-induced pneumonia due to the herbal medicine Gosha-jinki-gan was suspected, as Gosha-jinki-gan had been administered for 5 months for the treatment of a right knee pain. Her symptoms and the X-ray abnormality improved after cessation of administration. The lymphocyte stimulation test against Gosha-jinki-gan was positive. To the best of our knowledge, this is the first case of interstitial pneumonia caused by Gosha-jinki-gan.