Interaction between the premotor processes of eye and hand movements: possible mechanism underlying eye-hand coordination.

Interaction between the execution process of eye movement and that of hand movement must be indispensable for eye-hand coordination. The present study investigated corticospinal excitability in the hand muscles during the premotor processes of eye and/or hand movement to elucidate interaction between these processes. Healthy humans performed a precued reaction task of eye and/or finger movement and motor-evoked potentials in the hand muscles were evoked in the reaction time. Leftward eye movement suppressed corticospinal excitability in the right abductor digiti minimi muscle only when little finger abduction was simultaneously executed. Corticospinal excitability in the first dorsal interosseous muscle was not suppressed by eye movement regardless of whether or not it was accompanied by finger movement. Suppression of corticospinal excitability in the hand muscles induced by eye movement in the premotor period depends on the direction of eye movement, the muscle tested, and the premotor process of the tested muscle. The suppression may reflect interaction between the motor process of eye movement and that of hand movement particularly active during eye-hand coordination tasks during which both processes proceed.

Novel synthesis of cellulose-based diblock copolymer of poly(hydroxyethyl methacrylate) by mechanochemical reaction.

The mechanical fracture of polymer produces polymeric free radical chain-ends, by which liner block copolymers have been synthesized. A diblock copolymer of microcrystalline cellulose (MCC) and poly 2-hydroxyethyl methacrylate (pHEMA) was produced by the mechanochemical polymerization under vacuum and room temperature. The fraction of pHEMA in MCC-block-pHEMA produced by the mechanochemical polymerization increased up to 21 mol% with increasing fracture time (~6 h). Then, the tacticities of HEMA sequences in MCC-block-pHEMA varied according to the reaction time. In the process of mechanochemical polymerization, cellulose could play the role of a radical polymerization initiator capable of controlling stereoregularity.

Effect of lower-extremity muscle power training on muscle strength, balance function and walking ability in older adults with heart failure: a randomized controlled trial.

PURPOSE: This study investigated the combined effect of lower-extremity muscle power training and regular cardiac rehabilitation on muscle strength, balance function, and walking ability of older adults with heart failure. METHODS: Thirty-one patients, comprising 17 males and 14 females, aged between 66 and 89 years and diagnosed with non-severe heart failure, were randomly assigned to either the intervention group (n = 15) or control group (n = 16). Both groups participated in a 12-week regular rehabilitation program, with the intervention group receiving additional lower-extremity muscle power training. Various outcome measures, including muscle strength (the five-times-sit-to-stand test and knee extensor peak torque), balance function (Berg balance scale and functional reach test), and walking ability (4-m walk and Timed Up-and-Go tests) were assessed at baseline and 12 weeks after the intervention. RESULTS: Of the 31 participants, 27 completed the study protocol. The intervention group demonstrated significantly greater improvement in the five-times-sit-to-stand test time, indicating enhanced lower-extremity muscle power compared to the control group. Both groups showed significant differences in the Berg balance scale, functional reach test, 4-m walk test, and Timed Up-and-Go test between baseline and 12 weeks. However, the effect sizes for the changes during the study period were larger in the intervention group (d = 0.74-1.19) than the control group (d = 0.57-0.96). CONCLUSION: Combining lower-extremity muscle power training with regular cardiac rehabilitation may lead to additional improvements in muscle function for older adults with heart failure, resulting in enhanced dynamic balance and walking ability. TRIAL REGISTRATION NUMBER/DATE OF REGISTRATION: UMIN000032087/April 4, 2018.

Mechanoanions produced by mechanical fracture of bacterial cellulose: ionic nature of glycosidic linkage and electrostatic charging.

Mechanoanions were produced by heterogeneous scission of the glycosidic linkages of the main chain of bacterial cellulose (BC); scission was induced by mechanical fracture of the BC in a vacuum in the dark at 77 K. The mechanoanions were detected using electron-spin-trapping methods with tetracyanoethylene. The yield of mechanoanions was positively correlated with the absolute value of the change in the Mulliken atomic charge, which was used as a descriptor of the ionic nature of the glycosidic linkage. Homogeneous scission of the glycosidic linkages induced by mechanical fracture generated mechanoradicals, the electron affinity of which was estimated on the basis of the energy of the lowest unoccupied molecular orbital for the model structure of the mechanoradical. It was concluded that the electrostatic charging of BC is caused by electron transfer from mechanoanions to mechanoradicals, which have high electron affinities. The electrostatic charge density of BC in a vacuum in the dark at 77 K was estimated to be 6.00 × 10(-1) C/g.

Effects of cigarette smoking on the association between respiratory muscle strength and skeletal muscle mass in middle-aged and older adults: the Wakayama Study.

PURPOSE: This study aimed to examine whether cumulative smoking exposure affects the association between peak expiratory flow rate (PEFR) and skeletal muscle mass in middle-aged and older adults. METHODS: The study participants comprised 832 community-dwelling individuals aged 50-89 years (mean age: 69 years) without chronic obstructive pulmonary disease. Bioelectrical impedance analysis was performed to estimate the skeletal muscle mass of each participant. PEFR was assessed using an electronic spirometer. Cumulative smoking exposure was expressed in pack years, that is a product of the average number of packs of cigarettes smoked per day and smoking duration in years. RESULTS: The whole-body skeletal muscle mass progressively reduced with decreasing PEFR levels in both males and females. In the multiple regression analysis, PEFR was found to be significantly associated with skeletal muscle mass, independent of the potential confounding factors. When participants were stratified based on the cumulative smoking exposure, the association between low PEFR and reduced skeletal muscle mass persisted in individuals with non-smoking and light-to-moderate smoking exposure (< 30 pack-years). However, this association was not clearly observed in individuals with heavy smoking exposure (≥ 30 pack-years). CONCLUSION: The findings of this study support the notion that PEFR declines with a reduction in systemic skeletal muscle mass due to aging. However, chronic cigarette smoking induces respiratory dysfunction exceeding the expected values by age, and thus a low PEFR level may not be used as a marker of reduced muscle mass in older adults exposed to heavy smoking.

[Association of Cigarette Smoking with Muscle Mass Reduction and Low Muscle Strength in Community-Dwelling Elderly Men].

OBJECTIVES: Recently, attention has been paid to the impact of cigarette smoking on skeletal muscles, as its underlying pathophysiological mechanism has been gradually elucidated. In this study, we aimed to examine whether cigarette smoking is associated with muscle mass reduction and low muscle strength in elderly men. METHODS: The study participants comprised 417 community-dwelling elderly men (aged 73±6 years) without severe glucose intolerance, chronic kidney disease, or liver disease. Bioelectrical impedance analysis was performed to estimate appendicular skeletal muscle mass (ASM), which was normalized for height (ASM index, kg/m2). Handgrip strength (HGS) was measured using a Smedley grip dynamometer. Cumulative smoking exposure level during a lifetime was expressed in pack-years, which is a product of the average number of packs of cigarettes smoked per day and smoking duration in years. RESULTS: When the participants were stratified on the basis of cumulative smoking exposure (<10 pack-years, 10-39 pack-years, ≥40 pack-years), the ASM index and HGS progressively decreased with increasing exposure level (P for trend <0.01). In multiple regression analysis, heavy smoking (defined as ≥40 pack-years) was found to be a significant determinant of the ASM index and HGS, independent of potential confounding factors. Among former smokers, the subgroup that quit smoking for ≥20 years had a significantly higher ASM index and HGS than the subgroup that quit smoking for <10 years. The duration of smoking cessation was significantly associated with the ASM index and HGS, even after adjusting for cumulative smoking exposure. CONCLUSIONS: These findings suggest that cigarette smoking contributes to the loss of muscle mass and function in elderly men and that smoking cessation could reverse the impact of cigarette smoking on skeletal muscles.

Diblock copolymer of bacterial cellulose and poly(methyl methacrylate) initiated by chain-end-type radicals produced by mechanical scission of glycosidic linkages of bacterial cellulose.

Bacterial cellulose (BC) was mechanically fractured in vacuum at 77 K; this resulted in the scission of the ß-1,4 glycosidic linkages of BC. The chain-end-type radicals (mechanoradicals) generated from the scissions were assigned by electron spin resonance (ESR) spectral analyses. A diblock copolymer of BC and poly(methyl methacrylate) (BC-block-PMMA) was produced by the mechanical fracture of BC with MMA (methyl methacrylate) in vacuum at 77 K. Radical polymerization of MMA was initiated by the mechanoradicals located on the BC surface. The BC surface was fully covered with the PMMA chains of the BC-block-PMMA. Novel modification of the BC surface with the BC-block-PMMA was confirmed by spectral analyses of ESR, Fourier-transform infrared, (1)H NMR, and gel permeation chromatography.

An ESR spin-label study on molecular mobility in the interface between microphases of a diblock copolymer: effects of admixture of homopolymers that are miscible with one of the blocks.

Molecular mobility in the interfacial region of a microphase-separated structure was studied in binary mixtures of AB-type diblock copolymers and homopolymers (miscible with only A) by the spin-label technique. In this study, we prepared (a) binary blends of polystyrene-block-poly(methyl acrylate) (PS-block-PMA) and homopolymer poly(cyclohexyl acrylate)'s having the number-averaged molecular weight (Mn) of 1000 (PCHA-S) and (b) having the Mn of 17300 (PCHA-L), and (c) binary mixtures of the PS-block-PMA and homopolymer PS with the Mn of 900 (PS-1). Emphasis was placed on effects of the molecular weight and the miscibility of added homopolymers on the mobility in the interfacial region of the microphase separation. Selective incorporation of the added PCHA-S, PCHA-L, and PS-1 into the PS phase of the PS-block-PMA was confirmed by modulated-temperature differential scanning calorimetry (MDSC) measurement as a decrease in the glass transition temperature of the PS phase. Moreover, the MDSC and small-angle X-ray scattering (SAXS) measurements suggested that the spatial distributions of the PCHA-S and PS-1 in the PS phase were relatively uniform because of their small Mn. On the other hand, the distribution of the PCHA-L in the PS phase was somewhat heterogeneous because of the large Mn of the PCHA-L. The spin-label at the junction point of the PS-block-PMA allowed us to estimate the mobility in the interfacial region of the microphase separation. Influence of the PCHA-S and PCHA-L on the mobility in the interfacial region was negligible even though the relatively uniform distribution of the PCHA-S in the PS phase was suggested by the SAXS and MDSC. More uniform distribution of the PS-1 than that of the PCHA-S in the PS phase was suggested by the SAXS, and the mobility in the interfacial region was slightly enhanced by the addition of the PS-1. However, the mobility was almost constant against an increase in the PS-1. The PS-1 was considered to be penetrated into the interfacial region and activated the mobility, but the fraction of the PS-1 in the interfacial region was constant irrespective of the blended amount of the PS-1. These results suggest that effects of homopolymers on the mobility in the interface are significantly related to their spatial distribution in the host phase.

Cutaneous tissue angiotensin-converting enzyme may participate in pathologic scar formation in human skin.

BACKGROUND: Many studies have shown that up-regulation of angiotensin-converting enzyme (ACE) participates in adverse fibrous remodeling. Although this has become an accepted fact in the cardiovascular field, the relationship between ACE and cutaneous fibrous remodeling, such as keloid or hypertrophic scars, remains unknown. OBJECTIVE: We sought to investigate ACE in normal skin, wounded skin, and pathologic scars. METHODS: Ten samples undergoing a normal wound-healing process, 14 samples of pathologic scar tissue, and 15 samples of normal skin were used in this study. Cutaneous tissue ACE activities were measured with high-pressure liquid chromatography. Localization of ACE was assessed by immunohistochemistry. RESULTS: The ACE activity in pathologic scar tissue was significantly higher than in normal and wounded skin. Immunohistochemical studies demonstrated that myofibroblasts were stained with anti-ACE antibody. LIMITATIONS: The study is small. CONCLUSIONS: These results suggest that up-regulated ACE may participate in cutaneous pathologic scar formation the same as the cardiovascular system.

The regressive effect of an angiotensin II receptor blocker on formed fatty streaks in monkeys fed a high-cholesterol diet.

OBJECTIVES: To clarify the regressive effect of an angiotensin II type 1 receptor blocker (ARB) on already formed fatty streaks, we investigated the effect of the administration of an ARB, olmesartan, on formed fatty streaks in monkeys fed a high-cholesterol diet. METHODS: After the monkeys were fed a high-cholesterol diet for 6 months, intimal hyperplasia was clearly observed on intravascular ultrasound. For the next 6 months, the high-cholesterol diet was continued, and olmesartan (3 mg/kg per day) or placebo was administered. A control group was fed a normal diet for 12 months. RESULTS: Olmesartan did not significantly affect blood pressure or plasma cholesterol levels throughout the experiment. After 6 months of treatment with olmesartan, intimal hyperplasia was significantly lower than before treatment. Acetylcholine-induced relaxation in isolated carotid arteries was significantly less in the high-cholesterol diet placebo-treated group compared to the normal diet group, whereas its response was improved by olmesartan. Serum levels of monocyte chemoattractant protein were significantly increased with a high cholesterol load, but they were significantly suppressed by olmesartan. CONCLUSIONS: We have demonstrated for the first time that an ARB, olmesartan, was found to have a regressive effect on formed fatty streaks in monkeys.

Impact of chymase inhibitor on cardiac function and survival after myocardial infarction.

OBJECTIVES: Recent studies have demonstrated that hamsters, like humans, possess both angiotensin converting enzyme (ACE)- and chymase-dependent angiotensin (Ang) II-forming pathways in cardiovascular tissues. We recently found that, after myocardial infarction (MI) in hamsters, cardiac chymase was significantly activated. In order to determine whether suppression of cardiac chymase activity could provide prognostic benefit after MI, we examined the effects of NK3201, a novel, orally active and specific chymase inhibitor, on cardiac function and survival during the acute phase of MI in hamsters. METHODS: Two hundred and ten male Syrian hamsters were used in the present study. The left coronary artery of each hamster was ligated to induce MI. NK3201 at a dose of 30 mg/kg per day was administered orally by gastric gavage, starting either 3 days before or 1 day after MI. RESULTS: ACE and chymase activities were significantly increased in the infarcted left ventricle 3 days after MI. NK3201 treatment starting 3 days before MI significantly inhibited the increase in cardiac chymase activity, while it did not affect ACE activity either in plasma or in heart 3 days after MI. A significant improvement in cardiac function was observed 3 and 14 days after MI in the group receiving NK3201. Compared with vehicle treatment, NK3201 treatment initiated either 3 days before or 1 day after MI significantly reduced the mortality rate during the 14 days of observation following MI. CONCLUSIONS: These findings indicate that cardiac chymase plays an important role after MI and this finding may provide a novel therapeutic target in post-MI treatment.

Significant target organs for hypertension and cardiac hypertrophy by angiotensin-converting enzyme inhibitors.

To clarify the mechanisms by which angiotensin-converting enzyme (ACE) inhibitors lower blood pressure or inhibit cardiac hypertrophy, we analyzed the correlations among tissue ACE activities, blood pressure and cardiac hypertrophy. In spontaneously hypertensive rats (SHR), blood pressure, heart weight and ACE activities in plasma and various tissues were measured 3, 24 and 48 h after repeated daily treatment for 2 weeks with the ACE inhibitors trandolapril, perindopril, temocapril and enalapril. For all four ACE inhibitors, blood pressure and ACE activities in the plasma, aorta and kidney were significantly reduced 3 h after the last treatment. Although hypotensive effects were maintained at 24 h, ACE activities in plasma were not suppressed by temocapril and enalapril. Even at 3 h, enalapril could not suppress ACE activity in the brain, and temocapril and enalapril could not inhibit ACE activities in the heart. Significant correlations between ACE activity in the aorta and blood pressure were observed for all four ACE inhibitors, while the ACE activities in the heart and brain were not correlated with changes in blood pressure. Significant decreases in the ratio of heart weight to body weight were observed in SHR treated with trandolapril and perindopril, whereas they were not observed with temocapril and enalapril. The ratio of heart weight to body weight was significantly correlated with ACE activity in the heart. ACE activities in vascular tissues and the heart may be important targets in terms of the ability of ACE inhibitors to lower blood pressure or inhibit cardiac hypertrophy, respectively.

Comparative effects of candesartan and amlodipine in a monkey atherosclerotic model.

Angiotensin II receptor blockers could prevent the development of atherosclerosis beyond reducing blood pressure in monkeys fed a high-cholesterol diet. However, it has been unclear whether hypotensive effects improve atherosclerosis in primates. We investigated whether antihypertensive agents, an angiotensin II receptor antagonist, candesartan, and a calcium channel blocker, amlodipine, prevent areas of atherosclerotic lesions in the aorta of monkeys fed a high-cholesterol diet. Seventeen male monkeys fed a high-cholesterol diet for 6 months were grouped as follows: a high-cholesterol diet group (n=5), a candesartan-treated group (1 mg/kg per day, n=6) and an amlodipine-treated group (5 mg/kg per day, n=6). Candesartan and amlodipine showed a similar hypotensive effect by decreasing the systolic blood pressure approximately 20 mmHg, while these agents did not affect serum cholesterol levels. The ratio of atherosclerotic area to total area in thoracic aorta was significantly decreased by treatment with candesartan, but the ratio tended to be decreased by treatment with amlodipine. Although the angiotensin-converting enzyme activity in plasma was not changed by treatment with candesartan or amlodipine, the angiotensin-converting enzyme activity in the thoracic aorta was obviously reduced by treatment with candesartan, but not with amlodipine. Therefore, a blockade of angiotensin II action rather than a hypotensive effect may play an important role in preventing the development of atherosclerosis in primates.

A specific chymase inhibitor, NK3201, suppresses bleomycin-induced pulmonary fibrosis in hamsters.

We evaluated whether a chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[(3,4-dioxo-1-phenyl-7-(2-pyridyloxy))-2-heptyl]acetamide (NK3201), suppressed bleomycin-induced pulmonary fibrosis. Hamsters were orally administered NK3201 (30 mg/kg per day) or placebo, beginning 5 days before intratracheal instillation of bleomycin (10 mg/kg). Four weeks after the instillation of bleomycin, pulmonary chymase activity in placebo-treated hamsters was significantly higher than in control hamsters, whereas the activity in NK3201-treated hamsters was significantly lower than in placebo-treated hamsters. The ratio of fibrotic area to total area in NK3201-treated hamsters was significantly decreased to 54.0% of the ratio in placebo-treated hamsters. Therefore, NK3201 may be useful in the prevention of pulmonary fibrosis.

Beneficial effects of cardiac chymase inhibition during the acute phase of myocardial infarction.

Recently, the presence of the chymase-dependent angiotensin (Ang) II-generating system in hamsters, dogs, monkeys, as well as human cardiovascular tissues has been identified. We have reported that the activation of cardiac chymase was more prominent than that of angiotensin converting enzyme (ACE) and that AT1 receptor antagonist treatment rather than ACE inhibitor treatment alone provided significant beneficial effects on cardiac function and survival after MI in hamsters. The aim of the present study was to determine whether this different effects between AT1 receptor antagonist and ACE inhibitor were due to the activation of cardiac chymase after MI in hamsters by using 4-[1-[[bis-(4-methyl-pheny)-methyl]-carbamoyl]-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid (BCEAB), a novel, orally active and specific chymase inhibitor. The ACE and chymase activities in the infarcted left ventricle were significantly increased 3 days after MI. BCEAB (100 mg/kg/day, p.o.) treatment starting 3 days before MI significantly suppressed the cardiac chymase activity, while it did not affect the plasma and cardiac ACE activities 3 days after MI. A significant improvement in hemodynamics (maximal negative and positive rates of pressure development; left ventricular systolic pressure) was observed for the treatment with BCEAB 3 days after MI. BCEAB (100 mg/kg/day, p.o.) treatment starting 3 days before MI significantly reduced the mortality rate during 14 days of observation following MI (vehicle, 61.1%, n = 18; BCEAB, 27.8%, n = 18; P < 0.05). These findings demonstrated for the first time that cardiac chymase participates directly in the pathophysiologic state after MI in hamsters.

Increased local angiotensin II formation in aneurysmal aorta.

We investigated the levels and locations of angiotensin II-forming enzymes, angiotensin converting enzyme (ACE) and chymase, in aneurysmal and normal aortas. Aneurysmal aortic specimens (n = 14) were obtained at the time of operative aneurysm repair from 14 patients ranging in age from 57 to 84 y. Normal aortic specimens (n = 16) were obtained from 16 patients (48 to 72 y) who underwent coronary artery bypass surgery. The ACE and chymase activities were determined using each specimen. Sections of each specimen were immunostained with antibodies for ACE and chymase. The ACE activities in the aneurysmal and normal aortas were 0.82 +/- 0.10 and 0.14 +/- 0.05 mU/mg protein, respectively, and this difference was significant. The chymase activities in the aneurysmal and normal aortas were 17.9 +/- 2.40 and 1.02 +/- 0.18 mU/mg protein, respectively, and this difference was also significant. In the aneurysmal aorta, ACE-positive cells were detected with macrophages in the intima and media and chymase-positive cells were detected with mast cells in the media and adventitia, whereas positive ACE and chymase cells in the normal aorta were located only in the endothelium and adventitia, respectively. Angiotensin II-forming enzymes, chymase and ACE, were significantly increased in the aneurysmal aorta, and increased angiotensin II may be associated with the development of aneurysmal formations.

Chymase and angiotensin converting enzyme activities in a hamster model of glaucoma filtering surgery.

PURPOSE: Two pathways for the formation of angiotensin II (Ang II) in local tissues are known to exist, one involving angiotensin-converting enzyme (ACE), and the other in which chymase plays a role. It has been shown that chymase activity is present in monkey, dog, and hamster eyes. Because chymase activates various cytokines by increasing Ang II formation, thereby promoting the production of extracellular matrix, the role of Ang II in wound healing has attracted much interest. In this work, we created sclerocorneal wounds in hamster eyes and measured the levels of ACE and chymase activities in the eye during the wound healing process. METHODS: Sclerocorneal wounds were made at 6 locations on the corneal limbus of one eye in each of 36 hamsters. Using the contralateral eyes as controls, we measured levels of chymase and ACE activities in the overall eye at 3, 7, and 21 days postoperatively. Histopathological evaluations of the sclerocorneal wounds in the treated eyes were also carried out for samples stained with toluidine blue. RESULTS: Chymase activity in the treated eyes tended to be higher than that in the control at 21 days. ACE activity in the treated eyes was significantly higher than that in the control at 3, 7, and 21 days postoperatively. Histopathological examination revealed increased mast cells in the subconjunctival tissue and around the tunnel opening in the sclerocornea. CONCLUSIONS: These findings show that not only ACE but also chymase contributes to the formation of Ang II in the healing of sclerocorneal wounds in hamster eyes. This leads to the suggestion that ACE inhibitors or chymase inhibitors could potentially inhibit scarring in glaucoma filtering surgery.

Involvement of angiotensin II-dependent vascular endothelial growth factor gene expression via NADPH oxidase in the retina in a type 2 diabetic rat model.

PURPOSE: To clarify the involvement of angiotensin II-dependent vascular endothelial growth factor (VEGF) via NADPH oxidase in the retina in spontaneously diabetic Torii (SDT) rats, a type 2 diabetic rat model. In SDT rats, the plasma glucose level and angiotensin-converting enzyme (ACE) levels were measured, and effects of angiotensin II receptor blocker (ARB) and angiotensin II were also studied. MATERIALS AND METHODS: We evaluated the age-dependent changes in the peripheral and ocular angiotensin II-forming systems in SDT rats at 15 (n = 8), 20 (n = 8), 30 (n = 7), and 50 weeks of age (n = 8). We also evaluated the effect of an ARB (2.5 mg/kg/day candesartan) or angiotensin II (500 ng/kg/min) on retinal gene expressions of VEGF and p22phox, a subunit of NADPH oxidase. RESULTS: The plasma glucose level was significantly increased from 20 weeks of age. No significant changes in ACE activities in the plasma, aorta, and eye were observed until 30 weeks of age. At 50 weeks, ACE activity in the eyes was significantly increased, whereas ACE activities in the plasma and aorta were not. At 50 weeks, significant increases in VEGF and p22phox, an NADPH oxidase subunit, were significantly reduced by candesartan. Angiotensin II infusion resulted in significant increases in VEGF and p22phox levels. CONCLUSIONS: Angiotensin II is involved in the gene expression of VEGF via NADPH oxidase in the retina of SDT rats.