Biomedical subjects

Norifumi Metoki

Publications and source records attributed to Norifumi Metoki.

8 recordsLinked to original sources

PubMed2006

Interleukin-1beta enhances the angiotensin-induced expression of plasminogen activator inhibitor-1 through angiotensin receptor upregulation in human astrocytes.

Plasminogen activator inhibitor-1 (PAI-1) regulates not only fibrinolysis but extracellular matrix remodeling, and angiotensin II is known to play an important role in controlling the expression of PAI-1 in astrocytes. We have studied the effect of interleukin-1beta (IL-1beta), one of major cytokines also active in the nervous system, on the angiotensin II-induced expression of PAI-1 in human astrocytes. Cultures of normal human astrocytes were stimulated with IL-1beta and angiotensin II, and the expression of mRNAs for angiotensin II type 1 receptor (AT1) and PAI-1 was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) or real-time quantitative PCR. PAI-1 protein in astrocyte-conditioned medium was measured by enzyme-linked immunosorbent assay (ELISA). IL-1beta enhanced the expression of AT1 in astrocytes in time- and concentration-dependent manners. After 24-h stimulation, 10 ng/ml IL-1beta and 10 nM angiotensin II increased the levels of PAI-1 protein in astrocyte-conditioned medium by 1.9-fold and 1.8-fold of the basal value, respectively. There was no synergistic effect when the cells were stimulated simultaneously with IL-1beta and angiotensin II. When the cells were stimulated, with angiotensin II, 16 h after the stimulation with IL-1beta, the production of PAI-1 was enhanced by 1.4-fold as compared to the cells stimulated only with IL-1beta. CV-11794, an AT1 antagonist, inhibited the enhanced PAI-1 production in response to angiotensin II. We conclude that IL-1beta increases angiotensin II-induced PAI-1 secretion by astrocytes through the induction of AT1, and the enhanced secretion of PAI-1 may modulate functions of plasminogen activators in the nervous system.

Angiotensin II↗

PubMed2005

Platelet-activating factor enhances the expression of nerve growth factor in normal human astrocytes under hypoxia.

Nerve growth factor (NGF) is required for the survival of neurons. We have addressed the effect of platelet-activating factor (PAF), one of the mediators of ischemic injury of the brain, on NGF expression in astrocytes. Normal human astrocytes in culture were stimulated with PAF, and levels of NGF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). PAF increased the expressions of NGF mRNA and protein in astrocytes in time- and concentration-dependent manners. After 48-h stimulation, 10 nmol/L PAF increased the levels of NGF protein in astrocyte-conditioned medium by 1.4-fold. The PAF-induced stimulation of NGF expression was further enhanced (2.1-fold of the control) in the cells under hypoxic culture condition. BN52021 (Ginkgolide B), an antagonist for PAF binding sites, suppressed the effect of PAF. We conclude that PAF enhances NGF gene expression in human astrocytes, and the PAF-induced increase in the expression of NGF under hypoxia may benefit the protection of the nervous tissue by promoting neuronal survival.

Astrocytes↗

PubMed2005

Nocturnal blood pressure decrease is associated with increased regional cerebral blood flow in patients with a history of ischemic stroke.

BACKGROUND: It remains controversial whether there is a J-shaped relationship between blood pressure and recurrent stroke among patients with a recent history of ischemic stroke. OBJECTIVE: To investigate the relationship between regional cerebral blood flow (rCBF) and the dipping of nocturnal blood pressure in patients receiving antihypertensive treatment after ischemic stroke. METHODS AND RESULTS: Forty-seven patients with a previous history of ischemic stroke and 37 patients with a history of non-ischemic stroke underwent 24-h ambulatory blood pressure monitoring and rCBF measurement with single photon emission computed tomography. Of the 47 patients with ischemic stroke, 30 were diagnosed as having suffered atheromatous or embolic stroke, and 37 had an ischemic lesion in the territory of the carotid artery. Systolic and diastolic blood pressures during daytime and night-time were controlled at less than 140/90 mmHg by a low-salt diet or long-acting antihypertensive agents, or both. In patients with ischemic stroke, there were significant negative correlations between the percentage change in nocturnal blood pressure and rCBFs in the thalamus (r = -0.33, P = 0.02), putamen (r = -0.34, P = 0.02) and cerebral cortex (r = -0.31, P = 0.03). Multivariate analysis revealed that only the percentage change in nocturnal blood pressure was related to rCBF. There was a significant positive correlation between rCBFs in the thalamus and the cerebral cortex (r = 0.74, P < 0.05). In patients with non-ischemic stroke, there was no significant correlation between the percentage change in nocturnal blood pressure and rCBFs. CONCLUSIONS: These findings indicate that the decrease in nocturnal blood pressure is associated with the increase in rCBF in patients with a history of ischemic stroke in the territory of the carotid artery.

Adult↗

PubMed2003

Coagulation-fibrinolysis abnormalities in patients receiving antiparkinsonian agents.

Neuroleptic malignant syndrome (NMS) is induced by alteration of medication in Parkinson's disease (PD); and blood coagulation disorder is regarded as one of the mechanisms implicated in NMS. We have studied markers of blood coagulation and fibrinolysis in 270 patients with PD and 159 healthy controls matched in age and gender. The average values of prothrombin time (international normalized ratio) and plasma levels of prothrombin fragment(1+2), D-dimer, plasmin-alpha 2 antiplasmin complex, thrombomodulin and E-selectin were higher in patients receiving antiparkinsonian agents as compared to the patients without any medication or healthy controls. The effect of antiparkinsonian drugs was analyzed by dividing the patients into three groups according to the medication: the patients under the combination therapy with levodopa and a dopamine agonist, the patients administered levodopa, and those that received a dopamine agonist. Of the three groups, the patients under the combination therapy had the highest values of these markers, and those treated with only levodopa had the lowest values. PD patients receiving antiparkinsonian drugs are often associated with blood coagulation abnormalities, and plasma hemostatic markers should be routinely assessed in the management of such patients. Further study is needed to determine whether these abnormalities predispose to the development of NMS.

Aged↗

PubMed2003

Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in stroke patients.

BACKGROUND: The authors' previous investigations have disclosed low serum 25-hydroxyvitamin D (25-OHD) concentrations in 45 patients during long-term hospitalization following stroke (mean 5.9 ng/mL). This 25-OHD deficiency resulted from sunlight deprivation. OBJECTIVE: To evaluate the efficacy of sunlight exposure in increasing serum 25-OHD, in reducing the severity of osteoporosis in bone mineral density (BMD), and in decreasing the risk of hip fractures in chronically hospitalized, disabled stroke patients. METHODS: In a 12-month randomized and prospective study of stroke patients, 129 received regular sunlight exposure for 12 months, and the remaining 129 (sunlight-deprived) did not. RESULTS: At baseline, patients of both groups showed vitamin D deficiency. BMD increased by 3.1% in the sunlight-exposed group and decreased by 3.3% in the sunlight-deprived group (p = 0.0001). 25-OHD level increased by fourfold in the sunlight-exposed group. Six patients sustained hip fractures on the hemiplegic side in the sunlight-deprived group, and one hip fracture occurred among the sunlight-exposed group (p = 0421; odds ratio = 6.1). CONCLUSION: Sunlight exposure can increase the BMD of vitamin D-deficient bone by increasing 25-OHD concentration.

Aged↗

PubMed2003

Muscular atrophy in the hemiplegic thigh in patients after stroke.

OBJECTIVES: This study evaluated muscular atrophy in the hemiplegic limbs by assessing the muscle volume of the thighs in stroke patients. DESIGN: Muscle volume of the bilateral thighs was determined by computed tomographic scanning in 50 hemiplegic patients after stroke. RESULTS: The average muscle volume in the hemiplegic side was significantly lower than that in the nonhemiplegic side. When the patients were divided into the two groups aged <65 yr old and >/=65 yr, age-dependent reduction in the muscle volume was significant only in the nonhemiplegic side. In addition, the ratio of the muscle volume in hemiplegic side to that in non-hemiplegic side was lower in the younger group than in the older group, with close to significance (P = 0.07). Muscle volume in both hemiplegic and nonhemiplegic sides correlated positively with Barthel index and negatively with patient age. CONCLUSION: Muscle volume decreases in the hemiplegic side in stroke patients.

Age Factors↗

PubMed2002

Hyperhomocysteinemia in Japanese patients with convalescent stage ischemic stroke: effect of combined therapy with folic acid and mecobalamine.

Hyperhomocysteinemia is considered to be a risk factor for vascular diseases including ischemic stroke. It has been shown that plasma homocysteine level can be lowered by folic acid supplementation. Vitamin B(12) may be also beneficial when included in the supplement regimen with folic acid. We have examined in Japanese patients with ischemic stroke the homocysteine-lowering potential of a combination therapy with folic acid and vitamin B(12). Patients with ischemic stroke were randomized into three groups and each group received vitamin B(12) (1500 microg/day, n = 63), folic acid (5 mg/day, n = 64), or both vitamin B(12) and folic acid (n = 64) for 8 weeks. Plasma levels of homocysteine and these vitamins were followed. Significant reduction in plasma homocysteine was observed in all three groups, and the combination therapy yielded the most remarkable result, i.e., plasma total homocysteine was reduced by 38.5% and this was significantly larger than the reduction in other two groups (22.4% and 10.9% in the groups received folic acid and vitamin B(12), respectively). Vitamin B(12) synergizes with folic acid in reducing plasma homocysteine in Japanese patients with ischemic stroke and the combined therapy may be particularly effective in the secondary prevention.

Aged↗

PubMed2002

Effect of losartan on nocturnal blood pressure in patients with stroke: comparison with angiotensin converting enzyme inhibitor.

BACKGROUND: Treatment of nocturnal hypertension has been reported to be beneficial for primary and secondary prevention of stroke. We compared the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme inhibitor (quinapril) on nocturnal blood pressure (BP) and sympathetic nervous activity in patients with hypertension and stroke. METHODS: According to a prospective, randomized, cross-over design, 30 hypertensive patients with a previous history of stroke (25 hemorrhage, 5 infarction) were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regimen for an additional 4-week period. In the last week of each treatment, 24-h ambulatory BP monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. RESULTS: Neither systolic nor diastolic BP during daytime differed between losartan and quinapril treatments, but those during nighttime were lower with losartan treatment than with quinapril treatment. The nocturnal decreases in systolic and diastolic BP were both greater with losartan treatment than with quinapril treatment (systolic BP: 6.1% +/- 5.9% v 2.5% +/- 6.9%, diastolic BP: 6.4% +/- 6.5% v 3.3% +/- 7.8%, both P <.05). The nocturnal decrease in urinary norepinephrine excretion was greater with losartan treatment than with quinapril treatment (52.8% +/- 9.7% v 42.8% +/- 17.2%, P <.05). CONCLUSIONS: Losartan enhances the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke presumably by way of the suppression of nocturnal sympathetic nervous activity.

Adult↗