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Biomedical subjects

S Takaori

Publications and source records attributed to S Takaori.

At least 19 recordsLinked to original sources

Improvement of accessory symptoms of hypertension by TSUMURA Orengedokuto Extract, a four herbal drugs containing Kampo-Medicine Granules for ethical use: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled study was conducted to evaluate the efficacy, safety, and utility of TSUMURA Orengedokuto Extract Granules for Ethical Use (TJ-15) as a treatment for the accessory symptoms of hypertension. Two capsules of the study drug were administered orally 3 times daily (i.e., before meals) for 8 weeks. Among 265 patients enrolled in the study, 134 were assigned to the TJ-15 group and 131 were assigned to the placebo group, of whom 204 patients (103 in the TJ-15 group and 101 in the placebo group) were included in the efficacy and utility analyze and 251 patients (128 in the TJ-15 group and 123 in the placebo group) were included in the safety analysis. Efficacy was significantly higher in the TJ-15 group based on the total score for the accessory symptoms of hypertensions which was the primary efficacy endpoint (Wilcoxon's rank sum test, p=0.013). When each accessory symptom of hypertension was assessed separately, efficacy was higher for hot flushes and facial suffusion in the TJ-15 group (Wilcoxon's rank sum test, p=0.034, and 0.022, respectively). There were no significant differences between the TJ-15 and the placebo groups with respect to the decrease of blood pressure or the antihypertensive effect. There was also no significant difference between the two groups with regard to the overall safety rating. The utility rating was significantly higher in the TJ-15 group than in the placebo group (Wilcoxon's rank sum test, p=0.016). In conclusion, TJ-15 was superior to placebo with respect to efficacy, safety, and utility for the treatment of accessory symptoms of hypertension.

Adult↗

Pharmacodynamic equivalence study of CFC-free and CFC-containing procaterol hydrochloride metered-dose inhalers.

Equivalence between a CFC-free procaterol hydrochloride metered-dose inhaler using HFA-227 as a propellant (Meptin [HFA]) and a CFC-containing procaterol hydrochloride metered-dose inhaler (Meptin [CFC]) was assessed in 28 patients with bronchial asthma. The study was conducted in a randomized, double-dummy, double-blind crossover manner, using forced expiratory volume in the first second (FEV1) as an index of bronchodilatory effect. In Period I, the patients received 20 microg of either Meptin [HFA] or Meptin [CFC] and then crossed over in Period II after a washout interval of 3-28 days. Pharmacodynamic equivalence was assessed using AUC (FEV1)/h and peak FEV1 as indices, and the data was analyzed by analysis of variance. Factors used for the analysis were the treatment group and/or carryover effect, patients within each group, period, and treatment. The 90% confidence intervals for the differences between the two treatments were -0.0507 to 0.0039 (L) for mean AUC (FEV1)/h and -0.056 to 0.026 (L) for mean peak FEV1, both within the acceptance criteria of -0.15 to 0.15 (L). Meptin [HFA] was therefore assessed as being equivalent to the current Meptin [CFC].

Administration, Inhalation↗

Serum contents of the free forms of alpha(1)-microglobulin and ulinastatin: relation to diseased states in patients with mood disorders.

We have found previously that the relationship between the urinary contents of alpha(1)-microglobulin (alpha(1)M) and ulinastatin (UT) in patients with mood disorder differs from that of age-matched healthy subjects. However, it has yet to be determined whether or not the difference in the relation correlates with the contents of the free forms of alpha(1)M and UT in serum and whether changes in the existing forms of alpha(1)M and UT in serum reflect the actual disease states. The relation between serum contents of the free forms of alpha(1)M and UT in 10 patients with mood disorders was different from that of 17 age-matched healthy subjects. The regression plot between scores of the Hamilton Rating Scale for Depression and ratios of the free form content to total content (F/T ratio) of UT was more informative on the depressive state than that of alpha(1)M. The F/T ratios of UT may afford a useful objective index in monitoring the diseased state of a patient with mood disorder.

Biomarkers↗

Sex- and age-related changes in urinary contents of alpha 1-microglobulin and ulinastatin in mice.

1. Using two murine strains, ICR/Jcl and senescence-accelerated-prone inbred mouse 1 (SAMP1), age-associated changes in urine indices (e.g. urine volume, creatinine contents, contents of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) and the relation of urinary contents of alpha 1M and UT were investigated. 2. Sex-related differences in the indices were not observed in ICR nor in SAMP1 mice. 3. Urine indices per 24 h of ICR mice at 6 and 14 months of age were higher than those at 3 months of age, although indices of SAMP1 mice did not change with ageing. Urinary contents of alpha 1M and UT in ICR mice at 6 and 14 months of age were higher than those in SAMP1 mice. However, contents of alpha 1M and UT expressed as the contents per creatinine did not differ between these two strains. 4. In the relation between urinary contents of alpha 1M and UT, a positive correlation was displayed both in ICR and SAMP1 mice, and the regression slope did not significantly differ with ageing in these two strains. 5. These results suggest that ageing per se is not a factor which affects the relation of urinary contents of alpha 1M and UT.

Aging↗

Elevation of striatal interleukin-6 and serum corticosterone contents in MPTP-treated mice.

1. Changes in the content of striatal interleukins (IL-1 beta and IL-6) and serum corticosterone in relation to deterioration of the dopaminergic system induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; a dopaminergic neurotoxin; 20 mg/kg i.p., four administrations/12 h) in C57BL/6J mice were investigated. 2. Striatal dopamine, IL-1 beta, IL-6 and serum corticosterone were measured on days 1 and 7 post-MPTP. 3. Dopamine depletion was more severe on day 7 than on day 1 post-treatment. 4. Increases in IL-6 were observed on days 1 and 7 post-MPTP. The increase in striatal IL-6 content varied with the extent of dopamine depletion, although the IL-1 beta concentration remained unchanged compared with control values on days 1 and 7 post-treatment. 5. Serum corticosterone was not different from control on day 1 post-MPTP. However, marked increases in the serum corticosterone were observed on day 7 post-treatment. 6. These results suggest that changes in striatal IL-6 and serum corticosterone are closely associated with the severity of MPTP-induced dopaminergic degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Impairment of the correlation between urinary contents of alpha-1-microglobulin and ulinastatin is induced by intracerebroventricularly administered interleukin-6 in mice.

We have found previously that the correlation between urinary contents of alpha-1-microglobulin (alpha1M) and ulinastatin (UT) depends on the type of neuropsychiatric disease. Since interleukin (IL)-1beta and IL-6 are closely involved in pathophysiological aspects of various neuropsychiatric diseases, effects of intracerebroventricularly (i.c.v.) administered IL-1beta and IL-6 on the correlation between urinary contents of these two glycoproteins were examined in mice, a species in which alpha1M and UT and also the correlation between the urinary contents thereof are expressed similarly to humans. Indices (volume, contents of creatinine, alpha1M and UT, and alpha1M/UT ratio) in urine collected after i.c.v. administrations of 2 and 20 ng of either IL-1beta or IL-6 were not statistically different from those of the vehicle-treated (control) groups. Neither IL-1beta (2 and 20 ng) nor the lower dose of IL-6 (2 ng) affected the positive correlation between urinary contents of alpha1M and UT. However, a higher dose of IL-6 (20 ng) nullified the positive correlation for 2 days after administration. Recovery to a positive correlation was thereafter displayed. These findings suggest that central IL-6 plays an important role in correlating urinary contents of alpha1M and UT without affecting the renal functions.

Alpha-Globulins↗

Nullification of a positive correlation between urinary contents of alpha1-microglobulin and ulinastatin with intracerebroventricularly administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) in mice.

Striatal dopamine contents in C57BL/6J mice were reduced at 24 h after intracerebroventricular (ICV) administration of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) in a dose-dependent manner. A dose of 1.8 microg MPP+ significantly (P < 0.05) suppressed the dopamine contents, whereas a similar dose of MPTP did not. A definite positive correlation between urinary contents of alpha1-microglobulin (alpha1M) and ulinastatin (UT) existed in normal mice. However, this correlation was nullified by ICV administration of 18 and 36 microg MPTP or 1.8 and 18 microg MPP+. With 1.8 microg MPTP, a positive correlation between urinary contents of alpha1M and UT was displayed. The urine volume, creatinine content, glomerular filtration rate, alpha1M and UT contents, and alpha1M/UT ratio of urine collected for 24 h post-ICV administration of MPTP or MPP+, were not statistically different from those of control mice. Our findings suggest that the central effects of MPP+, a neurotoxic metabolite of MPTP, nullify the positive correlation between urinary contents of alpha1M and UT without affecting renal functions.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Ischemia induces a reduction in the content of ulinastatin-like substance in the murine hippocampus.

Effects of ischemia on the content of a ulinastatin (UT)-like substance in the murine cerebral cortex and hippocampus were studied. At 24 h post-ischemia, a significant (p < 0.05) decrease in the content of UT-like substance in the hippocampus but not the cerebral cortex and a concurrent increase in the activity of micro-calpain were observed. In in vitro experiments, a decrease was registered in the content of UT-like substance in the hippocampus in the presence of calcium. This decrease was inhibited by both EDTA and calpastatin treatments. These results implicate the destruction of UT-like substance by micro-calpain in the ischemic hippocampus.

Animals↗

Ethanol reduces spontaneous firing and potentiates GABA-induced currents in acutely dissociated rat medial vestibular nucleus neurons.

Effects of ethanol on acutely dissociated medial vestibular nucleus (MVN) neurons were examined using whole-cell patch clamp technique to elucidate the mechanism underling the inhibitory effects of this drug on the neurons observed in in vivo studies. Dissociated MVN neurons obtained from male Wistar rats were superfused with extracellular solution continuously at a flow rate of 1-3 ml/min. Whole-cell patch clamp recording was performed according to standard procedures. GABA was applied by pressure from a pipette placed near the neuron recorded. Ethanol was applied via pipette by pressure or through bath perfusion. Acutely dissociated MVN neurons regularly showed spontaneous firing. Under current-clamp conditions, bath application of ethanol at 0.1% caused hyperpolarization and reduced spontaneous firing in MVN neurons, while 0.1% ethanol did not affect spontaneous firing. Pulse application of higher concentrations of ethanol (0.1-1%) caused similar hyperpolarization. Under voltage-clamp conditions at a holding potential of -30 mV, GABA induced outward currents in a concentration-dependent manner. GABA-induced currents were potentiated in the presence of 0.01% ethanol. These results indicate that high concentrations of ethanol (0.1-1%) directly induce inhibition of spontaneous firing and low concentrations (0.01%) enhance GABA-induced inhibition in the MVN neurons.

Action Potentials↗

Nullification of a positive correlation between urinary levels of alpha 1-microglobulin and ulinastatin by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice.

The relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) were investigated in C57BL/6J mice, a species which reportedly possesses the gene similar to that of humans for synthesizing the precursor protein of alpha 1M and UT. A positive correlation was established in normal mice. However, repetitive administrations (20 mg/kg, IP, four administrations/12 h) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nullified the positive correlation. A similar phenomenon was induced by ICV-administered MPTP (18 and 36 micrograms) in the animals. Furthermore, L-dopa administration (50 mg/kg, IV) in MPTP-treated (1 week after the final IP administration of MPTP) mice reversed the tendency of MPTP, although the agent alone did not affect the positive correlation in normal mice. These results suggest that nullification of the positive correlation probably was induced by the central effects of MPTP. We have found previously that the lack of a positive correlation between urinary levels of alpha 1M and UT distinguishes Parkinson's disease from other neuropsychiatric diseases such as dementia (Alzheimer-type and vascular dementia), schizophrenia and mood disorders. Our present results displayed a phenomenon that the lack of correlation between urinary levels of alpha 1M and UT in patients with Parkinson's disease is reproducible in MPTP-treated mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Significant decreases of ulinastatin-like immunoreactive substance in the cerebrospinal fluid of patients with dementia.

Studies to elucidate changes in the contents of ulinastatin-like immunoreactive substance (UTIRS) and alpha 1-microglobulin-like immunoreactive substance (alpha 1 MIRS) in cerebrospinal fluid (CSF) of patients with dementia were performed. Levels of UTIRS in the dementia group were significantly (p < 0.01) lower than those in dementia-free subjects. In addition, lower levels of UTIRS were registered in subjects afflicted with a higher severity of dementia. However, the levels of alpha 1 MIRS were not affected in the dementia group compared with dementia-free subjects. Neither UTIRS nor alpha 1 MIRS contents were related to the existence and stages of Parkinson's disease. These results suggest that UTIRS levels in the CSF are associated with the severity of dementia.

Aged↗

Non-existence of a positive correlation between urinary levels of alpha 1-microglobulin and ulinastatin in patients with Parkinson's disease.

Urinary levels of alpha 1-microglobulin (alpha 1M) and of ulinastatin (UT) and the alpha 1M/UT ratio did not differ significantly between age-matched controls and patients with Parkinson's disease, and among subdivided groups based on Yahr's stages in Parkinson's disease. Furthermore, these indexes did not correlate with Yahr's stages. Although alpha 1M and UT levels did not correlate in patients with Parkinson's disease, a positive correlation was observed in the control group. The non-existence of a positive correlation between alpha 1M and UT levels distinguishes Parkinson's disease from other neuropsychiatric diseases such as dementia (Alzheimer-type and vascular dementia), schizophrenia and mood disorder.

Aged↗

Prospective, randomized, placebo-controlled, double-blind, multicenter study of exercise with enoxaparin pretreatment for stable-effort angina.

In this double-blind, placebo-controlled, multicenter trial, we examined the combined effects of repeated exercise and intravenous enoxaparin (low-molecular-weight heparin) on treadmill exercise capacity and angiographic collateral growth and compared them with the effect of repeated exercise with placebo. Fifty-two patients with stable-effort angina were randomly assigned to receive one of two doses of enoxaparin (40 or 60 mg) or placebo. In each patient, 20 treadmill exercise sessions were performed with the pretreatment of enoxaparin or placebo for 2 to 3 weeks. Before and after treatment, coronary cineangiography was repeated to evaluate the changes in coronary and collateral circulation. Improvement of rate-pressure product (RPP) at the onset of angina was taken as an index of enhanced collateral flow reserve. Although the mean differences in the magnitude of increase in RPP were not significantly different between the 3 groups, a heterogeneous response was observed: 1620 beats/min.mm Hg in 40 mg (p = 0.12), 3060 beats/min.mm Hg in 60 mg (p = 0.02), and 1090 beats/min.mm Hg in placebo (p = 0.44). The end-points of the exercise test were changed from chest discomfort to leg fatigue or dyspnea in 10 (28%) of 36 enoxaparin-treated patients but in only 1 (6%) of 16 placebo patients (p = value not significant (NS)). Similarly, the extent of coronary and collateral circulation to the completely obstructed coronary artery was increased in 17 (47%) of 36 enoxaparin-treated patients but only in 4 (25%) of 16 placebo patients (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changes in the ratio of urinary alpha 1-microglobulin to ulinastatin levels in patients with Alzheimer-type dementia and vascular dementia.

Relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) in patients with dementia were investigated. There were no significant differences in alpha 1M and UT levels and alpha 1M: UT ratios among three groups: age-matched control subjects, patients with either Alzheimer-type senile dementia (ATD) or vascular dementia (VD). Although a positive correlation was established between alpha 1M and UT levels in these groups, the regression of the demented patients differed significantly from that of controls (P < 0.05). A tendency towards a negative correlation between alpha 1M: UT ratios and the levels of severity or duration of the disease was displayed in the ATD group, whereas a tendency toward a positive correlation between alpha 1M: UT ratios and the levels of severity was observed in the VD group. These results suggest that changes in the relationships between urinary levels of alpha 1M and UT may provide a useful biochemical index for diagnoses of ATD and VD.

Aged↗

Demonstration of a human urinary trypsin inhibitor (urinastatin)-like substance in the murine brain.

A human urinary trypsin inhibitor (urinastatin)-like immunoreactive substance with trypsin-inhibitory activities was found in the murine brain. Regional levels of this urinastatin (UT)-like substance in the brain were within 5 ng/mg protein and were expressed in a descending order as follows: cerebral cortex not equal to hippocampus > hypothalamus > mesencephalon not equal to corpus striatum >> medulla oblongata > cerebellum. Mechanical lesioning of the cerebral cortex or hippocampus with a needle induced a rapid and intense appearance of a UT-like immunoreactive substance in the neuronal cells of injured sites. Conditioned fear-stress induction incited a reversible increase in the level of UT-like immunoreactive substance in the hippocampus. These results suggest that the UT-like immunoreactive substance is produced by neurons in response to brain injury and fear-stress stimuli.

Brain↗