Effects of physical and morphometric factors on nutrient removal properties in agricultural ponds.

Effects of physical and morphometric factors on nutrient removal properties were studied in small agricultural ponds with different depths, volumes, and residence times in western Japan. Average residence time was estimated to be >15 days, and it tended to decrease from summer to winter because of the increase in water withdrawal for agricultural activity. Water temperature was clearly different between the surface and bottom layers; this indicates that thermal stratification occurred in summer. Chlorophyll-a was significantly high (>20 µg/L) in the surface layer (<0.5 m) and influenced by the thermal stratification. Removal ratios of dissolved total nitrogen (DTN) and dissolved total phosphorus in the ponds were estimated to be 53-98% and 39-98% in August and 10-92% and 36-57% in December, respectively. Residence time of the ponds was longer in August than in December, and DTN removal, in particular, was more significant in ponds with longer residence time. Our results suggest residence time is an important factor for nitrogen removal in small agricultural ponds as well as large lakes.

Effects of the extract of the bark of Magnolia obovata and its biphenolic constituents magnolol and honokiol on histamine release from peritoneal mast cells in rats.

We have previously reported that saiboku-to, an Oriental herbal remedy composed of a mixture of 10 different herbal extracts, possesses anti-histamine release effect on mast cells in rats. This effect may be due mainly to the extract of the bark of Magnolia obovata (M. obovata), a constituent herb of saiboku-to. In the present study, it was demonstrated that the bark extract inhibited compound 48/80 (C48/80)-induced histamine release from mast cells in a concentration-dependent manner (50 % inhibitory concentration, IC(50) = 56.98 microg/ml). Furthermore, the inhibitory activity was found in the methanol fraction, but not in water and 50 % aqueous methanol fractions derived from the bark extract. Magnolol and honokiol isolated from the methanol fraction inhibited C48/80-induced histamine release from mast cells. The potency of magnolol (IC(50) = 1.04 microg/ml) was greater than that of honokiol (IC(50) = 2.77 microg/ml). Furthermore, the actual amount of magnolol (49.76 +/- 1.14 mg) contained in the bark of M. obovata (5 g) was greater than that (8.58 +/- 0.19 mg) of honokiol. Taken together, the present results suggest that magnolol may be responsible for the biological efficacy of the bark extract of M. obovata.

Effect of weekly or successive iron supplementation on erythropoietin doses in patients receiving hemodialysis.

AIMS: To conduct a 3-month prospective study to determine the optimal way for intravenous iron supplementation in hemodialysis (HD) patients with resistance to recombinant human erythropoietin (rHuEPO) therapy due to deficient iron storage. METHODS: Thirty-five HD patients with iron deficiency were divided into three groups: (1) patients receiving an intravenous infusion of 40 mg of iron during the first ten HD sessions (n = 12); (2) patients receiving 40 mg of iron injected once a week for 10 weeks (n = 12), and (3) patients without any iron supplementation (n = 11). The rHuEPO dosage was adjusted to maintain hemoglobin levels >10.0 g/dl, and the degree of anemia was assessed 3 months later. RESULTS: In group 1, the hemoglobin levels were significantly increased after 4 weeks and remained increased until the end of the study (p < 0.01). In group 2, the hemoglobin levels were gradually increased until the end of the study (p < 0.01). There was no difference in the final hemoglobin values between both groups. The rHuEPO dosage was significantly decreased from 131 +/- 18 to 90 +/- 17 U/kg/week in group 1 (p < 0.01), but could not be changed in group 2 during the observation period despite a similar elevation of the serum ferritin level. In group 3, the rHuEPO doses were rather increased at the end of the study (p < 0.05). CONCLUSION: Aggressive iron supplementation for the short term may be effective to restore rHuEPO hyporesponsiveness in HD patients with functional iron deficiency.

Inhibition of gastric acid secretion by saiboku-to, an oriental herbal medicine, in rats.

Intraduodenal saiboku-to (250-1000 mg/kg) dose-dependently reduced gastric acid secretion and histamine output, without altering acetylcholine output in pylorus-ligated rats. Saiboku-to also inhibited subcutaneous bethanechol (1 mg/kg) and tetragastrin (0.3 mg/kg) -induced increases in gastric acid secretion in vagotomized pylorus-ligated rats; however, it did not inhibit subcutaneous histamine (20 mg/kg) -induced increase in acid secretion. These results, taken together, suggest a possibility that saiboku-to may inhibit histamine release. Thus, the effect of saiboku-to on histamine release was directly investigated by using anti-dinitrophenyl IgE-sensitized rat peritoneal mast cells. Antigen (dinitrophenyl)-induced histamine release from the mast cells was clearly dose-dependently inhibited by saiboku-to at concentrations of 0.1-1.0 mg/ml. These results suggest that the inhibited gastric acid secretion with saiboku-to is due to inhibited histamine release.

Effects of an oriental herbal medicine, "Saiboku-to", and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats.

Effects of a traditional oriental herbal medicine, "Saiboku-to" and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats were investigated. Saiboku-to inhibited Compound 48/80-induced degranulation of and histamine release from the mast cells, suggesting that Saiboku-to not only possesses anti-histamine release effect from mast cells, but also contains active herbs with this effect. Significant inhibitions were found in 4 of 10 constituent herbs of Saiboku-to: Magnoliae Cortex, Perillae Herba, Bupleuri Radix and Hoelen. In the dose-response curves of the four herbs, the logarithmic linearity was observed for each herb, and 50% inhibitory concentration, the IC50 values, were calculated to be 56.8 microg/ml for Magnoliae Cortex, 175.8 microl/ml for Perillae Herba, 356.6 microg/ml for Bupleuri Radix, and 595.8 microg/ml for Hoelen. One mg/ml of Saiboku-to showing 75% inhibition of Compound 48/80-induced histamine release level from mast cells contains 88.5 microg of Magnoliae Cortex (it was estimated from the dose-response curve that this dose inhibits 62.68% of the Compound 48/80-induced histamine release level), 58.8 microg of Perillae Herba (21% inhibition), 205.9 microg of Bupleuri Radix (35.24% inhibition), and 147.1 microg of Hoelen (11.15% inhibition). From these results, it is suggested that the anti-histamine release effect of Saiboku-to, which contains 10 herbs, may be due mainly to the effect of Magnoliae Cortex and the synergism of the 3 other herbs.

Hypothalamic cholinergic regulation of body temperature and water intake in rats.

Without disturbing the behavior of unanesthetized rats, the perfusion of neostigmine through microdialysis probe into the anterior hypothalamus (AH), paraventricular nucleus (PVN) and lateral ventricle (LV) decreased body temperature and increased water intake. On the other hand, the perfusion into the supraoptic nucleus (SON) increased the body temperature. The perfusion of neostigmine increased the extracellular concentration of acetylcholine in the perfusion sites except LV. Changes, both decrease and increase, in body temperature and increase in water intake were correlated with increases in c-fos-like immunoreactivity (Fos-IR) in the hypothalamus, pons and medulla. Distinct Fos-IR was found in the PVN, SON, median preoptic nucleus (MnPO), locus coeruleus (LC), area postrema and nucleus of the solitary tract (NTS). Co-administration of atropine with neostigmine completely suppressed the changes in the body temperature, water intake and Fos-IR, all of which were induced by the neostigmine perfusion into AH, PVN and SON. In the LV-perfused rats, on the other hand, co-administration of atropine and neostigmine only partially prevented body temperature reduction and still induced significant hypothermia. These results suggest that muscarinic receptor activation in specific regions of the hypothalamus and the activation of LC and NTS are implicated in the regulation of body temperature and water intake. Other receptor processes are involved in the LV-induced changes.

Effects of subacutely administered saiboku-to, an oriental herbal medicine, on pharmacodynamics and pharmacokinetics of diazepam in rodents.

Subacute treatment with saiboku-to (2000 mg/kg, p.o., once a day) for 7 days induced an anxiolytic-like effect in rats. It did not, however, produce any other effects, such as sedative and hypnotic effects, anticonvulsive and muscle relaxant effects except for anxiolytic effect observed in diazepam-injected rats or mice. Diazepam (1.0 mg/kg, s.c.) induced anxiolytic-like effect was enhanced in saiboku-to treated rats as an additional effect of that induced by saiboku-to. To elucidate whether the enhancement of the anxiolytic-like effect following combined administration of diazepam and saiboku-to is due to the inhibition of hepatic drug-metabolizing enzymes, the pharmacokinetics of diazepam were further investigated in saiboku-to treated rats. The pharmacokinetic studies clearly demonstrated that subacute treatment with saiboku-to did not affect plasma concentration and protein binding rate of diazepam, and the activities of hepatic drug-metabolizing enzymes related to diazepam metabolism. These results, taken together, suggest that the enhancement of diazepam-induced anxiolytic-like effect observed in saiboku-to-treated rats is not due to an inhibition of diazepam metabolism.

Anxiolytic-like effect of saiboku-to, an oriental herbal medicine, on histaminergics-induced anxiety in mice.

Effect of saiboku-to, an oriental herbal medicine, on anxiety in mice was investigated using a light/dark test. Anxiogenic- and anxiolytic-like effects were evaluated on the basis of shortened and prolonged time spent in the light zone of the test. Subacute administration (once a day for 7 days) of saiboku-to (0.5-2.0 g/kg, p.o.) induced anxiolytic-like effect. To assess the effect of saiboku-to on brain histaminergic system in a state of anxiety, Compound 48/80 (1.0 microg/2 microl, i.c.v.), a non-neuronal mast cell histamine releaser, or thioperamide (10.0 mg/kg, i.p.), a neuronal histamine releaser possessing the inhibitory effect of histamine H(3) autoreceptors, induced decrease in the time spent in the light zone by co-injection with cimetidine (10.0 microg/2 microl, i.c.v.), a H(2) inhibitor, suggesting anxiety-like effect. These histaminergics-induced experimental anxieties were inhibited by pre-treatment with subacute administration of saiboku-to, as well as single treatment with diazepam. The results suggest that saiboku-to exhibits anxiolytic-like effect closely related to histaminergic system in the brain.

Comparative assessment of the anxiolytic-like activities of honokiol and derivatives.

Honokiol has previously been shown to be an effective anxiolytic-like agent in mice when administered for 7 days at 0.2 mg/kg/day prior to evaluation in an elevated plus-maze, while 20 mg/kg is required for efficacy as a single oral dose. The aim of this study was to find analogs of honokiol that are more effective for acute administration. Among the eight analogs evaluated, one partially reduced derivative of honokiol [3'-(2-propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diol] exhibited significant anxiolytic-like activity at 0.04 mg/kg. Following oral administration of 1 mg/kg of this analog, anxiolytic-like activity was clearly evident at 1 h, peaked at 3 h, and remained significant for longer than 4 h after treatment. Combined administration of the derivative with diazepam led to enhanced anxiolytic-like efficacy. Moreover, as with diazepam, the anxiolytic-like effect of the analog was reduced by flumazenil. In contrast, bicuculline, a GABA(A) antagonist, had no effect on the activity of the derivative. Taken together, these results suggest that this analog of honokiol acts at the benzodiazepine recognition site of the GABA(A)-benzodiazepine receptor complex.

The anxiolytic effect of two oriental herbal drugs in Japan attributed to honokiol from magnolia bark.

An improved elevated plus-maze test in mice revealed that seven daily treatments with two different traditional Chinese medicines, known as Kampo medicines in Japan, Hange-koboku-to (composed of extracts of 5 plants) and Saiboku-to (composed of extracts of 10 plants), produced an anxiolytic effect, and the effect was mainly due to the presence of honokiol derived from magnolia. This study was carried out to evaluate the anxiolytic potential of honokiol, Hange-koboku-to and Saiboku-to, which were prescribed with two different magnolia samples: Kara-koboku (Magnoliae officinalis) (KA) or Wa-koboku (Magnoliae obovata) (WA). The doses of test samples were adjusted to ensure a constant dose of honokiol at 0.2 mg kg(-1). Although the doses of magnolol (an isomer of honokiol), as well as those of undetermined chemicals, varied among samples, the seven daily treatments with 9 out of 10 test samples produced an anxiolytic effect almost equivalent to that produced by 0.2 mg kg(-1) honokiol. The only exception was the sample containing the lowest amount of honokiol. Magnolia-free preparations of Hange-koboku-to or Saiboku-to did not have any anxiolytic effect. These results confirm that honokiol derived from magnolia is the causal chemical of the anxiolytic effect of Hange-koboku-to and Saiboku-to.

Application of the elevated plus-maze test in mice for evaluation of the content of honokiol in water extracts of magnolia.

In our previous study using an improved elevated plus-maze in mice, the oriental herbal medicine Saiboku-to prolonged the time spent in open arms, showing an anxiolytic effect, and the effect was mainly caused by honokiol derived from magnolia. This study was carried out to compare the anxiolytic potentials of honokiol and water extracts of three magnolia samples; two being Kara-koboku (Magnolia officinalis) (KA: from Zhejiang-sheng, China; honokiol 0.25% and magnolol 1.16%, and KB: from Sichuan-sheng, China; honokiol 1.72% and magnolol 1.71%), and one being Wa-koboku (Magnolia obovata) (WA: from Iwate-ken, Japan; honokiol 0.32% and magnolol 0.81%). Seven daily treatments with 0.1-1 mg/kg honokiol, but not 0.2 and 1 mg/kg magnolol, revealed an anxiolytic effect with the peak potential at 0. 2 mg/kg. The anxiolytic potentials of 40 and 80 mg/kg KA, which contained the highest amount of magnolol, were almost equivalent to those of 0.1 and 0.2 mg/kg honokiol, respectively. KB, at 11.6 mg/kg, and 62.5 mg/kg WA resulted in almost the same anxiolytic potential as that of 0.2 mg/kg honokiol. No significant change in the ambulatory activity was produced by any drug treatment. These results suggest that honokiol is the chemical responsible for the anxiolytic effect of the water extract of magnolia and that the other chemicals including magnolol in magnolia scarcely influence the effect of honokiol. It is also considered that the elevated plus-maze test is applicable for evaluation of the content of honokiol in magnolia.

Effect of Saiboku-to, an Oriental Herbal Medicine, on gastric lesion induced by restraint water-immersion stress or by ethanol treatment.

The effect of saiboku-to on gastric lesions induced by restraint water-immersion stress and ethanol has been examined in rats. Thirty minutes after oral administration of saiboku-to, the rats were placed in restraint cages and immersed in water at 23 degrees C for 7 h, or orally administered 99.5% ethanol (1 mL) and placed in normal cages for 1 h. The stress for 7 h or the ethanol treatment for 1h induced erosion in the glandular area of the stomach. Histology showed that the surface epithelial cells were desquamated and part of the lamina propria mucosae was injured. The evaluation of lesion index, the cumulative length of the gastric lesion, on the gross appearance of the stomach, revealed that saiboku-to dose-dependently inhibited both the water-immersion stress-induced gastric erosion and ethanol-induced gastric erosion. To determine whether the anti-erosion effect of saiboku-to was because of a mild irritant effect, saiboku-to or 20% ethanol, which is known as a typical mild irritant, were given orally. After 30 min a strong irritant, 99.5% ethanol, was given orally. Histological examination was performed 30 min after administration of saiboku-to or the mild irritant, and 1 h after administration of the strong irritant. The mild irritant induced a reduction in surface epithelial cells 30 min after administration. Furthermore, the mild irritant protected the stomach against mucosal erosion produced by the strong irritant. Saiboku-to protected the strong irritant-induced erosion without producing mild irritation as observed in stomach treated with 20% ethanol. Pretreatment with saiboku-to also inhibited the decrease in the levels of hexosamine, gastric mucus glycoprotein, induced by the strong irritant. In pylorus-ligated rats, saiboku-to dose-dependently inhibited gastric acid secretion, a gastric aggressive factor. These results suggest that the anti-erosion effect of saiboku-to which is not a mild irritant, involves both inhibition of aggressive factors, such as gastric acid secretion, and augmentation of defensive factors, such as gastric mucus cells.

The correlation between erythropoiesis and thrombopoiesis as an index for pre-operative autologous blood donation.

We have previously reported that the platelet count and an increase in platelet number reflect individual erythropoietic capacity in pre-operative autologous blood donation (PABD). We have examined the correlation between erythropoiesis and thrombopoiesis by quantitative in vitro determination of thrombopoietin (TPO), erythropoietin (EPO), and interleukin-6 (IL-6) in patients with PABD. A sequential increase in platelet count with donation could not be explained by an increase in TPO. TPO showed a tendency to be inversely related to the pre-donation platelet count, and to be related to the pre-donation hemoglobin level. There was an inverse relationship between the TPO and EPO levels. As seen with these results, a high erythropoietic state induces restraint of thrombopoiesis, and a low erythropoietic state induces an increase in thrombopoiesis. These effects modulate EPO and TPO via negative feedback. These results provide some practical important information for performing autologous blood donation. Further studies are needed to elucidate the details of these correlations.

The platelet level indicates the erythropoietic capacity for preoperative autologous blood donation.

UNLABELLED: The erythropoietic capacity for preoperative autologous blood donation (ECPABD) shows marked inter individual variability. This study was performed to evaluate factors useful to predict individual ECPABD from data available before the first donation. The subjects consisted of 74 adult patients who received autologous blood donation, with a mean of 61 +/- 12.8 yr (SD). We classified the patients into four groups using our criteria for evaluating the ECPABD and investigated the relationships among age, disease, pre-platelet count, and the rate of platelet increase. RESULTS: (1) Advanced age and the status of disease were not distinctly correlated with low ECPABD. (2) Patients with a high pre-platelet levels had a low ECPABD regardless of the haemoglobin. (3) Patients in which the platelet count increased in accordance with the level of collection exhibited low pre-platelet counts and high ECPABD. CONCLUSION: In patients with high pre-platelet levels, we reduced the amount collected, considered early use of recombinant human erythropoietin and reevaluated the application of autologous blood donation.

Stimulation of rat hypothalamus by microdialysis with K+: increase of ACh release elevates plasma glucose.

The effects of stimulation of the ventromedial hypothalamus (VMH) or lateral hypothalamus (LH) with potassium chloride through a microdialysis probe were studied. The concentrations of ACh and norepinephrine (NE) in the dialysate obtained from the hypothalamic nuclei and plasma glucose concentration were measured. Stimulation of the hypothalamic nuclei, VMH and LH, with potassium increased the plasma glucose level as well as the extracellular concentrations of ACh and choline. Addition of atropine, a muscarinic ACh receptor antagonist, into the potassium solution reduced the increase in the level of plasma glucose. Cholinergic stimulation of these nuclei with neostigmine increased the extracellular concentrations of ACh and plasma glucose. Stimulation of the nuclei with potassium also increased the release of NE. However, stimulation of the VMH or LH with NE and/or pargyline, a monoamine oxidase inhibitor, through the dialysis probe membrane did not significantly increase the plasma glucose concentration. These results suggest that activation of the muscarinic cholinergic or ACh-receptive neurons in the hypothalamic nuclei, VMH and LH, contribute to the elevation of plasma glucose level.

Identification of magnolol and honokiol as anxiolytic agents in extracts of saiboku-to, an oriental herbal medicine.

The principal active anxiolytic components in Saiboku-to, an Oriental herbal medicine, have been isolated and identified as magnolol (5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol) and honokiol (3',5-di-2-propenyl-1,1'-biphenyl-2,4'-diol). Evaluation by means of an elevated plus-maze test showed that honokiol was at least 5000 times more potent than Saiboku-to when mice were treated orally for 7 days.

Comprehensive analysis of neurotransmitters and their metabolites including acetylcholine and choline in rat brain nuclei.

We have designed this method for the comprehensive and adequate analysis of neurotransmitters and metabolites including acetylcholine (ACh) and choline in specific brain nuclei. In physiological and pharmacological studies, the role of specific neurotransmitters in the central nervous system (CNS) has often been studied by microinjection of their agonist and antagonist into the target regions, with the action and role of the transmitter in question being deduced in a relatively straightforward manner from the results. However, none of these studies have investigated fluctuation in neurotransmitter and metabolite contents in response to a variety of stimuli in vivo. No comprehensive analysis of neurotransmitters in small specific area in the CNS has been undertaken due to the difficulties of proper analysis of ACh and choline. Different types of neuronal systems in the CNS affect each other. Thus, it is not necessarily clear that different types of neurons do in fact respond to an administered agonist and antagonist. For example, dopaminergic neuron mediated control of cholinergic interneuron in the striatum and dopaminergic regulation of cortical ACh release have been documented. Similarly, the cholinergic system affects dopaminergic and noradrenergic neurons. Intraventricular administration of an ACh esterase inhibitor, neostigmine, increases dopamine and noradrenaline release in the hypothalamus. So, an adequate comprehensive analysis of the transmitters and the metabolites in the same tissue sample provides valuable aid to clarify what types of neurons truly respond to the administered drugs and the excitation of physiological events. For an appropriate analysis we employed a microwave device, which made the estimation of ACh and choline possible. In addition to this, we employed a punch technique for the microdissection of the specific nuclei and area from the brain slice.

Hypothalamic cholinergic activity and 2-deoxyglucose-induced hyperglycemia.

To clarify the role of the hypothalamic cholinergic system in the regulation of peripheral glucose metabolism, we investigated hypothalamic cholinergic activities after administration of 2-deoxyglucose (2-DG). Intravenous administration of 2-DG (500 mg/kg) caused neuroglycopenia and marked hyperglycemia; the level of plasma glucose increased to 210% of the initial levels of 20 min. For evaluation of the cholinergic activity, we employed a microwave device and subsequently analyzed the contents of acetylcholine (ACh) and choline after microdissection of the hypothalamic nuclei, ventromedial hypothalamic nucleus (VMH), lateral hypothalamus (LH), and paraventricular nucleus (PVN). In addition, we analyzed fluctuation of extracellular levels of ACh using in vivo brain microdialysis. A decrease in the ACh content, and a corresponding increase in the choline content, was observed in those hypothalamic nuclei min after administration of 2-DG. In the microdialysis perfusate, on the other hand, extracellular level of ACh was increased by 2-DG administration. These data show that ACh release, which is cholinergic activity, was increased after 2-DG administration. Our results suggest the involvement and importance of the hypothalamic cholinergic system in 2-DG-induced hyperglycemia.

Effects of MK-801 and pentobarbital on cholinergic terminal damage and delayed neuronal death in the ischemic gerbil hippocampus.

The present study covers both the effects of MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, and pentobarbital on cholinergic terminal damage and delayed neuronal death (DND) in ischemic gerbil. To study the above effects, in vivo microdialysis, immunohistochemical, and morphological techniques were used. MK-801 (3 mg/kg) or pentobarbital (50 mg/kg) were injected intraperitoneally 1 h or 30 min before 5 min ischemia, respectively. Each estimation was then carried out 4, 7, or 14 days after ischemia. Ischemia induced a significant decrease in acetylcholine (ACh) release and a disappearance of choline acetyltransferase (ChAT)-immunoreactivity in the hippocampus in addition to inducing DND. On day 4, MK-801 protected ischemia-induced DND in the hippocampal CA1 subfield. However, MK-801 had no effect against the decrease in ACh release in spite of protection of the decrease in ChAT-immunoreactivity. On day 7 and 14, no protective effect of MK-801 was observed in all estimations. It became clear that the mechanism of cholinergic terminal dysfunction is different from that involved in pyramidal cell death, i.e., excitative neurotoxicity induced by overabundant extracellular glutamate. Pentobarbital also provided protection against DND. However, protective effects of pentobarbital on the decrease in ACh release and the low ChAT-immunoreactivity were incomplete. Our present study indicated a limitation on the efficacy of NMDA receptor antagonist and barbiturate against cerebral ischemia.

Choto-san in the treatment of vascular dementia: a double-blind, placebo-controlled study.

In an earlier placebo-controlled study, we demonstrated that a kampo (Japanese herbal) medicine called Choto-san (Diao-Teng-San in Chinese) was effective in treating vascular dementia. To evaluate its efficacy using more objective criteria, we carried out a multi-center, double-blind study of Choto-san extract (7.5 g/day) and a placebo, each given three times a day for 12 weeks to patients suffering from this condition. The study enrolled and analyzed 139 patients, 50 males and 89 females, with a mean age of 76.6 years. Choto-san was statistically superior to the placebo in global improvement rating, utility rating, global improvement rating of subjective symptoms, global improvement rating of psychiatric symptoms and global improvement rating of disturbance in daily living activities. Such items as spontaneity of conversation, lack of facial expression, decline in simple mathematical ability, global intellectual ability, nocturnal delirium, sleep disturbance, hallucination or delusion, and putting on and taking off clothes were significantly improved at one or more evaluation points in those taking Choto-san compared to those taking the placebo. Furthermore, the change in revised version of Hasegawa's dementia scale from the beginning point in Choto-san group was tended to be higher than that in placebo group with no statistical significance. These results suggest that Choto-san is effective in the treatment of vascular dementia.