OBJECTIVE: Although "qi, blood, and fluid" (QBF) is the most important concept for patients in Kampo medicine, there are few studies about the conditions of the QBF system among healthy populations. We used QBF pattern scores to determine whether or not medical students, presumed to be healthy, had any potentially pathological conditions. METHODS: Six consecutive fourth-year classes totaling 652 medical students evaluated their own QBF conditions using Terasawa's QBF pattern scores. The six conditions: "qi deficiency" (QD), "qi stagnation" (QS), "qi counterflow" (QC), "blood deficiency" (BD), "blood stasis" (BS), and "fluid disturbance" (FD), were categorized according to Terasawa's criteria. The Mann-Whitney U test was used to compare the score differences between the genders, Chi-square test was used to examine gender differences in the QBF diagnoses, and the Spearman's rank-order correlation coefficient analysis was used to analyze the correlation between each category of QBF. RESULTS: In all, 44.6% of the students met at least one diagnostic criterion in the QBF system. QC, BD, BS, and FD were established more in females, and QD and QS were established without gender differences. CONCLUSIONS: Most students who were presumed to be healthy were revealed to have some potentially pathological conditions using the QBF system.

OBJECTIVE: Japanese medical schools currently only offer students traditional Japanese Kampo medicine education for an extremely limited amount of time. The purpose of this study was to discover how to generate interest in and motivate learning Kampo medicine. METHODS: Kampo medical sessions, including a lecture series, written examinations, and small-group (12-14 students) EBL (experience-based learning) sessions, were provided for 4th-year medical students (N=117) at Tokai University School of Medicine. Students were taught about "qi, blood, and fluid" and the "deficiency-excess pattern," the two most important core concepts of Kampo medicine and connecting them to clinical application. We evaluated the teaching methods based on questionnaires and written examinations before and after the training course. The Wilcoxon signed-rank test was used to compare changes in awareness before and after the lectures and the Mann-Whitney U test to examine the relationship between the students' interest in Kampo medicine and their examination scores. RESULTS: This training method improved students' general understanding of Kampo medicine and increased their interest and motivation to study Kampo medicine. CONCLUSION: Considering the current status of Kampo education, this training method is effective to educate students in the basic concepts of Kampo medicine.

We report the case of a 33-year old man with ulcerative colitis and attacks of melena who responded positively to a change in prescription, in accordance with change in his disease state. His melena developed in May of the year XXXX. He was diagnosed with ulcerative colitis (proctitis) after a thorough evaluation at another medical institution, administration of 5-ASA, steroid suppositories and an antidiarrheal agent had brought no relief, and he consequently sought Kampo treatment at our institution. Saireito (9.0g/day) and kyukikyogaito(9.0g/day) extract granules were initially administered for two weeks in addition to the aforementioned drug therapy, which resulted in improvement of his melena. However, the same Kampo formulations prescribed later, when his attacks recurred, failed to effectively halt rectal bleeding. These recurrent attacks differed from his first, in that blood was seen after the elimination of feces (feces first, blood later), and as "feces-first, blood-later" conditions are described in the <I>Synopsis of the Golden Chamber</I> as "enketsu" indications for odoto decoction, his prescription was changed to odoto. After odoto administration for 2 months, his melena gradually resolved, and active rectal inflammatory change was improved as seen with colonoscopy. His melena then lessened after 1 month's administration, and symptoms of melena had almost completely disappeared after 2 month's administration. Amelioration of active rectal inflammatory change was also confirmed with colonoscopy findings. This was an interesting case where the progression of a clinical condition required a corresponding change in prescription for effective management of symptoms.

A model core curriculum was proposed by the government in 2001 that outlined the core structure for undergraduate medical education, in which a Kampo medicine educational program was established. The following year, it was introduced in pharmacy as well as medicine. For fourth-year students at Tokai Medical University, a lecture on Kampo herbal medicine, focusing on clinical pharmacy, was given using team- based learning. Students learned the fundamental mechanism of Kampo medicine through team discussions about their subjective assessment of herbal medicine "Keishito" using their sensory organs and comparing objective analysis data of the main ingredients of Cinnamomi Cortex. They found that knowledge about Kampo medicine can come not only from clinical trials but also from objective observation. Through this educational program, almost all had an increased interest in the possible therapeutic value of herbal medicine. The results of examinations on Kampo herbal medicine showed that this program motivated students, especially those who had less or little interest in Kampo medicine before the lecture. The lecture-style team-based format could also facilitate a mutually supportive atmosphere, because negative feelings and concerns regarding initial traditional medicine can freely be expressed. In future, pharmacists as medical staff will provide preventive and curative primary care; since, for example, the Japanese government is pressing forward to prevent metabolic syndrome, which is related to lifestyle, this project could not have been completed without the cooperation of health professionals such as pharmacists. The present educational program in Kampo medicine may also be recommended for clinical pharmacy education.

To examine whether benidipine hydrochloride, one of the calcium channel blockers, up-regulate uncoupling protein 3 (UCP3) expression in two skeletal muscles (gastrocnemius and soleus) in rats. Wistar rats were treated orally with benidipine hydrochloride at 4 mg/kg for 7 days. Blood pressure was measured after 4 days. At the end of experiments, the rats were weighed, and brown adipose tissue (BAT) and skeletal muscles (gastrocnemius and soleus muscles) were removed. The mRNA levels of uncoupling protein 1 (UCP1) and UCP3 were measured using the real-time quantitative reverse transcription-polymerase chain reaction method. Benidipine reduced body weight and also had a hypotensive effect. In rats treated with benidipine, UCP1 mRNA levels were significantly increased 1.4-fold in BAT, and UCP3 mRNA levels in BAT and gastrocnemius muscle were significantly increased 1.7 and 3.0-fold, respectively, compared with the control rats. There was no difference in UCP3 mRNA levels in soleus muscle between the two groups. We concluded that benidipine up-regulates not only UCP1 gene expression in BAT but also UCP3 gene expression in BAT and gastrocnemius muscle, which may contribute to thermogenesis in rats.

In the present study, using in vivo brain microdialysis, we investigated the basal extracellular dopamine (DA) and serotonin (5-HT) release in the caudal striatum (cSTR) of young (4-6 months old) and aged (10-12 months old) zitter mutant rats. The basal extracellular levels of DA release in both young and aged zitter rats were significantly lower than that of age-matched Sprague-Dawley (SD) rats, whereas only aged zitter rats showed a significant difference in the basal 5-HT release. Dopaminergic neurons were more vulnerable than serotonergic neurons in the cSTR of zitter mutant rats during aging. Perfusion of 60 mM potassium (K+) enhanced the extracellular levels of cSTR DA in the young zitter rats and the extracellular levels of both DA and 5-HT in the cSTR of the aged zitter rats. The firing rate of K+-stimulated monoamine release in the cSTR was significantly higher in the zitter rats than in the age-matched SD rats. These findings suggest that there are innate quantitative differences in the releasable pool and the availability of monoamines in the cSTR of zitter mutant rats.

1. The hypothesis that ultrasonic stimulation upregulates uncoupling protein (UCP) 2 and UCP3 in gastrocnemius muscle by a different mechanism of exercise was investigated in Wister rats. 2. The ultrasnonic-stimulated group was given ultrasonic stimulation to the leg (1 MHz frequency, 1 W/cm2 intensity, 10 min continuously). 3. The exercise group was given exercise training by swimming for 10 min in plastic barrels filled with warm water. 4. After 3 h, rats were killed and the gastrocnemius muscle was removed rapidly, weighed and frozen in liquid nitrogen for real-time quantitative reverse transcription-polymerase chain reaction analysis. 5. In gastrocnenius muscles of ultrasonic-stimulated rats, UCP3 mRNA abundance was significantly increased 3.6-fold and UCP2 mRNA abundance was significantly increased 2.2-fold compared with control rats. 6. In gastrocnenius muscles of exercised rats, UCP3 mRNA abundance was significantly increased 3.5-fold compared with control rats, but no change in UCP2 mRNA abundance was observed. 7. Plasma free fatty acid (FFA) levels were also significantly increased in the ultrasonic stimulation group, as well as the exercise group, compared with the control group. 8. These findings show that ultrasonic stimulation lipolyses subcutaneous fat into FFA and glycerol and upregulates UCP2 and UCP3 mRNA by a mechanism different to that of exercise.

Expression of uncoupling protein-1 (UCP1) is increased by cold acclimation and overfeeding, and reduced in fasting and genetic obesity. It is known that the mitochondrial UCP1 in the brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. On the other hand, ethanol (EtOH) alters thermoregulation in humans and laboratory animals. However, the relationship between EtOH intake and UCP1 expression is not yet clear. Accordingly, the present study employed the technique of real-time quantitative polymerase-chain reaction (PCR) to investigate the effects of EtOH (0.5 or 2.0 g/kg) on the expression of UCP1 mRNA in the mouse BAT. Control mice were injected with the same volume of physiological saline intraperitoneally (IP). IP injection of EtOH (0.5 g/kg) caused a decrease and an increase of the expression of BAT UCP1 mRNA at 1 and 4 hours, respectively. Treatment with EtOH (2.0 g/kg) caused an increases of the expression of BAT UCP1 mRNA at both 2 and 4 hours. BAT UCP1 mRNA levels in both groups increased at 4 hours after EtOH administration. The levels of UCP1 mRNA returned to the control levels by 8 hours after EtOH administration. The expression of BAT UCP1 mRNA was upregulated following EtOH administration, although a lower dose of EtOH initially reduced the expression of UCP1 mRNA in BAT. These findings suggest that EtOH-induced UCP1 mRNA expression in BAT reflects an alteration of the set point of thermogenesis.

1. In the present study, we conducted the first randomized, double-blind, placebo-controlled study of bofu-tsusho-san (BF), an oriental herbal medicine (24 mg/day ephedrine in Ephedrae Herba and an efficacy equivalent of 280 mg caffeine, judging from the phosphodiesterase-inhibitory effect of Glycyrrhizae Radix, Forsythiae Fructus and Schizonepetae Spica and another 14 crude drugs) in obese women with impaired glucose tolerance (IGT). 2. The aim of the present study was to determine whether BF was effective in decreasing visceral adiposity and insulin resistance. Eighty-one Japanese women (body mass index (BMI) 36.5 +/- 4.8 kg/m2) with IGT and insulin resistance (IR), who had been treated with a low-calorie diet (5016 kj/day: 1200 kcal) and an exercise regimen (1254 kj/day: 300 kcal), were randomized to receive either placebo (n=40) or BF treatment (n=41) three times a day. 3. After 24 weeks treatment, the BF group lost significantly (P <0.01) more bodyweight and abdominal visceral fat without a decrease in the adjusted resting metabolic rate (RMR), whereas the placebo group lost bodyweight (P <0.05) and had no significant change in abdominal visceral fat. The BF group had a lower fasting serum insulin level (P <0.05), a lower insulin area under the curve (P <0.05) and a lower level of the homeostasis model assessment of insulin resistance (P <0.01) compared with values before treatment. 4. We conclude that BF could be a useful herbal medicine in treating obesity with IGT.

Differences of alcohol drinking behavior, brain dopamine (DA) and serotonin (5-HT) levels and releases in the striatum were investigated in stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched stroke-resistant spontaneously hypertensive rats (SHRSR). Voluntary alcohol (EtOH) consumption in SHRSP rats increased at 1 and 2 hours in the 4 hour time access. In the DA level, SHRSP showed decreases in the caudate-putamen (C/P) and dorsal raphe nucleus (DRN) compared with in SHRSR. 5-HT levels in the C/P, ventral tegmental area-subtantia nigra (V/S) and DRN of the SHRSP were decreased compared with that in SHRSR. The basal extracellular levels of 5-HT release in the C/P were increased in SHRSP as compared with those in SHRSR. K(+)- or EtOH-induced DA and 5-HT releases in the C/P of the SHRSP were a lower magnitude than those in SHRSR. Increased basal extracellular 5-HT releases showing low levels of 5-HT in the C/P of SHRSP mean an abnormality of serotonergic neuronal functions in a normal physiological condition. Higher voluntary alcohol drinking behavior, so called lower susceptibility to EtOH, in the SHRSP may be associated with the degenerated rewarding system including the DRN. These results suggest that the hypertensive state causes the dysfunction in the striatum of the brain rewarding system and induces the risk for increasing alcohol consumption to compensate for the alteration of serotonergic neurons.

Kampo crude drug, daio (Rhei rhizoma) is frequently used as a purgative for a long time. We previously reported the extending life span of nematode treated with daio, however, its biological response by administration of daio remains unclear. In this study, to clarify the molecular mechanisms on life extension by daio in nematode, we screened the genes upregulated by administration of daio using microarray analysis. We obtained six genes transcriptionally activated more than 10 times by daio and their mammalian homologues were characterized in mice. By 2-week oral administration, expression of Nhe1, one of the six candidate genes, in kidney was upregulated similarly to that in nematode. These findings suggest that the Nhe1 encoding Na+/H+ exchanger protein plays an important role in maintaining kidney structurally and functionally. To use daio in animal experiments, we have also developed a method for preparing sennoside-reduced daio, which maintains most of other major components.