Long-term administration of anticonvulsants is necessary for patients prone to convulsions in order to prevent seizures. However, continuous administration of anticonvulsants can often provoke liver dysfunction and impair cognitive ability. Some Japanese herbal medicines (Kampo formulae) have long been known to inhibit seizures and to have a protective effect on liver function. To elucidate these effects, Kampo formulae (Saikokeishi-to and Shakuyakukanzo-to) were administered to patients with convulsive seizures and liver dysfunction due to cerebrovascular disorders, traumatic brain injury and brain tumors. Administration of anticonvulsant drugs was decreased simultaneously with administration of these Kampo formulae.
The results indicated inhibition of convulsive seizures and a definite recovery of liver function. Improvements were also observed in cognitive function. Based on these findings, it is suggested that Kampo formulae are useful for patients with seizures and/or liver dysfunction, and that the dosage of anticonvulsant drugs may be decreased when Kampo formulae are also being administered.

We have been studying the effect of preadministration of D-phenylalanin (DPA) on acupuncture analgesia for various types of pain. DPA is thought to suppress the activity of carboxypeptidase, which discomposes endorphins. In this double-blind placebo-controled study, clinical effectiveness of acupuncture with DPA preadministration in relieving chronic low back pain was examined.
DPA (4g) or placebo (lactose: 4g) was orally administered to thirty out patients with chronic low back or lower extremity pain 30 minutes before acupuncture treatment. A half of the patients were given placebo in the first session and DPA in the second one, and the other half were given DPA firstly and placebo secondly.
The patients were asked to rate their pain after treatment in comparison with pre-treatment condition. Successful pain relief was obtained in 60% of the patients given DPA prior to acupuncture and in 33.4% of those given placebo. Although it is said that there is a great individual variation in response to acupuncture therapy, this result demonstrates that preadministration of D-phenylalanin enhances analgesic effect of acupuncture therapy.

A study was conducted to clarify training ability in the recovery phase after coronary artery bypass graft surgery (CABG) . Thirty-one patients who underwent CABG were divided into four groups according to the degree of revascularization and graft patency: complete revascularization with graft patency (group A), complete revascularization without graft patency (group B), incomplete revascularization with graft patency (group C) and incomplete revascularization without graft patency (group D) . In all patients, exercise training was started one month after CABG and continued for one month. Treadmill exercise testing was performed at three points during the clinical course (one month before CABG, one month after CABG and at the end of exercise training) . Functional aerobic impairment (FAT), myocardial aerobic impairment (MAT), peripheral circulatory impairment (PCI) and electrocardiogram were measured at these points. The results obtained were as follows:
1) FAI was improved significantly after CABG as compared with before CABG in groups A and C, and was also improved significantly after exercise training as compared with before training in groups A and C. The degree of improvement in FAI in group A was larger than in group C.
2) Althought MAT was improved significantly after CABG as compared with before CABG in groups A and C, it was improved significantly after exercise training as compared with before training only in group A.
3) PCI remained unchanged before and after CABG in all groups. However, it was improved significantly after training as compared with before training in groups A and C.
4) The number of patients with a positive finding in the exercise test was reduced by CABG in all groups, and was decreased by training only in group A. However, CABG produced a significant decrease in groups A, B and C.
In conclusion, the present findings suggest that while graft patency is probably a major factor, the degree of revascularization may play only a subsidiary role in determining trainability soon after CABG.

A study was conducted to clarify the validity and availability of inclination of exponential curve-fitting model for oxygen uptake (VO₂) and heart rate (HR) during incremental exercise (IECOH) as an index of cardio-pulmonary functional reserve in healthy subjects. A treadmill exercise test was used to measure the VO₂ (L/kg/min) and HR (beat /min) during incremental exercise of all subjects. The IECOH was derived from the following equation : HR=A⋅exp^B·VO₂. The constant “B” represents the IECOH. The following three identifications were made : 1) the relationship between maximal oxygen uptake (VO₂max) and IECOH in 82 healthy males ; 2) the relationship between IECOH and age in 428 healthy males and females ; 3) the effect of physical training in 8 healthy males.
There was inverse correlation between IECOH and VO₂max (r= -0.824) . And also, there were inverse correlations between IECOH detected from submaximal tests and VO₂max (above r=-0.6) . There were no differences in the IECOH detected from maximal and submaximal tests. In Bland-Altman plot method, accuracy of measurment in the IECOH detected from submaximal exercise test was precise. There was a significant relationship between IECOH and age in male and female subjects (r=0.499 and r=0.310, respectively) . Physical training increased VO₂max and decreased IECOH significantly. The VO₂max before and after physical training correlated inversely with the IECOH before and after physical training (r=-0.514) .
In conclusion, these results suggest that IECOH is adequate and useful as an index of cardio-pulmonary functional reserve which can be measured by the submaximal exercise test in healthy subjects.

In previous papers, we experimentally demonstrated the enhancing effect of D-phenylalanine (DPA) administration on the analgesic effect of acupuncture by the increase of pain threshold. In the present study, we examined the effect of administration manners in the patients with chronic lumbago who visited our anaesthesiological department. We conducted a double-blind study with two different administration manners: “previous-day” and “just-before”.
METHODS
Fifty-six patients suffering from chronic low back pain for more than three months were devided into two groups. DPA or placebo was orally administered intwo different manners prior to low-frequency electro-acupuncture treatment. Group I patients (26 cases), took 0.5g three times (i. e. a total of 1.5g): after the evening meal and before go to bed on the day before, and after the beakfast on the day of acupuncture (“previous-day” administration). Group II patients (30 cases), took 4.5g 30 minutes before acupuncture treatment “just-before” administration. The treatment was undertaken twice with DPA administration and twice with placebo administration for each group. “Direct effect” was determined by the number scale method and a comparison between the two groups was made. In the additional experiment, three volunteers were orally given 4.0g or 1.5g DPA, and blood phenylalanine level was determined two hours, four hours and one month later.
RESULTS
In the group I (previous-day administration), “DPA+acupuncture” produced the following result: excellent 7.8%, good 69.2%, moderate 19.2%, (significantly different from placebo administration). In the group II (just-before administration), “DPA+acupuncture” produced the following result: excellent 23%, good 37%, moderate 20%, and no-effect 20% (significantly different from placebo administration). Comparing group I with group II, the percentage of the “excellent” or “good” cases in the former was larger than that of the latter (+17%). Blood phenylalanine level showed its high value 2-4 hours after administration of 4g DPA, whereas 2 hours after that of 1.5g DPA.
Conducting a clinical investigation into the effectual administration (timing and doses) of DPA, we found that previous-day administration is more effective than “just-before” administration in enhancing effect of acupuncture analgesia. Although there is room for further studies with a larger number of cases, considering that DPA has a “slow onset long acting” effect (Ehrenpreis), we can conclude that the series administration of DPA on the day before acupuncture treatment is advisable.

This study examined the effects of physical training on exercise hyperpnea (EH) in patients on hemodialysis (HD) . In baseline, 17 (trained group) and 12 (control group) patients on HD performed symptom limited exercise test using a treadmill. Trained group, but not control group, exercised 2 to 3 times weekly on non-dialysis days under medical supervision. Exercise testing was repeated 20 weeks after the baseline. Ventilatory response to exercise was evaluated using the regression slope relating minute ventilation (VE) to carbon dioxide output (VCO₂ ) during incremental exercise (VE/VCO₂ slope) below the point of respiratory compensation. In trained group, VE, oxygen uptake ( VO₂) and VCO₂ at peak exercise increased and VE/VO₂ and VE/VCO₂ decreased after physical training, respectively. No change was observed in control group. VO₂ at the anaerobic threshold increased in trained group, but not in control group. The post training VE/VCO₂ slope (33.9±5.0) was significantly (p<0.05) lower than the pre-training slope (38.0± 4.8) and remained constant in control group. In trained group, changes in the VE/VCO₂ slope correlated with those in peak VO₂ (p<0.05) . These results suggest that physical training decreases EH in patients on HD and that it correlates with changes in exercise tolerance.

This study was conducted to clarify the validity and availability of inclination of exponential curve-fitting model for oxygen uptake (VO₂) and heart rate (HR) during incremental exercise (I-ECOH) as an index of cardio-pulmonary functional reserve in patients with ischemic heart disease (IHD). A treadmill exercise test was used to measure the VO₂(L/kg/min) and HR (beat/min) during incremental exercise of all subjects. I-ECOH was derived from the following equation : HR=A·exp^B·VO2. The constant "B" represents I-ECOH. The following two identifications were made : 1) the relation between peak oxygen uptake (VO₂peak) and I-ECOH in IHD patients with normal left ventricular function and with chronic heart failure (CHF); 2) the relation between I-ECOH and the New York Heart Association (NYHA) functional classification of IHD patients with CHF.There were significant differences among IHD patients with normal left ventricular function, CHF patients, normal controls and long distance runners in I-ECOH and VO2peak, respectively (p<0.001). There were inverse correlations between I-ECOH and VO2peak in IHD patients with normal left ventricular function (r=-0.64, p<0.001) and CHF (r=-0.63, p<0.001). I-ECOH could be used to discriminate effectively between NYHA functional classes (p<0.001).In conclusion, these results suggest that I-ECOH is adequate and useful as an index of cardio-pulmonary functional reserve in patients with ischemic heart disease.

A study was conducted to clarify the effect of hyperoxia (HO) on exercise tolerance andhemodynamics in patients with ischemic heart disease (IHD) . The subjects were 10 patients with serious IHD who showed ischemic ST depression during low-intensity exercise testing. In all subjects, cardiopulmonary exercise testing (CPX) was performed using two types of inhalation : normoxia (NO) and HO (O₂: 60%, N₂: 40%) . Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), elapsed exercise duration and pressure rate product (PRP) were measured, and ECG was recorded during CPX according to the Bruce protocol. The peak oxygen uptake (VO₂peak) was calculated using the appropriate formula. These data were compared between the NO and HO groups, and the following results were obtained.
ST depressions on ECG, BP, HR and PRP after 20 min of rest showed no changes under NO. The other hand, only ST depression was improved after 20 min of rest under HO. The exercise duration in HO group was longer than in the NO group, and the VO₂peak in the HO group was higher than in the NO group. However, peak RPE showed no significant difference between the HO and NO groups. The incidence of ST depression as an endpoint of CPX showed no significant difference between the two groups. BP, HR and PRP at the CPX endpoint showed no significant differences between the HO and NO groups. In patients whose exercise duration was prolonged beyond the mean value by HO, peak HR and PRP were increased significantly. However, this tendency was not seen in patients whose exercise was prolonged for less than the mean value.
In conclusion, these results suggest that an increase in the oxygen supply to peripheral working muscles may play an important role in increasing exercise tolerance under HO in IHD patients.

BACKGROUND/AIMS: Although studies using conventional animal models have shown that specific stressors cause irritable bowel syndrome (IBS), it is unclear whether depression itself causes IBS. Our aim was to establish a rat model to determine if depression itself promotes the onset of IBS and to elucidate the role of gut microbiota in brain-gut axis pathogenesis during coincident depression and IBS. METHODS: Rat models of depression were induced using our shuttle box method of learned helplessness. Visceral hypersensitivity was evaluated by colorectal distension (CRD) to diagnose IBS. Gut microbiota compositions were analyzed using high-throughput sequencing. In the subanalysis of rats without depression-like symptoms, rats with posttraumatic stress disorder (PTSD) were also examined. RESULTS: The threshold value of CRD in depressed rats was significantly lower than that in control rats. Microbial community analysis of cecal microbiota showed that the relative abundance of Clostridiales incertae sedis, the most prevalent microbe, was significantly lower in depressed rats than in control rats. The distribution pattern of the microbiota clearly differed between depressed rats and control rats. Neither visceral hypersensitivity nor the composition of gut microbiota was altered in rats with PTSD-like phenotypes. CONCLUSIONS: Our rat model of depression is useful for clarifying the effect of depression on IBS and suggests that depression itself, rather than specific stressors, promotes the onset of IBS. Further, we provided evidence that various psychiatric diseases, viz., depression and PTSD, are associated with unique gut microbiota profiles, which could differentially affect the onset and progression of coincident IBS.
Animals ; Clostridiales ; Depression ; Dysbiosis ; Gastrointestinal Microbiome ; Helplessness, Learned ; Hypersensitivity ; Irritable Bowel Syndrome ; Methods ; Microbiota ; Models, Animal ; Phenotype ; Rats ; Stress Disorders, Post-Traumatic