Analysis of Urinary Retention Caused by Selective ß 3-adrenoceptor Agonists Using the Japanese Adverse Drug Event Report Database (JADER).

Overactive bladder (OAB) is a frequent chronic disorder which impairs quality of life by frequent, uncontrollable urination. Newly developed selectiveß 3-adrenoceptor agonists (sß 3-agonists) have the same efficacy in treating OAB but significantly fewer side effects than the traditionally used anti-muscarinics. However, safety data on these compounds are scarce. In this study, we analysed the occurrence of adverse effects in patients taking sß 3-agonists and their characteristics using the JADER database. The most frequently reported adverse effect associated with the use of sß 3-agonists was urinary retention [mirabegron; crude reporting odds ratios (ROR): 62.1, 95% confidence interval (CI): 52.0-73.6, P<0.001, vibegron; crude ROR: 250, 95% CI : 134-483, P<0.001]. Data from patients with urinary retention were stratified by sex. In both men and women, the rate of urinary retention was higher when using the mirabegron/anti-muscarinic drug when compared to mirabegron monotherapy; its occurrence was higher in men with a history of benign prostatic hypertrophy than in those without. Weibull analysis showed that approximately 50% of sß 3 agonist-induced urinary retention occurred within 15 days after initiation of treatment, and then gradually decreased. Although sß 3-agonists are useful against OAB, they may induce several side effects, especially urinary retention, which can further evolve into more severe conditions. Urinary retention occurs more frequently in patients concomitantly taking medication that either increases urethral resistance or has organic factors that block the urethra. When using sß 3-agonists, the concomitantly used medications and underlying diseases should be thoroughly reviewed, and safety monitoring should be instituted early during the treatment.

Juzentaihoto extract suppresses adipocyte hypertrophy and improves hyperglycemia in KKAy mice.

Juzentaihoto is a herbal medicine with reported anti-inflammatory effects, and it is predicted to improve inflammation and insulin sensitivity within obesity. In the present study, juzentaihoto hot water extract (JTT) was administered to obese type 2 diabetic model mice (KKAy) for 56 days. In addition, the effects of JTT on the adipose tissue, glucose metabolism, and blood lipids were evaluated for examining its impact on insulin sensitivity and obesity. As a result of JTT administration, KKAy mice exhibited suppressed adipocyte hypertrophy, decreased the mRNA levels of tumor necrosis factor α, and increased the mRNA levels of adiponectin in epididymal fat tissue. In addition, fasting blood glucose levels, blood triglyceride, and total cholesterol decreased. In summary, these data indicated that JTT administration suppressed the production of inflammatory cytokines and increased adiponectin levels in the adipose tissue. Therefore, with improved insulin sensitivity, blood glucose, and lipid decreased.

Quality control of hospital preparations: Establishment of a simple and rapid method for quantifying ulinastatin in vaginal suppositories.

Ulinastatin vaginal suppositories, used to prevent threatened premature delivery, are frequently used in hospitals. However, there is no established method for quantifying ulinastatin contained in suppositories. Therefore, we investigated a simple and efficient method for quantifying ulinastatin contained in suppositories. Our analytical method involved removal of the base; optimising the enzyme inhibition reaction time and enzyme reaction time; and measuring the absorbance. The modified method was reproducible, operation time was significantly shortened, and cost was reduced to approximately 1/17 of that of the previously reported method. This simple and rapid quantitative method could contribute to the improvement of quality control of ulinastatin vaginal suppositories as an extemporaneous hospital preparation.

Effects of deconditioning on the initial ventilatory and circulatory responses at the onset of exercise in man.

In order to elucidate the effects of deconditioning (inactivity) on the ventilatory and circulatory responses at the onset of exercise within 20 s, we initiated head-down bed rest and unilateral lower limb suspension experiments, and measured these responses to dynamic voluntary leg exercise and passive movements. Initial ventilatory and heart rate responses to voluntary exercise were attenuated after bed rest but showed no change after suspension or during passive movements, suggesting the minimal role of peripheral neural reflex.

Monitoring of Epstein-Barr virus load and killer T cells in pediatric renal transplant recipients.

AIM: The aim of this study is to establish a monitoring method to prevent Epstein-Barr virus (EBV)-associated symptoms including post-transplant lymphoproliferative disorder (PTLD) that occur after pediatric renal transplantation. SUBJECTS AND METHODS: Circulating EBV loads were quantified by real-time PCR every 1 - 3 months after grafting in 22 pediatric recipients (13 EBV-seronegative [R(-)] and 9 EBV-seropositive [R(+)] recipients before grafting). The peripheral blood cell populations of non-specific activated killer cells (CD8+HLA-DR+ phenotype) in 13 R(-) recipients and EBV-specific cytotoxic T cells (CTLs) reactive with a tetramer expressing HLA-A24-restricted EBV-specific antigens in 8 of 13 R(-) recipients were determined by flow cytometry. RESULTS: EBV-associated symptoms including PTLD (2 cases) were found in 4 R(-) and none of the R(+) recipients. The maximum of EBV load in the R(-) group was significantly higher that in the R(+) group. In R(-) recipients, 4 symptomatic cases had significantly more EBV genome than asymptomatic cases. EBV-specific CTLs were detected in 6 of the 8 R(-) recipients, but these CTLs could not be detected in 1 of the 2 cases at onset of PTLD. The percentage of CD8+HLA-DR+ cells was significantly higher in asymptomatic recipients than in recipients with EBV-associated symptoms whose EBV loads were over 400 copies/microg DNA. CONCLUSION: Monitoring of killer T cells and EBV loads may allow assessment of the risk of EBV-associated symptoms, and high EBV loads and low EBV-specific and/or non-specific CTL responses may be predictive for development of EBV-associated symptoms such as PTLD.

Intermittent hypoxia does not increase exercise ventilation at simulated moderate altitude.

Recent human studies have shown that resting hypoxic ventilatory response (HVR), which is an index of ventilatory chemosensitivity to hypoxia, increased after short-term intermittent hypoxia at rest. In addition, intermittent hypoxia leads to increases in ventilation and arterial oxygen saturation (SaO (2)) during exercise at simulated high altitude, with the increase in ventilation correlated to the change in HVR. However, no study has been made to clarify the relationship between ventilatory chemosensitivity and the exercise ventilation at moderate altitude following intermittent hypoxia during a resting state. The purpose of the present study, therefore, was to elucidate whether intermittent hypoxia at rest induces the increase in ventilation during exercise at moderate altitude that is accompanied by an increase in hypoxic chemosensitivity. Eighteen trained male runners were assigned to three groups, i.e., the first hypoxic group (H-1 group, n = 6), the second hypoxic group (H-2 group, n = 6), and a control group (C group, n = 6). The hypoxic tent system was utilized for intermittent hypoxia, and the oxygen levels in the tent were maintained at 15.5 +/- 0.1 % (simulated 2500 m altitude) for the H-1 group and 12.3 +/- 0.2 % (simulated 4300 m altitude) for the H-2 group. The H-1 and H-2 groups spent 1 hour per day in the hypoxic tent for 1 week. Maximal and submaximal exercise tests while breathing 15.5 +/- 0.01 % O (2) (simulated altitude of 2500 m) were performed before and after intermittent hypoxia. Resting HVR was also determined in each subject using a progressive isocapnic hypoxic method. In the H-2 group, HVR increased significantly (p < 0.05) following intermittent hypoxia, while no change in HVR was found in the H-1 or C group. Neither ventilation nor SaO (2) during maximal and submaximal exercise at a simulated altitude of 2500 m were changed in either group after 1 hour per day for 1 week of intermittent hypoxia. These results suggest that the change in resting hypoxic chemosensitivity after short-term intermittent hypoxia does not affect ventilation during exercise at moderate altitude.

The use of colour Doppler imaging in the diagnosis of retinal detachment.

DESIGN: Prospective study. PURPOSE: To evaluate real-time duplex colour Doppler examination with colour and pulse Doppler ultrasonography (US) (colour Doppler imaging (CDI)) for detection of the retinal detachment from membranous structures in the posterior segment. MATERIALS AND METHODS: In 33 consecutive patients with ophthalmoscopically invisible eyes (34 eyes), CDI was performed to detect the presence or absence of retinal detachment. The diagnostic criterion for retinal detachment was whether or not spectral waveforms were detected in membranous structures with colour and pulse Doppler US. In all cases, the absence or presence of retinal detachment was confirmed by surgery. RESULTS: In 27 of 34 eyes, membranes and/or opacities were observed in the vitreous cavity with CDI. In 12 of these 27 eyes, blood flow in those structures was detected by CDI. In all of these 12 eyes, retinal detachment was confirmed at surgery, and in 14 of the 15 eyes in which blood flow was not detected by CDI, absence of retinal detachment was confirmed at surgery. When a diagnosis confirmed by surgery was used as the definitive finding, CDI had a sensitivity of 92.3%, specificity of 100%, positive predictive value of 100%, negative predictive value of 93.3%, and an accuracy in the detection of retinal detachment from membranes and/or opacities in the vitreous cavity of 96.3%. CONCLUSION: Real-time duplex colour Doppler examination with colour and pulse Doppler US (CDI) is a noninvasive method useful for the detection of retinal detachment from vitreous opacity and/or membrane in the posterior segment.

Gastric myoelectrical activity increases after moderate-intensity exercise with no meals under suppressed vagal nerve activity.

Postprandial gastric myoelectrical activity recorded by electrogastrogram (EGG) with the subject in a supine position has shown to be enhanced after moderate-intensity pedaling exercise in an upright seated position, despite the suppression of vagal nerve activity. However, it is still unknown whether the effect is due to the exercise itself and/or a meal or how the position change has influenced the effects. To address this, we used a position-controllable cycle ergometer to examine the effects of the moderate-intensity exercise on EGG activity and the high-frequency (HF) component of heart rate variability (HRV), an index of vagal nerve activity. To eliminate the effect of position change, we carried out the exercise and the EGG recording in the supine position. The peak amplitude of the EGG was enhanced by prior moderate-intensity exercise with a reduced HF component of HRV, which did not differ for postexercise conditions with or without a meal. The small amount of meal itself, however, enhanced both the peak amplitude of the EGG and the HF component of HRV. The peak frequency of EGG was reduced and the instability coefficient of EGG was increased only after the exercise itself. Taken together, these results suggest that the enhanced amplitude of gastric myoelectrical activity can be induced by moderate-intensity exercise itself, even with suppressed vagal nerve activity, and that the mechanism underlying the exercise effects would differ from that underlying the effect of a meal alone.

Intermittent hypobaric hypoxia increases the ability of neutrophils to generate superoxide anion in humans.

1. We investigated the effect of intermittent exposure to hypobaric hypoxia on the ability of neutrophils to generate.O2-. 2. Seven male volunteers were exposed intermittently to hypobaric hypoxia, equivalent to an altitude of 4500 m, for 7 successive days. Peripheral blood samples were collected before and after the 2 h course of hypobaric hypoxia on days 1 and 7 and neutrophils were subjected to a chemiluminescence assay for.O2- production. 3. On day 1, 2 h exposure to hypobaric hypoxia induced granulocytosis (P < 0.01), but the ability of neutrophils to generate.O2- was unchanged. 4. On day 7, such granulocytosis was not observed, suggesting acclimatization to hypobaric hypoxia. 5. The ability of neutrophils to generate.O2- was significantly increased on day 7 (P < 0.01), although there was no definite change in the mRNA expression of NADPH oxidase subunits in the cells. 6. The results suggest that the ability of neutrophils to generate.O2- may be gradually potentiated by intermittent exposure to hypobaric hypoxia, even after the number of neutrophils in peripheral blood stabilizes.

Chiral recognition of dipeptide methyl esters by an anionic beta-cyclodextrin.

Chiral recognition of dipeptide methyl esters by anionic heptakis[6-carboxymethylthio-6-deoxy]-beta-cyclodextrin (per-CO(2)(-)-beta-CD) was studied in D(2)O at pD 7.0 by means of (1)H NMR spectroscopy. The methyl esters of alanylalanine (Ala-Ala-OMe), alanylleucine (Ala-Leu-OMe), alanyltryptophan (Ala-Trp-OMe), glycyltryptophan (Gly-Trp-OMe), valyltryptophan (Val-Trp-OMe), leucyltryptophan (Leu-Trp-OMe), and tryptophylalanine (Trp-Ala-OMe) were used as the dipeptides. The binding constant (K) determined from NMR titration increases in the order Ala-Ala-OMe < Ala-Leu-OMe < Ala-Trp-OMe, suggesting that van der Waals interactions between the host and the guest participate in complexation. Coulomb interactions between the protonated dipeptide methyl esters and the anionic host seem to be another attractive force. Per-CO(2)(-)-beta-CD interacts with the (R,R)-enantiomers of the dipeptide methyl esters more strongly than the (S,S)-enantiomers. Such enantioselectivity corresponds to that for alpha-amino acid methyl esters such as Leu-OMe and Trp-OMe, whose (R)-enantiomers are the preferable guests. The enantioselectivity is mainly dominated by amino acid residue at the C-terminal and chirality at the N-terminal residue plays an assistant role. An asymmetrically twisted shape of the host cavity may be essential for chiral recognition.

Intermittent hypoxia increases ventilation and Sa(O2) during hypoxic exercise and hypoxic chemosensitivity.

The purpose of this study was 1) to test the hypothesis that ventilation and arterial oxygen saturation (Sa(O2)) during acute hypoxia may increase during intermittent hypoxia and remain elevated for a week without hypoxic exposure and 2) to clarify whether the changes in ventilation and Sa(O2) during hypoxic exercise are correlated with the change in hypoxic chemosensitivity. Six subjects were exposed to a simulated altitude of 4,500 m altitude for 7 days (1 h/day). Oxygen uptake (VO2), expired minute ventilation (VE), and Sa(O2) were measured during maximal and submaximal exercise at 432 Torr before (Pre), after intermittent hypoxia (Post), and again after a week at sea level (De). Hypoxic ventilatory response (HVR) was also determined. At both Post and De, significant increases from Pre were found in HVR at rest and in ventilatory equivalent for O2 (VE/VO2) and Sa(O2) during submaximal exercise. There were significant correlations among the changes in HVR at rest and in VE/VO2 and Sa(O2) during hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily exposure to 1 h of hypoxia significantly improved oxygenation in exercise during subsequent acute hypoxic exposures up to 1 wk after the conditioning, presumably caused by the enhanced hypoxic ventilatory chemosensitivity.

Effect of intermittent hypoxia on cardiovascular adaptations and response to progressive hypoxia in humans.

The aim of the present study was to elucidate (1) the cardiovascular adaptations and response to hypoxic stimuli during short-term intermittent hypoxia and (2) whether the change in cardiovascular response to hypoxia is correlated to the change in hypoxic ventilatory chemosensitivity. Fourteen subjects were decompressed in a chamber to 432 torr, simulating an altitude of 4500 m, over a period of 30 min and were maintained at that pressure for 1 h daily for 7 days. Ventilatory (DeltaV(I)/DeltaSa(O2); Sa(O2) is arterial oxygen saturation), systolic and diastolic blood pressure (DeltaSBP/DeltaSa(O2) and DeltaDBP/DeltaSa(O2)), and heart rate (DeltaHR/DeltaSa(O2)) responses to progressive isocapnic hypoxia were measured before and after intermittent hypoxia. Resting ventilation, SBP, DBP, and HR did not change after intermittent hypoxia. DeltaSBP/DeltaSa(O2) and DeltaDBP/DeltaSa(O2) increased significantly after intermittent hypoxia accompanied by an enhanced DeltaV(I)/DeltaSa(C2), but there was no change in DeltaHR/DeltaSa(C2). There were significant correlations between the change in DeltaV(I)/DeltaSa(O2) and both the changes in DeltaSBP/DeltaSa(O2) and DeltaDBP/DeltaSa(O2) following intermittent hypoxic exposure. These results suggest that short-term intermittent hypoxia leads to the enhanced arterial BP response to hypoxic stimuli in humans, and that the enhanced peripheral chemosensitivity to hypoxia after intermittent hypoxia may play an important role in the increased arterial BP response.

[Supraciliochoroidal fluid at an early stage after trabeculectomy].

PURPOSE: To examine the supraciliochoroidal fluid(SCF) by ultrasound biomicroscopy(UBM) at an early stage after trabeculectomy. SUBJECTS AND METHODS: Fifteen eyes without post-operative complications were examined by UBM before the operation and less than 2 weeks after trabeculectomy with mitomycin C. RESULTS: SCF was detected postoperatively in 6 eyes. One eye had choroidal detachment under indirect-ophthalmoscope and 5 eyes(33%) had SCF without choroidal detachment. The SCF in 4 eyes disappeared within 4 weeks after trabeculectomy. The intraocular pressure was 6.4 +/- 3.4 mmHg(mean +/- standard deviation) when SCF was detected and it rose to 13.2 +/- 7.2 mmHg when SCF disappeared. The intraocular pressure was 11.4 +/- 4.0 mmHg in the eyes without SCF, which was significantly higher than in the eyes with SCF. CONCLUSION: At an early stage after trabeculectomy, SCF was detected by UBM in some cases without ophthalmoscopic choroidal detachment. Compared with the reported frequency of SCF after 3 or 6 months, our study revealed that SCF was present more frequently at an early stage after trabeculectomy. Our results may indicate that the presence of SCF is related to early low intraocular pressure and that disappearance of SCF induces the elevation of intraocular pressure.

Cross transfer effects of muscular endurance during training and detraining.

BACKGROUND: To clarify 1) how the cross-transfer effect, obtained in a contralateral untrained forearm through a 4-week ipsilateral endurance training regimen, is changed during detraining; and 2) how blood flow to the untrained limb is related to the transfer effect of muscular endurance during training and detraining periods. METHODS: Training regimen: hand-grip training by means of a hand-ergometer with a work-load of 1/3 of the maximum handgrip strength 5 times a week for 4 weeks. Blood flow: a mercury-in-rubber strain-gauge for venous occlusion plethysmography. MEASURES: 1) maximal number of contractions to determine the muscular endurance; 2) reactive hyperaemic blood flow response (RHBF3) to determine whether maximal vasodilatory capacity would be changed in both the forearms post-training and detraining; and 3) maximal work-related blood flow. RESULTS: We found significant increments both in the muscle endurance and the maximal work-related blood flow not only in the trained (+125%, +30%) but also in the untrained (+40%, +19%) forearms. During detraining, we found decreases both in the muscle endurance and the maximal work-related blood flow (-22%, p<0.01; -16%, p=0.053) of the trained forearm. However, in the untrained arm (-3%, NS) the cross-transfer effect of muscular endurance remained unchanged despite a drop in the maximal work-related blood flow (-17%, p<0.05). The RHBF3 did not change in either of the forearms during the whole periods. CONCLUSIONS: These findings suggest that the maintenance of the cross transfer effect of muscle endurance during detraining cannot be explained on the basis of changes in forearm blood flow.

Initial ventilatory and circulatory responses to dynamic exercise are slowed in the elderly.

To elucidate the characteristics of ventilatory and circulatory responses at the onset of brief and light exercise in the elderly, 13 healthy, elderly men, aged 66.8 yr (mean), exerted bilateral leg extension-flexion movements for only 20 s with a weight around each ankle, with each weight being approximately 2.5% of their body mass. Similar movements were passively performed on the subjects by the experimenters. These results were compared with those of 13 healthy, young men (22.9 yr). Minute ventilation increased at the onset of voluntary exercise and passive movements in both groups but showed a slower increase in the elderly. Heart rate also increased in both groups but showed less change in the elderly. Mean blood pressure temporarily decreased in both groups but less in the elderly. The magnitude of relative change (gain) of heart rate in the elderly was significantly smaller than that in the young, whereas the increasing rate to reach one-half of the gain (response time) of ventilation in the elderly was significantly slower than that in the young. Similar tendencies were observed in the passive movements. It is concluded that the elderly show slower ventilatory response and attenuated circulatory response at the onset of dynamic voluntary exercise and passive movements.

Vitamin E supplementation attenuates leakage of enzymes following 6 successive days of running training.

The purpose of this study was to examine whether vitamin E supplementation in humans would attenuate an increase of serum enzymes as an indirect marker of muscle damage following a sudden large increase in the running distance in a 6-day running training or not. A randomized and placebo-controlled study was carried out on fourteen male runners who were supplied vitamin E (alpha-tocopherol 1200 IU x day(-1); E) or placebo (P) 4 weeks prior to (T1) and during 6 successive days of running training (48.3 +/- 5.7 km x day(-1), means +/- SD). Resting venous blood samples were obtained before maximal treadmill running, at T1, the day immediately before (T2), the next day (T3), and three weeks (T4) after the running training. Serum levels of alpha-tocopherol, lipid peroxidation products (thiobarbituric acid; TBA), creatine kinase (CK), lactate dehydrogenase (LDH), and LDH isozyme 1-5 were quantitatively analyzed. No significant difference was found in maximal oxygen uptake (VO2max) and maximal heart rates following the exhaustive exercise between the P and E group during the experiments. Vitamin E supplementation significantly increased serum alpha-tocopherol (p<0.001) and decreased TBA levels (p < 0.001) compared with pre-supplementation levels. Although serum CK and LDH activities increased significantly at T3 in either group, significantly lower CK (p < 0.05) and LDH (p < 0.001) levels were observed in the E group compared with the P group. The ratio of LDH1 to LDH2 (LDH1/LDH2) decreased significantly at T3 in either group compared with the T1 levels, since there was no significant difference in the LDH1/LDH2 between the P and E group throughout the experiments. These results indicate that vitamin E supplementation can reduce the leakage of CK and LDH following 6 successive days of endurance running. The protective effect of vitamin E against free radicals probably inhibits free-radical-induced muscle damage caused by a sudden large increase in the running distance.

Cardiovascular response to hypoxia after endurance training at altitude and sea level and after detraining.

The purpose of this study was to elucidate 1) the effects of endurance exercise training during hypoxia or normoxia and of detraining on ventilatory and cardiovascular responses to progressive isocapnic hypoxia and 2) whether the change in the cardiovascular response to hypoxia is correlated to changes in the hypoxic ventilatory response (HVR) after training and detraining. Seven men (altitude group) performed endurance training using a cycle ergometer in a hypobaric chamber of simulated 4,500 m, whereas the other seven men (sea-level group) trained at sea level (K. Katayama, Y. Sato, Y. Morotome, N. Shima, K. Ishida, S. Mori, and M. Miyamura. J. Appl. Physiol. 86: 1805-1811, 1999). The HVR, systolic and diastolic blood pressure responses (DeltaSBP/DeltaSa(O(2)), DeltaDBP/DeltaSa(O(2))), and heart rate response (DeltaHR/DeltaSa(O(2)); Sa(O(2)) is arterial oxygen saturation) to progressive isocapnic hypoxia were measured before and after training and during detraining. DeltaSBP/DeltaSa(O(2)) increased significantly in the altitude group and decreased significantly in the sea-level group after training. The changed DeltaSBP/DeltaSa(O(2)) in both groups was restored during 2 wk of detraining, as were the changes in HVR, whereas there were no changes in the DeltaDBP/DeltaSa(O(2)) and DeltaHR/DeltaSa(O(2)) throughout the experimental period. The changes in DeltaSBP/DeltaSa(O(2)) after training and detraining were significantly correlated with those in HVR. These results suggest that DeltaSBP/DeltaSa(O(2)) to progressive isocapnic hypoxia is variable after endurance training during hypoxia and normoxia and after detraining, as is HVR, but DeltaDBP/DeltaSa(O(2)) and DeltaHR/DeltaSa(O(2)) are not. It also suggests that there is an interaction between the changes in DeltaSBP/DeltaSa(O(2)) and HVR after endurance training or detraining.

Effect of Sho-saiko-to extract on HGF and TGF-beta levels of intraorgans in liver-injured rats after partial hepatectomy.

To examine the effects of Sho-saiko-to extract on liver regeneration, Sho-saiko-to extract (0.75%, 1.5% or 3%) was administered to 70% partial hepatectomized rats with dimethylnitrosamine-induced liver-injury. S phase cell number, liver retinoid levels, hepatocyte growth factor (HGF) and transforming growth factor-beta (TGF-beta) levels in each intraorgan were measured as indicators of liver regeneration. Three to seven days after hepatectomy, HGF and TGF-beta levels of the liver and spleen of the Sho-saiko-to extract groups were significantly different from the levels of the ordinary food group (P < 0.05-0.1). HGF levels in the Sho-saiko-to extract groups were approximately 1.3-1.8 times higher in the liver and approximately 1.8-2.1 times higher in the spleen compared with the levels found in the ordinary food group. TGF-beta levels in the Sho-saiko-to extract groups were approximately 0.38-0.47 times the level in the liver and 0.58-0.77 times the level in the spleen of the ordinary food group. There was no difference in HGF and TGF-beta levels of the kidney and lung between the Sho-saiko-to extract group and the ordinary food group. There was a significant and positive correlation between HGF level and S phase cell number in the liver (r = 0.826, P < 0.01). There was a significant and negative correlation between TGF-beta level and the retinoid level in the liver (r = -0.696, P < 0.01). In addition, the levels of the active constituents of Sho-saiko-to extract (glycyrrhetic acid, baicalin and baicalein) showed high values in the liver and spleen of partial hepatectomized rats, and increased from the third day after partial hepatectomy. These results show that Sho-saiko-to extract induces liver regeneration by increasing the production of HGF and suppressing the production of TGF-beta in the liver and spleen of partial hepatectomized rats. It was considered that the increase in the Sho-saiko-to extract active constituent levels in the liver and spleen greatly influences this action.