Biomedical subjects

K Terasawa

Publications and source records attributed to K Terasawa.

At least 19 recordsLinked to original sources

PubMed2006

Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines.

Transcription factor 2 gene (TCF2) encodes hepatocyte nuclear factor 1beta (HNF1beta), a transcription factor associated with development and metabolism. Mutation of TCF2 has been observed in renal cell cancer, and by screening aberrantly methylated genes, we have now identified TCF2 as a target for epigenetic inactivation in ovarian cancer. TCF2 was methylated in 53% of ovarian cancer cell lines and 26% of primary ovarian cancers, resulting in loss of the gene's expression. TCF2 expression was restored by treating cells with a methyltransferase inhibitor, 5-aza-2'deoxycitidine (5-aza-dC). In addition, chromatin immunoprecipitation showed deacetylation of histone H3 in methylated cells and, when combined with 5-aza-dC, the histone deacetylase inhibitor trichostatin A synergistically induced TCF2 expression. Epigenetic inactivation of TCF2 was also seen in colorectal, gastric and pancreatic cell lines, suggesting general involvement of epigenetic inactivation of TCF2 in tumorigenesis. Restoration of TCF2 expression induced expression of HNF4alpha, a transcriptional target of HNF1beta, indicating that epigenetic silencing of TCF2 leads to alteration of the hepatocyte nuclear factor network in tumours. These results suggest that TCF2 is involved in the development of ovarian cancers and may represent a useful target for their detection and treatment.

Base Sequence↗

PubMed2005

Vasodilative effect of perillaldehyde on isolated rat aorta.

The vasodilative effect of perillaldehyde, one of the major oil components in Perilla frutescens BRITTON, was studied using isolated rat aorta. Perillaldehyde at final concentrations of 0.01 to 1 mM showed dose-dependent relaxation of the aorta contracted by treatment with prostaglandin F2alpha or norepinephrine. Neither the presence of NG-nitro-L-arginine methyl ester nor removal of the aortic endothelium affected the vasodilatation, suggesting that perillaldehyde exerts a direct effect on vascular smooth muscle cells. The vasodilative effect of perillaldehyde was not inhibited by pretreatment with a beta-adrenergic receptor blocker (propranolol), an inhibitor of phosphodiesterase (theophylline), a delayed rectifier K+ channel blocker (tetraethylammonium chloride), or an ATP-sensitive K+ channel blocker (glibenclamide). However, perillaldehyde showed contrasting effects on vasodilatation of the aorta contracted by an influx of extracellular Ca2+ - perillaldehyde caused little vasodilatation on the aorta contracted by the Ca2+ ionophore A23187, while it inhibited the vasoconstriction induced by treatment with high-concentration K+, which dominantly opened the voltage-dependent Ca2+ channel. These results suggest that the vasodilative effect of perillaldehyde is derived from blocking the Ca2+ channels.

Animals↗

PubMed2005

The effect of Juzen-taiho-to/TJ-48 on the expression of killer-cell immunoglobulin-like receptors (CD158a/b) on peripheral lymphocytes in vitro experiment.

Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia or fatigue. It is well known that the treatment of TJ-48 result in the decrease of patient's complaints, as well as the increase of NK cytolytic activity (NK activity) although its augmentation is not clear in the other kampo formula from the clinical viewpoint. To investigate its biological activities, such as the augmentation of NK activity, we analyzed the effects of TJ-48 on the expression of killer-cell immunoglobulin-like receptors (KIRs) in vitro experiment. The peripheral lymphocytes were incubated in medium alone, or medium containing TJ-48 or interleukin-2 (IL-2) plus TJ-48 at several concentrations for 48 h. After each incubation, cells were collected and their KIRs were detected by flow cytometry using monoclonal antibodies CD158a and CD158b. TJ-48 increased the populations of CD16+CD158a+ and CD16+CD158b+ cells in a dose-dependent manner. In contrast, CD16-CD158a/b+ cells did not increase. Additionally, the extract of TJ-48 enhanced the increase of KIRs expression induced by IL-2. These actions contribute to the augmentation of NK cytolytic activity by TJ-48, and might explain, in part, its antitumor effects which has been observed in vivo.

Adjuvants, Immunologic↗

PubMed2005

A randomized double blind placebo-controlled clinical trial of Hochuekkito, a traditional herbal medicine, in the treatment of elderly patients with weakness N of one and responder restricted design.

OBJECTIVE: To evaluate the effects of Hochuekkito, a traditional Japanese and Chinese medicine, in the treatment of elderly patients with general weakness. To devise a suitable study design for assessing the clinical effectiveness of traditional herbal medicines. METHODS: Fifteen elderly patients (mean +/- SD: age 78.4 +/- 7.8; m/f 3/12) participated in this study. A multicenter, prospective, randomized, double-blind, placebo-controlled study with N of one and responder restricted design was performed. After the run-in period, the patients were divided into responders and non-responders. Only responders were entered in the study, and were randomized into three groups: an active-placebo group, a placebo-active group and an active-active group. The study consisted of two 6-week terms with a 2-week washout period in between. We assessed the Short Form 36 Health Survey (SF-36) and Profile of Mood States (POMS) as an endpoint of quality of life (QOL). In addition, we assessed the biodefense status by measuring the natural killer cytolytic activity (NK activity), IL-2 producing activity of peripheral lymphocytes, lymphocyte proliferating activity and lymphocyte cell-surface antigens. RESULTS: The physical component summary of the SF-36 analysis significantly improved in the Hochuekkito-treated group. Four components (A-H: anger-hostility, F: fatigue, T-A: tension-anxiety, C: confusion) out of six improved in the Hochuekkito-treated group in the POMS analysis. Lymphocyte proliferating activity improved in the Hochuekkito-treated group but not significantly. Concerning the surface antigens of peripheral lymphocytes, the population of CD3 positive cells and CD3CD4 double positive cells increased in the Hochuekkito-treated group. CONCLUSION: We revealed that Hochuekkito improved the QOL and immunological status of elderly patients with weakness by randomized controlled trial. Our study design might be useful for assessing the efficacy of traditional herbal medicine in the future.

Affect↗

PubMed2004

Protective effect of keishi-bukuryo-gan and its constituent medicinal plants against nitric oxide donor-induced neuronal death in cultured cerebellar granule cells.

Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan) (KBG) is a traditional Chinese/Japanese medical (Kampo) formulation that has been administered to patients with "Oketsu" (blood stagnation) syndrome. In the process of neuronal cell death induced by brain ischemia, excessive generation of nitric oxide (NO) free radicals is implicated in the neurotoxicity. In the present study, we examined the protective effects of KBG and its constituent medicinal plants against NO donors, sodium nitroprusside (SNP) and 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (NOC18)-induced neuronal death in cultured rat cerebellar granule cells (CGCs). MTT assay showed cell viability to be significantly increased by the addition of KBG extract (KBGE) (100 microg/ml), Cinnamomi Cortex extract (CCE) (3, 10 and 30 microg/ml), Paeoniae Radix extract (PRE) (100 microg/ml) and Moutan Cortex extract (MCE) (10 and 30 microg/ml) compared with exposure to SNP (30 microM, 24 h) only. Also, cell viability was significantly increased by the addition of KBGE (100 and 300 microg/ml), CCE (30 and 100 microg/ml), PRE (100 and 300 microg/ml) and MCE (30 and 100 microg/ml) compared with exposure to NOC 18 (100 microM, 48 h) only. Persicae Semen extract and Hoelen extract did not protect against NO donor-induced neuronal death. These results suggest that KBG has protective effect against NO-mediated neuronal death in cultured CGCs and that it is derived from Cinnamomi Cortex, Paeoniae Radix and Moutan Cortex.

Animals↗

PubMed2004

Effect of docosahexaenoic acid-containing food administration on symptoms of attention-deficit/hyperactivity disorder - a placebo-controlled double-blind study.

OBJECTIVES: To investigate whether docosahexaenoic acid (DHA) supplementation was able to ameliorate attention-deficit/hyperactivity disorder(AD/HD) symptoms in AD/HD children. DESIGN AND SUBJECTS: A placebo-controlled double-blind study with 40 AD/HD (including eight AD/HD-suspected) children of 6-12 y of age who were mostly without medication. Subjects of a DHA group (n=20) took active foods containing fish oil (fermented soybean milk, bread rolls and steamed bread; 3.6 g DHA/week from these foods) for 2 months, whereas those of a control group (n=20) took indistinguishable control foods without fish oil. The following items were measured at the start and end of the study: (1) attention deficit, hyperactivity and impulsivity (AD/HD-related symptoms according to DSM-IV criteria); (2) aggression assessed by both parents and teachers; (3) visual perception (finding symbols out of a table); (4) visual and auditory short-term memory; (5) development of visual-motor integration; (6) continuous performance; (7) impatience. RESULTS: Changes in tests 1, 2, 3, 5 and 7 over time did not significantly differ between the two groups. However, visual short-term memory and errors of commission (continuous performance) significantly improved in the control group compared with the changes over time in the DHA group (P=0.02 and 0.001, respectively). Recalculation without AD/HD-suspected subjects (n=4 each group) showed similar P-values with regard to both measures. CONCLUSION: DHA supplementation did not improve AD/HD-related symptoms. Treatment of ADHD with fatty acids deserves further investigation, but careful attention should be paid as to which fatty acid(s) is used.

Aggression↗

PubMed2004

Effects of Keishi-bukuryo-gan on vascular function and hemorheological factors in spontaneously diabetic (WBN/kob) rats.

Keishi-bukuryo-gan (Gui-zhi-fu-ling-wan) is a formula used for the improvement of blood circulation. Recently it has often also been used for arteriosclerosis. One of the mechanisms involved is thought to be the improvement of endothelial dysfunction, but the details are still unclear. In this study, the effect of Keishi-bukuryo-gan on vascular function and hemorheological factors in spontaneously diabetic (WBN/kob) rats was studied. Rats were given Keishi-bukuryo-gan in chow for 30 weeks. Body weight, blood glucose, endothelium-dependent/-independent relaxation, vasocontraction by free radical-induced and contractive prostanoids, triglyceride, advanced glycation endproduct, lipid peroxides, serum NO2-/NO3- and blood viscosity were measured. The results indicated that Keishi-bukuryo-gan caused a decrease in endothelium-dependent relaxation by acetylcholine to become significantly increased, and vasocontraction induced by free radicals and contractive prostanoids was significantly decreased. Furthermore, serum NO2-/NO3- and blood viscosity were significantly decreased. From these results, it was supposed that Keishi-bukuryo-gan exerted a protective effect on the endothelium. The WBN/kob rat is a useful study model for the complications of human diabetes, and Keishi-bukuryo-gan showed a protective effect against vascular injury in the susceptible rat.

Administration, Oral↗

PubMed2004

The effects of a herbal medicine (Mao-to) in patients with chronic hepatitis C after injection of IFN-beta.

We found that a herbal medicine (Mao-to) relieves the side effects of interferon (IFN)-beta and the combination therapy improves the biochemical response rate. However, the exact mechanism by which Mao-to is effective remains to be established. We conducted a controlled trial to clarify the effects of Mao-to. The study was carried out in 18 patients with chronic hepatitis C, and we examined subjective symptoms, body temperature and cytokines such as interleukin (IL)-beta, IL-1receptor antagonist (ra), IL-6 and TNF-alpha. Each patient received 6 million units of IFN-beta intravenously. Mao-to was given orally just before, just after, and 1 hour after IFN administration. The control study was carried out 6 months after the combination therapy of Mao-to and IFN-beta. The scores for general malaise, arthralgia and discomfort were significantly lower in the combination group than in control group. Body temperature did not significantly differ between the two groups. Plasma IL-6 level and IL-1ra were significantly elevated in the combination group compared to control (P = 0.0057 and 0.0003, respectively). Mao-to did not affect plasma concentrations of IL-1beta and TNF-alpha. We considered the increment of IL-1ra caused by Mao-to is to be one of the key factors involved in reducing the flu-like symptoms accompanying IFN-beta and improving the biochemical response rate.

Adult↗

PubMed2004

Comparisons of LET distributions for protons with energies between 50 and 200 MeV determined using a spherical tissue-equivalent proportional counter (TEPC) and a position-sensitive silicon spectrometer (RRMD-III).

Experiments have been performed to measure the response of a spherical tissue-equivalent proportional counter (TEPC) and a silicon-based LET spectrometer (RRMD-III) to protons with energies ranging from 50-200 MeV. This represents a large portion of the energy distribution for trapped protons encountered by astronauts in low-Earth orbit. The beam energies were obtained using plastic polycarbonate degraders with a monoenergetic beam that was extracted from a proton synchrotron. The LET spectrometer provided excellent agreement with the expected LET distribution emerging from the energy degraders. The TEPC cannot measure the LET distribution directly. However, the frequency mean value of lineal energy, y(-)(f), provided a good approximation to LET. This is in contrast to previous results for high-energy heavy ions where y(-)(f) underestimated LET, whereas the dose-averaged lineal energy, y(-)(D), provided a good approximation to LET.

Linear Energy Transfer↗

PubMed2003

Measurement of plasma procyanidin B-2 and procyanidin B-3 levels after oral administration in rat.

Using a high-performance liquid chromatographic method and mass spectrometry analysis, we successfully measured the absorption of orally administered procyanidin B-2 and procyanidin B-3 isolated from Cinnamonomi cortex (the bark of Cinnamomum cassia Blume) in the rat plasma. This method used a TSK- GEL ODS-80TS column, two solvents (A: 0.01% acetic acid; B: methanol with 0.01% acetic acid) in a linear gradient at a flow-rate of 1.0 ml/min, and fluorescence detection at excitation and emission wavelengths of 220 and 327 nm.

Administration, Oral↗

PubMed2003

Comparative efficacy of Keishi-bukuryo-gan and pentoxifylline on RBC deformability in patients with "oketsu" syndrome.

Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan) (KBG) is one of the prescriptions in Japanese traditional medicine for improving the "oketsu" syndrome, so-called blood stasis syndrome. "Oketsu" syndrome is an important pathological conception in Japanese traditional medicine and often accompanies cerebro-vascular disorders. Previously, we were able to reveal a deterioration of RBC (Red blood cell) deformability and viscoelasticity in patients with "oketsu" syndrome. The purpose of the present study was to evaluate whether KBG has an effect on RBC deformability in comparison with pentoxifylline (PXF). The subjects were 30 male patients with multiple lacunar infarctions. Eighteen patients (44-79 yrs, mean +/- SD, 66.1 +/- 10.7 yrs) were treated with 12 g of KBG daily for 4 weeks (KBG group). Twelve patients (59-78 yrs, 70.7 +/- 6.4 yrs) were treated with 300 mg of PXF daily for 4 weeks (PXF group). Based on the "oketsu" score, the patients of each group were divided into two subgroups, a non-"oketsu" group ("oketsu" score 20 points or less) and an "oketsu" group ("oketsu" score 21 points or higher). KBG had significant effects on RBC deformability as evaluated by filtration method. KBG also significantly increased intracellular ATP content, as did PXF. Moreover, KBG was more effective for patients with a more severe "oketsu" state. However, PXF was effective only in patients with "oketsu" syndrome, who might have deteriorated RBC deformability. In conclusion, the effect of KBG on RBC deformability was by no means inferior to PXF.

Administration, Oral↗

PubMed2002

LET distributions from CR-39 plates on Space Shuttle missions STS-84 and STS-91 and a comparison of the results of the CR-39 plates with those of RRMD-II and RRMD-III telescopes.

The LET distributions during the Space Shuttle missions STS-84 (altitude 270-412 km, average 375 km; inclination angle, 51.6 degrees) and STS-91 (altitude 328-397 km, average 373 km; inclination angle, 51.6 degrees) were measured using CR-39 plastic nuclear track detectors. A correction for the dip-angle dependence of the track-formation sensitivity of the CR-39 plates was applied to the data analysis. The absorbed doses and the dose equivalents around RRMD Detector Units, estimated from the LET distributions in the LET region of 4-200 keV/micrometers, fluctuated with standard deviations of +/- 21% to +/- 35% in both flight experiments. The LET distributions obtained from the CR-39 plates agreed well with that obtained from RRMD-II in STS-91. However, the particle fluxes obtained from RRMD-III in STS-84 and STS-91 were two or three times higher than those obtained from RRMD-II and the CR-39 plates. It was concluded that the LET distributions obtained from RRMD-II and the CR-39 plates in the present flight experiments did not include the contribution of target-fragmented secondary heavy particles produced by low-LET particles, such as relativistic or semi-relativistic protons and helium ions, whereas RRMD-III was able to detect these secondary particles because of its low triggering level.

Cosmic Radiation↗

PubMed2002

Effects of Choto-san on hemorheological factors and vascular function in stroke-prone spontaneously hypertensive rats.

Choto-san is a formula used for the treatment of headache and vertigo. Recently it has often also been used for hypertension and dementia. One of the mechanisms involved is thought to be the improvement of blood circulation, but the details are still unclear. In this study, the effect of Chotosan was studied on nitric oxide (NO) function, hemorheological factors and endothelial function in stroke-prone spontaneously hypertensive rats (SHR-SP). Rats were given Choto-san in drinking water for eight weeks. Body weight, blood pressure, serum NO2-/NO3-, lipid peroxides, blood viscosity, erythrocyte deformability and endothelium-dependent/-independent relaxation were measured. The results indicated that Choto-san caused a decrease in blood pressure and an increase in erythrocyte deformability and NO function. Blood viscosity was not changed. Furthermore, endothelium-dependent relaxation by acetylcholine was significantly increased as compared to control. In this study, it was supposed that Choto-san had a protective effect on the endothelium. SHR-SP is a useful model for human brain stroke, and Choto-san showed a protective effect against cerebral vascular injury in the susceptible rat.

Acetylcholine↗

PubMed2002

Effect of Seihai-to, a Kampo medicine, in relapsing aspiration pneumonia--an open-label pilot study.

Two published case reports described palliation of disease after Seihai-to therapy for refractory aspiration pneumonia caused by recurrent laryngeal nerve paralysis and cerebrovascular disease. We undertook an open-label trial in patients with relapsing aspiration pneumonia. Fifteen patients with relapsing aspiration pneumonia were randomly divided into conventional therapy group (n = 8) or Seihai-to group (n = 7). In Seihai-to group, patients were treated with Seihai-to in addition to conventional therapy (Western medicines). Frequency of feverish days and antibiotics-use, CRP value and chest CT or X-ray findings were compared between the two groups during the study period of 16 weeks. In the Seihai-to group, the latency of swallowing reflex was measured in 6 patients before and after administration of Seihai-to. The mean values of fever index, CRP value and antibiotics-use in the Seihai-to group were decreased significantly, compared with those of the conventional therapy group. However, the latency of the swallowing reflex after 4 weeks of treatment was not significantly changed (p = 0.249), compared with the latency before administration of Seihai-to. No adverse reaction was observed in either group. Seihai-to was effective in reducing relapse of aspiration pneumonia in this small group. Seihai-to might not improve the swallowing reflex, but might instead improve a defense mechanism or excessive inflammation caused by pneumonia in the lower airway. Further evaluation of Seihai-to therapy for patients with aspiration pneumonia in a larger population is warranted.

Aged↗

PubMed2002

Incidence and clinical features of liver injury related to Kampo (Japanese herbal) medicine in 2,496 cases between 1979 and 1999: problems of the lymphocyte transformation test as a diagnostic method.

We retrospectively examined the summaries of all admission records of patients from 1979 to 1999 in our department, and selected for further study all liver injuries suspected of being related to Kampo medicines. Among 2,496 summaries, 30 summaries described liver disorders suspected of being related to Kampo medicines. Whether there was a causal relationship between the use of Kampo medication and the occurrence of liver injury was assessed according to the criteria described by Haller and Benowitz (2000), independently of the results of the lymphocyte transformation test (LTT). Among 30 events, we concluded that 9 were definitely unrelated, and 6 were probably unrelated to the use of Kampo medicines. Nine events (0.36% of 2,496 patient admissions and 0.06% of 14,616 outpatients) were considered possibly related, and only 6 events (0.24% of 2,496 patient admissions and 0.04% of 14,616 outpatients) were judged to be definitely or probably related to Kampo medicines. Low-grade eosinophilia was observed in a few patients of these "related" groups, and no fever or rash was observed in these "related" groups. Other clinical features, including type of liver injury, duration of Kampo medicine-use, recovery period and laboratory data, were not different from liver injuries associated with western drugs. Most patients in the definitely "unrelated" group were positive in the LTT for the suspect Kampo medicine, suggesting that the LTT may be unreliable for the diagnosis of Kampo-medicine-induced liver injury. From 1979 to 1999, our use of Kampo medicines to treat patients resulted in a low rate of liver injury and no fatalities.

Adolescent↗

PubMed2002

Inhibitory effects of Choto-san (Diao-teng-san), and hooks and stems of Uncaria sinensis on free radical-induced lysis of rat red blood cells.

The present study is designed to test our hypothesis that the ingestion of Uncaria sinensis (US), the main medicinal plant of Choto-san (Diao-teng-san, CS), would protect red blood cell (RBC) membrane from free radical-induced oxidation if polyphenolics in US could be absorbed and circulated in blood. When incubated with RBC suspension, Choto-san extract (CSE) and Uncaria sinensis extract (USE) exhibited strong protection for RBC membrane against hemolysis induced by 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH), an azo free-radical initiator. The inhibitory effect was dose-dependent at concentrations of 50 to 1000 microg/mL. Ingestion of 200 mg of USE was associated with a significant decrease in susceptibility of RBC to hemolysis in rats. Furthermore, caffeic acid, an antioxidative hydroxycinnamic acid, was identified in rat plasma after administration of URE.

Amidines↗

PubMed2002

The efficacy of a herbal medicine (Mao-to) in combination with intravenous natural interferon-beta for patients with chronic hepatitis C, genotype 1b and high viral load: a pilot study.

Patients with chronic hepatitis C, with a high serum viral load (> or = 1 Meq/ml) and genotype 1b seem to be resistant to interferon (IFN) therapy. To evaluate the efficacy of a herbal medicine (Mao-to) in combination with natural IFN-beta for the treatment of these patients, eighteen Japanese patients were enrolled in this study. Every patient received 6 million units (MU) of IFN-beta intravenously daily for 8 weeks. Mao-to was given orally 3-4 times a day during the IFN-beta administration, Sixteen of the 18 patients (89%) became negative for serum HCV RNA at the end of treatment, but only 2 of them (11%) remained negative for the virus RNA at 6 months of follow-up. Serum ALT levels normalized in 17 patients (94%) at 2 weeks of follow-up after the cessation of therapy, and 11 patients (61%) retained normal ALT levels for more than 6 months of follow-up. This rate of biochemical response was high as compared with that of therapy with IFN-beta alone (19%) in the largest IFN-beta trial in Japan. Serum hyaluronic acid levels were decreased significantly from 147.0 +/- 110.5 ng/ml to 77.4 +/- 67.4 ng/ml in the sustained biochemical response group (P = 0.003). None of the patients needed to interrupt therapy because of side effects of IFN-beta. Thus, Mao-to administration together with IFN-beta treatment could increase the sustained biochemical response rate, and reduce liver fibrosis.

Adult↗

PubMed2002

A comparative study between excess-dose users and regular-dose users of rhubarb contained in Kampo medicines.

With prolonged use of rhubarb-containing Kampo medicines, some patients come to ask for high-dose rhubarb because of deteriorated reactivity to rhubarb. We divided patients into two groups in terms of rhubarb-dose, and compared clinical backgrounds between regular-dose group and excess-dose group. Patients who were treated with rhubarb-containing Kampo extracts (manufactured prescriptions) or Kampo formulae (decoctions) for more than 12 months were enrolled. These two groups were compared for age, sex, shape of stool, abdominal symptoms, existence of hemorrhoids, Kampo diagnosis of abdomen, past stimulant laxative use, duration of stimulant laxative use before the first administration of rhubarb, duration of rhubarb use in our hospital, and initial existence of stimulant pain caused by taking stimulant laxatives for the first time. No significant difference was shown between the two groups in terms of age, duration of stimulant laxative-use before the first prescription of rhubarb, shape of stool, abdominal symptoms, existence of hemorrhoids, or duration of rhubarb-use. However, most patients in the regular-dose group had initial stimulant pain of the abdomen upon taking stimulant laxatives for the first time, but most patients in the excess-dose group did not (p < 0.001). All patients except one in the regular dose group had the sign of "umbilical region tenderness on pressure", but half of the excess-dose group did not have it (p = 0.041). Based on these findings, the absence of "initial stimulant pain" and the absence of "umbilical region tenderness on pressure" may predict increasing or excess use of rhubarb, and long-term use of rhubarb should be discouraged more strongly in the patients without these signs.

Cathartics↗