An online survey on differences in knowledge and stigma about epilepsy among the Tokyo metropolitan area and non-urban areas in Japan, a post-hoc study.

PURPOSE: Extant research elucidating the domains of knowledge and bias on epilepsy has consistently underscored a deficiency in cognizance and an inclination toward bias within non-urban areas. Investigations into geographical disparities concerning epilepsy awareness and prejudice within the Japanese context remain conspicuously absent. To address this lacuna in the literature, we undertook a post-hoc analysis to elucidate the discernible regional differentials in epilepsy awareness and the associated stigma. METHODS: From July to August 2021, we conducted an internet questionnaire survey for 310 people with epilepsy (PWE) and 213 ordinary people without epilepsy who registered on the database of the Japanese Research Company. We inquired PWE to answer the Epilepsy Self-Stigma Scale (ESSS), the Rosenberg Self-Esteem Scale (RSES), and the Epilepsy Knowledge Scale (EKS). We inquired to answer ordinary people without epilepsy EKS. We analyzed residential addresses separately for Greater Tokyo and non-urban areas by comparing the degree of knowledge of people with epilepsy and people without epilepsy. RESULTS: The average knowledge of people with and without epilepsy in the Greater Tokyo area was 39.60 and 28.43 points, although in non-urban areas (nine regions from all over Japan except for the Greater Tokyo, Tokai region, and Kinki region), the knowledge averages were 38.44 and 28.66 points of 100. In addition, self-stigma was highest in the Greater Tokyo area: 22.99 and in non-urban areas: 22.77. An two-way ANOVA with knowledge as the dependent variable and epilepsy diagnosis status and region (Greater Tokyo area/non-urban areas) as the independent variables revealed no interaction between diagnosis and region (F(1,346) = 1.48, η2 = 0.003). Knowledge was significantly higher in PWE than in people without epilepsy, but we could not identify any significant difference between ESSS (t = 0.24, d = 0.03) and RSES (t = 1.16, d = 0.16) in the Greater Tokyo/non-urban areas. CONCLUSIONS: We obtained specific information about regional differences in the level of knowledge and stigma about epilepsy in Japan. Because Japan underwent educational reforms after World War II and more than 90% of the population received equally advanced education, the results found no regional differences in knowledge and stigma about epilepsy. We believe collecting information about the respondents' birth and upbringing environment and conducting a thorough investigation is necessary in the future.

Internet survey on knowledge and perceptions of epilepsy among the general public in Japan.

Objective: To improve the life quality of people with epilepsy, it is necessary to provide comprehensive epilepsy care and disseminate accurate information related to epilepsy to the public. In Japan, reports of traffic accidents involving people with epilepsy started to draw attention in the media in 2011. Ever since that, the association between the image of epilepsy from the general public, "Epilepsy," and "Danger," was more robust in 2013. Since 2017, no previous surveys have examined the perceptions and knowledge of epilepsy among the public in Japan. As an essential source of information for epilepsy care, we conducted a nationwide Internet-based survey to elucidate the current state of knowledge and perceptions of epilepsy among the public without epilepsy in Japan. Methods: We conducted an online survey from July 29 to August 2, 2021, with 213 respondents (115 male, 97 female, and one unidentified; mean age: 50.52 ± 12.34 years) registered with an online survey service in Japan. In this survey, we first questioned whether or not a respondent had epilepsy, and then those with epilepsy were excluded from participation. We collected basic demographic information, administered the Epilepsy Knowledge Scale (18 items), and asked the open-ended response question, "What kind of disease do you think epilepsy is? If you do not know, please describe epilepsy in your words." We adopted quantitative text analysis using KH Coder3 and co-occurrence network analysis to examine the connections between words. Results: Among the respondents, 92% have heard of epilepsy, and 26.8% have observed an epileptic seizure before the survey. The knowledge scale yields an average score of 27.96 ± 21.3 (out of 100), with the question with the highest percentage of correct responses being "People with epilepsy are just as capable as other people" at 51.64%. The question with the lowest percentage of correct responses was "If the person with epilepsy only has seizures during sleep, the person can have a driver's license," at 9.85%. The average number of Japanese characters responding to open-ended text questions was 10.45 ± 8.87 characters (including Kanji, Hiragana, and Katakana). We found that the word "froth" appeared more frequently with experience of observing a seizure, and the words "occur" and "brain" appeared more frequently with higher knowledge of epilepsy. Furthermore, comparing the sources of information from what they learned about epilepsy, the words "seizure," "faint," and "consciousness" appeared more frequently in school, with family and friends, and in newspapers and television, respectively. Conclusion: We identified the level of knowledge and perceptions of epilepsy among the general public in Japan in 2021. By analyzing the qualitative aspects of open-ended text responses, we gathered information that might be useful for informing the public of future efforts to provide accurate information related to epilepsy.

A study of factors influencing self-stigma in people with epilepsy: A nationwide online questionnaire survey in Japan.

OBJECTIVE: Epilepsy carries a significant stigma. While there is some evidence that self-stigma accompanies a lack of knowledge about epilepsy, there are no studies in Japan. This study aimed to determine factors contributing to self-stigma in Japan. METHODS: We conducted an online questionnaire survey. Three hundred and ten patients completed the questionnaire (mean age of 47.8 ± 11.9) in contrast to the total registered users on the questionnaire site as 28 315 from Jul 29 to Aug 2, 2021. We asked about demographic variables, satisfaction with treatment, limitations in life, support status, seizure frequency, the Epilepsy Self-Stigma Scale (ESSS), the Rosenberg Self-Esteem Scale (RSES), and the Epilepsy Knowledge Scale (EKS). We conducted the statistical analysis on self-stigma, self-esteem, knowledge of epilepsy, and seizure frequency associations by Spearman's rank correlation. RESULTS: The mean value of the EKS was 40.19 ± 18.75, the ESSS was 17.69 ± 6.25, and the RSES was 26.02 ± 6.13. We identified a significant moderate negative correlation between self-esteem and self-stigma (P < .001, ρ = -.423), a significant weak positive correlation between self-esteem and knowledge (P = .005, ρ = .177), and a significant weak negative correlation between seizure frequency and self-stigma (P < .001, ρ = -.162). Of the 186 respondents who were working or studying, 91 (49%) participants had experienced any discrimination due to epilepsy. The use of psychosocial support, that is, participating in epilepsy self-help groups and educational programs, was 5.8%. SIGNIFICANCE: There was no correlation between the strength of self-stigma and the knowledge, while there was a positive correlation between self-esteem and knowledge (P = .005, ρ = .177). There was a negative and weak correlation between seizure frequency and self-stigma (p < .001, ρ = -.162). These results suggest that sufficient knowledge may improve the self-esteem and thus reduce the self-stigma. In addition, short-term treatment for seizure control is insufficient to reduce self-stigma. The dissemination for people to enable sufficient epilepsy knowledge and positive perceptions of epilepsy by increasing self-efficacy throughout a lifetime may reduce self-stigma.

Diagnostic accuracy of ultra-low-dose CT colonography for the detection of colorectal polyps: a feasibility study.

PURPOSE: The aim of this feasibility study was to evaluate the diagnostic accuracy of ultra-low-dose CT colonography using iterative reconstruction algorithms with reference to standard colonoscopy. MATERIALS AND METHODS: Prior to this study, a phantom study was performed to investigate the optimal protocol for ultra-low-dose CT colonography. A total of 206 patients with average/high risk of colorectal cancer were recruited. After undergoing full bowel preparation, the patients were scanned in the prone and supine positions with the CT conditions set to 120 kV, standard deviation 45 to 50, and an adaptive iterative reconstruction algorithm applied. Two expert readers read the images independently. The main outcome measures were the per-patient and per-polyp accuracies for the detection of polyps ≥ 10 mm, with colonoscopy results as the reference standard. RESULTS: Two hundred patients (102 females, mean age 67.5 years) underwent both ultra-low-dose CT colonography and colonoscopy on the same day. The mean radiation exposure dose was 0.64 ± 0.34 mSv. On colonoscopy, 39 patients had 45 polyps ≥ 10 mm (non-polypoid morphology 7), including 4 cancers. Per-patient sensitivity, specificity, and accuracy of CT colonography for polyps ≥ 10 mm were 0.74, 0.96, and 0.92 for reader one, and 0.74, 0.99, and 0.94 for reader two, respectively. Per-polyp sensitivities for polyps ≥ 10 mm were 0.73 for reader one and 0.71 for reader two. On subgroup analysis by morphology, non-polypoid polyps ≥ 10 mm were not detected by both readers. CONCLUSION: Extreme ultra-low-dose CT colonography had an insufficient diagnostic performance for the detection of polyps ≥ 10 mm, because it was unable to detect non-polypoid polyps. This study showed that the problem with ultra-low-dose CT colonography was the lack of detectability of small-size polyps, especially non-polypoid polyps. To use ultra-low-dose CT colonography clinically, it is necessary to resolve the problems identified by this study.

[Assessments and Treatments for Neurological Symptoms That Do Not Match Organic Findings].

Many clinicians treat patients with neurological symptoms such as muscle weakness and involuntary movements, that do not correspond to organic findings. The differential diagnosis of patients with medically unexplainable symptoms includes conversion disorder, somatic symptom disorder, and illness anxiety disorder among others. Conversion disorder is a mental disorder with pseudo-neurological symptoms that are not due to an organic abnormality. For its diagnosis it is necessary to show that the symptoms and findings are not compatible with neurological diseases. Conversion disorder and any neurological diseases can coexist, in which cases neurologists and psychiatrists should cooperate when treating the patient. However, it is difficult to clearly distinguish individual symptoms by their mechanism. Patients complaining of physical symptoms, including those with conversion disorder, require careful explanation that takes into account the patient's explanatory model. Clinicians must switch from an acute disease model to a chronic disease model. These patients are more likely to concentrate consciously on their physical condition and clinicians should help patients avoid ruminating on their physical symptoms. Because it is not simple to completely exclude physical disorders and prove that the symptoms are psychogenic, confirming a diagnosis should be performed carefully.

[Psychogenic Retrograde and Anterograde Amnesia].

Patients with dissociative retrograde amnesia, under the influence of high stress, lose access to past autobiographical event memories that should have been remembered. Patients with dissociative anterograde amnesia cannot recall extremely emotional experiences. If dissociative anterograde amnesia is experienced repeatedly in daily life, something in daily life becomes a fear stimulus. Fear conditioning in dissociative anterograde amnesia is often related to past memories of child abuse that can not be recalled due to dissociative amnesia.

Adverse events during CT colonography for screening, diagnosis and preoperative staging of colorectal cancer: a Japanese national survey.

OBJECTIVES: To retrospectively evaluate the frequencies and magnitudes of adverse events associated with computed tomographic colonography (CTC) for screening, diagnosis and preoperative staging of colorectal cancer. METHODS: A Japanese national survey on CTC was administered by use of an online survey tool in the form of a questionnaire. The questions covered mortality, colorectal perforation, vasovagal reaction, total number of examinations, and examination procedures. The survey data was collated and raw frequencies were determined. Fisher's exact test was used to determine differences in event rates between groups. RESULTS: At 431 institutions, 147,439 CTC examinations were performed. No deaths were reported. Colorectal perforations occurred in 0.014% (21/147,439): 0.003% (1/29,823) in screening, 0.014% (13/91,007) in diagnosis and 0.028% (7/25,330) in preoperative staging. The perforation risk was significantly lower in screening than in preoperative staging CTC procedures (p = 0.028). Eighty-one per cent of perforation cases (17/21) did not require emergency surgery. Vasovagal reaction occurred in 0.081% (120/147,439): 0.111% (33/29,823) in screening, 0.088% (80/91,007) in diagnosis and 0.028% (7/25,330) in preoperative staging. CONCLUSIONS: The risk of colorectal perforation and vasovagal reaction in CTC is low. The frequency of colorectal perforation associated with CTC is least in the screening group and greatest in the preoperative-staging group. KEY POINTS: • The colorectal perforation rate during preoperative-staging CTC was 0.028 %. • The perforation rates for screening and diagnosis were 0.003 % and 0.014 %, respectively. • The perforation risk is significantly lower in screening than in preoperative staging. • Eighty-one per cent of perforation cases did not require emergency surgery. • Use of an automatic colon insufflator can reduce the risk of bowel perforation.

Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.

OBJECTIVES: The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists. METHODS: This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ≥6 mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated. RESULTS: Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ≥6 mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ≥10 mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8 min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ≥10 mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists. CONCLUSIONS: CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ≥6 mm than did radiologists, although their interpretation time was longer than that of radiologists.

Diagnostic Performance and Patient Acceptance of Reduced-Laxative CT Colonography for the Detection of Polypoid and Non-Polypoid Neoplasms: A Multicenter Prospective Trial.

Purpose To evaluate the diagnostic accuracy and patient acceptance of reduced-laxative computed tomographic (CT) colonography without computer-aided detection (CAD) for the detection of colorectal polypoid and non-polypoid neoplasms in a population with a positive recent fecal immunochemical test (FIT). Materials and Methods Institutional review board approval and written informed consent were obtained. This multicenter prospective trial enrolled patients who had positive FIT results. Reduced-laxative CT colonography and colonoscopy were performed on the same day. Patients received 380 mL polyethylene glycol solution, 20 mL iodinated oral contrast agent, and two doses of 20 mg mosapride the day before CT colonography. The main outcome measures were the accuracy of CT colonography for the detection of neoplasms 6 mm or larger in per-patient and per-lesion analyses and a survey of patient perceptions regarding the preparation and examination. The Clopper-Pearson method was used for assessing the 95% confidence intervals of per-patient and per-lesion accuracy. Survey scores were analyzed by using the Wilcoxon and χ2 tests. Results Three hundred four patients underwent both CT colonography and colonoscopy. Per-patient sensitivity, specificity, positive predictive value, and negative predictive value of CT colonography for detecting neoplasms 10 mm or larger were 0.91 (40 of 44), 0.99 (255 of 258), 0.93 (40 of 43), and 0.98 (255 of 259), respectively; these values for neoplasms 6 mm or larger were 0.90 (71 of 79), 0.93 (207 of 223), 0.82 (71 of 87), and 0.96 (207 of 215), respectively. Per-lesion sensitivities for detection of polypoid and non-polypoid neoplasms 10 mm or larger were 0.95 (40 of 42) and 0.67 (six of nine), respectively; those for neoplasms 6 mm or larger were 0.90 (104 of 115) and 0.38 (eight of 21), respectively (P < .05 for both). Patient acceptance of preparation and examination with CT colonography was significantly higher than that with colonoscopy, and 62% (176 of 282) of patients would choose CT colonography as the first examination if they have a positive FIT result in the future. Conclusion Reduced-laxative CT colonography without CAD is accurate in the detection of polypoid neoplasms 6 mm or larger but is less accurate in the detection of non-polypoid neoplasms. Reduced-laxative CT colonography has high patient acceptance and is an efficient triage examination for patients with a positive FIT. © RSNA, 2016 Online supplemental material is available for this article.

Physicians' attitudes toward the definition of "death from age-related physical debility" in deceased elderly with aspiration pneumonia.

AIM: Deaths from aspiration pneumonia in elderly patients are occasionally considered to be "death from age-related physical debility", because most aspiration pneumonias are a result of aging and lead to death without any definitive therapy. The aim of the present study was to assess physicians' attitudes toward the diagnosis of and actual description of "death from age-related physical debility" on death certificates for deceased patients with aspiration pneumonia. METHODS: This study surveyed 62 Japanese physicians including 36 pulmonologists and 26 other physicians who treat patients with pneumonia. Their attitudes regarding consideration and actually recorded "death from age-related physical debility" for deceased patients with aspiration pneumonia were assessed by using anonymous questionnaires, which included the decision-making process and the necessity of detailed diagnostic criteria. RESULTS: A total of 32 (52%) respondents had considered deceased patients with aspiration pneumonia to be "death from age-related physical debility", and 10 (16%) have actually stated this on the death certificate. Advanced age, bedridden status, inability of oral intake and disturbance of consciousness including dementia were major factors in their decision-making. A total of 34 (55%) of the respondent physicians wanted detailed criteria to be established. CONCLUSIONS: Physicians' attitudes toward the definition of "death from age-related physical debility" vary a great deal depending on the respondent. The description in death certificates therefore might inaccurately reflect the results of current mortality statistics in Japan.

Medical professionals' attitudes toward tube feeding for themselves or their families: a multicenter survey in Japan.

BACKGROUND: Many studies have shown a lack of advantages to tube feeding for elderly with advanced dementia, but tube feeding is still considered standard care in Japan. The aim of this study is to investigate what nutrition method health care professionals want for themselves or their families, if they fall into a bedridden state due to irreversible impaired cognition in old age. METHODS: In 2010 we surveyed 1321 Japanese health care professionals including 251 medical doctors and 1070 nurses. Their attitudes toward tube feeding were assessed by using an anonymous questionnaire, which included desired feeding methods for themselves or their families and propriety of card-based declaration of intent for end-of-life care. RESULTS: Rates of accepting tube feeding for themselves and their families were 14.4% and 43.4%, respectively. In multivariate analyses, working at a municipal hospital and high frequency of taking care of tube-fed elderly patients were predictors of refusing tube feeding for themselves. Working at a municipal hospital and being a medical doctor were predictors of refusing tube feeding for their families. The rate of welcoming card-based declaration of intent for end-of-life care including feeding methods was 65.2%. CONCLUSIONS: Many doctors and nurses, especially with more frequent contact with tubefed patients, rejected tube feeding for themselves on their own deathbed, but did not always refuse this option for their families.

Anti-influenza virus principles from Muehlenbeckia hastulata.

Extracts of Chilean medicinal plants were evaluated in vitro for their activities against influenza virus proliferation in MDCK cells. The most potent extract obtained was from Muehlenbeckia hastulata (Polygonaceae), known as Quilo in Chile, from which three active principles were isolated and identified as pheophorbide a (1), hypericin (2) and protohypericin (3). Minimum inhibitory concentration (MIC) values of 42 ng/ml for compound 1, 2.1 ng/ml for compound 2 and 1.5 ng/ml for the authentic hypericin were determined by using an endpoint assay which comprises pre-incubation of serially diluted specimens with a given amount of the influenza virus, incubation of the pre-incubated virus/specimen with MDCK cells and determination of the hemagglutination (HA) titer of the culture supernatant. Compound 3 was easily converted to 2 on exposure to visible light and, in due course, showed an anti-influenza virus activity (3.1 ng/ml) similar to 2. Although compounds 1-3 were previously isolated from other plants, this is the first report of their isolation from M. hastulata. The high content of 1 (0.06% dry weight of whole plant) is noteworthy. In addition, this is the first report on the isolation of compounds 2 and 3 from a plant other than the genus Hypericum.

Metabolic fate of fraxin administered orally to rats.

Naturally occurring fraxin (1) was administered orally to rats to investigate its metabolism. Urinary metabolites were analyzed by three-dimensional HPLC, and fraxetin-7-O-sulfate (2), fraxetin-7-O-beta-glucuronide (3), fraxetin (4), 6,7,8-trihydroxycoumarin (5), and fraxidin (6) were isolated. Fraxin (1) was extensively metabolized to 4, which was partly metabolized to 5 in a rat fecal suspension after incubation for 24 h. Urinary excretion of 4 and 5 in rats administered orally with 1 was substantially reduced when the rats were treated with antibiotics to suppress their intestinal flora. Incubation of 1 with a rat liver S-9 mixture yielded 6. These results suggest that hydrolysis and demethylation of 1 are performed by intestinal microflora, while methylation occurs in the liver.

Antipyretic, analgesic and muscle relaxant activities of pueraria isoflavonoids and their metabolites from Pueraria lobata Ohwi-a traditional Chinese drug.

We evaluated the antipyretic, analgesic, and muscle relaxant activities of Pueraria isoflavonoids and their metabolites in mice. The glycosides daidzin and genistin significantly reduced fever induced by lipopolysaccharide (LPS). Their metabolites, daidzein and p-ethylphenol, also significantly reduced fever induced by LPS. In addition, daidzin, daidzein, dihydrodaidzein, and p-ethylphenol showed analgesic activity as assessed by the acetic acid-induced writhing test. Furthermore, equol and p-ethylphenol showed muscle relaxant activity in the rotarod and horizontal wire test. These results suggest that these compounds play a major role in the therapeutic activity of Pueraria isoflavonoids.

Metabolic fate of orally administered phyllodulcin in rats.

Naturally occurring phyllodulcin (1) was orally administered to rats to investigate its metabolic fate. Urinary metabolites were analyzed by three-dimensional HPLC. Phyllodulcin-3'-O-sulfate (2), phyllodulcin-3'-O-beta-glucuronide (3), 2-[2-(3,4-dihydroxyphenyl)ethyl]-6-hydroxybenzoic acid (4), and one novel bibenzyl derivative, 2-[2-(3-hydroxy-4-methoxyphenyl)ethyl]-6-hydroxybenzoic acid (5), together with thunberginol G (6) and hydrangenol (7) were isolated from the phyllodulcin-treated urine. 1 was extensively metabolized to 4-6 by a rat fecal suspension after incubation for 24 h. Urinary excretion of 4-6 in rats administered phyllodulcin orally was substantially reduced when the rats were treated with antibiotics to suppress their intestinal flora. On the other hand, the incubation of 1 with rat liver S-9 mix showed the presence of 7 together with 4 and 5.

[Effect of Kampo medicines on the peripheral blood flow rate of betamethason-induced Oketsu syndrome mice by laser Doppler flow meter].

Stagnation of peripheral blood flow is the cause of various diseases. Changes in peripheral blood flow after oral administration of Kampo medicines in mice with betamethasone-induced oketsu syndrome and normal mice were examined using a laser Doppler blood flow meter. The Kampo medicines used were: Toki-shakuyaku-san; Kami-shoyo-san; Keishi-bukuryo-gan; Daio-botanpi-to; Tokaku-joki-to; Goshuyu-to; and Hange-koboku-to. In the oketsu mice, blood flow was improved by single-dose administration of Toki-shakuyaku-san, Kami-shoyo-san, Keishi-bukuryo-gan, Daio-botanpi-to, Tokaku-joki-to, and Goshuyu-to, but only Toki-shakuyaku-san increased blood flow significantly in normal mice. In addition, blood flow decreased after single-dose administration of Keishi-bukuryo-gan, Daio-botanpi-to, and Tokaku-joki-to in normal mice.

Urinary metabolites of nobiletin orally administered to rats.

During the course of our systematic investigation of the metabolism of flavonoids, the polymethoxyflavone nobiletin, occurring in the fruits of Citrus depressa, was orally administered to rats. The urinary metabolites were separated and identified by three-dimensional HPLC equipped with a photodiode array detector and the structure was determined by spectroscopic methods to be 4'-hydroxy-3',5,6,7,8-pentamethoxyflavone (1).

Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test.

We studied the effects of apigenin and 2,4,5-trimethoxycinnamic acid (TMCA) on the behavioral despair test (forced swimming test), and the central noradrenergic, dopaminergic and serotonergic activities in mice. Apigenin at intraperitoneal doses of 12.5 and 25 mg/kg significantly decreased the duration of immobility in the forced swimming test in mice. At 100 mg/kg, the duration of immobility was returned to the control level in the test. On the other hand, TMCA treatment (25-200 mg/kg, i.p.) failed to significantly alter the duration of immobility. Based on the behavioral data, we examined changes in the monoamine turnover in mice having been subjected to forced swimming for 40 min. The monoamine turnover was measured in seven brain regions. Forced swimming exposure induced a significant decrease in dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) in the striatum and amygdala and in 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytriptamine (5-HT) in the hypothalamus, and a significant increase in DOPAC/DA in the thalamus and hypothalamus and in 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG)/norepinephrine (NE) in the amygdala, frontal cortex, hypothalamus, and midbrain. Apigenin (25 mg/kg) treatment produced attenuation of forced swim test-induced decrease of DA turnover in the amygdala and increase of DA turnover in the hypothalamus. Furthermore, intraperitoneal administration of haloperidol (0.2 mg/kg), a dopamine D(2) antagonist, blocked the apigenin (25 mg/kg)-induced decrease in immobility in the forced swimming test. These behavioral and biochemical results indicate the antidepressant properties of apigenin, which may be mediated by the dopaminergic mechanisms in the mouse brain.

Inhibitory effects of urinary metabolites on platelet aggregation after orally administering Shimotsu-To, a traditional Chinese medicine, to rats.

Shimotsu-To, which consists of four herbal extracts, has been used clinically for improving abnormal blood coagulation, fibrinolysis, atherosclerosis and chronic inflammation in Japan and China. We have investigated the pharmacological relationship between the effects and chemical components of Shimotsu-To after oral administration to rats. The urinary constituents were separated and identified by three dimensional (3D-) HPLC equipped with a photodiode array detector as a new tool and the chemical structures were determined by spectroscopic methods to be trans-ferulic acid-3-O-sulfate (1), vanillic acid (2), m-hydroxyphenylpropionic acid (3), trans-ferulic acid (4) and cis-ferulic acid (5). Of these compounds, 2-5 strongly inhibited platelet aggregation induced by ADP and arachidonic acid. Compound 1, the sulfate conjugate of 4, did not show any inhibitory effect, which suggested that the inhibitory effect on platelet aggregation was inactivated by sulfate conjugation. These results indicated that compounds 2-5 partly contributed to the anti-Oketsu effect of Shimotsu-To through the inhibition of platelet aggregation.

Metabolites of orally administered Magnolia officinalis extract in rats and man and its antidepressant-like effects in mice.

As a part of our search for the active metabolite from the bark of Magnolia officinalis (Magnoliaceae), the aqueous extract was orally administered to rats, and metabolites in the urine were analysed by a high-performance liquid chromatograph equipped with a photodiode array detector. When the extract was given to rats, five metabolites (sinapic acid-4-O-sulfate (1), sinapic acid-4-O-beta-glucuronide (2), sinapic acid (3), 3-[2',6-dihydroxy-5'-(2-propenyl)[1,1'-biphenyl]-3-yl]-(E)-2-propenoic acid (4), and an unchanged form, magnolol (5)) were detected in the urine. It was revealed that metabolites 1-3 and 4 were respectively derived from syringin and magnolol contained in the extract. In a human urine sample, metabolites 3-5 and dihydroxydihydromagnolol (6) were detected. These structures were identified by a combination of spectral methods and/or by comparison with authentic compounds obtained by synthesis. Among these free form metabolites (3-6), acute treatments with magnolol and dihydroxydihydromagnolol (50-100 mg kg(-1), i.p.) attenuated the forced swim-induced experimental depression in mice. The results indicated that magnolol and dihydroxydihydromagnolol were the antidepressant constituents of Magnolia officinalis.