Yoshiro Hirasaki

Yokukan-san: a review of the evidence for use of this Kampo herbal formula in dementia and psychiatric conditions.

Japanese traditional herbal medicine (Kampo) has its origins in traditional Chinese medicine (TCM). It was introduced to Japan in the middle of the sixth century and has evolved over the past 1,400 years after combining with Japan’s original folk remedies. While it retains some similarities to TCM, Kampo has evolved in Japan, resulting in a system of medicine that has many differences from TCM. Kampo medicine is considered to be very safe; in Japan, Kampo herbal formulas are manufactured by licensed pharmaceutical companies, prescribed by Western-trained medical doctors (usually as a freeze-dried extract), and have quality control standards similar to those of prescription drugs. The present study examined Yokukan-san (Yi-Gan San in TCM), a Kampo formula that has been used empirically in Japan for more than 400 years. Accumulating clinical trials have demonstrated Yokukan-san’s efficacy in treating patients with behavioral and psychological symptoms of dementia, which has resulted in the Japanese Society of Neurology listing it in the Japanese Guidelines for the Management of Dementia 2010. Efficacy in other diseases and conditions, such as sleep disorders, tardive dyskinesia, aggression, and impulsivity has also been reported. This article reviews both clinical and basic studies of Yokukan-san, with the goal of clarifying its clinical indications.

Repressor of GATA negatively regulates murine contact hypersensitivity through the inhibition of type-2 allergic responses

Repressor of GATA (ROG) inhibits Th2 cell differentiation and allergic airway inflammation in the lung. To determine the role of ROG in the pathogenesis of contact hypersensitivity (CHS), a hapten-induced mouse model of CHS using ROG Tg and ROG-deficient (ROG(-/-)) was used. ROG Tg mice showed little ear swelling, while ROG(-/-) mice showed enhanced ear swelling in comparison to wild type mice. Interstitial edema and mast cell degranulation at the local inflammation sites were mild in ROG Tg mice and exacerbated in ROG(-/-) mice. In addition, the serum total IgE and hapten-specific IgG1 levels were increased in ROG(-/-) mice. Adoptive transfer of ROG(-/-) CD4(+) T cells exacerbated CHS in wild type mice, while transfer of ROG Tg CD4(+) T cells resulted in the attenuation of CHS. These results indicate ROG negatively regulates the induction of CHS by controlling the CD4(+) T cell-mediated allergic responses, including IgE generation and mast cell degranulation.

Extraction Efficiency of Shosaikoto (Xiaochaihu Tang) and Investigation of the Major Constituents in the Residual Crude Drugs

Shosaikoto (Xiaochaihu Tang) is one of the frequently used traditional herbal medicines (Kampo medicines, Japan). To realize the effective use of precious crude drugs, we investigated the major constituents in the residual crude drugs after decoction and aimed for extraction efficiency of shosaikoto with regard to the extract, tannin content, and major constituents. We found that the residual crude drugs had large amounts of compounds, especially saikosaponin b2, which had a 78.3% yield compared to that in the first decoction. The extraction efficiency increased when decoction time and volume of water increased. Both increases had an additive effect on the yield of the extract and saikosaponin b2 in particular. We also found that the size of crude drug pieces that are available in Japanese markets is suitable for decoction because of quick permeation of water. From our study, the second decoction may be a valuable contribution to medical treatment and of effective use of crude drugs. Moreover, time and volume of water should be increased when patients have trouble in preparing a decoction. Our study revealing the factors that influence the extraction efficiency of shosaikoto will be the basis for empirical evidence about decocting Kampo medicine.

A Valid Approach in Refractory Glossodynia: A Single-Institution 5-Year Experience Treating with Japanese Traditional Herbal (Kampo) Medicine

Glossodynia is often refractory to conventional medicine, and there is only limited evidence to guide clinicians in its management. Patients with refractory glossodynia are often introduced to Japanese traditional herbal (Kampo) medicine experts under such circumstances because Kampo medicine has become known in Japan to be effective in treating a wide variety of symptoms refractory to conventional medicine. Herein, we report our single-institution 5-year experience treating patients with Kampo medicine for primary glossodynia that was refractory to conventional medicine. We found that 69.2% of patients reported a beneficial effect of Kampo medicine on glossodynia, and the average onset of improvement was 8.0 ± 7.7 weeks after starting Kampo treatment. The top two frequently used Kampo medicines for glossodynia were seinetsuhokito and mibakuekkito among high responders who showed a decrease of severity by 50% or more. The top four most overlapped herbs among effective Kampo medicines for glossodynia were Glycyrrhiza Root, Ginseng Root, Hoelen, and Atractylodes (lancea) Rhizome, which compose an essential Kampo prescription called shikunshito. Although more research is required to further clarify the effectiveness of Kampo medicine, it has valid efficacy even in cases of glossodynia that remain incurable by conventional treatments.

Study of Factors Involved in Tongue Color Diagnosis by Kampo Medical Practitioners Using the Farnsworth-Munsell 100 Hue Test and Tongue Color Images

In traditional Japanese medicine (Kampo medicine), tongue color is important in discerning a patients constitution and medical conditions. However, tongue color diagnosis is susceptible to the subjective factors of the observer. To investigate factors involved in tongue color diagnosis, both color discrimination and tongue color diagnosis were researched in 68 Kampo medical practitioners. Color discrimination was studied by the Farnsworth-Munsell 100 Hue test, and tongue color diagnosis was studied by 84 tongue images. We found that overall color discrimination worsened with aging. However, the color discrimination related to tongue color regions was maintained in subjects with 10 or more years of Kampo experience. On the other hand, tongue color diagnosis significantly differed between subjects with <10 years of experience and ≥10 years of experience. Practitioners with ≥10 years of experience could maintain a consistent diagnosis of tongue color regardless of their age.

A Case of Aromatase Inhibitor (Anastrozole)–Induced Side-Effects Successfully Treated with Kampo Medicines

OBJECTIVES Breast cancer is the fourth most frequent cause of death, and it is currently the most frequent cause of death among Japanese women. As to breast cancer therapy, lengthy hormonal therapy is very important for the treatment and prevention of recurrence. Aromatase inhibitors (AIs) are the initial drug of choice for postoperative adjuvant therapy of breast cancer in Japan. AIs require long-term use and occasionally cause serious side-effects. In this report, the effects of Kampo medicines (Japanese traditional medicines) on AIs-induced side-effects are described. SUBJECT A 55-year-old woman visited the Kampo outpatient department of Chiba University Hospital for atypical genital bleeding and arthralgia. At the age of 54, she suffered from left breast cancer and underwent left total mastectomy followed by chemotherapy for 6 months. Afterwards, 1 mg/day of anastrozole, one of the AIs, was used for therapy. Three (3) months later, atypical genital bleeding from vaginal mucosa and joint pains of bilateral hands and knees occurred as side-effects of anastrozole. Her attending doctor could only prescribe nonsteroidal external medicine for the inflammation of vaginal mucosa and do close follow-up. However, her symptoms showed no improvement. INTERVENTIONS AND OUTCOME Her deficiency of both ki (qi) and ketsu (Blood) was diagnosed based on Kampo diagnostics. Juzentaihoto was used for treatment. After taking juzentaihoto for 5 weeks, the atypical genital bleeding disappeared, and she no longer need topical medicine. Because her arthralgia showed no improvement, powdered processed aconitine root was added. After taking 3.0 g/day of this medication, her arthralgia almost completely disappeared. CONCLUSIONS Controlling the side-effects is a clinical issue from the viewpoint of adherence to drug treatment. Kampo therapy should be considered one of the choices for side-effects in the process of cancer treatment.

Proteomics analysis of altered proteins in kidney of mice with aristolochic acid nephropathy using the fluorogenic derivatization-liquid chromatography-tandem mass spectrometry method

Aristolochic acid (AA) causes interstitial renal fibrosis, called aristolochic acid nephropathy (AAN). There is no specific indicator for diagnosing AAN, so this study aimed to investigate the biomarkers for AAN using a proteomics method. The C3H/He female mice were given ad libitum AA-distilled water (0.5 mg/kg/day) and distilled water for 56 days in the AA and normal groups, respectively. The AA-induced proteins in the kidney were investigated using a proteomics study, including fluorogenic derivatization with 7-chloro-N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide, followed by high-performance liquid chromatography analysis and liquid chromatography tandem mass spectrometry with a MASCOT database searching system. There were two altered proteins, thrombospondin type 1 (TSP1) and G protein-coupled receptor 87 (GPR87), in the kidney of AA-group mice on day 56. GPR87, a tumorigenesis-related protein, is reported for the first time in the current study. The renal interstitial fibrosis was certainly induced in the AA-group mice under histological examination. Based on the results of histological examination and the proteomics study, this model might be applied to AAN studies in the future. TSP1 might be a novel biomarker for AAN, and the further role of GPR87 leading to AA-induced tumorigenesis should be researched in future studies.

Adverse event associated with auriculotherapy: Auriculotherapy adverse event

A 76‐year‐old man with tympanic membrane perforation and hearing loss in the right ear since childhood was hospitalized in September 2015 due to deterioration of renal function. On cranial magnetic resonance imaging (MRI) to evaluate possible cerebrovascular disorder, an artifact was observed. Further, cranial computed tomography (CT) showed seven metallic objects in the region extending from the right external ear canal to the right middle ear.

An elderly patient with advanced lung cancer achieved long-term survival using Chinese medicine: An alternative treatment strategy for cancer patients aged 80 or older without a tissue confirmed diagnosis.

Lung cancer is the leading cause of cancerrelated mortality in China.1,2Meanwhile,the average life expectancy in the aging population has increased from46 years in 1950 to 75 years in 2010.3The incidence of lung cancer is very low in individuals aged85 years.Older patients are often excluded from clinical trials because of their limited life expectancy and unwillingness

Various Descriptions of Abdominal Examinations among Traditional Kampo Medical Books Beyond the Showa Era

a Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan b Department of Medical History, Kitasato University Oriental Medicine Research Center, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan c Department of Japanese Oriental (Kampo) Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuoku Chiba-city, 260-8670, Japan