YAKUGAKU ZASSHI
 Abstracts 
Vol.122, No. 6 (2002)

--Reviews--

The Plant Origins of Herbal Medicines and Their Quality Evaluation

Sansei NISHIBE

Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

The caulis (stem and leaf) of Trachelospermum jasminoides (Lindl.) Lem. (Apocynaceae) is listed as the plant origin of Luoshiteng in the Chinese Pharmacopeia. However, preparations from the caulis of Ficus pumila L. (Moraceae) or Psychotria serpens L. (Rubiaceae) are distributed on the Chinese market. The fruit of Forsythia suspensa Vahl (Oleaceae) is listed as the plant origin of Forsythia Fruit in the Chinese Pharmacopeia, although the fruits of two Forsythia species, F. suspensa and F. viridissima Lindley, are listed as the plant origins in the Japanese Pharmacopeia, and fruits of three Forsythia species, F. viridissima, F. koreana Nakai, and F. suspensa, are listed in the Korean Pharmacopeia. The whole plant of Plantago asiatica L. (Plantaginaceae) is listed as the plant origin of Plantago Herb in the Japanese Pharmacopeia, but the whole plants of two Plantago species, P. asiatica and P. depressa Wild, are listed as the plant origins in the Chinese Pharmacopeia. The leaves of two Plantago species, P. lanceolata L. and P. major L., are distributed as Plantain on the European market. Each of these herbal medicines is reviewed based on the differences in plant origins and their quality evaluation from the viewpoints of the morphological properties, chemical components, and biological activities, respectively.

Key words--herbal medicine; difference in plant origin; quality evaluation; morphological property; chemical component; biological activity

--Regular Articles--

Case Report Summary Browsing System for Education of Pharmaceutical Students through the Internet

Tadashige ABE,^a Kyoko OBAYASHI,^a Yuko KONNO,^b Koujirou YAMAMOTO,^a,b Satoshi KATAOKA,^c Mayumi MOCHIZUKI,^c Shiro UEDA,^c kazuhiko OHE,^d Gen-ichi HASHIMOTO,^a and Ryuya HORIUCHI^a,b

Department of Pharmacy,^a Department of Clinical Pharmacology,^b Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi 371-8511, Japan and Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University,^c 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan and Hospital Computer Center, University of Tokyo Hospital,^d 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

We have developed a patient case database at Gunma University Hospital. The transmission of the data contained in this database via the Internet is protected by SSH encryption technology. The database may also function as an education tool for medical and pharmaceutical students who can access this system through the Internet using a special browser system that we have also developed. In a survey questionnaire relating to our system conducted among graduate students, most responded positively to its usefulness as an opportunity for exposure to actual clinical practice. Because this system can introduce students to realistic and daily practices at hospitals, it might have a great impact on Japanese pharmaceutical education in universities or pharmaceutical colleges where early exposure to actual hospital practices is not appropriately included in the curriculum. In addition, our system will function to establish a mutual feedback system between hospitals and basic research institutions such as pharmaceutical universities.

Key words--education of pharmaceutical students; case report summary; Internet; SSH encryption technology

--Regular Articles--

A Checking System for Injectable Anticancer Drugs Using Each Patient's Own Data and Its Evaluation

Yasuaki OHTSUBO, Keizo ISHIMOTO,* Momoe TANIOKA, Keiko UCHIUMI, Naoko FUJIMOTO, Tadashi ISHIMITSU, Yutaka UCHIDA, and Akira KAMIYA

Department of Pharmacy, Yamaguchi University Hospital, 1-1-1 Minamikogushi, Ube 755-8505, Japan

A checking system was developed for risk management of injectable anticancer drug use. Because the dosage and administration of injectable anticancer drugs vary with each patient, checking the prescription and aseptic i.v. admixing can be markedly complicated and time-consuming for pharmacists. The system we investigated in this study provided real-time checking of dosage, drip infusion rate, dosing periods, and dosing-free periods. The prescription parameters for this check included height, weight, body surface area, the medical history of each patient, the patient's ICD10 code' and disease indication from the package insert. Moreover, when preparing for aseptic i.v. admixing, the liquid volume after the anticancer drug has been mixed with other injectable drugs is calculated automatically. The time limits for stability after mixing and clinical laboratory test results are listed on the Work Sheet. As a result, 24 medication errors were prevented in the first 6 months of use of this system. These consisted of over- and under-doses, excessive dosing periods, insufficient dosing-free periods' etc. The time required for preparation of aseptic i.v. admixing decreased by 73% after introducing this system. Because clinical laboratory test results were referenced beforehand, patients to whom the drug should not be administered were recognized in advance. Thus 13 such cases were identified before i.v. admixing. Therefore this system may be useful in terms of rational anticancer drug use and risk management.

Key words--anticancer drug; checking system; risk management; rational drug use; aseptic i.v. admixture; patient's own data

--Regular Articles--

Herbal Medicine and False-Positive Results on Lymphocyte Transformation Test

Naoki MANTANI,*^,a Shinya SAKAI,^a Toshiaki KOGURE,^a Hirozo GOTO,^b Naotoshi SHIBAHARA,^b Toshiaki KITA,^b Yutaka SHIMADA,^a and Katsutoshi TERASAWA,^a

Department of Japanese Oriental (Kampo) Medicine, Faculty of Medicine,^a Department of Kampo Diagnositics, Institute of Natural Medicine,^b Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan

In vitro mitogenic activity of 16 herbs and 3 Kampo (herbal medicine) formulae have been reported in experimental studies. It is not known how many herbs and Kampo formulae in total have mitogenic activity. Lymphocyte transformation test (LTT) is generally utilized to diagnose drug-induced liver injury. In LTT, mitogenic activity is assessed by measuring ³H-thymidine incorporation. The objective of the present study was to determine which herbs and which Kampo formulae caused false-positivity on LTT. We examined 2496 summaries of all admission records from 1979 to 1999 in our department. We selected patients in whom liver injuries were diagnosed as definitely unrelated to Kampo medication. In these patients, LTT was performed for some herbs contained in the suspect Kampo medicines, resulting in positive LTT for 17 herbs: Evodiae Fructus (Goshuyu), Zizyphi Fructus (Taiso), Ginseng Radix (Ninjin), Zingiberis Rhizoma (Shokyo), Hoelen (Bukuryo), Aconiti Tuber (Bushi), Angelicae Radix (Toki), Cnidii Rhizoma (Senkyu), Rehmanniae Radix (Jio), Ephedrae Herba (Mao), Anemarrhenae Rhizoma (Chimo), Cinnamomi Cortex (Keihi), Bupleuri Radix (Saiko), Artemisiae Capillari Spica (Inchinko), Persicae Semen (Tonin), Moutan Cortex (Botanpi) and Paeoniae Radix (Shakuyaku). These results were considered false-positive, because the results were observed in the “definitely unrelated”patients. Mitogenic activity inherent to some herbs and Kampo formulae may sometimes cause false-positivity on LTT in clinical situations. These examples suggest that LTT for Kampo formulae may be unreliable as a diagnostic method for drug-induced liver injury.

Key words--Kampo medicine; lymphocyte transformation test; false-positive; mitogen; liver injury

--Regular Articles--

Rhubarb Use in Patients Treated with Kampo Medicines--A Risk for Gastric Cancer?

Naoki MANTANI,* Nobuyasu SEKIYA, Shinya SAKAI, Toshiaki KOGURE, Yutaka SHIMADA, and Katsutoshi TERASAWA

Department of Japanese Oriental (Kampo) Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan

In vitro mutagenic effects have been reported for ingredients contained in rhubarb. Therefore, rhubarb (Rhei Rhizoma) as an anthranoid laxative could be associated with a risk of developing gastric cancer as well as colorectal cancer. We are not aware of any reports that have examined the relationship between the use of rhubarb and the development of gastric cancer. During the period between 1979 and 1999, we treated 14616 patients using various Kampo medicines, which sometimes contained rhubarb. In the present study, we determined whether patients, diagnosed with gastric cancer during the period between 1979 and 1999, had been administered rhubarb before the development of gastric cancer. Among the 10 enrolled patients, only 2 patients had been administered rhubarb before the development of gastric carcinoma. The other 8 patients had never received rhubarb before the development of gastric carcinoma. Rhubarb use may have little connection with the development of gastric cancer in practice, even if some ingredients in rhubarb have shown carcinogenic activity in experimental studies.

Key words--rhubarb; stomach neoplasm; mutagen; carcinogen; Rhei Rhizoma

--Notes--

Relation of Bile Hydrogen Peroxide Level and Liver Super Oxide Dismutase Activity in Selenium-Deficient Rats

Ken-ichiro MATSUMOTO,* Iori UI, Takayuki MOCHIDA, Reiko SAKAMOTO, and Kazutoyo ENDO

Department of Physical Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan

The relationship of hydrogen peroxide (H₂O₂) levels in bile with liver SOD and GSH-Px activity in selenium (Se)-deficient rats is discussed. Normal rats and 7 groups of rats fed a Se-deficient diet with different feeding periods were examined. H₂O₂ levels in bile were measured using the spin-trapping method with electron spin resonance (ESR). Bile H₂O₂ levels in the initial stage (20-60 min from start of the cannulation) of measurement were increased depending on the length of the feeding period with the Se-deficient diet and absence of Se. Bile H₂O₂ levels in the later stage (60-120 min) of measurement first increased with the length of feeding with the Se-deficient diet and then decreased with longer feeding periods. Bile H₂O₂ levels immediately after the operation were relatively low in almost all cases. The operation may result in oxidative stress to generate H₂O₂. Liver GSH-Px activity decreased depending on the length of the feeding period with the Se-deficient diet and existence of Se. Liver SOD activity increased in Se-deficient groups. It is suggested that the H₂O₂ levels in bile are related to decreased GSH-Px activity, SOD activity, and also the oxidative stress caused by surgery. Therefore the H₂O₂ levels in bile can be used as an index of sensitivity to oxidative stress. Although severe oxidative stress may decrease SOD activity, Se deficiency can induce liver SOD activity.

Key words--oxidative stress; X-band ESR; Fenton's reaction; spin trapping; hydroxyl radical; glutathione peroxidase

--Notes--

Interaction between Acyclic Phenol-Formaldehyde Oligomers and Quaternary Ammonium Ions

Department of Chemistry and Chemical Engineering, Faculty of Engineering, Yamagata University, 4-3-16, Jonan, Yonezawa 992-8510, Japan

The interaction between acyclic phenol-formaldehyde oligomers (1) and quaternary ammonium ions (5) was investigated by ¹H-NMR spectroscopy. From the induced chemical shift change of 5 in the presence of 1, the cation-π interaction between the N⁺-(CH₃)₃ moiety of 5 and the π-base of 1 occurs during the formation of the complex. Another important observation is that the OH proton signals of 1 are considerably broadened upon addition of 5, indicating that hydrogen bonding occurs between exchangeable protons of 1 and iodide anion of 5. These interactions play an important role in the binding of 5.

Key words--phenol-formaldehyde oligomer; quaternary ammonium ion; cation-π interaction; hydrogen bonding

--Articles--

Pilot Study of the Practical Use of Internet in Medical Services: The Questionnaire for Pharmacists in Japan

Tomoko TERAJIMA,*^,a Eri MACHIDA,^a Shin-ichi YAMAGATA,^a Nobunori SATOH,^a Mayumi MOCHIZUKI,^b and Shiro UEDA^a

Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University,^a 1-33 Yayoicho, Inage-ku, Chiba 263-8522, Japan and Division for Evaluation and Analysis of Drug Information Center for Clinical Pharmacy and Clinical Sciences, Kitasato University,^b School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

We performed a questionnaire survey to 260 pharmacists as a pilot study, in order to know the actual application of IN to medical services in Japan. The response rate of our questionnaire was 40% (105 persons), and 91% of the answers were from pharmacists who works in hospitals, community pharmacies, or clinics. According to the results, 90 of the 105 pharmacists had had some experience of using IN, and 68% of whom (58% of respondents) use IN daily as a means of problem solution on their works. IN was probably used as a relatively reliable information source something like text-books in such cases as acquiring the medical information for patients or other medical staffs. In addition, IN may have been esteemed its facilities and the informational usefulness and reliability. However, since this survey is just a pilot trial, the result dose not necessarily reflect a general situation around IT use. Consequently, this study result could be need by still further research.

Key words--internet; pilot study; questionnaire; pharmacist; information