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YAKUGAKU ZASSHI, 125(7),531-547, 2005
Bacteria of the genus Vibrio are normal habitants of the aquatic environment and play roles for biocontrole of aquatic ecosystem, but some species are believed to be human pathogens. These species can be classified into two groups according to the types of diseases they cause: the gastrointestinal infections and the extraintestinal infections. The pathogenic species produce various pathogenic factors including enterotoxin, hemolysin, cytotoxin, protease, siderophore, adhesive factor, and hemagglutinin. We studied various pathogenic factors of vibrios with special emphasis on protease and hemolysin of V. vulnificus. V. vulnificus is now recognized as being among the most rapidly fatal of human pathogens, although the infection is appeared in patients having underlying disease(s) such as liver dysfunction, alcoholic cirrhosis or haemochromatosis. V. vulnificus protease (VVP) is thought to be a major toxic factor causing skin damage in the patients having septicemia. VVP is a metalloprotease and degrades a number of biologically important proteins including elastin, fibrinogen, and plasma proteinase inhibitors of complement components. VVP causes skin damages through activation of the Factor XII-plasma kallikrein-kinin cascade and/or exocytotic histamine release from mast cells, and a haemorrhagic lesion through digestion of the vascular basement membrane. Thus, the protease is the most probable candidate for tissue damage and bacterial invasion during an infection. Pathogenic roles and functional mechanism of other factors including hemolysins of V. vulnificus and V. mimicus are also shown in this review article.
Key words--pathogenic vibrios; Vibrio vulnificus; metalloprotease; hemolysin
YAKUGAKU ZASSHI, 125(7),549-554, 2005
Memory deficits are induced during the late stage (20-25 days) of thiamine-deficient (TD) feeding. In this review, the role of cholinergic neurons on the memory deficit induced by TD feeding are summarized. Although memory deficit cannot be suppressed by an injection of thiamine once it appears, such impairment was found to be protected by early treatment with thiamine during TD feeding. Administration of muscarinic M1 agonist McN-A-343 reversed the memory deficit observed in TD mice, although the muscarinic M2 antagonist methoctramine did not. The “kampo” (traditional herbal) medicine, “kami-untan-to” (KUT), protected against the memory deficit observed in TD mice. Choline acetyltransferase (ChAT) fluorescence intensity, a marker of presynapse of cholinergic neurons, was decreased in the cortex and hippocampus at an early stage (14th day) of TD, and it was decreased in a wide range of brain areas at a late stage (25th day) of TD. Early KUT treatment inhibited the reduction of ChAT in the hippocampus of TD mice. These findings suggested that the memory deficit may be caused by a reduction in the cholinergic function at an early stage of TD, and that the activation of cholinergic neurons may play an important role in the improvement of TD-induced memory deficit.
Key words--thiamine deficiency; memory; choline acetyltransferase; kami-untan-to; muscarinic receptors
YAKUGAKU ZASSHI, 125(7),555-565, 2005
To establish a system for collecting and reporting information from community pharmacists such as that on adverse effects, the Japan Pharmaceutical Association (JPA) conducts Drug Event Monitoring (DEM). In the fiscal year 2002, a survey was carried out to clarify the incidence of sleepiness due to antiallergic drugs. The investigated active ingredients were ebastine, fexofenadine hydrochloride, cetirizine hydrochloride, and loratadine. Community pharmacists asked the following question to patients who visited their pharmacies: “Have you ever become sleepy after taking this drug?” During a 4-week survey period, reports of 94256 cases were collected. To evaluate the incidence of sleepiness, we analyzed cases in which reports showed alleged absence of concomitant oral drugs, and drug use in conformity with the dose and method described in package inserts. The incidence of sleepiness was significantly different among the drugs (x2-test, p < 0.001). The observed incidences of sleepiness due to the drugs (8.8-20.5%) were higher than those described in each package insert (1.8-6.35%). This may be because an active question was used (“Have you ever become sleepy after taking this drug?”). Active intervention by pharmacists may be useful for collecting more information on improvement in the QOL of patients and safety. In addition, the pharmacists were asked to report events other than “sleepiness” in the free description column of the report. Some symptoms not described in the package inserts were reported, suggesting that DEM may lead to the discovery of new adverse effects. These results suggest that community pharmacists have a good opportunity to collect information in DEM, and safety information such as that on adverse effects can be obtained from pharmacies.
Key words--community pharmacy; pharmacist; drug event monitoring; antiallergic drug
YAKUGAKU ZASSHI, 125(7),567-577, 2005
Purpose: There are many regimens for cancer chemotherapy, and thus information management is complicated. It is thought that the safe and appropriate use of cancer chemotherapy can be achieved by developing a system that involves information-sharing among medical staff. A system facilitating the choice of regimen was developed in our institution using an electronic medical chart network. In addition, a questionnaire was distributed to evaluate the usefulness of the cancer chemotherapy regimen database (DB). Methods: Microsoft Access 2000 was used for the DB. Microsoft Internet Information Services Ver. 6.0 included in the Windows 2003 Server was used as the management software of the Web-version DB. Results: With the Web-version DB, it was possible to offer chemotherapy regimen information to all departments in the hospital. The DB received an excellent evaluation based on the questionnaire results. The reasons for this were the exceptional ability to share information among medical staff and the appeal of a checking system. Conclusion: Obtaining information regarding cancer chemotherapy regimens became easier with the Web-version DB, which received an excellent evaluation by all medical staff. Proactive use of the Web-version DB can contribute to proper cancer chemotherapy choice and strengthening of hospital risk management.
Key words--cancer chemotherapy regimen; anticancer drug; malpractice; risk management; information system
YAKUGAKU ZASSHI, 125(7),579-582, 2005
Although disease modifying anti-rheumatic drugs (DMARDs) are used in the treatment of rheumatoid arthritis (RA), the selection of agents in the case of relapse (escape phenomenon) lacks clear-cut standards. We compared the effectiveness in a salazosulfapyridine and then methotrexate (SASP→MTX) group with that in the mothotrexate (SASP+MTX) group after escape phenomenon expression in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) data. Outpatients of the Matsubara Mayflower Hospital with a history of DMARD administration during the 4 years prior to May 2003 were studied. The CRP level in the SASP→MTX group (n=8) after the escape phenomenon expression showed a decline after 3 months, but no decline was seen even after 3 months the two in the CRP level in the SASP+MTX group (n=10). However, the difference between groups was not significant. The fluctuation in ESR was similar to that in CRP. However, ESR was significantly lower in the SASP→MTX group 20 weeks after escape phenomenon expression. In evaluating treatment effectiveness after escape phenomenon expression in each group, SASP→MTX was effective in 10 and SASP+MTX in 7 patients. Side effects necessitated cessation of treatment in 1 patient in the SASP→MTX group. Treatment continued in 4 patients in the SASP→MTX group and 2 in the SASP+MTX group, even though side effects occurred. It should be borne in mind that combination therapy often has greater clinical benefit than single agent therapy but not always.
Key words--rheumatoid arthritis; disease modifying anti-rheumatic drugs; escape phenomenon; salazosulfapyridine; methotrexate
YAKUGAKU ZASSHI, 125(7),583-586, 2005
A certain Chinese herbal book presented to the emperor in 1505 shows a drawing of maize under the caption of Yiyi-ren (Job's Tears). Also, a Chinese poem written around 1368 contains a term yumi, which indicates maize. These new findings offer clear evidence that maize existed in China in the pre-Columbian era, or before 1492. Details of this evidence are discussed here.
Key words--maize; pre-Columbian; China
YAKUGAKU ZASSHI, 125(7),587-591, 2005
Oxidized low-density lipoprotein (ox-LDL) is the main etiologic factor in atherogenesis, and antioxidants are accepted as effective treatment of atherosclerosis. The aim of this study was to clarify whether the mechanism of the antiatherogenic effects of the herb Phyllanthus Emblica, which is widely used to treat atherosclerosis-related diseases, is associated with ox-LDL via its compounds of soluble tannin, corilagin (beta-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), and its analogue Dgg16 (1,6-di-O-galloyl-beta-d-glucose). Human umbilical vein endothelial cells, ECV-304, were incubated with ox-LDL (50 mg/l), treated with corilagin or Dgg16 at different doses (0.0001-0.1 mmol/l), and then incubated with monocytes. Malondialdehyde (MDA) in the culture media was determined and the number of monocytes adhering to ECV-304 cells was counted with cytometry. In another experiment, the rat vascular smooth muscular cells (VSMC) were incubated in media with or without ox-LDL (50 mg/l), and with corilagin or Dgg16 also at different doses (0.0001-0.1 mol/l), the proliferation of which was assayed with MTT. The results showed that both corilagin and Dgg16 were able to decrease MDA, prevented ECV-304 cells from being adhering to by monocytes, and inhibited VSMC proliferation activated by ox-LDL. The results suggest that the two compounds are effective in inhibiting the progress of atherosclerosis by alleviating oxidation injury or by inhibiting ox-LDL-induced VSMC proliferation, which may be promising mechanisms for treating atherosclerosis.
Key words--corilagin; endothelial cell; smooth muscle cell; oxidation injury; proliferation
YAKUGAKU ZASSHI, 125(7),593-599, 2005
We have introduced improvements and new approaches into our teaching methods by exploiting 4 active learning methods for pharmacy students of first year. The 4 teaching methods for each lesson or take home assignment are follows: 1) problem-based learning (clinical case) including a student presentation of the clinical case, 2) schematic drawings of the human organs, one drawing done in 15-20 min during the week following a lecture and a second drawing done with reference to a professional textbook, 3) learning of professional themes in take home assignments, and 4) short test in order to confirm the understanding of technical terms by using paper or computer. These improvements and new methods provide active approaches for pharmacy students (as opposed to passive memorization of words and image study). In combination, they have proven to be useful as a learning method to acquire expert knowledge and to convert from passive learning approach to active learning approach of pharmacy students in the classroom.
Key words--lecture; teaching methods (drawing, PBL, IT, test); student readership