1.Food and Drug Interactions: Effect of Acanthopanax senticosus Harms on CYP2C9 Activity (Part 2)
Tsunehisa TAKAHASHI ; Takashi SATOH ; Kazuhiro WATANABE
Japanese Journal of Complementary and Alternative Medicine 2014;11(1):9-15
Objective: Acanthopanax senticosus Harms extract (ASE) is an ingredient of functional foods, such as health supplements, in Japan. We investigated the effects of ASE on CYP2C9 activity.
Methods and Results: CYP2C9-catalyzed diclofenac 4′-hydroxylase activities in human intestinal and liver microsomes (abbreviated as HIM and HLM, respectively) were significantly decreased by the addition of ASE in a concentration-dependent manner. Kinetic studies of diclofenac 4′-hydroxylase in HLM revealed that ASE addition significantly decreased Vmax but had no effect on Km. These results suggest that diclofenac 4′-hydroxylase activity is suppressed by ASE addition in a non-competitive manner. Then, we investigated the time courses of diclofenac 4′-hydroxylase activity in rat liver microsomes after ASE oral administration (50 to 400 mg/kg). Diclofenac 4′-hydroxylase activities were significantly lowered by the administration of 200 and 400 mg/kg ASE at 0.5 to 4 hr compared with control (0 hr). Furthermore, we investigated the effects of ASE oral administration on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. The area under the concentration-time curve of tolbutamide after ASE oral administration (400 mg/kg) was enhanced by approximately 1.6 times compared with that without ASE oral administration.
Conclusion: These findings indicated that ASE inhibits human intestinal and hepatic CYP2C9 activities.
2.Residue of Organochlorine Pesticide and PCB in Humans
Takeshi Sugaya ; Kazuhiro Watanabe ; Shiro Sasaki
Journal of the Japanese Association of Rural Medicine 1984;33(2):140-146
Organochlorine insecticides (BHC, DDT, etc) have been used in massive quatities in Japan. But in 1971, the goverment put a ban on their use as insecticides. We continued the residue analyses of organochlorine insecticide in human bodies from 1971 to 1982. This paper deals with the results of our residue analyses from 1980-1982. In paralel, We have also continued to analyze the residue of PCB.
(1) A total of 264 specimens have been analyzed for human mother milk, the adipose tissue, the liver, the kidney and the spleen.
(2) β-BHC and pp'-DDE were detected from all of these specimens.
(3) Over a span 12 years, the decrease of total-DDT was smaller than that of β-BHC.
(4) In the adipose tissue, there were no signs of a decrease in total DDT.
(5) PCB was detected from all specimens of mother milk, the adipose tissue and the liver.
It is conceivable that the pollution of human bodies by BHC, DDT. PCB, and other chemicals will last for a long time.
There is a need to keep constant surveillance over the tendency of these chemicals in the environment and human bodies.
3.Status of Provision of Drug Information to Hypertensive Patients at Community-based Pharmacies
Kazuhiro Watanabe ; Fumiaki Nakamura ; Shinji Matsumura ; Shunichi Fukuhara
General Medicine 2011;12(2):75-82
Objective: The present study examined the status of the provision of drug information to hypertensive patients at community-based pharmacies by evaluating patients' satisfaction, understanding, and wishes.
Design: A cross-sectional study was conducted by surveying patients using a self-administered questionnaire.
Methods: Three items were evaluated: 1) the level of patient satisfaction with provision of drug information; 2) the level of patient understanding of information provided on antihypertensive drugs; and, 3) patient wishes regarding provision of drug information.
Results: The level of satisfaction with provision of drug information was high (86.6%). Although patients were found to understand the precautions for use of antihypertensive drugs, their understanding of drug efficacy was insufficient. Also, patients wished to receive more explanation from pharmacists regarding the efficacy of drugs in addition to explanations of associated adverse reactions or precautions for use of the drugs.
Conclusions: Hypertensive patients were highly satisfied with the provision of drug information at community-based pharmacies, but did not show sufficient understanding of the efficacy of antihypertensive drugs, an issue to be addressed in the future by pharmacists in their instructions to patients on the use of drugs.
4.Food and Drug Interactions: Effect of Acanthopanax senticosus Harms on CYP3A4 and CYP2C9 Activities (Part 3)
Tsunehisa TAKAHASHI ; Masaki IGARASHI ; Takashi SATOH ; Kazuhiro WATANABE
Japanese Journal of Complementary and Alternative Medicine 2014;11(1):17-24
Objective: By using human liver microsomes (HLM), we analyzed the effects of 14 known components of A.senticosus Harms on the activities of CYP2C9 and CYP3A4.
Methods and Results: Sesamin and quercetin inhibited both enzyme activities, whereas quercitrin strongly inhibited CYP3A4 activity. The 50% inhibitory concentrations (IC50s) of sesamin and quercetin on CYP2C9 activity were approximately 124- and 59-fold higher and the IC50s of sesamin, quercetin, and quercitrin on CYP3A4 activity were approximately 427-, 135-, and 22-fold higher than that of A. senticosus Harms extract (ASE), respectively. All these components inhibited both CYP3A4 and CYP2C9 in a non-competitive manner. However, these components are present in small amounts in ASE.
Conclusion: Therefore, the food-drug interactions caused by A. senticosus Harms are presumed to be due to the additive or synergistic interaction of these components or the other existing components, including their metabolites.
5.Black Tea Inhibits Small Intestinal α-Glucosidase Activity in db/db Mouse
Masaki IGARASHI ; Takashi SATOH ; Hiroshi YAMASHITA ; Kazuhiro WATANABE
Japanese Journal of Complementary and Alternative Medicine 2014;11(1):25-33
The inhibitory effects of the freeze-dried powder of the aqueous extract of black tea leaf (JAT) on α-glucosidase activity were investigated. We initially examined the effects of JAT addition on yeast α-glucosidase activity. JAT significantly and dose-dependently inhibited α-glucosidase activity and more strongly inhibited the activity than acarbose, the positive control. Then, we examined the effects of oral administration of JAT on sucrose tolerance in type 2 diabetes mellitus model db/db mice. Both JAT and acarbose administered groups showed a dose-dependent decrease in plasma glucose levels after the sucrose loading compared with the control group. Notable was that the plasma glucose levels of the 500 mg/kg JAT administered group exhibited a significant decrease 30 min or longer after the sucrose loading. On the other hand, no significant difference in plasma insulin levels was seen between the JAT administered group and the control group. We also measured small intestinal sucrase activity in db/db mouse at 30 min after JAT oral administration. Compared to control mice, small intestinal sucrase activity was significantly decreased in the 500 mg/kg JAT administered mice. These findings indicate that JAT may be a useful natural material for the prevention and therapy of type 2 diabetes mellitus.
6.Questionnaire-based Survey on Subjective Understanding of Drug Effectiveness and Side Effects and Intention to Reduce Medication in Patients on Polypharmacy
Yotaro ARIMA ; Takashi WATANABE ; Yuzou SHITOU ; Kazuhiro SUMITOMO ; Kouji OKADA
An Official Journal of the Japan Primary Care Association 2024;47(2):34-42
Introduction: This study aimed to survey patients on polypharmacy regarding their own intention and inclination to reduce medication use, and their subjective understanding of drug effectiveness and side effects. We aimed to contribute to the establishment of an information base to address polypharmacy.Methods: We enrolled 100 adult patients who had been admitted and administered ≥ 5 oral medications. A questionnaire was utilized to assess their willingness and inclination to reduce their medications, as well as their subjective understanding of drug effectiveness and side effects.Results: Sixty-two patients expressed an intention to reduce their medication use, citing reasons including medication management, drug combinations, and side effects. The proportion of patients with this intention increased as the number of prescribed medications increased. Of the 38 individuals who responded that they had no intention of reducing their medication, 21 (55.3%) cited the reason as being that they received the prescription from a physician. The level of understanding about the effectiveness of their own medications was significantly lower among those aged ≥ 75 years. However, the level of understanding of side effects did not vary based on age or number of prescriptions.Conclusion: To promote the optimization of prescriptions, it is necessary to ascertain patients' intentions, and the relationship between patients and prescribing physicians.
7.Total Aortic Arch Replacement in a Patient with a Patent Right Internal Thoracic Artery Graft Crossing between the Sternum and the Ascending Aortic Aneurysm
Shigeki Koizumi ; Kenji Minakata ; Hisashi Sakaguchi ; Kentaro Watanabe ; Tomohiro Nakata ; Kazuhiro Yamasaki ; Tadashi Ikeda ; Ryuzo Sakata
Japanese Journal of Cardiovascular Surgery 2016;45(3):144-147
We report a case of 76 year-old woman who had previously undergone coronary artery bypass grafting (CABG) with the right internal thoracic artery (RITA) bypassed to the left anterior descending artery. Six years after CABG, she developed acute type A aortic dissection, and she was medically treated because the false lumen was thrombosed and it was considered that surgical intervention would be high risk for the patent RITA graft crossing between the sternum and the ascending aorta. During follow-up, her aortic aneurysm enlarged to 57 mm in diameter, and finally she was referred to our hospital for surgical intervention. In this case, preservation of the patent RITA graft was thought to be critical because the RITA graft was the only blood source for the left anterior descending artery. Prior to re-median sternotomy, we performed a right anterior minithoracotomy to make sufficient space between the sternum and the RITA graft, and then instituted peripheral cardiopulmonary bypass to decompress the heart. After re-sternotomy, we ensured minimum dissection of the RITA graft, and we successfully accomplished graft replacement of the ascending aorta to the aortic arch without injuring the patent RITA graft. In cases with a patent RITA graft and an ascending aortic aneurysm close to the sternum, our strategy is considered to be efficient for re-median sternotomy.
8.EFFECT OF SELF-MONITORING APPROACH DURING CARDIAC REHABILITATION ON EXERCISE MAINTENANCE, SELF-EFFICACY, AND PHYSICAL ACTIVITY OVER A 1-YEAR PERIOD AFTER MYOCARCIAL INFARCTION
KAZUHIRO P. IZAWA ; SATOSHI WATANABE ; KOICHIRO OKA ; NAOHIKO OSADA ; KAZUTO OMIYA
Japanese Journal of Physical Fitness and Sports Medicine 2006;55(Supplement):S113-S118
We conducted a randomized, controlled trial to evaluate the effect of self-monitoring approach (SMA) on exercise maintenance, self-efficacy for physical activity (SEPA), and objective physical activity (OPA) over the long-term after supervised cardiac rehabilitation (CR). Forty-five myocardial infarction (MI) patients (mean age 64.2 years) were recruited following completion of an acute-phase exercise-based CR program. Patients were randomly assigned to a SMA or control group. Along with CR, the SMA group performed self-monitoring of their weight and OPA for 6-months ; the control group participated in CR only. Twelve months after MI onset, exercise maintenance, SEPA scores, and OPA as a caloric expenditure were assessed. More patients maintained their exercise routine in the SMA than the control group. Mean SEPA score and mean OPA after CR were significantly higher in the SMA than control group. SMA during CR may effectively increase exercise maintenance, SEPA, and OPA over a 1-year after MI.
9.Clinical efficacy of the external preparation Metronidazole in the treatment of malodor associated with advanced and recurrent breast cancer
Hiromi Shinano ; Kazuhiro Watanabe ; Seigo Nakamura ; Yoko Tamahashi ; Masao Tsuchiya ; Junko Kizu ; Tadao Inoue
Palliative Care Research 2007;2(2):218-222
The external preparation Metronidazole (MTZ) is reported to be useful in controlling the malodor associated with advanced and recurrent breast cancer patients. We prepared two different MTZ external preparations, a 1% MTZ Hydrophilic Ointment and a 0.8% MTZ Carbopol Gel. These preparations were then used to control malodor associated with breast cancer and the results were clinically evaluated. Malodor disappeared within 1 week of administration of either preparation and no adverse reactions were observed. These MTZ external preparations were thus found to be useful in the elimination of malodor as part of the treatment of those patients with advanced and recurrent breast cancer.
10.Vasculo-Behcet Disease with Multiple Surgery and Reconstructed by Extraanatomic Bypass.
Toshiyuki Yuda ; Shigeru Fukuda ; Masaaki Koga ; Syuniti Watanabe ; Riitirou Toda ; Yuusuke Umebayashi ; Tosiaki Miyazaki ; Kazuhiro Arikawa
Japanese Journal of Cardiovascular Surgery 1996;25(1):59-63
A 52-year-old man suffering from Behçet's disease had undergone 6 operations for recurrent aneurysms of the bilateral iliac and femoral arteries. Thereafter, the patient underwent graft replacement for abdominal aortic aneurysm. Six years later he complained of lower abdominal pain and back pain. Abdominal CT-scan revealed abnormality of the proximal anastomotic site. The proximal suture line was completely dehiscent. The distal edge of infra-renal abdominal aorta was closed with interrupted mattress sutures. A right axillo-iliac bypass using a Dacron graft was performed for arterial reconstruction of the lower extremity. The patient has been free of recurrence for 4 years after the operation.