巻号一覧
131 巻, 3 号
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誌上シンポジウム
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本島 和典, 篠崎 亮介2011 年 131 巻 3 号 p. 315-316
発行日: 2011年
公開日: 2011/03/01
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菱川 和宏, 中川 秀彦, 宮田 直樹2011 年 131 巻 3 号 p. 317-324
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーNitric oxide (NO) is a key molecule in blood pressure regulation, neuromodulation, and biodefense. Since it is an unstable gas under ambient conditions, various NO donors have been developed and employed for biological studies as an alternative to direct NO application. However, many of them release NO via spontaneous decomposition, so that it is difficult to control the NO release. Therefore, NO donors from which NO release can be temporally and spatially well-controlled by means of photoexcitation offer considerable advantages. Various NO donors from which NO release is activated by photoirradiation have been reported. However, the maximum absorption of these NO donors is generally limited to the UV or short-wavelength visible light range, which does not adequately penetrate living tissues. To overcome this limitation, NO donors working via two-photon excitation (TPE) were developed by Ford and Prasad, based on NO release from Fe-nitrosyl complex. We have also developed TPE-type NO donors based on our photo-controllable 2,6-dimethylnitrobenzene derivatives, and investigated their NO-releasing properties. Here, we present an overview of photocontrollable NO donors and discuss their properties in relation to biological applications.
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大金 賢司, 闐闐 孝介, 橋本 祐一2011 年 131 巻 3 号 p. 325-334
発行日: 2011年
公開日: 2011/03/01
ジャーナル フリーThe retinitis pigmentosa (RP)-causing mutant of rhodopsin, Pro23His (P23H) rhodopsin, is folding defective and unable to traffic beyond the endoplasmic reticulum (ER). This ER retention, and in some cases, aggregation are proposed to result in ER-stress and eventually cell death. The endogenous rhodopsin ligand 11-cis-retinal and its isomer 9-cis-retinal have been shown to act as pharmacological chaperones, promoting proper folding and trafficking of the P23H rhodopsin. In spite of this promising effect, the development of retinals and related polyenealdehydes as pharmacological agents has been hampered by their undesirable properties, which include chemical instability, photolability, and potential retinoidal actions. Here we report the design and synthesis of a class of more stable nonpolyene-type rhodopsin ligands, structurally distinct from, and with lower toxicity than, retinals. A structure-activity relationship study was conducted using cell-surface expression assay to quantify folding/trafficking efficiency of P23H rhodopsin.
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谷野 哲也, 市川 聡, 魚谷 幸一, 大山 洋, 松田 彰2011 年 131 巻 3 号 p. 335-346
発行日: 2011年
公開日: 2011/03/01
ジャーナル フリーThis review describes the synthesis and structure-activity relationship (SAR) study of muraymycins (MRYs), which are potent antibacterial nucleoside antibiotics. The key elements of our synthetic approach include the preparation of L-epi-capreomycidine via a C-H amination reaction and a convergent assemblage to construct of the framework of MRYs using Ugi four component reaction. With this approach the first total synthesis of MRY D2 and its epimer, epi-MRY D2, which does not have lipophilic substituents, has been accomplished. The fact that MRY D2 and it's epimer did not show any antibacterial activity indicated the lipophilic substituents of MRYs plays an important role in membrane-permeability. Hence, MRY analogues with lipophilic substituents were designed and synthesized simply by altering the aldehyde component in Ugi four-component assemblage. The MRY analogues with lipophilic substituents exhibited improved antibacterial activity against anti drug-resistant bacteria. It was also suggested that the accessory urea-dipeptide motif might contribute to MraY inhibitory and antibacterial activity. Our synthetic approach would effectively provide a variety of MRY analogues and resultant SAR information brings us directions to create further MRY analogues.
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深井 良祐, 鄭 暁霞, 本島 和典, 加来田 博貴2011 年 131 巻 3 号 p. 347-351
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーNon-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve physical and mental pain, and to improve patients' quality of life. However, stomach irritation is a major side effect. Most NSAIDs inhibit cyclooxygenases (COXs), and inhibition of COX-1 on the stomach mucous membrane is thought to be responsible for the gastric disturb- ance. Consequently, development efforts have focused on COX-2-selective inhibitors, while COX-1-selective inhibitors have been rather neglected. Subsequently, however, it was shown that inhibition of either COX-1 or COX-2 alone does not induce gastric damage. Therefore, we have developed the COX-1-selective inhibitor N-(4-aminophenyl)-4-trifluoromethylbenzamide (TFAP), which shows analgesic activity without causing gastric damage. However, metabolism of TFAP generates a colored metabolite, resulting in red-purple coloration of urine after administration. In addition, the analgesic activity of TFAP is weaker than that of indomethacin. Thus, we designed a series of new COX-1-selective inhibitors, the 5-amino-2-ethoxy-N-(substituted)benzamide (ABEX) series, in order to avoid formation of the colored metabolite by modifying the diaminopyridine skeleton. As a result of structural modification and in vitro and in vivo testing of compounds in the ABEX series, we found a novel COX-1-selective inhibitor, 5-amino-2-ethoxy-N-(3-trifluoromethylphenyl)benzamide (ABEX-3TF), which shows better analgesic activity than indomethacin, and does not cause coloration of urine.
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藤原 泰之, 木村 朋紀2011 年 131 巻 3 号 p. 353-354
発行日: 2011年
公開日: 2011/03/01
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高橋 勉2011 年 131 巻 3 号 p. 355-358
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーThe clinical utility of anticancer drugs is seriously limited by the development of adverse effects and acquisition of resistance to these drugs by tumor cells. The mechanism underlying the toxicity of anticancer drugs is still not fully understood. To elucidate the mechanisms underlying the toxicity of anticancer drugs in greater detail, we performed a screen for determinants of sensitivity to adriamycin, an anthracycline antitumor antibiotic, using budding yeast as a model eukaryote. We found that overexpression of Akl1, a protein kinase of uncertain function, confers resistance to adriamycin. We investigated the function of Akl1 in adriamycin resistance and found that downregulation of the internalization step in endocytosis by Akl1 might be closely involved in the mechanism of adriamycin resistance. In human cells, overexpression of AAK1 and a human homologue of Akl1, also decreased adriamycin toxicity, suggesting that downregulation of endocytosis via phosphorylaiotn might be involved in the acquisition of adriamycin resistance not only in yeast cells but also in human cells. Further detailed investigation of the relationship between the endocytosis pathway and adriamycin toxicity might contribute further information for the improvement of chemotherapy with adriamycin.
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菅野 裕一朗, 井上 義雄2011 年 131 巻 3 号 p. 359-365
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーAnimals including human beings have defense mechanisms against the toxicity of xenobiotics such as medicinal compounds and environmental pollutants. Receptor-type transcriptional factors, such as aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR) and pregnane X receptor (PXR), play important roles in the defense against xenobiotic toxicities. In the absence of stimuli, these receptors are distributed predominantly in the cytoplasmic compartment. Following xenobiotic stimuli, receptors translocate into the nucleus and transactivate its target genes. However, the exogenously expressed CAR translocates spontaneously into the nucleus in immortal cells. Previously, we identified subcellular localization signals in rat CAR: nuclear localization signal (NLS), nuclear export signal (NES) and cytoplasmic retention region (CRR). Lack of CRR function might be responsible for the spontaneous nuclear accumulation of CAR in immortal cells. Further, the nuclear import of CAR is regulated by the importin-Ran system, which is required for maintaining an intact microtubule network. Clarifying the mechanisms underlying the nuclear translocation of CAR would be useful for the establishment of novel assay systems for the screening of ligands and activators of CAR using immortal cells without sacrificing animals.
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井上 健一郎, 高野 裕久原稿種別: Review
2011 年 131 巻 3 号 p. 367-371
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーAlthough the adverse health effects of diesel exhaust particles (DEP) have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions (pathological conditions) have not been fully identified. On the other hand, there exist hypersensitive subjects against particulate matters. In this review, we provide insights into the immunotoxicity of DEP as an aggravating factor in hypersusceptible subjects, especially those with allergic pulmonary diseases using our in vivo experimental model. In brief, we examined the effects of DEP on allergic asthma in vivo, and showed that repetitive pulmonary exposure to DEP has promoting effects on allergic airway inflammation, including adjuvanticity on Th2-milieu. Further, we propose a causal machinery regarding the adverse impacts, i.e., via inappropriate activation of antigen-presenting cells such as dendritic cells.
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伊藤 美千穂2011 年 131 巻 3 号 p. 373-374
発行日: 2011/03/01
公開日: 2011/03/01
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牧野 利明2011 年 131 巻 3 号 p. 375-382
発行日: 2011年
公開日: 2011/03/01
ジャーナル フリーIn Japanese hospitals or pharmacies, crude drugs and natural products are used as the components of kampo medicine and dietary supplements. Clinical pharmacy can provide information such as the efficacy, adverse action, or interactions of crude drugs or natural products as well as chemical drugs. However, it is very difficult for a clinical pharmacist without a knowledge of pharmacognosy to offer full information, because crude drugs and natural products have very different pharmaceutical characteristics from chemical drugs containing a single compound. Drug information provided by such a pharmacist is sometimes ridiculous and may be misleading by suggesting the unusefulness of crude drugs. Therefore, in order to use crude drugs and kampo medicine effectively and safely, it is necessary to integrate the clinical pharmacy and pharmacognosy as “clinical pharmacognosy”. Clinical pharmacognosy would also be capable of handling kampo medicine, a Japanese traditional medicine. Since basic pharmacognosy is a modern pharmaceutical science, pharmacognosists are limited in their understanding of a kampo formula and its clinical usefulness solely with a knowledge of that field. I suggest here that clinical pharmacognosy would better adopt the knowledge of traditional Chinese medicine that includes a theory of traditional pharmacology of the crude drugs used in kampo medicine.
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川原 信夫2011 年 131 巻 3 号 p. 383-393
発行日: 2011年
公開日: 2011/03/01
ジャーナル フリーThe Western Pacific Regional Forum for the Harmonization of Herbal Medicines (FHH) was established in 2002. The general proposed objective of the FHH is to promote public health by recognizing and developing standards and technical guidelines that aim to improve the quality, safety and efficacy of herbal medicines. At a sub-committee meeting of FHH nomenclature and standardization held in Tokyo, all the participants recognized the importance of comparing the descriptions of herbal medicines contained in member countries' pharmacopoeias or monograph standards as the first step in the harmonization of nomenclature and standardization. It was agreed to set up five expert working groups (EWG) to carry out the following specific tasks: 1) Nomenclature, 2) Testing Methods in Monographs, 3) List of Chemical Reference Standards (CRS) and Reference of Medicinal Plant Materials (RMPM), 4) List of Analytically Validated Methods, and 5) Information on General Tests. In this review, we report four topics of FHH activities from 2002-2009 as follows: 1) Comparative study on testing methods and specification values for crude drugs used in monographs among four Western Pacific regional countries (Japan, China, Korea and Vietnam), 2) Comparative study on TLC conditions for identification, chemical assay conditions for component quantification used in monographs among the four countries, 3) Comparative study on general testing methods for crude drugs among the four countries, 4) Comparative study on TLC identification for crude drugs used in monographs among the four countries considering harmonization and clean analysis.
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山浦 高夫2011 年 131 巻 3 号 p. 395-400
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーSoon after its foundation in 1919, Nippon Shinyaku Co., Ltd began to develop the domestic production of Santonin, an anthelmintic agent, which, until then, had been totally imported from Russia. In 1927, Artemisia maritima ssp. monogyna was introduced from Europe and confirmed to contain Santonin. This European aster plant was named Mibu-yomogi after the place name of the headquarters of Nippon Shinyaku. In 1934, Yamashina Experimental Farm was founded to breed Mibu-yomogi cultivars of high quality as a plant material for Santonin production in Japan. In 1953, the Experimental Farm was reorganized into the Institute for Botanical Research for the continuous breeding of Santonin-containing aster plants and for the development of any new medicines from medicinal plants. Through the breeding of Santonin-containing aster plants, many cultivars including Yamashina No. 2 from Mibu-yomogi, Penta-yomogi and Hexa-yomogi which were crosssed with Mibu-yomogi and A. kurramensis, were bred. Furthermore, we still have four ethical drug products originated from medicinal plants. Since 1994, the Institute has become a botanical garden in order to maintain, develop and exhibit the plant collection and for the cultivation studies of rare plants.
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川添 和義2011 年 131 巻 3 号 p. 401-405
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーPharmacists consider pharmacognosy to be a part of Kampo-related education. However, actually, pharmacists cannot generally apply pharmacognosy to their work in clinical settings because they do not have sufficient opportunities to learn about the relationship between pharmacognosy and Kampo in the Faculty of Pharmacy. Meanwhile, in the Faculty of Medicine, education in Kampo has spread at an accelerated rate since the amendment of the medical education core curriculum in 2001, leading to the present condition of 73 out of a total of 80 Faculties of Medicine in Japan already having adopted Kampo as a part of that curriculum. However, clinical education is often focused on, while items of pharmacognosy are hardly mentioned; therefore, pharmacognosy remains not as important in medical education. It is thus often very difficult for pharmacists who have only learned Kampo based on pharmacognosy to understand the prescription of a physician who has received Kampo education, and this remains a considerable problem for pharmacists who are required to explain how to take a drug to a patient in clinical practice. What role does pharmacognosy have to play to bridge the gap between such physicians and pharmacists? Here, I would like to describe what I believe is necessary regarding pharmacognosy education in the future, both from the perspectives of pharmacists and physicians who prescribe Kampo medicine.
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総説
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新岡 丈典原稿種別: Review
2011 年 131 巻 3 号 p. 407-413
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーCytochrome P450 (CYP) 2C19 (CYP2C19) genotype is regarded as a useful tool to predict area under the blood concentration-time curve (AUC) of proton pump inhibitors (PPIs). In our results, however, CYP2C19 genotypes had no influence on AUC of all PPIs during fluvoxamine treatment. These findings suggest that CYP2C19 genotyping is not always a good indicator for estimating AUC of PPIs. Limited sampling strategies (LSS) were developed to estimate AUC simply and accurately. It is important to minimize the number of blood samples because of patient's acceptance. This article reviewed the usefulness of LSS for estimating AUC of three PPIs (omeprazole: OPZ, lansoprazole: LPZ and rabeprazole: RPZ). The best prediction formulas in each PPI were AUCOPZ=9.24×C6h+2638.03, AUCLPZ=12.32×C6h+3276.09 and AUCRPZ=1.39×C3h+7.17×C6h+344.14, respectively. In order to optimize the sampling strategy of LPZ, we tried to establish LSS for LPZ using a time point within 3 hours through the property of pharmacokinetics of its enantiomers. The best prediction formula using the fewest sampling points (one point) was AUCracemic LPZ=6.5×C3h of (R)-LPZ+13.7×C3h of (S)-LPZ−9917.3×G1−14387.2×G2+7103.6 (G1: homozygous extensive metabolizer is 1 and the other genotypes are 0; G2: heterozygous extensive metabolizer is 1 and the other genotypes are 0). Those strategies, plasma concentration monitoring at one or two time-points, might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in the case of coadministration of CYP mediators.
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関本 征史2011 年 131 巻 3 号 p. 415-422
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーCytochrome P450 1A subfamily enzymes (CYP1As) are important molecules in the metabolic activation of carcinogens such as polycyclic aromatic hydrocarbons and heterocyclic amines and are induced by their substrate exposure. There are species, sex, and organ differences in the induction of CYP1As, and susceptibilities to carcinogens are closely related to the constitutive and carcinogen-induced levels of CYP1As in target organs of experimental rodents. In this study, we investigated the induction of CYP1As and their species or sex differences after treatment with various chemicals using experimental animals and cultured cell lines. We found that: 1) newly established reporter cell lines, HepG2-A10 and KanR2-XL8, can be used for determining of activation of the aryl hydrocarbon receptor (AhR), a key transcription factor in the expression of CYP1As; 2) monocyclic aromatic amine (2-methoxy-4-nitroaniline) induced hepatic CYP1As in rats but not in other rodents in an AhR-independent manner; 3) androgen suppressed the constitutive expression or heterocyclic aromatic amine (Trp-P-1)-dependent induction of these enzymes in pigs and mice; and 4) nicardipine, a dihydropyridine calcium channel blocker, increased hepatic CYP1A expression in rats and augmented 3-methylcholanthrene-mediated induction of CYP1As and DNA-adduct formation in HepG2 cells. These findings indicate that there are species or sex differences in the induction of hepatic CYP1As via AhR-independent and unexplained transcriptional mechanisms. The elucidation of these mechanisms will aid in finding new predictors or developing new prevention strategies for chemical-induced carcinogenesis.
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一般論文
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Xiaolu FENG, Jincai LU, Hailiang XIN, Lei ZHANG, Yuliang WANG, Kexuan ...原稿種別: Regular Article
2011 年 131 巻 3 号 p. 423-429
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーThe aim of this study was to ascertain the anti-arthritic active fraction of Capparis spinosa L. (Capparidaceae) fruits and its chemical constituents. The adjuvant arthritic rat model was developed to evaluate the anti-arthritic effects of different fractions of ethanol extraction from C. spinosa L. The fraction eluted by ethanol-water (50:50, v/v) had the most significant anti-arthritic activity. The chemical constituents of this fraction were therefore studied; seven known compounds were isolated and identified as: (1) P-hydroxy benzoic acid; (2) 5-(hydroxymethyl) furfural; (3) bis (5-formylfurfuryl) ether; (4) daucosterol; (5) α-D-fructofuranosides methyl; (6) uracil; and (7) stachydrine.
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Raisa N. KAZI, Munavvar A. SATTAR, Nor A. ABDULLAH, Md A. Hye KHAN, Ha ...原稿種別: Regular Article
2011 年 131 巻 3 号 p. 431-436
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーα1D-Adrenoceptors are involved in the genesis/maintenance of hypertension in spontaneously hypertensive rats (SHR). This study aims to investigate the role of α1D-adrenoceptors in the antinatriuretic and antidiuretic responses in SHR subjected to high sodium (SHRHNa) and normal sodium (SHRNNa) intake for six weeks. Renal inulin clearance study was performed in which the antinatriuretic and antidiuretic responses to phenylephrine were examined in the presence and absence of α1D-adrenoceptors blocker BMY7378. Data, mean±S.E.M. were subjected to ANOVA with significance at p<0.05. Results show that feeding SHR for six weeks with high salt did not cause any change in blood pressure. SHRHNa had higher (all p<0.05) urine flow rate (UFR), fractional and absolute excretion of sodium (FENa and UNaV) compared to SHRNNa. Phenylephrine infusion produced significant reduction in UFR, FENa and UNaV in both SHRHNa and SHRNNa. The antidiuretic and antinatriuretic responses to phenylephrine in both groups were attenuated in the presence of BMY7378. Moreover, the antidiuretic and antinatriuretic responses to phenylephrine and BMY7378 were independent on any significant changes in renal and glomerular hemodynamics in both groups. Thus we conclude that high sodium intake did not bring any further increase in blood pressure of SHR, however, it results in exaggerated natriuresis and diuresis in SHRHNa. Irrespective of dietary sodium changes, α1-adrenoceptors are involved in mediating the antinatriuretic and antidiuretic responses to phenylephrine in SHR. Further, high sodium intake did not significantly influence the functionality of α1D-adrenoceptors in mediating the adrenergically induced antinatriuresis and antidiuresis.
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Arunachalam MUTHURAMAN, Sumeet Kumar SINGLA, Ajay RANA, Atinderjeet SI ...原稿種別: Regular Article
2011 年 131 巻 3 号 p. 437-443
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーThis study was aimed to evaluate the role of flunarizine on gentamicin (GEM) induced nephrotoxicity in rat. Administration of GEM (40 mg/kg, s.c. for 10 consecutive days) significantly increased blood urea nitrogen (BUN), N-acetyl β-d-glucosaminidase (NAG), thiobarbituric acid reactive substances (TBARS) and total calcium whereas, decreased body weight, fractional excretion of sodium (FrNa), creatinine clearance (CrCl), reduced glutathione (GSH), mitochondrial cytochrome c oxidase (Cyt-C oxidase) and ATP levels resulting in nephrotoxicity. Further, flunarizine (100, 200 and 300 μmol/kg, p.o.) was administered to evaluate its renoprotective effect against GEM induced nephrotoxicity and the results were compared with cylcosporin A (CsA, 50 μmol/kg, p.o.). Flunarizine resulted in the attenuation of renal dysfunction and oxidative marker changes in rats subjected to GEM induced nephrotoxicity in a dose dependent manner. Medium and higher doses of flunarizine produced significant renal protective effect which was comparable to cyclosporin A. The results of this study clearly revealed that flunarizine protected the kidney against the nephrotoxic effect of GEM via mitochondrial permeability transition pore (MPTP) inactivation potential.
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中村 浩規, 横山 晴子, 矢口 武廣, 鈴木 優司, 徳岡 健太郎, 渡邊 昌之, 北川 泰久, 山田 安彦2011 年 131 巻 3 号 p. 445-452
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーIn this study, we investigated the effect of histamin H2 receptor antagonist (H2RA) or proton pump inhibitor (PPI) for the prevention of upper gastrointestinal lesions associated with low-dose aspirin. We carried out a retrospective study of 2811 patients who had been prescribed low-dose aspirin (Bayaspirin® 100 mg) for more than 30 days at Tokai University Hachioji Hospital from 2006 to 2008. We classified them into three groups: aspirin alone group (n=1103), aspirin with H2RA group (n=844) and aspirin with PPI group (n=864). Patients who developed upper gastrointestinal lesions were diagnosed with gastric ulcer, duodenal ulcer, gastritis or duodenitis by gastroscopy. We then compared the incidence of upper gastrointestinal lesions among the groups. The incidence in aspirin alone group, aspirin with H2RA group and aspirin with PPI group was 2.54%, 1.54% and 1.04%, respectively; that of aspirin with PPI group being significantly lower (p<0.05). Additively, the odds ratio (OR) of aspirin with H2RA group and aspirin with PPI group was 0.60 (95% confidence interval [95%CI]: 0.31-1.17) and 0.40 (95% CI: 0.19-0.86) as compared with aspirin alone group, respectively. The upper gastrointestinal lesions were developed within two years in all groups. Our results suggest that the combined administration of low-dose aspirin and PPI is effective for the prevention of upper gastrointestinal lesions associated with low-dose aspirin. Also, the pharmacists should be especially careful for upper gastrointestinal lesions development within two years after administration of low-dose aspirin, regardless of combined whether H2RA or PPI.
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小倉 次郎, 藤川 あす歌, 丸山 創, 小林 正紀, 板垣 史郎, 井関 健原稿種別: Regular Article
2011 年 131 巻 3 号 p. 453-462
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーAlteration of P-glycoprotein (P-gp) expression influences the pharmacokinetics of P-gp substrates after intestinal ischemia-reperfusion (I/R). Fasting before intestinal I/R affects intestinal I/R injury. However, the effect of fasting on the alteration of P-gp expression after intestinal I/R has not been clarified. We previously reported that P-gp expression was altered after intestinal I/R following feeding. In the present study, we investigated the expression of P-gp after intestinal I/R following 16-h fasting. The mdr1a levels were decreased at 6 h in the jejunum, at 1 h in the ileum, at 6 and 24 h in the liver and at 6 h in the kidney. The mdr1b levels were decreased at 6 h in the ileum and at 1 and 6 h in the kidney. The mdr1b level in the liver was increased at 1 and 6 h. The expression of P-gp was decreased at 6 h in the jejunum, at 1, 6 and 24 h in the ileum, and at 6 h in the kidney. These alterations were different to those after intestinal I/R following feeding. In particular, the decrease in P-gp expression in the 16-h fasting I/R rats occurred at an early time during reperfusion compared with that in the feeding I/R rats. In conclusion, feeding condition affects the alteration of P-gp expression after intestinal I/R. Therefore, it is important to understand the patient's feeding condition for safe drug therapy.
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川野 千尋, 平山 武司, 黒山 政一原稿種別: Regular Article
2011 年 131 巻 3 号 p. 463-467
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーOpioid rotation has been proposed for management of cancer pain. No studies directly investigating dose equivalence between morphine injection (continuous IV administration) and the transdermal fentanyl patch have been reported. Therefore, we examined dose conversion ratios in patients undergoing opioid rotation from morphine injection to fentanyl patches. The subjects consisted of 45 patients admitted to Kitasato University East Hospital. Medical records were consulted to determine the “basic dose of morphine injection immediately prior to rotation” and the “basic dose of fentanyl patch after rotation”. Equivalent doses and conversion ratios obtained with the expression of (daily dose of morphine injection (mg)/daily delivered dose of fentanyl patch (mg)) were determined from the relationship between the data by regression analysis. The regression equation obtained was Y=50.882X-13.96, r2=0.8922, where X and Y are daily doses of morphine injection and fentanyl patch, respectively. Equivalent doses and conversion ratios for daily dose of morphine injection (mg): daily delivered dose of fentanyl patch (mg) (patch dose mg/3 days) were 16.6 mg: 0.6 mg (2.5 mg)=28:1, 47.1 mg: 1.2 mg (5 mg) = 39:1 and 169.2 mg: 3.6 mg (15 mg)=47:1. In other reports, the ratio of morphine vs. fentanyl at 50:1 had no relation to the dose. While the present study suggested that in opioid rotation from low dose, 50:1 is not enough for the fentanyl patch. The dose conversion ratio of morphine injection to fentanyl patch was different at the low doses and high doses of morphine.
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ノート
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植木 哲也, 長井 惠子, 大江 宣春, 中嶋 弥穂子, 西田 孝洋, 中村 純三, 中嶋 幹郎原稿種別: Note
2011 年 131 巻 3 号 p. 469-476
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーConstipation is a common problem in hospitalized patients; however, the relative risks of its development with various factors have not been clarified. To clarify the risk factors associated with constipation, we performed a case-controlled study of 165 hospitalized patients who were not laxative users on admission. They were divided into case (n=35) and control (n=130) groups according to laxative administration during hospitalization. Comparison of the patient backgrounds in the two groups revealed significant differences in the activities of daily living, length of fasting, rest level on admission, cerebrovascular disease, and administration of hypnotics. Multiple logistic regression analysis using these five factors as autonomous variables showed that administration of hypnotics (odds ratio, 2.79; 95% confidence interval, 1.10-7.06; p=0.031) was significantly related to laxative use. Therefore, the administration of hypnotics may be the principal cause of constipation development in hospitalized patients and they should be used with caution.
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菊池 千草, 堀 英生, 前田 徹, 松永 民秀, 鈴木 匡2011 年 131 巻 3 号 p. 477-483
発行日: 2011/03/01
公開日: 2011/03/01
ジャーナル フリーOne of the Specific Behavioral Objectives (SBOs) of pharmaceutical education model-core curriculum is as follows: “Understand patient's state of mind and be sensitive to patient's feelings”. We performed learning through simulation of diabetes drug therapy as a means to achieve the objective and evaluated the educational effects of the learning. The simulation was performed and a questionnaire survey was conducted among the 4th-year students of the 6-year curriculum before and after simulation. The score of “level of understanding patient's feelings” was significantly increased after simulation (p<0.001). In addition, the score tended to be associated (R2=0.192) with an increased score in two factors that affect patients' self-care action: “Consciousness of diabetes mellitus” (β=0.251, p=0.062) and “Time and effort for drug therapy” (β=0.248, p=0.065). The main topics of discussion about the simulation included “Lack of sense of critical illness”, “Lifestyle”, “Dose regimen” and “Necessity of support from patients' family and others close to them”. Therefore, the learning through simulation diabetes drug therapy was effective to understand patients' states of mind because students learned the importance of some factors affecting self-care action.
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