著者

平塚 祥子 熊野 宏昭 片山 潤 岸川 幸生 菱沼 隆則 山内 祐一 水柿 道直

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.120, no.2, pp.224-229, 2000-02-01 (Released:2008-05-30)

参考文献数

11

被引用文献数

5 7

---

The failure of patients to comply with treatment regimens recommended by their physicians is a significant clinical problem. Researches on the assessment of compliance have, however, been precluded by methodological difficulties such as lack of adequate measures. The purpose of this study was to develop a self-administered questionnaire to evaluate drug compliance. First, questionnaire containing a 52-items complied by two doctors, a pharmacist and a nurse, was tested on 81 outpatients, all volunteers, attending the departments of psychosomatic medicine and internal medicine. Four items were temporarily removed for later analysis because they directly inquired about drug compliance (drug compliance items). The other 48 items were analyzed and three factors consisting of 26 items were further studied : expectation on taking medicine, rejection to taking medicine and seeking knowledge of drugs. Chronback's alpha coefficients representing internal consistency of the three factors were sufficiently high (ranging from .75 to .84). Furthermore, we preformed a simplified pill count to validate the 4 drug compliance items. There was a weak to moderate correlation between the result of pill count and each of 4 drug compliance items. A new self-administered questionnaire of 30 items was thus developed and named the Drug Compliance Scale.

著者

原田 利一 水野 瑞夫 加藤 智雄

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.72, no.4, pp.591-593, 1952-04-25 (Released:2010-02-19)

参考文献数

4

被引用文献数

1 1

---

The alcoholic extracts of 53 kinds of shelf-fungi were tested for their antibacterial action against Staphylococcus aureus (Friedlender) and E. coli by the dilution method. Digests of Grifola sp. and Fomes sp. were found to have the most strong action against Staphylococus aureus.

著者

堤 広之

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.8, pp.925-931, 2012-08-01 (Released:2012-08-01)

参考文献数

24

被引用文献数

3 4

---

Two crystals of a complex of (−)-gallocatechin-3-O-gallate (GCg) with caffeine and crystals of the complexes of (+)-catechin (CA) and (−)-catechin-3-O-gallate (Cg) with caffeine were prepared, and their stereochemical structures and intermolecular interactions were determined in X-ray crystallographic analysis. GCg formed 1:2 and 2:2 complexes with caffeine, and π-π interactions formed between the aromatic rings of GCg and caffeine in both complexes. In addition, CA of nongalloylated catechins formed a 1:1 complex with caffeine through intermolecular hydrogen bonds, whereas Cg of galloylated catechins formed a 1:2 complex with caffeine, which was formed by face-to-face and offset π-π interactions and intermolecular hydrogen bonds.

著者

平川 宣幸 矢ノ下 良平 吉井 大 矢野 博子

出版者

公益社団法人 日本薬学会

雑誌

薬学雑誌. 乙号 (ISSN:00316903)

巻号頁・発行日

vol.130, no.7, pp.971-975, 2010

---

&nbsp;&nbsp;Six allergic conjunctivitis patients (12 eyes) and 4 healthy volunteers (8 eyes) were investigated in terms of the effect of cooling sheets on eye itching and tear histamine concentration, before and 5 min after cooling the eyelids with cooling sheets. The severity of itching was evaluated with a five-level itching score. The combination treatment of levocabastine with cooling sheets significantly reduced eye itching, while no significant change in tear histamine concentration was observed before and after cooling sheet use. The cooling sheets are useful for reducing eye itching in the therapy of allergic conjunctivitis. The tear histamine concentration did not correlate with the antiitching effect of cooling sheets in this study.<br>

著者

大谷 道輝 山田 伸夫 高山 和郎 小瀧 一 江藤 隆史 假家 悟 内野 克喜 伊賀 立二

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.122, no.1, pp.107-112, 2002-01-01 (Released:2003-02-13)

参考文献数

14

被引用文献数

8 8

---

A commonly used admixture of commercially available ointments and/or creams was selected from the prescribed sheets in our hospital, and questionnaire to dermatologists. To assess the relationship between permeability of corticosteroid through murine skin and clinical effects in human, we attempted to investigate the vasoconstrictor activity of these admixtures of topical corticosteroid by double-blind controlled study. Test samples were occluded at random on the back of 20 healthy volunteers for 4 hours. The vasoconstrictor activity of corticosteroid creams (Lidomex®) alone was significantly large as compared with that of ointments alone. The vasoconstrictor activity of corticosteroid in the admixture of Lidomex® ointment and urea ointments or heparinoid ointment was 1.5—2 fold significantly larger than that from ointments alone. The extent of the stability of the emulsion after mixing was related to the vasoconstrictor activity. These experiments demonstrated a close relationship between the vasoconstrictor activity of human skin and permeability of hairless mice skin. These results suggested that the vasoconstrictor activity of topical corticosteroids mixed with commercially available ointments and/or creams depends upon their physicochemical characteristics.

著者

Shoji SHIBATA

出版者

The Pharmaceutical Society of Japan

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.120, no.10, pp.849-862, 2000-10-01 (Released:2008-05-30)

参考文献数

62

被引用文献数

263 372

---

Licorice, the root of Glycyrrhiza spp. (Fabaceae), has been used since ancient Egyptian, Greek, and Roman times in the West and since the Former Han era (the 2nd-3rd century B.C.) in ancient China in the East. In traditional Chinese medicine, licorice is one of the most frequently used drugs. In Japan, the oldest specimen of licorice introduced from China in the middle of the 8th century still exists in Shosoin, the Imperial Storehouse, in Nara. Extracts of licorice were recommended as a remedy for gastric ulcer by Revers of the Netherlands in 1946, which was soon withdrawn owing to its side effects. Carbenoxolon sodium, glycyrrhetinic acid (GA) hemisuccinate Na, was prepared from licorice to treat peptic ulcer in the UK. In Japan for the past 60 years, a glycyrrhizin (GL) preparation under the name of Stronger Neo-Minophagen C (SNMC) has been used clinically as an antiallergic and antihepatitis agent. GL and GA sometimes induce edema, hypertension, and hypokalemia in patients treated with higher doses and long-term administration. The mechanism of this side effect, pseudoaldosteronism, has been explained as due to the 11-hydroxy-steroid dehydrogenase inhibitory activity of GL and GA. The excess of endogenous cortisol produced combines with the renal mineral corticoid receptor, which promotes an aldosterone-like action. GL and GA reduce alanine transaminase (ALT) and aspartate transaminase (AST) values in the serum. This hepatoprotective effect has recently been explained as the inhibitory effects of GL and GA on immune-mediated cytotoxicity against hepatocytes and on nuclear factor (NF)-κB, which activates genes encoding inflammatory cytokines in the liver. To exclude the side effects and enhance the therapeutic activities, chemical modification of GL and GA has been performed. Deoxoglycyrrhetol (DG), homo- and heteroannular diene homologs of dihemiphthalates, showed a remarkable improvement in antiinflammatory, antiallergic, and antiulcer activities in animal experiments. Immunomodulating effects of GL, GA, and DG derivatives, which induce interferon-γ and some other cytokines, have been demonstrated in relation with their antiviral activities. Antiinflammatory, antitumorigenic, and antimalarial effects of licorice flavonoids have also been investigated.

著者

鈴木 登紀子

出版者

公益社団法人 日本薬学会

雑誌

薬学雑誌. 乙号 (ISSN:00316903)

巻号頁・発行日

vol.135, no.12, pp.1335-1340, 2015

被引用文献数

3

---

&nbsp;&nbsp;Adenosine and its precursors, ATP and ADP, exert various physiological effects <i>via</i> binding to purinergic receptors. We previously used co-immunoprecipitation, bioluminescence resonance energy transfer (BRET) and immunoelectron microscopy to demonstrate the hetero-oligomerization of purinergic receptor subtypes. Furthermore, pharmacological studies found significant changes in receptor-mediated signaling in human embryonic kidney (HEK) 293T cells co-transfected with these receptors. These findings suggest that heterodimers of purinergic receptors may have distinct pharmacological profiles, possibly due to dimerization-induced conformational changes, further suggesting that hetero-dimerization may be employed to &ldquo;fine-tune&rdquo; purinergic receptor signaling. Adenosine A_2A receptor (A_2AR), P2Y₁ receptor (P2Y₁R) and P2Y₁₂ receptor (P2Y₁₂R) are predominantly expressed on human platelets. ADP activates human platelets by stimulating both P2Y₁R and P2Y₁₂R, which act sequentially and in concert to achieve complete platelet aggregation. In contrast, adenosine stimulates Gs-coupled A_2AR, followed by activativation of adenylate cyclase, leading to an increase in intracellular cAMP levels, which potently inhibits platelet activation. We examined the hetero-oligomerization and functional interactions of A_2AR, P2Y₁R, and P2Y₁₂R. In HEK293T cells triply expressing all three receptors, hetero-oligomerization was observed among the three receptors. Additionally, P2Y₁R agonist-evoked Ca²⁺ signaling was significantly inhibited by co-treatment with an A_2AR antagonist in HEK293T cells. In human platelets, we identified endogenous A_2AR/P2Y₁R and A_2AR/P2Y₁₂R heterodimers. We also observed functional Ca²⁺-signaling-related cross-talk similar to those found in HEK293T cells, and found that they appeared to affect platelet shape. These results collectively suggest that intermolecular signal transduction and specific conformational changes occur among components of the hetero-oligomers formed by these three receptors.<br>

著者

名取 良浩

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.141, no.1, pp.15-24, 2021-01-01 (Released:2021-01-01)

参考文献数

32

被引用文献数

2

---

Iminosugars are one of the compounds that mimic the structure of monosaccharides. Such sugar mimics have the ability to effectively and specifically inhibit various glycosidases and glycosyltransferases. After studying iminopyranose, miglitol, which has α-glucosidase inhibitory activity, was approved and used in the clinical treatment of diabetes. This study focused on l-iminofuranose derivatives to develop new anti-diabetic drug. As a result, it was found that l-iminofuranose having an alkyl group at C1 position show potent α-glucosidase inhibitory activity. Further structural-activity relationship studies were conducted, and interesting findings were obtained. This paper describes the details of those research developments.

著者

ヒキノ ヒロシ 神 久徳 竹本 常松

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.95, no.5, pp.590-595, 1975-05-25 (Released:2008-05-30)

参考文献数

11

---

Incorporation of [4-14C]cholesterol and [2-14C]mevalonic acid lactone into the phytoecdysones, inokosterone and ecdysterone, in Achyranthes fauriei seedlings and their homogenate, respectively, was demonstrated.

著者

柴田 ゆうか 河本 昌志 木平 健治

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.2, pp.163-167, 2015 (Released:2015-02-01)

参考文献数

3

被引用文献数

1

---

In an effort better to understand the application of pharmaceutical services in the operating room (OR) we conducted a survey among OR department directors of 526 hospitals throughout Japan. A total of 202 directors responded to the survey. Pharmacists are expected to achieve better outcomes in pharmacotherapy as well as play major roles as members of diverse perioperative care teams. Besides implementing medication safety standards, pharmacists' roles include optimizing drug therapy and other clinical interventions, both in OR and wards. Presently, few pharmacists in Japan participate in perioperative care, which is one of the reasons that the majority of pharmacy schools in Japan have been providing fewer lectures or rotations related to perioperative care. Yet, developing general perioperative management as another crucial role OR pharmacists play and incorporating it into pharmaceutical education would be important. Enriching perioperative care provided by pharmacists can contribute toward improving clinical competence in these professionals.

著者

永井 恒司

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 = Journal of the Pharmaceutical Society of Japan (ISSN:00316903)

巻号頁・発行日

vol.123, no.3, pp.143-150, 2003-03-01

参考文献数

11

被引用文献数

4

---

In Japanese pharmaceutical community, there seems to be a lack of “Science of Science” and “Research on Research” which are to utilize unit sciences and research for the benefit of human being. In other words, pharmaceutical people in Japan should have much more pharmaceutical philosophy. The late Professor Komei Miyaki, founder Editor-in-Chief of FARUMASHIA, the monthly membership magazine of Pharmaceutical Society of Japan, under whom I worked as one of editorial board members, taught me that scientists should have their own philosophy of their sciences. Such a pharmaceutical philosophy as mentioned above should be established on the basis of complete separation of medical profession between doctors and pharmacists, which form the most important and necessary issue in safety assurance for patients with the complete zero defect (ZD action), as there is a long history for that in Europe since the separation was completed by King Friedrich II in 1240. Therefore, we have to learn the social status of European/American pharmacist practitioners who are the great No. 1 among all the professions. European pharmacists guarantee the safety of every chemical used for human body and pets, such as medicines, cosmetics, foods, tooth stuffs and so on. Regarding the pharmaceutical sciences in Japan also there seems to be a lack of pharmaceutical philosophy, as pharmaceutical scientists have no identity in research object that may be similar to basic scientists who are non-pharmacy graduates. Japanese sciences generally have developed along the lines of the Western model, reaching the current high level. We now not only should receive profits from the outside but also should embark on a mission to support pharmaceutical sciences throughout the world, especially Asian courtiers. At the present, we do not seem to be fulfilling our mission to do that, even though general activity includes significant international exchange. We have to make much more effort for international contribution/participation. For that, the most important and necessary issue is to make change in fundamental sense in Japanese pharmaceutical community, though an internationalization of technological issues is usually taken into consideration. In this connection, regarding the new drug development, we must have a change in the sense to establish pharmaceutical philosophy and jump up in conception from the existing one. Based on the above mentioned pharmaceutical philosophy, seven star pharmacists should be educated as described in 2000 FIP Statement of Policy: Good Pharmacy Education Practice, who could be a (1) care giver; (2) decision maker; (3) communicator; (4)leader; (5) manager; (6) life-long learner; (7)teacher.<br>

著者

石橋 祐二 井上 義雄 谷口 彰良

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.6, pp.699-704, 2012 (Released:2012-06-01)

参考文献数

31

被引用文献数

2

---

Human bronchial mucins, such as MUC5AC, have traditionally been defined as a family of high-molecular weight glycoproteins. Changes in the contents of sugar chains on MUC5AC are among the fundamental features in inflammatory respiratory disease. The changes have been shown to lead to unfavorable alterations in the viscosity of mucus, resulting in impairment of mucociliary transport, vulnerability to viral/bacterial infection as sugar chains play an important role in adhesion of some viruses and bacteria to the epithelium, and finally inflammatory cell infiltration in the airway. Recently, we found that expression of some glycosyltransferases associated with the contents and structure of sugar chains is regulated by phosphatidylinositol-phospholipase (PI-PL) C signaling in cells. L-Carbocisteine, a mucoregulatory drug, normalized or balanced fucosylated and sialylated sugar chains, such as sialyl Lewis x through inhibition of PI-PL C signaling. We prepared MUC5AC fusion protein with tandem repeats associated with MUC5AC, and confirmed that L-carbocisteine inhibited the increases in viscosity associated with sialyl Lewis x expression levels. In addition, the clinical study (2008) noted that L-carbocisteine reduced the frequency of common colds and exacerbation of symptoms in patients with COPD. These favorable effects in patients may be due to normalization of sugar chain contents on mucins. We suggest that the inhibitory effect on infection of airway epithelial cells by rhinoviruses, respiratory syncytial virus, and influenza viruses by treatment with L-carbocisteine may also be based on the regulation of sugar chain contents or structures on mucins.

著者

佐藤 捨三郎

出版者

公益社団法人 日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.1912, no.361, pp.217-241, 1912-03-26 (Released:2018-08-31)

被引用文献数

1

---

曩ニ内務省東京衛生試驗所ニ奉職中東京市内ノ混砂米及之カ淘洗米ニ就テ試驗セシ結果假令混砂米ト雖トモ水洗宜シキヲ得レハ砂粉ヲ附着スルノ虞ナク從テ衛生上何等障害ナキヲ報告セリ當時精米業者ハ玄米搗精ノ目的ヲ以テ珪酸及其當時ヨリナレル早搗粉(俗ニ荒粉ト云フ)ノ少量ヲ加フルノミニテ他ニ何物ヲモ混セサルモノト信セシガ其後京都府ニ轉任シ當市ニ於ケル精米業者ヲ觀ルニ彼等ノ多クハ搗精ノ目的ヲ以テ使用スル荒粉ハ極メテ少量ナルニ反シ増量若クハ化装用トシテ土粉(俗ニ青本粉ト云フ)又ハ石粉ト稱スル粉末ノ多量ヲ混シ以テ不正ノ利ヲ貪リツ、アルヲ知レリ故ニ當府ニ於テハ昨年市内販賣店ヨリ收去セル混砂米百九十六種ニ就キ試驗ヲ遂ケシ結果灰分ノ量無水物レシテ一プロセント」以上ノモノハ混砂ノ量多キモノト認メ警察犯處罰令ニ據リ相當取締ヲ加フルコト、ナセリ

著者

有吉 眞理子 大谷 淳二 白川 昌宏

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.1, pp.3-9, 2015-01-01 (Released:2015-01-01)

参考文献数

17

---

DNA methylation is one of the major epigenetic marks in the mammalian genome to define chromatin higher-order structure, and plays essential roles in various developmental processes. In the mammalian genome, DNA methylation mainly occurs at the 5th position of cytosine bases in a palindromic 5′-CG-3′dinucleotide sequence. Methyl CpG binding domain (MBD) proteins recognize symmetrically methylated CpG sites (5mCG/5mCG) through a conserved MBD, and recruit transcriptional repressors or chromatin modifiers. One of the MBD proteins, MBD4, uniquely contains a C-terminal glycosylation domain together with an N-terminal MBD, and functions as a mismatch DNA repair enzyme specific for T/G or U/G mismatch bases generated by spontaneous deamination of 5-methylcytosine. The base excision activity of MBD4 is also implicated in active DNA demethylation initiated by the conversion of 5-methylcytosine to thymine by deaminases. Unlike other MBD proteins, MBD4 recognizes not only 5mCG/5mCG but also T/G mismatched sites generated by spontaneous deamination of 5-methylcytosine (5mCG/TG). In addition, our biochemical data demonstrate that MBD also binds to intermediates in DNA demethylation pathways, such as 5-hydroxymethyl-cytosine (hmC), 5-carboxyl-cytosine and 5-hydroxy-uracil. The crystal structures of MBDMBD4 in complex with 5mCG/TG, 5mCG/5mCG or 5mCG/hmCG provide new structural insights into the versatility of base recognition by MBD4. A DNA interface of MBD4 has flexible structural features, in which an extensive hydration water network supports the versatile base specificity of MBD4. The versatile base recognition by MBDMBD4 implies multi-functional roles of MBD4 in the regulation of dynamic DNA methylation patterns.

著者

緒方 潤 河村 麻衣子 袴塚 高志 花尻(木倉) 瑠理

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.12, pp.1501-1508, 2020-12-01 (Released:2020-12-01)

参考文献数

18

被引用文献数

3

---

In Japan, mitragynine, 7-hydroxymitragynine and Mitragyna speciosa Korth. (M. speciosa, “Kratom”) were controlled as Designated Substances under the Pharmaceutical and Medical Device Act from March 2016. In this study, the origins of 16 Kratom products obtained from the illegal drug market in Japan were investigated by DNA analyses and LC-MS analyses. When the PCR-restriction fragment length polymorphism (RFLP) was performed using the restriction enzyme XmaI (as reported by Sukrong et al. to be able to distinguish M. speciosa), the same DNA fragment patterns were obtained from all 16 products. On the other hand, as a result of the identification of the plant species of each product by nucleotide sequence analyses, the sequences of M. speciosa were detected in only 14 products. Despite the facts that mitragynine and 7-hydroxymitragynine were detected also in the other two products by the LC-MS analyses, M. speciosa DNAs were not amplified from these products by the PCR. Moreover, the DNA amplicons of the other psychotropic plant (Mesembryanthemum sp., e.g. “Kanna”) were detected. This plant PCR amplicon has the restriction site for the XmaI at the same position of the M. speciosa PCR amplicon and it is difficult to distinguish “Kratom” and “Kanna” by the conventional PCR-RFLP. When the restriction enzyme XhoI was used simultaneously with the Xmal, the specific DNA fragment was only observed from the M. speciosa amplicon and it was possible to distinguish both species using this improved PCR-RFLP method. This method is useful to identify the origin of Kratom products distributed in the illegal drug market.

著者

田頭 秀章 福永 浩司

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.2, pp.167-172, 2012-02-01 (Released:2012-02-01)

参考文献数

32

被引用文献数

2 6

---

Selective serotonin reuptake inhibitors (SSRIs) are known to reduce post-myocardial infarction (MI)-induced morbidity and mortality. However, the molecular mechanism underlying SSRI-induced cardioprotection remains unclear. Here, we investigated the role of sigma-1 receptor (Sig-1R) stimulation with fluvoxamine on myocardial hypertrophy and cardioprotection. Male ICR mice were subjected to transverse aortic constriction (TAC) in the cardiac aortic arch. To confirm the cardioprotective role of Sig-1R stimulation by fluvoxamine, we treated mice with fluvoxamine (0.5 or 1 mg/kg) orally once a day for 4 weeks after onset of aortic banding. Interestingly, in untreated mice, Sig-1R expression in the left ventricle (LV) markedly decreased over 4 weeks with increased hypertrophy. By contrast, fluvoxamine administration significantly attenuated TAC-induced myocardial hypertrophy concomitant with recovery of Sig-1R expression in LV. Fluvoxamine also attenuated hypertrophy-induced impaired LV fractional shortening. The fluvoxamine cardioprotective effect was nullified by treatment with a Sig-1R antagonist, NE-100 (1 mg/kg). Importantly, another SSRI with very low affinity for Sig-1R, paroxetine, did not exhibit antihypertrophic effects in TAC mice and in cultured cardiomyocyte treated with angiotensin II. Fluvoxamine treatment significantly restored TAC-induced impaired Akt and eNOS phosphorylation in LV. Our findings suggest that fluvoxamine protects heart against TAC-induced cardiac dysfunction via upregulation of Sig-1R and stimulation of Sig-1R-mediated Akt-eNOS signaling in mice. This is the first report of a potential role of Sig-1R stimulation by fluvoxamine in preventing cardiac hypertrophy and myocardial injury in TAC mice.

著者

池田 義人

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.11, pp.1329-1334, 2020-11-01 (Released:2020-11-01)

参考文献数

28

---

Biliary lipids primarily consist of bile salts, phospholipids, and cholesterol. Bile salts have potent detergent properties and deleterious effects on the cell membrane and are cytotoxic to hepatocytes. We have previously reported that phosphatidylcholine (PC), the predominant bile phospholipid, protects hepatocytes from the cytotoxicity of bile salts, whereas cholesterol reverses the cytoprotective effects of PC against bile salts. ABCB4, a member of the ATP-binding cassette transporter family, secretes biliary phospholipids, especially PC, from the hepatocytes into the bile. Using Abcb4 knockout mice and HEK293 cells that stably expressed ABCB4, we examined the effects of taurine- or glycine-conjugated cholate, ursodeoxycholate, and hyodeoxycholate on the ABCB4-mediated efflux of PC. We observed that the biliary secretion of PC in wild-type mice significantly increased following infusion of all the tested bile salts, especially taurohyodeoxycholate. On the other hand, the biliary secretion of PC in Abcb4 knockout mice was not affected by the bile salt infusions. The results also demonstrated that the efflux of PC from ABCB4-expressing HEK293 cells was significantly stimulated by taurohyodeoxycholate, which has a strong potential to form mixed micelles with PC. Furthermore, the results of our study emphasized the possibility that the specific interactions of bile salts with ABCB4 are necessary for the release of PC molecules from the binding pocket of ABCB4 into the aqueous environment. Further understanding of this mechanism will aid in the development of novel therapeutic agents for cholestatic liver diseases.

著者

石井 康子 谷澤 久之 池本 長司 滝野 吉雄

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.101, no.3, pp.254-258, 1981

被引用文献数

4 7

---

Cathartic effects of Aloe pulv. (J. P. IX) and pulv. of Aloe arborescens MILL. var. natalensis BERGER (Kidachialoe) were examined in mice and rats by oral administration. It was found that rats were more suitable than mice. Additionally, no sex difference in rats was observed. Cathartic activity (ED<SUB>50</SUB>) in male rats was 84.3 mg/kg in Aloe pulv., and 900 mg/kg in Kidachialoe pulv. Several experiments to find the mechanism of cathartic effect of Aloe were done. It was considered that Aloe acted on the large intestine mainly, and that process of activation of Aloe by intestinal flora was necessary to act. It was considered that main cathartic component of Aloe was barbaloin by comparision of barbaloin contents in Aloe and cathartic activity. Then, it was concluded that barbaloin represented cathartic activity of Aloe.

出版者

公益社団法人 日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.1893, no.132, pp.193-240, 1893-02-26 (Released:2018-08-31)

被引用文献数

1

著者

齊藤 将之 前田 徹 市原 利彦 岩尾 岳洋 鈴木 匡

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.140, no.10, pp.1269-1274, 2020-10-01 (Released:2020-10-01)

参考文献数

19

被引用文献数

1

---

We previously reported that tolvaptan may influence warfarin pharmacodynamics in vivo; however, the mechanism responsible for this influence was not clear. In this study, we investigated the drug-drug interactions between warfarin and tolvaptan by measuring warfarin blood concentrations in 18 patients who received warfarin therapy and in 24 who received warfarin+tolvaptan therapy. The free warfarin concentrations significantly increased in patients who were also receiving oral tolvaptan (p=0.04). In vitro albumin-binding experiments showed that the free warfarin concentrations significantly increased with the addition of tolvaptan, in a dose-dependent manner, through albumin-binding substitution (approximately 2.5 times). Both clinical and in vitro data showed that tolvaptan increased the unbound warfarin serum concentration. The prothrombin time-international normalized ratio (PT-INR) tended to increase within 2 weeks when tolvaptan was added at clinically used doses (p=0.14). Special attention is warranted in cases with a serum tolvaptan concentration of ≥125 ng/mL (≥7.5 mg/d) for at least 2 weeks following oral tolvaptan administration.