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of licorice were recommended as a remedy for gastric ulcer by Revers of the Netherlands in 1946, which was soon withdrawn owing to its side effects.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

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

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

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

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.

著者

山本 緑 石井 祐次

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.1397-1403, 2020-11-01 (Released:2020-11-01)

参考文献数

25

被引用文献数

3

---

Pharmacological cognitive enhancement (PCE) usually refers to the use of medical substances by healthy individuals to improve mental performance. Given that certain substances have been frequently used for years, the long-term effectiveness and safety are essential to know but particularly difficult and costly to determine. Although PCE is a widespread and frequent phenomenon among university students in other countries, PCE prevalence in Japan has not been elucidated. The present study aimed to investigate the prevalence of and the attitude toward PCE among Japanese undergraduates over 3 years (2017-2019). Almost no student had ever used prescription drugs for cognitive enhancement. When asked, “Would you like to use drugs to enhance your cognitive performance?” 68.6-72.0% of the students answered, “No,” 25.4-26.7% answered, “I couldn't say,” and 2.5-4.8% answered, “Yes.” These answers were associated with sex (2017-2018) and stress sensitivity (2019) but not with drinking, smoking, or stress of academic performance. Half of the students had used energy drinks for neural enhancement prior to an examination, which is similar to Western usage. The users of soft enhancers, such as energy drinks, are more likely to use other drugs. Given that caffeine can be a gateway for cognitive enhancement, future education addressing PCE among students should emphasize the side effects of prescription drugs as well as health risks of caffeine products.

著者

馬来 秀行 白石 朗 三木 晶子 佐藤 宏樹 小西 ゆかり 浅井 康平 舟橋 健一 臼井 順信 澤田 康文

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.137, no.8, pp.1041-1049, 2017-08-01 (Released:2017-08-01)

参考文献数

4

被引用文献数

2 4

---

In our previous research, there was no collaboration between care workers and pharmacists, for the most part. As a result, it was discovered that in some cases, problems concerning medication of nursing home residents had not been resolved. To solve this issue, we brought together care workers and pharmacists for a workshop we conducted. We assigned 12 care workers with at least two years of experience and 12 pharmacists to four mixed groups and guided them in the management of in-home long-term medical care and conducted small group discussions (SGD) using the KJ method. In the pre-survey before the workshop, all 12 care workers replied “yes” to having experienced “concerns over medication” and nine (75%) replied “no” to having experienced “discussions (consultations) with pharmacists regarding the medication of residents”. As a result of the SGD, “information sharing among professionals” was revealed as a problem common to all groups. Furthermore, common countermeasures for this issue included communication notes and holding collaborative meetings. In the post-survey after the workshop, 67% of the participants replied that their thoughts concerning countermeasures were “coherent”, and everyone replied that their “awareness was increased”. In a follow-up survey after the workshop, 82% of the participants replied that they were using some form of what they had learned and discovered in the workshop in their actual work.

著者

玉木 啓文 佐藤 宏樹 堀 里子 澤田 康文

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.138, no.10, pp.1305-1312, 2018-10-01 (Released:2018-10-01)

参考文献数

17

被引用文献数

1 1

---

Similar-appearing press-through package (PTP) sheets (also known as blister packs) that contain different medicines may result in incorrect medication due to confusion errors. To evaluate the significance of this problem and to identify the factors that may lead to such errors, we conducted a questionnaire survey for pharmacists. Three hundred and eighty-two pairs of PTP sheets with similar appearance were included in the questionnaire. Factors related to color (sheet color at the front of the sheet 90.9%, color of tablet/capsule 57.1%, print color at the front of the sheet 45.9%) were most frequently selected as influencing the perceived similarity of the reported pairs, followed by tablet/capsule shape (46.2%), sheet size (32.4%), and mark and character positioning on sheets (6.8%). In the pairs of similar PTP sheets, pairs manufactured by the same pharmaceutical company accounted for 15%. The frequency of confusion errors or near-errors due to similar appearance of PTP sheets was highest at the time of collecting PTP sheets from the medicine shelf and returning the sheets to the medicine shelf, followed by the time of inspection of prepared medicines and medication instructions. The questionnaire results also indicate that patients themselves can confuse similar PTP sheets and take the wrong medicine. Further quantitative studies are needed to clarify the key factors that cause confusion errors due to similar appearance and to identify potential remedial measures.

著者

飯塚 幸澄 桜井 栄一 田中 頼久

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.121, no.5, pp.365-369, 2001-05-01 (Released:2002-09-27)

参考文献数

12

被引用文献数

8 10

---

The antidiabetic effect of hot water extracts from Folium Mori was investigated in GK rat; one of the animal models of non-insulin dependent diabetic mellitus types. Folium Mori extracts (150 mg/kg) significantly reduced the blood glucose of GK rat from 203.8±29.8 to 138.5±21.2 mg/dl at 14 days after oral administration. However, in normal rats, blood glucose and insulin levels were not changed by treatment with Folium Mori. The Folium Mori also decreased blood glucose and improved glucose tolerance at 14 days after repeated administration in GK rats. The Folium Mori treatment significantly increased glucose metabolism in the glucose clamp test for GK rats. These results suggest that Folium Mori has quite unique properties such as raising insulin sensitivity and improving insulin resistance.

著者

陳 福君 中島 登 木村 郁子 木村 正康

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.115, no.6, pp.476-482, 1995-06-25 (Released:2008-05-30)

参考文献数

12

被引用文献数

70 93

---

Averaged blood glucose levels were 400 mg/dl in nonfasted mice, and 250 mg/dl in fasted mice in 4 weeks after injection with streptozotocin (STZ, 150 mg/kg, i.v.). These mice were used for experiments. Hypoglycemic effects of hot water extracts (W) from Folium Mori (Mulberry leaves, Morus alba L., China and Japan) or Cortex Mori Radicis (Morus alba L., China) were observed in fasted and nonfasted STZ-induced diabetic mice at a single dose of 200 mg/kg (i.p.). The W from Folium Mori exhibited most potent hypoglycemic effects. The most potent fractions of Folium Mori and Cortex Mori Radicis were ethanol-insoluble extracts (A2). These A2 fractions demonstrated a fall in blood glucose levels of 24.6±6.0% and 60.5±9.1% at nonfasted STZ-mice, and 81.4±7.9% and 77.3±5.8% at fasted STZ-mice, respectively. The increase in glucose uptake was a mechanism of hypoglycemic actions by W and A2 of Folium Mori.

著者

八木 秀樹 益子 高

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.133, no.9, pp.939-945, 2013-09-01 (Released:2013-09-01)

参考文献数

17

---

Antibodies have greatly contributed to the development of medical science and pharmacology, because of their high specificity. The cell fusion method has developed monoclonal antibodies (mAb) technology, such that massive amounts of mAb with a uniform structure can be produced. Although mAb have been produced against many proteins so far, the production of mAb against multi-pass transmembrane proteins, such as G-protein coupled receptor (GPCR) and various transporter proteins has been extremely difficult. The complicated structures, poorly extracellular regions, and high hydrophobicity of multiple-transmembrane proteins make it difficult to produce mAb against them. Production of mAb that recognize the extracellular region of living cells is thought to be important in determining the ability of a protein. Based on these findings, we tried to produce mAb against a multi-pass transmembrane transporter using green fluorescent protein (GFP)-fused full-length target proteins as immunogens. Furthermore, the immunizing method has proved to be important in generating functional mAb. We succeeded in producing functional mAb that react against the extracellular region of a 12-pass transmembrane transporter in a living cell. Based on this success, we began to produce mAb against seven-transmembrane GPCR. In this symposium, we report on the results of producing mAb against S1P receptors, a type of GPCR.

著者

輿石 徹 奥山 清

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.136, no.12, pp.1675-1679, 2016-12-01 (Released:2016-12-01)

参考文献数

7

被引用文献数

1 1

---

A 70-year-old woman, residing in a nursing home, was admitted to our hospital because of cerebral hemorrhage. She had excessive sweating, a temperature above 37°C, and intermittent muscle spasm such as myoclonus, since the time of admission. We suspected that these symptoms were related to side effects caused by the milnacipran she was taking for depression, prior to hospitalization. After we discontinued milnacipran, the patient began exhibiting withdrawal symptoms such as excitement and insomnia. When we substituted milnacipran with mianserin, the withdrawal symptoms diminished and the excessive sweating and involuntary movement disappeared. Serotonin-norepinephrine reuptake inhibitor (SNRI) and selective serotonin reuptake inhibitor (SSRI) have been widely utilized in the clinic to treat depression; serious side effects such as serotonin syndrome and withdrawal syndrome associated with their discontinuation, have been reported. However, it is unlikely that serotonin syndrome and withdrawal syndrome due to a precedent use of milnacipran would have been reported. This case was suspected to be related to serotonin syndrome and withdrawal syndrome from the course of treatment. This case provides valuable information for addressing new similar cases caused by milnacipran.

著者

宗 可奈子

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.1, pp.1-6, 2020-01-01 (Released:2020-01-01)

参考文献数

14

被引用文献数

3

---

Dysesthesia is an unpleasant abnormal sensation, often accompanied by pain, paresthesia (abnormal sensation), and numbness (decrease or loss of sensation). Dysesthesia has been associated with various conditions, although its underlying mechanisms are largely unknown. This study assessed the roles of transient receptor potential ankyrin 1 (TRPA1) in dysesthesia by utilizing three animal models of dysesthesia characterized by reductions in blood flow to the skin: a transient hindlimb ischemia/reperfusion model, characterized by spontaneous licking and tactile hypoesthesia of the ischemic hindpaw; a streptozotocin-induced diabetic neuropathy model in mice, characterized by cold hypersensitivity, which is likely parallel to the reduced skin blood flow of the hindpaw; and a hindlimb ischemia model. TRPA1 inhibition or deficiency blocked spontaneous licking in the transient hindlimb ischemia/reperfusion model and cold hypersensitivity in the diabetic mouse model mice. Consistent with these results, the nocifensive behaviors induced by intraplantar injection of a TRPA1 agonist were enhanced in the diabetic neuropathy and hindlimb ischemia models. Hypoxia enhanced H2O2-induced TRPA1 responses in human TRPA1-expressing cells and cultured mouse dorsal root ganglion neurons, with this hypoxia-induced TRPA1 sensitization to H2O2 being associated with hypoxia-induced inhibition of the hydroxylation of prolyl hydroxylases. These results suggest that dysesthesia following blood flow reduction is caused by the activation of TRPA1 sensitized by hypoxia and that hypoxia-induced TRPA1 sensitization plays a pivotal role in painful dysesthesia induced by peripheral blood flow reduction.

著者

佐藤 洋美

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.8, pp.963-968, 2020-08-01 (Released:2020-08-01)

参考文献数

30

---

Metabolome analysis is an approach to investigate cell characteristics from the metabolites that are constantly produced and changed by those cells. We conducted a metabolome analysis of the response of 786-O renal cell carcinoma (RCC) cells to histone deacetylase (HDAC) inhibitors, which are expected to increase anticancer drug sensitivity, and compared the response with that of drug-resistant cells. Trichostatin A (TSA), an HDAC inhibitor, increased the sensitivity of 786-O cells to sunitinib. Moreover, TCA cycle and nucleotide metabolism of the cells were promoted. The findings that acetylated p53 (active form) and early apoptotic cells were increased suggests that the mechanism involved enhancement of mitochondrial metabolism and function. In addition, established sunitinib-resistant RCC cells were exposed to a combination of sunitinib and TSA, resulting in significant growth inhibition. Principal component analysis revealed that the parent and resistant cells were obviously different, but approximately half their fluctuations were illustrated by the same pathways. In summary, it was suggested that TSA reduced sunitinib resistance by triggering intracellular metabolome shifts in energy metabolism. This was the first recognized mechanism of action of TSA as an HDAC inhibitor.