著者

Hayato Akimoto Takuya Nagashima Kimino Minagawa Takashi Hayakawa Yasuo Takahashi Satoshi Asai

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1514-1523, 2021-10-01 (Released:2021-10-01)

参考文献数

57

被引用文献数

8

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Drug-induced liver injury (DILI) is a common adverse drug event. Spontaneous reporting systems such as the Japanese Adverse Event Report Database (JADER) have been used to evaluate the association between drugs and adverse drug events. However, the association of drugs with adverse drug events may be overestimated due to reporting biases. Therefore, it is important to objectively evaluate the association using liver function test values. The aim of the present study was to predict potential hepatotoxic drugs using real-world data including electronic medical records and the JADER database. A total of 70009 (2779 with DILI and 67230 without DILI) and 438515 (10235 with DILI and 428280 without DILI) Japanese adult patients were extracted from electronic medical records and the JADER database, respectively. Drugs with ≥100 DILI patients in both of the two databases were regarded as suspected drugs for DILI. We used multivariate logistic regression to evaluate the association between the suspected drugs and increased risk of DILI. Among the suspected drugs, broad-spectrum antibiotics such as meropenem, tazobactam/piperacillin and ceftriaxone were significantly associated with an increased risk of DILI, and meropenem had a greater risk of DILI in both of the two databases. Additionally, there were significant associations of mosapride and L-carbocisteine with increased risk of DILI. In addition to well-known associations between antibiotic drugs and DILI, mosapride and L-carbocisteine were found to be new potential signals of drugs causing hepatotoxicity. This study indicates potential hepatotoxic drugs that require further causality assessment.

著者

Shungo Imai Yasuyuki Nasuhara Kenji Momo Hiromitsu Oki Hitoshi Kashiwagi Yuki Sato Takayuki Miyai Mitsuru Sugawara Yoh Takekuma

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1499-1505, 2021-10-01 (Released:2021-10-01)

参考文献数

27

被引用文献数

4

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A major adverse effect of benzbromarone is hepatotoxicity. Therefore, periodic liver function tests are required at least for the first 6 months of benzbromarone administration. However, it is not clear whether the relevant blood tests are implemented appropriately. Here, we performed a cross-sectional survey of the implementation status of liver function tests in patients who were newly prescribed benzbromarone, using the Japanese large claims database. Male patients who were newly prescribed benzbromarone from January 2010 to December 2016 were included. We targeted patients who continued benzbromarone during the observation period (up to 180 d from the start of administration). The primary endpoint was the proportion of patients in whom periodic liver function tests were implemented. A periodic liver function test was defined as one or more liver function tests performed during both 1–90 and 91–180 d of initial benzbromarone administration. We labeled the tests as a “periodic test” or “non-periodic test” based on whether periodic liver function tests were performed or not, respectively. Furthermore, factors influencing non-periodic test were analyzed. Periodic testing was implemented only in 28.7% of patients. Additionally, factors such as number of hospital beds ≤19 (compared to 100–199 beds) and duration of the first prescription of benzbromarone were associated with non-periodic testing. Our study revealed that periodic liver function tests are not performed sufficiently in Japan. Thus, clinicians prescribing benzbromarone should be educated about the test. Our blood-test-based approach should be applied to other drugs and countries in future research.

著者

Yutaka Matsuda Brian A. Mendelsohn

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.10, pp.976-983, 2021-10-01 (Released:2021-10-01)

参考文献数

78

被引用文献数

35

---

Antibody–drug conjugates (ADCs) are biopharmaceuticals produced by chemically linking small molecules (payloads) to antibodies that possess specific affinity for the target cell. The ADCs currently on the commercially market are the result of a stochastic conjugation of highly-potent payloads to multiple sites on the monoclonal antibody, resulting in a heterogeneous drug–antibody ratio (DAR) and drug distribution. The heterogeneity inherent to ADCs not produced site-specifically may not only be detrimental to the quality of the drug but also is less-desirable from the perspective of regulatory science. An ideal method or unified approach used to measure the DAR for ADCs, a critical aspect of their analysis and characterization, has not yet been established in the ADC field and remains an often-challenging issue for bioanalytical chemists. In this review we describe, compare, and evaluate the characteristics of various DAR determination methods for ADCs featuring recently reported technologies. The future landscape of bioconjugate DAR analysis is also discussed.

著者

Yu Inoue Seiji Hasegawa Yuichi Hasebe Mika Kawagishi-Hotta Ryosuke Okuno Takaaki Yamada Hiroaki Adachi Katsuma Miyachi Yoshie Ishii Kazumitsu Sugiura Hirohiko Akamatsu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1403-1412, 2021-10-01 (Released:2021-10-01)

参考文献数

29

被引用文献数

6

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Currently, human-skin derived cell culture is a basic technique essential for dermatological research, cellular engineering research, drug development, and cosmetic development. But the number of donors is limited, and primary cell function reduces through cell passage. In particular, since adult stem cells are present in a small amount in living tissues, it has been difficult to obtain a large amount of stem cells and to stably culture them. In this study, skin derived cells were isolated from the epidermis, dermis, and adipose tissue collected from single donor, and immortalization was induced through gene transfer. Subsequently, cell lines that could be used as stem cell models were selected using the differentiation potential and the expression of stem cell markers as indices, and it was confirmed that these could be stably cultured. The immortalized cell lines established in this study have the potential to be applied not only to basic dermatological research but also to a wide range of fields such as drug screening and cell engineering.

著者

Yosuke Hashimoto Matthew Campbell Keisuke Tachibana Yoshiaki Okada Masuo Kondoh

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1380-1390, 2021-10-01 (Released:2021-10-01)

参考文献数

110

被引用文献数

18

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Claudin-5 is the dominant tight junction protein in brain endothelial cells and exclusively limits the paracellular permeability of molecules larger than 400 Da across the blood–brain barrier (BBB). Its pathological impairment or sustained down-regulation has been shown to lead to the progression of psychiatric and neurological disorders, whereas its expression under physiological conditions prevents the passage of drugs across the BBB. While claudin-5 enhancers could potentially act as vascular stabilizers to treat neurological diseases, claudin-5 inhibitors could function as delivery systems to enhance the brain uptake of hydrophilic small-molecular-weight drugs. Therefore, the effects of claudin-5 manipulation on modulating the BBB in different neurological diseases requires further examination. To manipulate claudin-5 expression levels and function, several claudin-5 modulating molecules have been developed. In this review, we first describe the molecular, cellular and pathological aspects of claudin-5 to highlight the mechanisms of claudin-5 enhancers/inhibitors. We then discuss recently developed claudin-5 enhancers/inhibitors and new methods to discover these molecules.

著者

Takashi Ichiyanagi Masayuki Nashimoto Norihiko Terahara

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.4, no.4, pp.136-141, 2021 (Released:2021-09-02)

参考文献数

21

被引用文献数

8

---

Ternatins, polyacylated anthocyanins that contain two or more aromatic acyl groups, are found in the petals of butterfly pea (Clitoria ternatea L.). We examined the gastrointestinal absorption of ternatins in rats after oral administration of the extract of the butterfly pea petals. Ingested ternatins were absorbed rapidly in the gastrointestinal tract in their original acylated forms. Nine ternatins were detected, together with preternatin A3, in rat blood plasma at 15 min after oral administration. After a single oral dose of 0.0527 mmol/kg ternatin, the maximum plasma concentration and area under the plasma concentration curve for total ternatin was 0.141 ± 0.035 μM and 16.398 ± 1.542 μM·min, respectively, during the 8-h period post-administration. The absorption of ternatins in blood plasma tended to negatively correlate with increasing order of molecular weight; however, ternatins carrying symmetrical substitution patterns and glucosyl terminals on the both side chains at the 3′ and 5′ positions of the aglycone were exceptionally bioavailable.

著者

Kazuaki Matoba Nobuo N. Noda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.9, pp.1337-1343, 2021-09-01 (Released:2021-09-01)

参考文献数

35

被引用文献数

3

---

Autophagy is an intracellular degradation system regulating cellular homeostasis. The two ubiquitin-like modification systems named the Atg8 system and the Atg12 system are essential for autophagy. Atg8 and Atg12 are ubiquitin-like proteins covalently conjugated with a phosphatidylethanolamine (PE) and Atg5, respectively, via enzymatic reactions. The Atg8–PE conjugate binds to autophagic membranes and recruits various proteins through direct interaction, whereas the Atg12–Atg5 conjugate recognizes Atg3, the E2 enzyme for Atg8, and facilitates Atg8–PE conjugation by functioning as the E3 enzyme. Although structural and biochemical analyses have well established the Atg8-family interacting motif (AIM), studies on the interacting sequence for Atg12 are rare (only one example for human ATG12–ATG3), thereby making it challenging to define a binding motif. Here we determined the crystal structure of the plant ATG12b as a complex with the ATG12b-binding region of ATG3 and revealed that ATG12b recognizes the aspartic acid (Asp)–methionine (Met) motif in ATG3 via a hydrophobic pocket and a basic residue, which we confirmed critical for the complex formation by mutational analysis. This recognition mode is similar to that reported between human ATG12 and ATG3, suggesting that the Asp–Met sequence is a conserved Atg12-interacting motif (AIM12). These data suggest that AIM12 mediates E2-E3 interaction during Atg8 lipidation and provide structural basis for developing chemicals that regulate autophagy by targeting Atg12-family proteins.

著者

Toshinari Suzuki Yuki Kosugi Kimiyo Watanabe Haruka Iida Tetsuji Nishimura

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.9, pp.840-853, 2021-09-01 (Released:2021-09-01)

参考文献数

70

被引用文献数

5

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Active pharmaceutical ingredients (APIs) have become a public concern owing to their possible adverse effects on aquatic organisms. Ministry of Health, Labor and Welfare in Japan (MHLW) issued “Guidance on the Environmental Risk Assessment (ERA) in new pharmaceutical development” in 2016. To evaluate the validity of phase 1 in the MHLW’s ERA guidance, we monitored the measured environmental concentrations (MECs) of approved APIs in urban rivers and sewage treatment plants (STPs) in Japan and compared these MECs with the predicted environmental concentration (PEC). We collected water samples from urban seven rivers and three STPs during each season. Fifty-one APIs for human and veterinary use and the artificial sweetener sucralose were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Forty-four APIs were observed in the rivers and 42 were found in the influent and effluent of STPs, with levels ranging from nanograms to micrograms per liter. The action limit in phase I of the MHLW’s guidance was set to 10 ng/L, and there was no API except for ketoprofen, for which PEC of the MHLW’s guidance (PECjapan) was lower than 10 ng/L and the maximum MEC (MECmax) was 10 ng/L or greater. Almost all APIs also had median MECs that were lower than those of the respective PECjapan. These results indicate that the PECjapan values in phase I of the MHLW’s guidance were appropriate. However, some APIs had MECmax values that were greater than those of the respective PECjapan due to overestimation of the dilution factor of river water and/or underestimation of API production.

著者

Kenroh Sasaki Fumihiko Yoshizaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.6, pp.806-808, 2002 (Released:2002-06-01)

参考文献数

18

被引用文献数

28 34

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A tyrosinase inhibitor was isolated from the peel of Citrus fruit by activity-guided fractionation, and identified as 3′,4′,5,6,7,8-hexamethoxyflavone (nobiletin) by comparison with reported spectral data. Nobiletin (IC50 of; 46.2 μM) exhibited more potency than Kojic acid (IC50; 77.4 μM) used as a positive control, and it was found to be potentially an effective inhibitor of the production of melanin.

著者

Toshinari ASAKURA Hiroaki SEINO Seishiro NOZAKI Ryuzo ABE

出版者

The Pharmaceutical Society of Japan

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.121, no.6, pp.459-463, 2001 (Released:2002-09-27)

参考文献数

11

被引用文献数

20 24

---

注射針を輸液剤等のゴム栓に穿刺するときに, ゴム栓からゴム片が削り取られるというコアリングが報告されている. 実際に自己注射を行っている患者のインスリンバイアルでもコアリングが発生しているかを確認した. 入院患者30名よりインスリンカートリッジを回収し, 空打ち液, 注入液, カートリッジ残液を試料とした. 発生したゴム片を顕微鏡下で観察し形状と個数, 大きさを測定した. コアリングの発生率は, 空打ち液の発生率は73%, 注入液は47%, カートリッジ残液は97%であった. 形状は, 針を通過している空打ち液と注入液では塊状が多く, 針を通過していないカートリッジ残液では針状が多かった. 空打ち液と注入液では小さなゴム片が多数確認されたことにより, ゴム片が皮下内に注入される可能性が強く示唆された. コアリングの原因としては, 針を同一個所に回転させて刺すためと考えられる. そのため, 今後はペン型注射器への針の装着について構造上の改良が必要である. コアリングは注射液の異物混入という点で, 医学的にも薬学的にも非常に重大な問題である. 今後はラテックスアレルギーやリポディストロフィーなどとの関連も検討する必要がある.

著者

Alexandre Nesterov Jifu Zhao David Minter Carmen Hertel Wenwen Ma Padmapriya Abeysinghe Mei Hong Qi Jia

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.56, no.9, pp.1292-1296, 2008-09-01 (Released:2008-09-01)

参考文献数

23

被引用文献数

24 31

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A series of diarylpropane compounds was isolated by screening a plant extract library for inhibitors of mushroom tyrosinase. The most potent compound, 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane (UP302: CAS# 869743-37-3), was found in the medicinal plant Dianella ensifolia. Synthetic and plant-derived versions of UP302 inhibited mushroom tyrosinase with similar potencies. UP302 inhibited mushroom tyrosinase with Ki=0.3 μM, in a competitive and reversible fashion. UP302 was 22 times more potent than Kojic acid in inhibiting murine tyrosinase, with IC50 values of 12 and 273 μM respectively. Experiments on mouse melanoma cells B16-F1 and on human primary melanocytes demonstrated that UP302 inhibits melanin formation with IC50 values of 15 and 8 μM respectively. Long-term treatment of cultured melanocytes with up to 62 μM of UP302 revealed no detectable cytotoxicity. In a reconstructed skin model (MelanoDermTM) topical application of 0.1% UP302 resulted in significant skin lightening and decrease of melanin production without effects on cell viability, melanocyte morphology or overall tissue histology. In conclusion, UP302 is a novel tyrosinase inhibitor that suppresses melanin production in both cultured melanocytes and reconstructed skin with high potency and without adverse side effects.

著者

小木曽 彰 佐藤 藹也 樫田 育子 杉村 征夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.22, no.1, pp.144-151, 1974-01-25 (Released:2008-03-31)

被引用文献数

1 3

---

A key point of the synthesis of aglycones (12 and 33) derived from poriolide (1) and isoporiolide (2), the toxic constituents of Leucothoe keiskei, is the construction of the unsymmetric biphenyl compounds, this point was effected by application of the rearrangement reaction of suitable phenyltropone derivatives to biphenyl compounds.

著者

Dalia Seleem Veronica Santana Freitas-Blanco Juliana Noguti Bruna Raquel Zancope Vanessa Pardi Ramiro Mendonça Murata

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.8, pp.1299-1302, 2018-08-01 (Released:2018-08-01)

参考文献数

24

被引用文献数

1 6

---

Monolaurin is a natural compound that has been known for its broad antimicrobial activities. We evaluate the antifungal activity of monolaurin against Candida albicans biofilms in vivo using a novel bioluminescent model to longitudinally monitor oral fungal infection. Oral fungal infection in vivo was performed using bioluminescent engineered C. albicans (SKCa23-ActgLUC) biofilms on Balb/c mice. The antifungal activity of monolaurin was determined by comparing three groups of mice (n=5/group): monolaurin, vehicle control, and positive control (nystatin). All mice were immunosuppressed with cortisone acetate and oral topical treatments were applied for 5 d. In vivo imaging system (IVIS) imaging was used to monitor the progression of infection over a 5-d period. Total photon flux and ex vivo microbiological analysis of the excised tongues were used to determine the overall fungal burden. Oral topical treatments of monolaurin have resulted in a significant decrease (p<0.05) in the total photon flux over 4 and 5 d post-infection in comparison to the vehicle control group. Furthermore, monolaurin treated group had a significant decrease in colony formation unit of tongue tissue compared to the vehicle control. Our findings support monolaurin as a promising antifungal compound in vivo, which may translate to its future use in the treatment of oral candidiasis.

著者

Kazuya Ooi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.8, pp.1037-1043, 2021-08-01 (Released:2021-08-01)

参考文献数

42

被引用文献数

4

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Dry skin is a common symptom of various conditions, and elderly individuals commonly exhibit this physiological symptom. Dry skin develops owing to sebum deficiency; however, the use of moisturizers can typically overcome this issue, particularly in patients in whom there are no other skin problems. If dry skin is left untreated, itching and eczema can occur, resulting in skin damage. Additionally, hemodialysis patients exhibit reduced barrier function and can experience pain associated with repeated needle insertion; the repeated use of lidocaine tape to manage the pain can cause further skin damage. To reduce the occurrence of dry skin, the skin is hydrated using moisturizers. Dry skin is also prominent in patients with varicose veins in the lower extremities, and many biochemical studies have shown that skin immunity is altered in patients with dry skin. Moreover, the incidences of dry skin and pruritus differ in male and female patients. Furthermore, in elderly patients, zinc deficiency is likely to cause dry skin, and zinc supplementation may maintain skin hydration. To date, few reports have described dry skin from a clinical point of view. In this review, research on dry skin is presented, and the findings of basic research studies are integrated.

著者

Iqbal Julian Takuya Iwamoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.8, pp.1050-1059, 2021-08-01 (Released:2021-08-01)

参考文献数

40

被引用文献数

1

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Skin rash is a common adverse event associated with erlotinib therapy. In severe conditions, the rash could affect patients’ QOL. If the rash occurrence can be predicted, erlotinib treatment failures can be prevented. We designed an in vivo study that applied erlotinib regimens resembling its clinical application to evaluate possible erlotinib-induced skin rash biomarkers for humans and simultaneously observe the effects of erlotinib discontinuation, followed with or without dose reduction, on rash development. Rats were divided into four groups: placebo, constant (erlotinib 35 mg/kg on d1–d21), intermittent (erlotinib 70 mg/kg on d1–d7 and d15–d21), and mimic (erlotinib 70 mg/kg on d1–d7 and erlotinib 35 mg/kg on d15–d21). Blood sampling was performed on d1, d8, d15, and d22. The samples were used to measure erlotinib concentrations, the level of hepatic and renal function markers, immune cell percentages, and immune cells’ CD45 expression levels. Erlotinib 70 mg/kg generated high mean circulating erlotinib concentrations (>1800 ng/mL) that led to severe rashes. Erlotinib dose reduction following rash occurrence reduced circulating erlotinib concentration and rash severity. After the treatment, the escalation of neutrophil percentages and reduction of neutrophils’ CD45 expression levels were observed, which were significantly correlated with the rash occurrence. This study is the first to show that erlotinib-induced skin rash may be affected by the reduction of neutrophils’ CD45 expression levels, and this is a valuable finding to elucidate the erlotinib-induced skin rash formation mechanism.

著者

Tomoki Nakayoshi Koichi Kato Eiji Kurimoto Akifumi Oda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.7, pp.967-975, 2021-07-01 (Released:2021-07-01)

参考文献数

39

被引用文献数

1

---

Isomerized aspartic acid (Asp) residues have previously been identified in various aging tissues, and are suspected to contribute to age-related diseases. Asp-residue isomerization occurs nonenzymatically under physiological conditions, resulting in the formation of three types of isomerized Asp (i.e., L-isoAsp, D-Asp, and D-isoAsp) residues. Asp-residue isomerization often accelerates protein aggregation and insolubilization, making structural biology analyses difficult. Recently, Sakaue et al. reported the synthesis of a ribonuclease A (RNase A) in which Asp121 was artificially replaced with different isomerized Asp residues, and experimentally demonstrated that the enzymatic activities of these artificial mutants were completely lost. However, their structural features have not yet been elucidated. In the present study, the three-dimensional (3D) structures of these artificial-mutant RNases A were predicted using molecular dynamics (MD) simulations. The 3D structures of wild-type and artificial-mutant RNases A were converged by 3000-ns MD simulations. Our computational data show that the structures of the active site and the formation frequencies of the appropriate catalytic dyad structures in the artificial-mutant RNases A were quite different from wild-type RNase A. These computational findings may provide an explanation for the experimental data which show that artificial-mutant RNases A lack enzymatic activity. Herein, MD simulations have been used to evaluate the influences of isomerized Asp residues on the 3D structures of proteins.

著者

Keita Kitamura Kenta Umehara Ryo Ito Yoshiyuki Yamaura Takafumi Komori Hanae Morio Hidetaka Akita Tomomi Furihata

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.7, pp.984-991, 2021-07-01 (Released:2021-07-01)

参考文献数

35

被引用文献数

9

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In vitro blood–brain barrier (BBB) models are essential research tools for use in developing brain-targeted drugs and understanding the physiological and pathophysiological functions of the BBB. To develop BBB models with better functionalities, three-dimensional (3D) culture methods have gained significant attention as a promising approach. In this study, we report on the development of a human conditionally immortalized cell-based multicellular spheroidal BBB (hiMCS-BBB) model. After being seeded into non-attachment culture wells, HASTR/ci35 (astrocytes) and HBPC/ci37 cells (brain pericytes) self-assemble to form a spheroid core that is then covered with an outer monolayer of HBMEC/ci18 cells (brain microvascular endothelial cells). The results of immunocytochemistry showed the protein expression of several cellular junction and BBB-enriched transporter genes in HBMEC/ci18 cells of the spheroid model. The permeability assays showed that the hiMCS-BBB model exhibited barrier functions against the penetration of dextran (5 and 70 kDa) and rhodamine123 (a P-glycoprotein substrate) into the core. On the other hand, facilitation of 2-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl]amino)-2-deoxyglucose (2-NBDG; a fluorescent glucose analog) uptake was observed in the hiMCS-BBB model. Furthermore, tumor necrosis factor-alpha treatment elicited an inflammatory response in HBMEC/ci18 cells, thereby suggesting that BBB inflammation can be recapitulated in the hiMCS-BBB model. To summarize, we have developed an hiMCS-BBB model that possesses fundamental BBB properties, which can be expected to provide a useful and highly accessible experimental platform for accelerating various BBB studies.

著者

Shiroh Futaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.7, pp.601-607, 2021-07-01 (Released:2021-07-01)

参考文献数

57

被引用文献数

10

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Biomembranes are important targets in molecular design. Our laboratory has been exploring the design of functional peptides that modulate membrane barrier function, lipid packing, and structure. Evaluation of the results obtained and analyses of cellular mechanisms have yielded peptides with more refined designs and functions. This review highlights the progress made in our laboratory towards the development of unique peptides that modulate membrane properties.

著者

脇田 桂子 吉本 昌文 宮本 秀一 渡辺 英俊

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.34, no.11, pp.4663-4681, 1986-11-25 (Released:2008-03-31)

参考文献数

14

被引用文献数

46 62

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For the calculation of the aqueous solubility of organic compounds, we defined new fragment solubility constants (fs) which were empirically determined on the basis of compiled data from the literature. First, 6 fundamental fs values were determined from data on 46 liquid alliphatic hydrocarbons. THese fs values were fixed, and data on 249 liquid aliphatic compounds with diverse functional groups were employed to optimize another 19 fs values of the groups. Then, 15 fs values of aromatic compounds were calculated based on the solubility data on 58 aromatic liquids and the aliphatic fs values.It has been shown that there is a linear relationship between the logarithims of the aqueous solubilities of organic liquids and the octanol-water partition constants (log P), and that the water solubilities can be calculated by using the correlation equation and log P values. The present paper is concerned with a method to calculate the aqueous solubilities of organic liquids simply, directly and more accurately on the basis of fs values. Furthermore, the calculation of the water solubilities of organic solids was attempted with a correction based on the melting points, in addition to using the fs values.

著者

Kodai Ishida Tomohiro Yako Miruto Tanaka Wataru Otsu Shinsuke Nakamura Masamitsu Shimazawa Hideshi Tsusaki Hideaki Hara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.7, pp.937-946, 2021-07-01 (Released:2021-07-01)

参考文献数

45

被引用文献数

4

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The corneal epithelium is continuously exposed to oxygen, light, and environmental substances. Excessive exposure to those stresses is thought to be a risk factor for eye diseases. Photokeratitis is damage to the corneal epithelium resulting in a painful eye condition caused by unprotected exposure to UV rays, usually from sunlight, and is often found in people who spend a long time outdoors. In modern life, human eyes are exposed to artificial light from light-emitting diode (LED) displays of computers and smartphones, and it has been shown that short-wavelength (blue) LED light can damage eyes, especially photoreceptors. However, the effect of blue LED light on the cornea is less understood. In addition, it is important to develop new treatments for preserving human eyesight and eye health from light stress. Here, we used human corneal epithelial cells-transformed (HCE-T) cells as an in-vitro model to investigate the protective effect of NSP-116, an imidazolyl aniline derivative, against the oxidative stress induced by light in the corneal epithelium. Treatment with 10 µM NSP-116 significantly increased the cell viability and reduced the death ratio following UV or blue LED light exposure. Furthermore, NSP-116 treatment decreased light-induced reactive oxygen species production and preserved the mitochondrial membrane potential. Immunoblotting data showed that NSP-116 suppressed the stress response pathway. Finally, NSP-116 treatment prevented corneal epithelial apoptosis induced by blue LED light in an in-vivo mouse model. In conclusion, NSP-116 has a protective effect against oxidative stress and corneal cell death from both UV and blue LED light exposure.