Folia Pharmacologica Japonica最新文献

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[Development of optical probes with excellent intracellular retention]. [开发具有出色细胞内保留能力的光学探针]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23068
Minoru Kawatani, Mako Kamiya, Yasuteru Urano
{"title":"[Development of optical probes with excellent intracellular retention].","authors":"Minoru Kawatani, Mako Kamiya, Yasuteru Urano","doi":"10.1254/fpj.23068","DOIUrl":"10.1254/fpj.23068","url":null,"abstract":"<p><p>Small-molecule based activatable fluorescence probes for detecting specific enzyme activity with high sensitivity can visualize the expression site of marker genes and cancers where the enzyme is highly expressed. However, the enzyme-catalyzed fluorescent hydrolysis product easily leaks out and diffuses from the reaction site, making it difficult to perform long-term tracking and immunohistochemical analysis which needs washing/fixation procedure. Our group have focused on quinone methide chemistry and developed series of activatable fluorescence probes with excellent intracellular retention that are converted to quinone-methide or aza-quinone-methide intermediates upon reaction with enzymes, which are then react with intracellular nucleophiles such as proteins and glutathione to be retained in cells and to exhibit significant increase in fluorescence. Based on this molecular design, we have developed fluorescence probes targeting β-galactosidase and γ-glutamyltranspeptidase with different colors. We also developed photo-functional probes such as activatable photosensitizers and caged fluorophores. These probes can visualize or kill target enzyme-expressing cells with high selectivity by suppressing the leakage of hydrolysis products from target cells, and fluorescence imaging in combination with immunostaining was possible due to the high tolerance of the obtained fluorescence signal even after washing and fixation.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 1","pages":"18-24"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Contribution to the world of 3D cell products created by bio 3D printing technology and to the life science field]. [对生物三维打印技术创造的三维细胞产品世界和生命科学领域的贡献]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23049
Toshihiko Maekawa
{"title":"[Contribution to the world of 3D cell products created by bio 3D printing technology and to the life science field].","authors":"Toshihiko Maekawa","doi":"10.1254/fpj.23049","DOIUrl":"10.1254/fpj.23049","url":null,"abstract":"<p><p>We have been making 3D tissues consist of cells only, based on the corporate philosophy of \"contributing to dramatic advances in medical care through the practical application of innovative 3D cell stacking technology.\" Currently, in the field of regenerative medicine, we are working toward obtaining approval from the Ministry of Health, Labor and Welfare and commercializing large artificial organs that are made from patients' own cells and have functions such as nerve regeneration, osteochondral regeneration, and blood vessels. On the other hand, this three-dimensional cell stacking technology can be extended to technology for culturing cells in an environment similar to the human body, and is expected to serve as a new methodology for evaluating the effects of new products in various fields on living organisms. Therefore, we are planning a business to provide developers of pharmaceuticals, foods, cosmetics, etc. with a small device called \"Functional Cell Device (FCD)\" that reproduces some of the functions of human organs outside the body. As the first step, we have developed a three-dimensional liver construct (3D mini-liver). The in vitro human liver model has a wide range of usage, such as evaluation of hepatotoxicity of drugs, elucidation of drug metabolism mechanism, and model of liver disease. In this report, we will outline it together with actual examples in regenerative medicine.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 3","pages":"144-149"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Dementia with Lewy bodies and Parkinson disease dementia, their diagnoses and treatment strategies]. [路易体痴呆症和帕金森病痴呆症及其诊断和治疗策略]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23064
Atsushi Takeda
{"title":"[Dementia with Lewy bodies and Parkinson disease dementia, their diagnoses and treatment strategies].","authors":"Atsushi Takeda","doi":"10.1254/fpj.23064","DOIUrl":"10.1254/fpj.23064","url":null,"abstract":"<p><p>Parkinson's disease (PD), which has characteristic motor symptoms such as tremor, muscle rigidity, and akinesia, and as the disease progresses, Lewy bodies spread throughout the brain, eventually causing Parkinson disease dementia (PDD). The clinical picture of PDD is similar to Dementia with Lewy bodies (DLB) and their pathological features are indistinguishable from each other. More than 80% of PD cases will eventually develop dementia and their prognosis are generally 3 to 4 years from the onset of dementia, regardless of disease duration or age of onset. We found that patients with severe olfactory impairment had lower cognitive function scores, more frequent onset of dementia, brain atrophy, and prominent cerebral metabolic abnormalities in a 3-year longitudinal study (Brain 135:161-169, 2012). This study demonstrated for the first time in the world that olfaction tests are useful in predicting dementia in PD, and similar results have been followed up worldwide. Based on these results, a randomized, double-blind, multicenter comparative study of donepezil in PD with severe olfactory dysfunction (DASH-PD study) was conducted and completed a 4-year follow-up period. The results were recently published showing the efficacy and safety of cholinesterase inhibitors for PD without dementia (eClinicalMedicine 51: 101571, 2022).</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 1","pages":"6-11"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Mechanism of action of tezepelumab (TEZSPIRE®) and clinical trial results in ‍asthma]. [特珠单抗(TEZSPIRE®)的作用机制和‍哮喘的临床试验结果]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23066
Mengxi Niu, Tadataka Yabuta, Naoyuki Makita
{"title":"[Mechanism of action of tezepelumab (TEZSPIRE<sup>®</sup>) and clinical trial results in ‍asthma].","authors":"Mengxi Niu, Tadataka Yabuta, Naoyuki Makita","doi":"10.1254/fpj.23066","DOIUrl":"10.1254/fpj.23066","url":null,"abstract":"<p><p>Tezepelumab (TEZSPIRE<sup>®</sup> Subcutaneous Injection 210 ‍mg), a biologic medicine with a novel mechanism, was approved in Japan in September 2022 for the treatment of bronchial asthma. Tezespire auto-injector was approved in Japan in August 2023 as an additional dosage. It is indicated for severe or refractory patients whose asthmatic symptoms cannot be controlled by currently available treatment. Tezepelumab binds to the epithelial cytokine thymic stromal lymphopoietin (TSLP) and disrupts TSLP signaling via the heterodimeric receptor. In the Phase 3 NAVIGATOR trial, the annual asthma exacerbation rate was significantly reduced by tezepelumab when administered subcutaneously every 4 weeks over a 52-week period to patients with uncontrolled, severe asthma who had received medium- or high-dose inhaled glucocorticoids. Its efficacy in reducing asthma exacerbations was observed regardless of blood eosinophil (bEOS) count, fractional exhaled nitric oxide (FeNO) levels, or serum total IgE at baseline. Significant improvements were noted in lung function, health-related quality of life, and change from baseline in asthma control. Reductions in the levels of inflammatory biomarkers (bEOS, FeNO, and IgE) was also noted. Clinical pharmacology trials demonstrated the efficacy of tezepelumab in improving airway hyperresponsiveness. In this article, we reviewed pharmacological characteristics, pharmacokinetics, clinical efficacy, and the safety profile of tezepelumab.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 1","pages":"53-60"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Pharmacological characteristics and clinical outcomes of Epcoritamab (recombinant) (Epkinly® subcutaneous injection ) for malignant lymphoma]. [埃普柯利单抗(重组)(Epkinly® 皮下注射)治疗恶性淋巴瘤的药理特征和临床疗效]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23076
Kana Takaura, Hiroshi Ando, Edward Ramirez Ganoza
{"title":"[Pharmacological characteristics and clinical outcomes of Epcoritamab (recombinant) (Epkinly<sup>®</sup> subcutaneous injection ) for malignant lymphoma].","authors":"Kana Takaura, Hiroshi Ando, Edward Ramirez Ganoza","doi":"10.1254/fpj.23076","DOIUrl":"10.1254/fpj.23076","url":null,"abstract":"<p><p>The prognosis of patients with B-cell non-Hodgkin lymphoma (B-NHL) has improved with the use of anti-CD20 based immunochemotherapy. However, management of relapsed or refractory disease remains a challenge, indicating a high unmet need for novel treatments. Epcoritamab (recombinant) is a humanized immunoglobulin G1 (IgG1) bispecific antibody that simultaneously binds to CD3 on T cells and CD20 on B cells or tumor cells inducing T-cell mediated cytotoxicity against CD20-positive B cells. It demonstrated consistent cytotoxic effects in B-cell lymphoma cell line-derived xenograft models, patient-derived xenograft models, and cynomolgus monkey studies. Pharmacological studies in cynomolgus monkeys showed peak plasma concentrations of cytokines were lower with subcutaneous versus intravenous administration. To reduce the risk of cytokine release syndrome (CRS) and improve convenience, Epcoritamab has been developed as a subcutaneous formulation.To further reduce the risk of CRS, clinical trials utilized a priming dose and incremental dose increases. In Phase I/II overseas trials with relapsed, progressive, or refractory B-NHL patients, the recommended Phase II trial dose was determined based on safety, efficacy, and pharmacokinetic model simulation results. The Phase II dose-expansion part demonstrated the efficacy and high tolerability of epcoritamab monotherapy at the recommended dose. Similar efficacy and tolerability were observed in Japanese Phase I/II trials in relapsed or refractory B-NHL patients. Based on these results, epcoritamab received the approval in September 2023 for the treatment of \"relapsed or refractory large B-cell lymphoma (DLBCL, HGBCL, PMBCL)\" and \"relapsed or refractory follicular lymphoma (Grade 3B)\" in Japan.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 1","pages":"61-68"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[The 145th Regional Meeting (Kinki Area)]. [第 145 次地区会议(近畿地区)]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.S24054
{"title":"[The 145th Regional Meeting (Kinki Area)].","authors":"","doi":"10.1254/fpj.S24054","DOIUrl":"https://doi.org/10.1254/fpj.S24054","url":null,"abstract":"","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 Supplement","pages":"S245-S268"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Delivery of JAL-TA9 to the brain by nasal application]. [通过鼻腔向大脑输送 JAL-TA9]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24075
Yusuke Hatakawa
{"title":"[Delivery of JAL-TA9 to the brain by nasal application].","authors":"Yusuke Hatakawa","doi":"10.1254/fpj.24075","DOIUrl":"https://doi.org/10.1254/fpj.24075","url":null,"abstract":"<p><p>We have reported on two Catalytides (Catalytic peptides), JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMI). Both peptides belong to the Tob/BTG family proteins and cleave Aβ42. Although Catalytides must be delivered to the brain parenchyma to treat Alzheimer's disease, the blood-brain barrier (BBB) limits their entry into the brain from the systemic circulation. Thus, we evaluated the direct route of ANA-TA9 from the nasal cavity to the brain to bypass the BBB. In this study, we present our findings on JAL-TA9. Animal studies using rats and mice clarified that the plasma clearance of JAL-TA9 was more rapid than its in vitro degradation in plasma, whole blood, and cerebrospinal fluid (CSF). After nasal administration of JAL-TA9, brain concentrations were significantly higher than after intraperitoneal administration, despite much lower plasma concentration. This observation strongly suggests direct delivery of JAL-TA9 to the brain from the nasal cavity. Similar findings were observed for its transport to CSF after nasal and intravenous administration. The concentration of JAL-TA9 in the olfactory bulb peaked at 5 ‍min, while those in the frontal brain peaked at 30 ‍min and in the occipital brain at 60 ‍min. In conclusion, JAL-TA9 was efficiently delivered to the brain by nasal application compared to other routes.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 6","pages":"396-401"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Exploring non-hormonal therapies and drug repositioning for endometriosis: insights from mouse model studies]. [探索子宫内膜异位症的非激素疗法和药物重新定位:小鼠模型研究的启示]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24041
Satoko Osuka
{"title":"[Exploring non-hormonal therapies and drug repositioning for endometriosis: insights from mouse model studies].","authors":"Satoko Osuka","doi":"10.1254/fpj.24041","DOIUrl":"https://doi.org/10.1254/fpj.24041","url":null,"abstract":"<p><p>The mainstay of treatment for endometriosis is hormonal therapy, which suppresses ovulation; therefore, patients cannot conceive during treatment. There is a dilemma with ovarian-sparing surgery, known as laparoscopic cystectomy, as it can potentially damage the ovaries. Therefore, there is a need for non-hormonal drug therapies. We addressed these challenges in endometriosis treatment, aiming to maintain ovarian function while achieving effective treatment through basic research. Herein, we present two studies using different mouse models of endometriosis. The first study investigates the effects of a nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inhibitor in a mouse model of ovarian endometriotic cysts. We confirmed the increased expression of NLRP in ovarian endometriotic cysts compared with that in the uterine endometrium in both patient-derived samples and mouse model lesions. Administering an NLRP3 inhibitor to model mice resulted in lesion reduction. The second study used a peritoneal lesion mouse model to examine bacterial infection in the endometrium and its association with endometriosis development. Using existing databases and patient-derived samples, we identified that Fusobacterium was involved in the development of endometriosis and lesion enlargement when infecting the endometrium in the model. Furthermore, antibiotic treatment led to a reduction in the lesions. These studies highlight the potential of repositioning existing drugs with NLRP3 inhibitory effects or antibiotics as new non-hormonal treatments for endometriosis.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 6","pages":"374-380"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Pharmacologic properties and results of a clinical study of oxybutynin hydrochloride lotion (APOHIDE® Lotion 20%) as a novel treatment for primary palmar hyperhidrosis]. [盐酸奥昔布宁乳液(APOHIDE® 20%乳液)作为原发性手掌多汗症新疗法的药理特性和临床研究结果]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24037
Koji Okawa, Takaaki Terahara
{"title":"[Pharmacologic properties and results of a clinical study of oxybutynin hydrochloride lotion (APOHIDE<sub>®</sub> Lotion 20%) as a novel treatment for primary palmar hyperhidrosis].","authors":"Koji Okawa, Takaaki Terahara","doi":"10.1254/fpj.24037","DOIUrl":"https://doi.org/10.1254/fpj.24037","url":null,"abstract":"<p><p>APOHIDE<sub>®</sub> Lotion 20% is a topical agent for treating primary palmar hyperhidrosis that contains the active ingredient oxybutynin hydrochloride. Oxybutynin hydrochloride has anticholinergic effects and inhibits sweating by binding to the M<sub>3</sub> receptor, a subtype of the muscarinic acetylcholine receptor, in eccrine sweat glands. The clinical response to oxybutynin hydrochloride treatment also involves N-desethyloxybutynin, an active metabolite of oxybutynin. A clinical study in Japanese patients with primary palmar hyperhidrosis showed superiority of APOHIDE<sub>®</sub> Lotion 20% over placebo, i.e., there were significantly more responders (i.e., patients with a reduction in sweat volume ≥50% from baseline) in the APOHIDE<sub>®</sub> Lotion 20% group (APOHIDE<sub>®</sub> Lotion 20% group: 52.8%, placebo group: 24.3%; treatment difference: 28.5%; P < 0.001, Fisher's exact test). This and other clinical studies reported some adverse events (AEs) associated with the drug's anticholinergic effects and some application site AEs, but most of the AEs were mild. Clinical response did not decrease with long-term (52-week) treatment, and only a few patients (2 of 125) discontinued treatment because of AEs. Taken together, study results indicate that APOHIDE<sub>®</sub> Lotion 20% may be an effective and safe new treatment option for patients with primary palmar hyperhidrosis.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 6","pages":"413-422"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Preface]. [序言]。
Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24073
Motoaki Saito, Fumiaki Ito
{"title":"[Preface].","authors":"Motoaki Saito, Fumiaki Ito","doi":"10.1254/fpj.24073","DOIUrl":"https://doi.org/10.1254/fpj.24073","url":null,"abstract":"","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 6","pages":"385"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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