Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献_第9页

[Placental Toxicity of Nanomaterials and Assessment of Their Impact on Maternal and Child Health]. [纳米材料的胎盘毒性及其对母婴健康影响的评估]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00161-4

Kazuma Higashisaka

{"title":"[Placental Toxicity of Nanomaterials and Assessment of Their Impact on Maternal and Child Health].","authors":"Kazuma Higashisaka","doi":"10.1248/yakushi.25-00161-4","DOIUrl":"10.1248/yakushi.25-00161-4","url":null,"abstract":"Nanomaterials have unique functions due to their increased specific surface area compared to conventional materials. Various nanomaterials are already used in the production of many pharmaceuticals, cosmetics, and foods; however, this also means that, regardless of age or gender, it is now impossible to avoid exposure to these unique materials. Currently, there are concerns that nanomaterials may induce unexpected toxicities due to their small size. In addition, safety evaluations related to the exposure of pregnant women and fetuses, who are particularly vulnerable to the toxic effects of chemicals, are lacking globally; therefore, our understanding of the reproductive and developmental effects of nanomaterials is insufficient. Our group expects that understanding more about how the toxic effects of nanomaterials manifest not just in the mother and fetus but also in the placenta, an essential organ for maintaining pregnancy and fetal development, will be crucial for improving our understanding of the mechanisms that underly the reproductive and developmental toxicities of nanomaterials. Based on this, we have conducted a correlation analysis of the physicochemical properties, kinetics, and toxicities of nanomaterials, focusing on the placenta. In this review, we introduce the results of our research about effects of silica nanoparticles on trophoblast syncytial formation and placental kinetics of silica nanoparticles.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 4","pages":"299-302"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Effects of Environmental Chemicals on the Development of the Central Nervous System: Establishment of Endpoints for the Evaluation of Behavioral Effects in Mice]. [环境化学物质对中枢神经系统发育的影响：小鼠行为影响评价终点的建立]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00161-2

Fumihiko Maekawa

{"title":"[Effects of Environmental Chemicals on the Development of the Central Nervous System: Establishment of Endpoints for the Evaluation of Behavioral Effects in Mice].","authors":"Fumihiko Maekawa","doi":"10.1248/yakushi.25-00161-2","DOIUrl":"10.1248/yakushi.25-00161-2","url":null,"abstract":"Chemical substances are an indispensable part of the development of civilization; however, there are many known cases of health hazards induced by exposure to chemicals and their byproducts. In particular, the effects of exposure on the developing cerebral nervous system, even after a single exposure, may have lifelong effects; therefore, careful evaluation is required. In this paper, we provide examples of assessments conducted by our research group regarding the effects of exposure to chemicals in the environment during development, as well as the endpoints at which we were able to assess these effects. This will ultimately deepen our understanding of developmental neurotoxicity. Here, we demonstrate a case of late-onset abnormalities in female behavior and reproductive physiology due to developmental exposure to tris(2,6-dimethylphenyl)phosphate (TDMPP), a phosphorus-based flame retardant that exhibits typical estrogen-like effects. Also, we used IntelliCage, a fully automated behavioral measurement system for group-reared mice, to assess basal activity and adaptation to the social environment. An example of how IntelliCage can be used to assess behavior is dioxins, which are chemicals that are unintentionally produced. We focused on brominated dioxins and reported a case of abnormal exploratory behavior in a novel environment. Currently, there is growing public concern regarding substances and particle bodies that have not been adequately evaluated for use in the developing brain, such as PFAS and micro/nanoplastics. We believe that the establishment of more sophisticated evaluation methods and endpoints, including those introduced here, will continue to be necessary for building a foundation for a safe and secure society.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 4","pages":"285-290"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Relationship between Hypercalcemia and Renal Function with Eldecalcitol]. 高钙血症与肾功能的关系[j]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00104

Shinji Oda, Takayuki Miyoshi, Kenichi Furuta, Kenshi Takechi, Takashi Otsuka

{"title":"[Relationship between Hypercalcemia and Renal Function with Eldecalcitol].","authors":"Shinji Oda, Takayuki Miyoshi, Kenichi Furuta, Kenshi Takechi, Takashi Otsuka","doi":"10.1248/yakushi.25-00104","DOIUrl":"10.1248/yakushi.25-00104","url":null,"abstract":"Eldecalcitol (ELD), an active vitamin D3 analog, is extensively prescribed in Japan for the treatment of osteoporosis. However, hypercalcemia remains a significant concern, particularly in patients with impaired renal function. Data on the extent to which renal dysfunction increases the risk of hypercalcemia are limited. This retrospective study investigated the relationship between hypercalcemia and renal function in 212 ELD-treated outpatients at Matsuyama Shimin Hospital. Hypercalcemia was observed in 17.0% of the patients. A weak negative correlation was observed between follow-up serum calcium levels and estimated glomerular filtration rate (eGFR). Receiver operating characteristics (ROC) analysis identified a baseline eGFR cutoff of ≤45.9 mL/min, and propensity score matching (1 : 1) adjusted for 12 covariates, including baseline calcium, demonstrated a significantly higher incidence of hypercalcemia in patients with eGFR ≤45.9 mL/min. These findings indicate that a low baseline eGFR predisposes patients to hypercalcemia during ELD therapy. In clinical practice, patients with baseline eGFR ≤45.9 mL/min may require more frequent calcium monitoring and consideration of alternative treatments such as alfacalcidol, with close collaboration between physicians and pharmacists.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 3","pages":"253-258"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Molecular Mechanisms of Antitumor Effect in Targeted Alpha-radionuclide Therapy]. 靶向α -放射性核素治疗抗肿瘤作用的分子机制

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00146-3

Yasuhiro Ohshima

{"title":"[Molecular Mechanisms of Antitumor Effect in Targeted Alpha-radionuclide Therapy].","authors":"Yasuhiro Ohshima","doi":"10.1248/yakushi.25-00146-3","DOIUrl":"10.1248/yakushi.25-00146-3","url":null,"abstract":"Targeted α-radionuclide therapy (TAT) is a systemic therapy for cancer with cancer-targeting compounds conjugated with α-emitters. Since the linear energy transfer (LET) of α-particles are high, relative biological effectiveness is higher than low LET radiation, such as X-rays and β-particles, and the damage to the normal tissues surrounding the tumor is minimal because path length of α-particle is short (a few cells). TAT has demonstrated remarkable therapeutic effects in patients and has attracted considerable attention from physicians and researchers worldwide. In particular, a study published in 2016 showed that disseminated tumors in patients with castration-resistant prostate cancer disappeared following treatment with an actinium-225 (225Ac)-labeled prostate-specific membrane antigen ligand. What is the powerful antitumor effect of TAT? The molecular mechanisms underlying the antitumor effects of radiation have been well studied in external beam radiation therapy (EBRT). However, as EBRT and TAT are fundamentally different in terms of dose rate, irradiation uniformity, and exposure time, extrapolating the knowledge of EBRT to TAT is difficult. Compared to the research on the development of new TAT agents, studies focusing on the radiobiology of TAT are limited, and the detailed mechanisms of its antitumor effects remain poorly understood. We have developed α-emitting meta-[astatine-211 (211At)]astato-benzylguanidine ([211At]MABG) as a novel TAT agent, and investigated radiobiological responses caused by [211At]MABG using comprehensive gene expression analysis. Here, we introduce the mechanism of the antitumor effects of TAT based on our studies on [211At]MABG.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 3","pages":"205-210"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Cross-sectional Exploratory Study on Symptom Correlations in Multiple Myeloma Patients During Initial Treatment Using the Edmonton Symptom Assessment System. 应用埃德蒙顿症状评估系统对多发性骨髓瘤患者初始治疗期间症状相关性的横断面探索性研究。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00135

Junya Ehara, Atsunobu Sagara, Kota Ishida, Takeshi Yoshimi, Naoko Takahashi, Osamu Hosoya

{"title":"A Cross-sectional Exploratory Study on Symptom Correlations in Multiple Myeloma Patients During Initial Treatment Using the Edmonton Symptom Assessment System.","authors":"Junya Ehara, Atsunobu Sagara, Kota Ishida, Takeshi Yoshimi, Naoko Takahashi, Osamu Hosoya","doi":"10.1248/yakushi.25-00135","DOIUrl":"10.1248/yakushi.25-00135","url":null,"abstract":"The Edmonton Symptom Assessment System-Revised (ESAS-r) is a simple, reliable, patient-reported outcome measure designed to assess nine symptoms experienced by cancer patients, including multiple myeloma (MM). While each symptom can be evaluated individually, limitations in time or resources may make it difficult to assess all items in routine practice. In such cases, asking about \"well-being,\" the simplest and most general item in the ESAS-r, may still provide clinically meaningful insight into a patient's overall condition. Although \"well-being\" is an essential indicator of a patient's overall health, its correlation with the other eight symptoms remains poorly understood. In this hypothesis-generating cross-sectional study, we aimed to understand the symptoms of MM patients during initial treatment using the ESAS-r and analyzed the relationship between the patient's \"well-being\" and each symptom. The study included 36 patients with first-episode MM who had started induction therapy with bortezomib, lenalidomide, and dexamethasone. \"Well-being\" was found to be correlated with pain (rs=0.711) and anxiety (rs=0.638). In addition, pain (p=0.0053) and anxiety (p=0.0336) were also significantly associated with the clinical cutoff value. The findings of this study indicate that focusing on \"well-being\" can increase the likelihood of early intervention in MM patients for symptoms that are difficult to express, such as pain and anxiety. Thorough screening of \"well-being\" and early introduction of care as needed, even within the limited time of consultation, through multidisciplinary collaboration including pharmacists, may be significant in terms of improving the quality of life of MM patients.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 3","pages":"259-263"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Aging and Proteostasis]. [衰老和蛋白质平衡]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.26-00010

Ryoya Takahashi

引用次数: 0

[The Role of Pharmaceutical Universities in Strengthening Japan's Drug Discovery Capabilities: A Pharmaceutical Industry Perspective]. [药科大学在加强日本药物研发能力中的作用：制药业视角]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00167-2

Osamu Okuda

{"title":"[The Role of Pharmaceutical Universities in Strengthening Japan's Drug Discovery Capabilities: A Pharmaceutical Industry Perspective].","authors":"Osamu Okuda","doi":"10.1248/yakushi.25-00167-2","DOIUrl":"10.1248/yakushi.25-00167-2","url":null,"abstract":"Japan's pharmaceutical industry faces declining global competitiveness despite its historical strength in drug discovery. This paper examines the perspective of research-oriented pharmaceutical companies, focusing on the roles that pharmaceutical universities are expected to fulfill by the pharmaceutical industry. The diversification of therapeutic modalities-from small molecules to antibodies, middle-sized molecules, nucleic acids, and gene/cell therapies-requires new approaches to pharmaceutical research education. Using Chugai Pharmaceutical as a case study, we analyze the human resource composition across different functions, revealing an increasing demand for specialized researchers with Ph.D. degrees and diverse scientific backgrounds. Pharmaceutical companies seek three core qualities in researchers: scientific thinking capability, proactive collaboration skills, and patient-centered mindset. To develop these qualities, pharmaceutical universities should focus on cultivating strong scientific foundations through research experience; engaging in interdisciplinary collaboration with medical, engineering, and information sciences; and maintaining patient-centered perspectives through clinical training. The creation of a robust drug discovery ecosystem requires coordination between academia, pharmaceutical companies, startups, and regulatory authorities. Pharmaceutical universities play a crucial role in developing cutting-edge researchers and creating new drug discovery seeds and modality technologies. By strengthening both research and education in pharmaceutical universities, and fostering industry-academia collaboration, Japan can revitalize its pharmaceutical industry as a key economic sector and continue contributing to global healthcare through innovative medicines.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 6","pages":"569-576"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Metabolic Activations and Pharmacokinetics of Drugs Using Data-driven Modeling]. [使用数据驱动建模的药物代谢激活和药代动力学]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.26-00087

Hiroshi Yamazaki

{"title":"[Metabolic Activations and Pharmacokinetics of Drugs Using Data-driven Modeling].","authors":"Hiroshi Yamazaki","doi":"10.1248/yakushi.26-00087","DOIUrl":"https://doi.org/10.1248/yakushi.26-00087","url":null,"abstract":"Pharmacological and toxicological assessments of a wide array of chemicals typically involve estimating human clearance through allometric extrapolation of in vivo animal data, using empirical compartmental and physiologically based pharmacokinetic (PBPK) models. Parameters for pharmacokinetic absorption, distribution, and metabolic clearance can be calculated and applied to models that replicate observed plasma drug concentration-time profiles. In patients with genetically impaired cytochrome P450 (P450) enzymes who are prescribed only certain drugs, moderate plasma exposure should be noted as a precaution on drug labels, as genetic variants can cause changes in blood concentrations similar to those caused by drug-drug interactions. For new approach methodologies that do not rely on experimental data, human PBPK model input parameters for various compounds have been effectively estimated using in silico-generated chemical descriptors and machine learning tools to assess internal exposure in humans. Many drug oxidations are facilitated by species-dependent and polymorphic P450s and flavin-containing monooxygenases (FMOs). For instance, in rats, the main oxidation product of thalidomide was deactivated 5'-hydroxythalidomide, along with sulfate and glucuronide conjugates. However, the species-specific teratogen thalidomide induces human P450 3A and is activated by P450 3A through the primary human metabolite 5-hydroxythalidomide, leading to its conjugation with nonspecific proteins. The metabolic capacity of polymorphic FMO3 was evaluated based on urine tests for food-derived trimethylamine N-oxide levels. This pharmacokinetic modeling approach, incorporating polymorphic drug-metabolizing enzyme information, could be applied in clinical settings and during computational data-driven evaluations of potential risks associated with a broad spectrum of chemicals.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 9","pages":"741-748"},"PeriodicalIF":0.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Current Status of Drug Lag in Rare Disease Treatment and a Multifaceted Approach to Resolving It]. [罕见病治疗药物滞后的现状及多方面解决方法]。

IF 0.2 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00140-2

Kota Kodama

{"title":"[Current Status of Drug Lag in Rare Disease Treatment and a Multifaceted Approach to Resolving It].","authors":"Kota Kodama","doi":"10.1248/yakushi.25-00140-2","DOIUrl":"https://doi.org/10.1248/yakushi.25-00140-2","url":null,"abstract":"Patients with rare diseases worldwide face substantial unmet therapeutic needs. In Japan, drug lag-delays in drug approval compared to other countries-has resurfaced as a pressing public health issue. This study analyzes orphan drugs (ODs) approved in the United States (U.S.) from 2005 to 2021, examining OD lag trends, and research and development (R&D) models to streamline OD development in Japan. Despite increased OD approval in the U.S. since 2018, the number of unapproved ODs in Japan has substantially increased. Although OD lag had once decreased, it has shown a tendency to resurge since 2017. This is largely due to changes in the R&D strategies of pharmaceutical companies, which are driven by the growing presence of U.S.- and Europe-based small- to mid-sized enterprises (SMEs) and the evolving industry landscape. Large foreign pharmaceutical companies have shifted toward a global development strategy for Japan, aiming for more efficient development and competitive advantage. This has been propelled by a move toward in-licensing earlier-stage drug candidates with global exclusivity from SMEs. Japanese pharmaceutical companies have focused on in-licensing late-stage drug candidates for the Japanese market from SMEs without a business presence in Japan, which have not been developed locally, thereby employing a bridging strategy for Japan. With the increase in ODs developed in the U.S. by these SMEs, this practice has substantially exacerbated the OD lag. As these SMEs are unlikely to enter the Japanese market, it is crucial for Japanese pharmaceutical companies to proactively pursue earlier, more proactive global partnerships with SMEs.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"146 1","pages":"25-34"},"PeriodicalIF":0.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Development of Disease Therapy Using Extracellular Vesicles Derived from Mammalian Cells]. [利用源自哺乳动物细胞的细胞外囊泡治疗疾病的进展]。

IF 0.4 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2026-01-01 DOI: 10.1248/yakushi.25-00171-1

Yuki Takahashi

引用次数: 0