{"title":"[Inspection of Residual Veterinary Drugs at Tokyo Metropolitan Institute of Public Health: Bioassay and LC-MS/MS Analysis].","authors":"Maki Kanda","doi":"10.1248/yakushi.24-00164-4","DOIUrl":"10.1248/yakushi.24-00164-4","url":null,"abstract":"<p><p>Veterinary drugs are used worldwide to prevent and treat diseases and promote growth in animals, fisheries, and beekeeping. Despite their effectiveness, the illegal and improper use of these drugs can result in livestock and fishery products, potentially impacting human health by causing allergic reactions, cytotoxicity, and antimicrobial resistance. To mitigate these adverse effects, the Japanese government established a positive list system in 2006. Maximum residue levels (MRLs) have been defined for approximately 300 veterinary drugs. The regulation of certain antimicrobial drugs without defined MRLs uses in zero tolerance. Residual veterinary drugs in meat, fish, eggs, milk, and honey are inspected to ensure compliance with legal limits. Initially, samples are screened using bioassay and LC-MS/MS. If residues are detected, they are confirmed and quantified using more precise methods. We have detailed the detection of residual norfloxacin in honey. Additionally, we are currently developing new analytical methods. This study introduces an analytical method for the residue screening of sulfonamides and quinolones. After residue detection by bioassay, the same test solutions were analyzed by LC-MS/MS for accurate identification and quantification. This method has also proven to be more environmentally friendly compared to other quantitative methods. We present the ingenuity used to realize the combined method, performance evaluation results, examples of applications to actual samples, and future prospects.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 2","pages":"109-115"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081251","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}
{"title":"[Role of Median Raphe Serotonergic Neurons in Positive and Negative Information Processing].","authors":"Hiroyuki Kawai","doi":"10.1248/yakushi.24-00150","DOIUrl":"10.1248/yakushi.24-00150","url":null,"abstract":"<p><p>Serotonergic neurons play a critical role in processing reward and aversive information. Rewarding stimuli activate serotonergic neurons in the dorsal raphe nucleus (DRN), whereas optogenetic activation of DRN serotonergic neurons induces reward-like effects. However, the pharmacological enhancement of serotonin neurotransmission does not induce rewarding or aversive effects. These findings suggest the presence of another serotonergic neuron that plays a role opposite to that of the DRN in processing reward and aversion information. Previous reports suggested that the median raphe nucleus (MRN) processes negative emotional stimuli. To elucidate the function of MRN serotonergic neurons in these processes, we recorded the changes in serotonergic activity in mice in response to rewarding and aversive stimuli. We also used optogenetic manipulation to determine whether these changes could induce rewarding and aversive behaviors. The activity of MRN serotonergic neurons decreased in response to rewarding stimuli and increased after aversive stimuli. Optogenetic inhibition of MRN serotonergic neurons induced reward-related behavior, while optogenetic stimulation induced aversion-related behavior. Furthermore, we found that the projection pathway from MRN serotonergic neurons to the interpeduncular nucleus is crucial for these processes. These results indicate that MRN serotonergic neurons play a pivotal role in processing reward and aversive information, functioning oppositely to DRN neurons.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 2","pages":"79-84"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081253","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}
{"title":"[Challenges in Development of Appropriate Drugs for Children].","authors":"Hiroyuki Kawagishi, Yasunari Kanda","doi":"10.1248/yakushi.24-00171-F","DOIUrl":"https://doi.org/10.1248/yakushi.24-00171-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 4","pages":"273-274"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773131","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}
{"title":"[Attempts to Improve Non-clinical Evaluation Predictability by In Vivo Imaging and Microphysiological Systems: The Cases of the CNS Seizure Risk Assessment and Drug Delivery to the Alveoli].","authors":"Kaoru Sato, Yuji Taquahashi, Ikuro Suzuki","doi":"10.1248/yakushi.24-00165-2","DOIUrl":"https://doi.org/10.1248/yakushi.24-00165-2","url":null,"abstract":"<p><p>To increase success rates of clinical studies, preclinical evaluation systems have been expected to improve human predictability. In addition, future preclinical studies need to become more sophisticated and efficient on the back ground of the adoption of FDA Modernization Act 2.0 and the 3R principle promotion of animal tests. In this review, we will discuss about the efficiency of in vivo imaging in preclinical studies taking 'an attempt to establishment of in vitro in vivo extraporation (IVIVE) model for seizure risk assessment using microphysiological system (MPS) and magnetic resonance imaging (MRI)', and 'an attempt to predict drug delivery to the alveoli' as examples. In the seizure risk assessment of new drugs so far, primary cultures of rodent neurons and in vivo behavioral observation have been mainly used, however, since the human induced pluripotent stem cell (iPSC) technology was reported, the need for IVIVE model is more and more increasing to improve human predictability. As an MPS, we here introduce microelectrode array (MEA) system recording of primary culture of rodent neurons, while as in vivo experiments, we here introduce the measurement of cerebrospinal fluid (CSF) concentrations and MRI imaging of forebrains of the rats i.p. injected with seizurogenic compounds. In case of inhalation drugs, it has been difficult to confirm whether or not the drugs surely reach alveoli. We visualized two-dimensional spatial localization of inhaled ciclesonide (CIC) in rat lungs after administration of a single dose of a CIC aerosol using by desorption electrospray ionization-time of flight mass spectrometry imaging (DESI-MSI).</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 6","pages":"501-505"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200203","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}
{"title":"[Analysis of Asparagine Deamidation and Its Impact on γS-Crystallin Aggregation].","authors":"Koichi Kato","doi":"10.1248/yakushi.25-00122","DOIUrl":"https://doi.org/10.1248/yakushi.25-00122","url":null,"abstract":"<p><p>Nonenzymatic posttranslational modifications of proteins occur under physiological conditions, leading to structural alterations and functional impairments that contribute to age-related diseases and reduced efficacy of antibody drugs. Among these modifications, deamidation of asparagine (Asn) residues in crystallins, a major lens protein, is implicated in the development of age-related cataracts. This study investigated the conditions that promote Asn deamidation and analyzed its impact on γS-crystallin aggregation. Molecular dynamics simulations and quantum chemical calculations revealed that deamidation propensity is influenced by the main-chain conformation on the N-terminal side of Asn. Specifically, the activation barrier for deamidation decreased by approximately 9-20 kJ/mol when the α-hydrogen and the amide hydrogen of the Asn main chain adopted a syn-periplanar conformation, This finding enabled identification of backbone structures susceptible to deamidation. However, residues prone to deamidation and those that significantly affect protein structure upon modification do not always overlap. To further explore these effects, deamidation-mimetic mutants of γS-crystallin (N14D, N37D, N53D, N76D, N143D) were constructed. Structural and aggregation analyses revealed that deamidation at Asn37 significantly reduced thermal stability and promoted aggregation of γS-crystallin. These findings enhance our understanding of the aggregation mechanisms underlying cataract formation and may contribute to the development of novel preventive and therapeutic strategies for cataracts and other age-related diseases associated with nonenzymatic posttranslational modifications of proteins.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 10","pages":"809-813"},"PeriodicalIF":0.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207744","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}
{"title":"[Evaluation of the Usefulness of Pharmacy Lectures to Non-pharmaceutical Students Majoring in Life Sciences: A Questionnaire Survey].","authors":"Mihoko Hayafune, Masaki Takigawa, Yasuhiro Sasaki, Masako Kinoshita, Masayuki Masuda","doi":"10.1248/yakushi.25-00042","DOIUrl":"https://doi.org/10.1248/yakushi.25-00042","url":null,"abstract":"<p><p>Since pharmacy is a discipline based on natural and life sciences, learning about pharmacy is considered useful for science students outside this field. In this survey, we investigated whether pharmacy lectures delivered to students majoring in life sciences were useful for their studies within their respective fields. A questionnaire was sent to the students enrolled in the course, asking them to evaluate, on a five-point scale, whether the lectures were helpful in deepening their learning in their field of study, both overall and for each lecture theme. Additionally, we conducted a Customer Satisfaction (CS) analysis, using the overall evaluation of the lectures as the objective variable and the evaluation of each lecture theme as the explanatory variable. The response rate was 75.0% (72/96). Overall, 98.6% of the respondents found the lectures helpful in deepening their learning in their field of study. The satisfaction rate for each lecture topic exceeded 80%. When the CS graph was created, the lecture themes categorized as \"priority maintenance field\" were \"Pain, psychology, analgesics, psychotic drugs\" and \"Adverse event.\" In contrast, the themes identified as \"priority improvement field\" were \"Hypertension and the therapeutic agent\" and \"Drug interactions.\" These findings suggest that pharmacy lectures might be useful for deepening the learning of students majoring in life sciences.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 10","pages":"849-856"},"PeriodicalIF":0.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207901","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}
{"title":"[Diversification of Unsaturated Hydrocarbons via An Azo-Ene Reaction].","authors":"Yusuke Kuroda","doi":"10.1248/yakushi.25-00110","DOIUrl":"https://doi.org/10.1248/yakushi.25-00110","url":null,"abstract":"<p><p>Unsaturated hydrocarbons represent one of the most abundant and synthetically versatile classes of organic molecules. Consequently, the development of new strategies to enable their facile transformation into value-added molecules is a longstanding goal in modern organic chemistry. In this review, we summarize our recent progress in the diversification of simple unsaturated hydrocarbons via ene reactions with 1,2,4-triazoline-3,5-diones (TADs), a highly reactive class of azo compounds. A key breakthrough involved the use of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as the solvent, which significantly facilitates otherwise sluggish azo-ene reactions. The resulting TAD-ene adducts-presumably generated through a stepwise pathway-underwent diverse downstream functionalizations, including reactions with Grignard reagents and transition metal catalysts, to access structurally and functionally complex products. Notably, HFIP also promotes an unusual [3+2] cycloaddition between TADs and alkynes, leading to the discovery of unprecedented mesoionic compounds-five-membered heterocycles that cannot be represented satisfactorily by any one covalent or polar structure.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 10","pages":"823-831"},"PeriodicalIF":0.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207834","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}
{"title":"[Pharmacist-Led Shared Decision-Making in a Pediatric Patient with Crohn's Disease and Growth Failure: A Case Report].","authors":"Momoko Konaka-Yamamoto, Ikkou Hirata, Maho Hamaguchi, Yuki Ohta, Ryohkan Funakoshi","doi":"10.1248/yakushi.25-00041","DOIUrl":"https://doi.org/10.1248/yakushi.25-00041","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is an illness of unknown etiology, leading to chronic intestinal inflammation. It is characterized by repeated periods of remission and relapse. In the current treatment of IBD, multiple therapeutic drugs are listed in the Japanese treatment guidelines. Therefore, selecting a drug that matches the patient's condition and lifestyle is important, and the treatment decisions should be made using shared decision-making (SDM). For children, there is no specific age at which decision-making becomes possible. Therefore, medical professionals must make appropriate assessments regarding their decision-making ability. Although SDM has been shown to be useful in adults, there are no reports of SDM use in children. In this case report, a pharmacist performed multiple SDM for a 15-year-old patient with Crohn's disease. The SDM process reflected the child's changing values, leading to the introduction and continuation of biologic agents, and addressing growth disorders after the disease activity was controlled. To our knowledge, this is the first reported case in which a pharmacist performed SDM based on the condition of a pediatric patient with IBD, effectively implemented treat-to-target strategies, and improved the growth disorder. This case demonstrates the importance of properly controlling disease activity in pediatric patients with IBD and highlights the important role of pharmacists in adjusting drug therapy to suit a child's condition.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 10","pages":"857-862"},"PeriodicalIF":0.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207852","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}
{"title":"[Basic and Clinical Research on Placental Function for Drug Development Research].","authors":"Kazuma Higashisaka, Mikihiro Yoshie","doi":"10.1248/yakushi.24-00174-F","DOIUrl":"https://doi.org/10.1248/yakushi.24-00174-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 1","pages":"41-42"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932800","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}
{"title":"[Development of Selective Reactions in the Synthesis of Medicines].","authors":"Takeshi Sugai","doi":"10.1248/yakushi.25-00001","DOIUrl":"https://doi.org/10.1248/yakushi.25-00001","url":null,"abstract":"<p><p>This review summarizes the contributions to the discovery, evaluation, and functional development of microbial and enzyme catalysts, as well as the rational design of pathways that synergistically integrate chemical and biochemical reactions. In the introduction, the author outlines his strategies and principles: 1) He avoided biosynthetic enzymes and pathways, opting instead for degradative enzymes that offer broader substrate flexibility and a wider range of applications. 2) He focused on commercially available enzymes, prioritizing their reproducibility and accessibility for widespread use. All the microorganisms he identified have been deposited in public institutions, making them available to researchers in both academic and corporate settings. 3) He developed methods to enhance reactivity and selectivity by optimizing reaction conditions and substrate structures, without altering the enzymes themselves. The main body of the review is divided into two parts. Part 1, titled \"Chemo-enzymatic Synergistic Synthesis of Medicines,\" covers the following topics: 1) the synthesis of dihydroxymethylepoxyquinomicin (DHMEQ); 2) the synthesis of sialic acids; 3) the utilization of epoxide hydrolase; and 4) the synthesis of (S)-azetidine-2-carboxylic acid. Part 2, titled \"New Selective Reactions for Synthesis of Medicines,\" includes: 1) the optimization of reaction conditions in lipase-catalyzed transesterification and aminolysis; 2) the conversion of racemates into single enantiomers using hydrolytic enzymes through novel pathways; 3) the use of carbonyl reductases in conjunction with substrate design; 4) nitrile hydratase and amidase in Rhodococcus species; 5) selective acylation and deacylation of alcohols and phenols; and 6) the use of oligosaccharides as protective groups in the synthesis of polyphenol glycosides.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 5","pages":"365-378"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043360","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}