Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献_第7页

[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]. [试图通过体内成像和微生理系统提高非临床评估的可预测性：中枢神经系统癫痫发作风险评估和肺泡给药的案例]。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00165-2

Kaoru Sato, Yuji Taquahashi, Ikuro Suzuki

{"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":"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).","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}

引用次数: 0

[Development of Antibody-polymer Conjugates for the Treatment of Intractable Cancers]. 抗体-聚合物偶联物治疗顽固性癌症的研究进展

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00186-2

Yuki Mochida

{"title":"[Development of Antibody-polymer Conjugates for the Treatment of Intractable Cancers].","authors":"Yuki Mochida","doi":"10.1248/yakushi.24-00186-2","DOIUrl":"https://doi.org/10.1248/yakushi.24-00186-2","url":null,"abstract":"Antibody therapeutics have become a major modality for cancer treatment. Particularly, immune checkpoint inhibitors have shown remarkable efficacy against various cancers. However, similar to other antibody therapeutics, they have not demonstrated clinical efficacy against malignant brain tumors. The primary reason for this is the presence of the blood-brain tumor barrier (BBTB) in the endothelial cells of malignant brain tumors, which prevents antibodies from entering the tumor parenchyma. Additionally, treatment with immune checkpoint inhibitors is clinically challenged by the occurrence of immune-related adverse events (irAEs) owing to non-specific and excess activation of the immune system. To address these issues, we integrated synthetic polymer-based drug delivery systems with immune checkpoint inhibitors. Specifically, we modified anti-PD-L1 antibodies with multiple glucosylated poly(ethylene glycol) (PEG) chains via disulfide bonds. This glucose-PEG-conjugated anti-PD-L1 antibody effectively accumulates in glioblastoma by penetrating the BBTB through the interaction of glucose ligands with glucose transporter-1, which is overexpressed in glioblastoma endothelial cells. Subsequently, the PEG chains detach from the antibodies in response to the reductive environment within the glioblastoma, thereby blocking PD-L1 expression. Conversely, the PEG chains remain conjugated to antibodies in the bloodstream and normal tissues, masking their functions. The glucose-PEG-conjugated anti-PD-L1 antibody demonstrated significant efficacy against glioblastoma, while reducing the risk of irAEs in normal tissues. This technology is applicable to various antibody therapeutics and can be adapted to target other organs or specific cell types by exchanging ligand molecules, offering broad potential therapeutic applications.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 6","pages":"523-532"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200207","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 High-Performance Countercurrent Chromatography and Its Application in the Separation of Bioactive Compounds]. [高效逆流色谱法的发展及其在生物活性化合物分离中的应用]。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00187

Kazufusa Shinomiya

{"title":"[Development of High-Performance Countercurrent Chromatography and Its Application in the Separation of Bioactive Compounds].","authors":"Kazufusa Shinomiya","doi":"10.1248/yakushi.24-00187","DOIUrl":"10.1248/yakushi.24-00187","url":null,"abstract":"Countercurrent chromatography (CCC) is a form of liquid-liquid partition chromatography that eliminates the solid support used in column chromatography. This allows the recovery of all samples subjected to CCC separation of bioactive components without denaturation and adsorption caused by interacting with the column matrix. The CCC apparatus requires numerous and continuous partitioning processes composed of the sufficient mixing of the two-phase solvent system, separating into two liquid phases, and moving the mobile phase. The present paper introduces my studies over 35 years on the development and improvement of CCC including the rotation behavior of the coiled column, column configuration, tube design, and two-phase solvent system followed by the application to the separation of bioactive compounds. Among the CCC instruments developed or improved in those studies, the floor-standing type of cross-axis CCC was first domestically produced and prompted the fabrication of benchtop type small-scale cross-axis CCC to achieve satisfactory separation of proteins and enzymes without loss of their bioactivity using aqueous two-phase solvent systems. The coil satellite centrifuge designed and fabricated in our laboratory enabled sufficient separation using a two-phase solvent system after adjusting the suitable rotation speed combination of the sun axis, planet axis, and satellite axis. Better partition efficiency was achieved using an eccentric coil for the analytical-scale and multilayer coil for the preparative-scale. Notably, the multilayer coil wound with long-pressed locular tubing increased the peak resolution within shortened separation times. The high-performance of the CCC apparatus developed will expand the ability to reveal the mechanisms of cell particles.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 4","pages":"299-312"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773266","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

[Inspection of Residual Veterinary Drugs at Tokyo Metropolitan Institute of Public Health: Bioassay and LC-MS/MS Analysis]. 东京都公共卫生研究所兽药残留检验：生物测定和LC-MS/MS分析。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00164-4

Maki Kanda

{"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":"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.","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}

引用次数: 0

[Role of Median Raphe Serotonergic Neurons in Positive and Negative Information Processing]. 中缝正中5 -羟色胺能神经元在正负信息加工中的作用。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00150

Hiroyuki Kawai

{"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":"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.","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}

引用次数: 0

[Basic and Clinical Research on Placental Function for Drug Development Research]. [药物开发研究中胎盘功能的基础与临床研究]。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00174-F

Kazuma Higashisaka, Mikihiro Yoshie

引用次数: 0

[Development of Selective Reactions in the Synthesis of Medicines]. [药物合成中选择性反应的发展]。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.25-00001

Takeshi Sugai

{"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":"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.","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}

引用次数: 0

[Elucidating the Pathophysiology of Various Diseases by Investigating the Role of Molecules in Brain Wiring]. [通过研究分子在脑线路中的作用来阐明各种疾病的病理生理]。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00192

Kazunori Yukawa

{"title":"[Elucidating the Pathophysiology of Various Diseases by Investigating the Role of Molecules in Brain Wiring].","authors":"Kazunori Yukawa","doi":"10.1248/yakushi.24-00192","DOIUrl":"10.1248/yakushi.24-00192","url":null,"abstract":"Semaphorins and their receptors plexins are axon guidance molecules that navigate axons to their final destinations during neural development. Semaphorins and plexins exert distinct roles in regulating biological functions such as the immune system and bone homeostasis. They also participate in the development and progression of various diseases such as osteoporosis and allergic diseases. This review describes the varied phenotypes revealed by the analysis of semaphorin or plexin knockout mice and discusses the association with pathogenesis and therapy of atherosclerosis, agenesis of the corpus callosum, and neuropsychiatric diseases. The deletion of semaphorin 4D in atherosclerosis-prone Apolipoprotein E-deficient mice mitigated atherosclerotic lesions, indicating its crucial involvement in the progression of atherosclerosis. Semaphorin 4D is also implicated in apoptosis induced by the estrogen-dependent generation of soluble semaphorin 4D and the active form of plexin-B1 in the postnatal vaginal opening in mice. Plexin-A1 knockout BALB/cA mice exhibited the agenesis of corpus callosum. This study indicates the crucial role of plexin-A1 in the midline crossing of callosal pioneer axons projecting from the cerebral cortex during the early phase of callosal formation. Adult plexin-A1-deficient mice exhibit reduced prepulse inhibition deficit, an endophenotype of schizophrenia, in addition to excessive self-grooming. Parvalbumin-expressing interneurons in the medial prefrontal cortex are significantly decreased in plexin-A1 knockout mice. In the parvalbumin neurons, oxidative stress is significantly increased in plexin-A1 knockout mice. Accordingly, plexin-A1 deficiency may augment oxidative stress in parvalbumin neurons, thereby impairing the parvalbumin neuron network and leading to behavioral abnormalities relevant to neuropsychiatric diseases.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 2","pages":"133-143"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081250","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

[Translational Research on Pre-eclampsia with Existing Drugs Targeting Antioxidant Molecules]. [现有抗氧化药物对子痫前期的转化研究]。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00174-1

Kenji Onda

引用次数: 0

[Mechanism of the Molecular Pathophysiology for Familial Hypercholesterolemia]. [家族性高胆固醇血症的分子病理生理学机制]。

IF 0.3 4区医学

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan Pub Date : 2025-01-01 DOI: 10.1248/yakushi.24-00177-5

Mika Hori

{"title":"[Mechanism of the Molecular Pathophysiology for Familial Hypercholesterolemia].","authors":"Mika Hori","doi":"10.1248/yakushi.24-00177-5","DOIUrl":"10.1248/yakushi.24-00177-5","url":null,"abstract":"Familial hypercholesterolemia (FH) is characterized by high serum low-density lipoprotein cholesterol (LDL-C) levels from birth, tendon/skin xanthomas, and premature coronary artery disease. The prevalence of FH is 1 per 300 individuals in the general population. FH is caused by a pathogenic (rare) variant in the LDL receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In Japan, there has been only one reported case of a family with FH caused by the known APOB p.(Arg3527Gln) variant. Those without pathogenic variants in the LDLR or PCSK9 genes account for approximately 36% of patients with FH. Novel causative genes/variants of FH have been explored in patients with FH worldwide, but no gene variants with a large effect size have been found. Polygenic hypercholesterolemia accounts for approximately 10% of patients with clinical FH. We performed whole-exome sequencing in 122 families without pathogenic variants in the LDLR and PCSK9 genes. However, we could not find novel causative genes/variants of FH via family analysis. We examined all the APOB variants and showed that the low-frequency APOB p.(Pro955Ser) variant has a moderate effect size in FH patients via functional analysis of hepatocytes. We also reported that low-frequency PCSK9 variants contribute to the severity of the FH phenotype in patients with FH harboring an LDLR pathogenic variant. Thus, the combination of low-frequency variants and age, environmental factors such as diet, or other genetic factors contribute to the severity of or variability in the FH phenotype.","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 3","pages":"195-200"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537879","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