Biological & pharmaceutical bulletin最新文献

{"title":"Validation of Risk Prediction System for Denosumab-Induced Hypocalcemia with an External Clinical Dataset.","authors":"Keisuke Ikegami, Masami Tsuchiya, Shungo Imai, Yukiyoshi Fujita, Osamu Yasumuro, Hayato Kizaki, Ryohkan Funakoshi, Yasunori Sato, Satoko Hori","doi":"10.1248/bpb.b24-00768","DOIUrl":"https://doi.org/10.1248/bpb.b24-00768","url":null,"abstract":"<p><p>Denosumab is used to reduce skeletal-related events such as fractures in cancer patients with bone metastasis, but may cause severe hypocalcemia. We previously developed and updated a risk prediction model for ≥ grade 2 denosumab-induced hypocalcemia from a hospital-based administrative database and clinical datasets from two facilities. The final risk-scoring system using only calcium, albumin, and alkaline phosphatase levels provided high performance. Here, we aimed to externally validate the scoring system's performance using an independent clinical dataset from Gunma Prefectural Cancer Center. Clinical data (May 2017-November 2023) were retrospectively collected and the discriminant performance of the previously developed model (sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristic-area under the curve (ROC-AUC)) was evaluated. For 161 cases analyzed, the model demonstrated a sensitivity of 85.7%, specificity of 72.1%, positive predictive value of 12.2%, and negative predictive value of 99.1%. ROC-AUC was 0.813. All performance parameters were comparable to those in the previous study. The results strongly support the generalizability of the scoring system. This straightforward, easily interpretable, high-performance risk prediction system is expected to enhance the safety of denosumab treatment.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"860-863"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324448","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":"Surface Texture Influences Environmental Preference and Locomotion in Behaving Rats.","authors":"Ryosuke Yoshida, Kotaro Yamashiro, Yuji Ikegaya, Nobuyoshi Matsumoto","doi":"10.1248/bpb.b25-00094","DOIUrl":"https://doi.org/10.1248/bpb.b25-00094","url":null,"abstract":"<p><p>In rodents, the whiskers and paws are essential for somatosensory perception, yet their preference for specific textures remains unclear. Here, we examined the preference for rough versus smooth surfaces in rats using a custom open-field paradigm with a water-based motivator to ensure consistent and unbiased movement. We found that rats strongly preferred rough textures with longer interactions and increased dwell time. Notably, this preference persisted in darkness, confirming the tactile, but not visual, influence. These findings highlight the primacy of tactile input in behavioral choices and provide key insights into optimizing rodent environments.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"825-829"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274181","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":"Foreword.","authors":"Yuji Morita","doi":"10.1248/bpb.b25-ctf4803","DOIUrl":"https://doi.org/10.1248/bpb.b25-ctf4803","url":null,"abstract":"","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"195"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536431","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 Sensitive and Specific Determination Methods of Bioactive Compounds Based on Generation of High-Performance Antibodies.","authors":"Norihiro Kobayashi","doi":"10.1248/bpb.b25-00073","DOIUrl":"https://doi.org/10.1248/bpb.b25-00073","url":null,"abstract":"<p><p>Immunoassays enable the sensitive determination of various compounds and have been widely utilized in pharmaceutical and medical sciences. To develop practical assays, it is essential to obtain antibodies that capture the target analytes with high specificity and affinity. To date, we have generated high-performance antibodies and developed immunoassays for determining bioactive compounds, particularly focusing on haptens, such as steroids and synthetic drugs. In previous studies, we have produced specific anti-hapten antibodies by immunizing animals with reasonably prepared hapten-carrier conjugates. However, the resulting antibodies sometimes lacked sufficient affinity for a sensitive determination. Therefore, we challenged genetic engineering to produce artificially modified antibodies with improved affinity. Therein, native antibodies with insufficient affinities were converted into single-chain Fv fragments (scFvs), to which random point mutations were introduced to generate diverse scFv libraries. Mutated scFv species with increased affinities were selected and isolated with the aid of phage-display system combined with panning. Using this strategy, we obtained scFvs specific to several haptens, such as estradiol-17β (E₂) and cotinine, that show significantly improved affinity (K_a) than that of the parental scFv, enabling more sensitive enzyme-linked immunosorbent assays. However, the panning step often fails in straightforward selection and requires laborious trial-and-error work. Thus, we developed a \"clonal array profiling (CAP)\" system for more efficient isolation of the mutants with enhanced affinities, which successfully functioned generating multiple anti-cortisol scFvs with the K_a improved up to 63-fold and an anti-E₂ scFv with 372-fold larger K_a. In this study, we identified new strategies that allow for efficient site-directed mutagenesis to improve affinity. We expect that the engineered antibodies described here will open the door to next-generation immunoassays that will enable simpler and more reliable determination of bioactive compounds.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"475-494"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972593","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":"Incidence of Myocarditis Caused by Drugs Used for Ulcerative Colitis as Examined Using VigiBase, a Spontaneous Adverse Drug Reaction Reporting Database.","authors":"Yumi Kawai, Yasuko Kurata, Hirofumi Hamano, Takahiro Niimura, Mitsuhiro Goda, Yoshito Zamami, Keisuke Ishizawa, Hideki Nawa","doi":"10.1248/bpb.b24-00766","DOIUrl":"https://doi.org/10.1248/bpb.b24-00766","url":null,"abstract":"<p><p>Although myocarditis is listed as a serious adverse reaction in the package inserts of mesalazine and some other anti-ulcerative colitis (UC) drugs currently in use, and regulatory authorities have issued related warnings, the detailed characteristics of anti-UC drug-induced myocarditis remain unknown. We aimed to investigate the association between UC drugs and myocarditis development as an adverse event and its characteristics using data from a spontaneous adverse drug reaction reporting database. We searched for adverse event signals of five drugs, mesalazine, sulfasalazine, azathioprine, mercaptopurine, and budesonide, listed in the treatment guidelines for UC, using VigiBase. The information component was calculated, and a signal was considered present when the lower limit of the 95% confidence interval of the information component exceeded zero. The total number of VigiBase and myocarditis (as a target adverse event) reports was 38459016 and 71571, respectively. No trend was identified based on age or sex. Analysis of the five UC drugs for severity in VigiBase showed that most patients recovered, with a low reported mortality rate. However, the time to onset of adverse drug reactions varied among the drugs. Mesalazine signals were detected regardless of age or sex. This finding suggests that myocarditis, an adverse event, may be a potential complication regardless of patient characteristics. Our results also indicate that UC itself may induce myocarditis. Our findings warrant multifaceted investigations, including basic and clinical studies, on the characteristics of each drug regarding the development of myocarditis as an adverse event.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"383-389"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961087","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":"Effects of Calcineurin Inhibitors on Intestinal Barrier in Caco-2 Cells.","authors":"Reina Suzuki, Naohide Hirashima, Masahiko Tanaka","doi":"10.1248/bpb.b24-00875","DOIUrl":"https://doi.org/10.1248/bpb.b24-00875","url":null,"abstract":"<p><p>One of the side effects of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporin A (CsA), is intestinal mucosal damage leading to ulceration and bleeding. However, it remains to be elucidated whether these side effects are direct effects of calcineurin inhibitors on intestinal epithelial cells (IECs). To determine whether IECs are directly damaged by calcineurin inhibitors, we analyzed the effects of calcineurin inhibitors on the intestinal barrier in Caco-2 cells, a human intestinal cell line. Treatment of Caco-2 with calcineurin inhibitors such as FK506, CsA, and deltamethrin inhibited expression of zonula occludens-1, a tight junction protein, and increased permeability of Lucifer Yellow. These effects were observed in confluent cells, but not clear in subconfluent cells. Our findings suggest that calcineurin inhibitors can directly damage IECs.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"457-462"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956729","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":"Molecular Epidemiological Features of Methicillin-Resistant Staphylococcus aureus in Japan.","authors":"Hidemasa Nakaminami","doi":"10.1248/bpb.b23-00685","DOIUrl":"10.1248/bpb.b23-00685","url":null,"abstract":"<p><p>Recently, the epidemic types of methicillin-resistant Staphylococcus aureus (MRSA) in hospital and community settings in Japan have changed significantly. Before 2010, approximately 80% of the MRSA strains isolated from hospitals were typical healthcare-associated MRSA (HA-MRSA) with staphylococcal cassette chromosome (SCC) mec type II. However, USA400-like community-associated MRSA (CA-MRSA) with SCCmec type IV (defined as USA400/J) has become dominant in hospitals since 2014. By contrast, skin infections caused by the highly virulent CA-MRSA USA300 clone have increased. The USA300 clone is associated with intractable skin infections and necrotizing pneumonia because it carries a cytolytic pore-forming toxin, Panton-Valentine leukocidin (PVL), and an arginine catabolic mobile element that promotes skin colonization. In the past decade, the USA300 clone has shown limited prevalence and has not been considered a serious problem in Japan. However, the USA300 clone has recently spread in community and hospital settings. This review discusses the evolution and current status of the molecular epidemiological features of HA-MRSA and CA-MRSA strains in Japan.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"196-204"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536435","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":"Impact of a Collaborative Pharmacist-Cardiovascular Surgeon Protocol for High Risk of Postoperative Delirium on Benzodiazepine Prescription Trends in Hospitalized Patients.","authors":"Yuki Asai, Yuki Nakano, Tatsuki Yanagawa, Masaaki Takahashi, Takuya Iwamoto","doi":"10.1248/bpb.b24-00708","DOIUrl":"10.1248/bpb.b24-00708","url":null,"abstract":"<p><p>Benzodiazepine (BZD) therapy has been associated with several side effects in hospitalized patients. We developed a protocol-based pharmacotherapy management (PBPM) to recommend BZD discontinuation for patients at high risk for postoperative delirium (PD) following cardiovascular surgery. This study investigated whether implementing PBPM affects BZD prescription trends among cardiovascular surgeons for PD non-high-risk patients. This single-center retrospective cohort study collected all prescription orders of BZD from June 1, 2018, to May 31, 2023, and these orders were divided into 2 periods: 2 years and 6 months before and after PBPM. Changes in BZD prescription trends for patients with non-high-risk of PD were analyzed using interrupted time series (ITS). Furthermore, all patients in the department of cardiovascular surgery were also investigated as supplementary analysis. ITS analysis revealed that there was a significant level change in BZD prescriptions (-20%, 95% confidence interval: -37 to -2.8, p = 0.023), and the slope exhibited a downward trend (-0.90%, 95% confidence interval: -1.9 to 0.07, p = 0.068) in PD non-high-risk patients. In all patients, the level change was -21% (95% confidence interval: -0.36 to -0.9, p = 0.004) and the slope change was -0.85% (95% confidence interval: -1.7 to -0.02, p = 0.045). These results suggest that PBPM implementation significantly reduced the BZD prescription rate among cardiovascular surgeons for patients with a non-high-risk of PD. The alteration in prescription trends might be attributed to pharmacist interventions targeting patients with a high risk of PD, which influenced the prescribing behavior of cardiovascular surgeons.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"177-183"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536423","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":"Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, FG4592, Induces Endogenous Metallothionein3 Expression in Human Neuronal Cell Line, ReNcell CX Cells.","authors":"Mizuki Tsuru, Taisei Ito, Kazuki Komai, Fukuto Kunitomo, Yukie Nakayama, Takanori Murakami, Kazuki Ohuchi, Yasuhiro Shinkai, Tomoki Kimura, Nobuhiko Miura, Yoshito Kumagai, Isao Hozumi, Masatoshi Inden, Hisaka Kurita","doi":"10.1248/bpb.b24-00792","DOIUrl":"10.1248/bpb.b24-00792","url":null,"abstract":"<p><p>Metallothionein (MT) is a small-molecule protein that functions in essential trace element homeostasis. Among MT isoforms, MT3 is involved in neuronal activity, and its expression is reported to be decreased in patients with neurodegenerative conditions such as Alzheimer's disease; however, only a few effective drugs have been reported to induce MT3 expression. In this study, we evaluated existing drugs for the induction of MT3 expression in the neuronal cell line of ReNcell CX cells. Using recombinant proteins of MT isoforms with the 3× Flag tag, we performed Western blotting (WB) with the primary antibodies against MT3 or Flag tag, and this method of WB for MT3 was confirmed specifically to detect the MT3 protein. We treated ReNcell CX cells with several HIF-PH inhibitors and evaluated MT3 expression via real-time RT-PCR. We found that FG4592 significantly enhanced MT3 expression at both RNA and protein levels. FG4592 treatment increased the amount of hypoxia-inducible factor 1 alpha (HIF1α) binding to the MT3 promoter. These findings indicate that FG4592 induces MT3 expression via increased HIF1α. In conclusion, we found FG4592 to be an endogenous MT3 inducer in the cells of the nervous system in this study. The findings of this study are expected to lead to the development of new MT3-inducing drugs for neurodegenerative diseases based on FG4592.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"137-143"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490668","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":"Pharmacological Profile of NCP-322, a Novel G Protein-Coupled Receptor 119 Agonist, as an Orally Active Therapeutic Agent for Type 2 Diabetes Mellitus.","authors":"Hideki Nakamura, Tsuyoshi Endo, Makoto Tsuda","doi":"10.1248/bpb.b24-00737","DOIUrl":"10.1248/bpb.b24-00737","url":null,"abstract":"<p><p>Pharmacological activation of G protein-coupled receptor 119 (GPR119) produces pleiotropic beneficial effects, including the promotion of insulin secretion from pancreatic β-cells, enhancement of glucagon-like peptide (GLP)-1 secretion from intestinal L cells, glucose-dependent insulin secretion, and food intake and body weight gain suppression. Thus, GPR119 has attracted attention as a promising new target for type 2 diabetes mellitus (T2DM) treatment. Here, we identified a new small GPR119 agonist, NCP-322. This compound showed potent enhancing effects on insulin and GLP-1 secretion, which played a role in pancreatic β-cells and intestinal L cells. In the oral glucose tolerance test, NCP-322 administration reduced glycemic excursions that were only exhibited during hyperglycemia. Furthermore, NCP-322 administration did not induce hypoglycemia, the main side effect of antidiabetic drugs. These results suggest the promising therapeutic potential of NCP-322 for T2DM treatment.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"65-74"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078578","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}