Biological & pharmaceutical bulletin最新文献

{"title":"Change in Vancomycin Absorption after Intraperitoneal Injection and Correlation between Intraperitoneal Vancomycin Absorption and Peritoneal Equilibration Test Score in Mice with Peritoneal Injuries.","authors":"Akihiro Moritsuka, Hirotaka Miyamoto, Yukina Takahashi, Haruna Hirata, Yuki Kawauchi, Shintaro Fumoto, Koyo Nishida","doi":"10.1248/bpb.b24-00687","DOIUrl":"https://doi.org/10.1248/bpb.b24-00687","url":null,"abstract":"<p><p>Peritonitis is a serious complication in peritoneal dialysis patients and requires antibiotic administration. Intraperitoneal vancomycin is an empiric therapy for peritonitis caused by Gram-positive cocci; however, there is no way to predict vancomycin absorption after intraperitoneal administration. Therefore, we aimed to evaluate the changes in vancomycin absorption after intraperitoneal injection into mice with chlorhexidine gluconate (CG) induced peritoneal injuries. Additionally, we examined the correlation between intraperitoneal vancomycin absorption and peritoneal equilibration test (PET) score. PET score was determined using glucose concentration in the peritoneal dialysis fluid at each dwell time (D_t) and D₂ (2 h of dwell time)/D₀ (0 h of dwell time) glucose ratio. Vancomycin was injected into the peritoneal cavity of mice, blood was collected after 1-8 h, and peritoneal fluid was recovered. The residual ratio of intraperitoneal vancomycin was significantly decreased in the CG group at all time points compared to that in the vehicle group. CG group significantly exhibited higher serum vancomycin concentrations than the vehicle group, and the maximum serum concentration increased depending on CG concentration, with 0.05 and 0.1% CG groups showing 3.9- and 6.1-times higher vancomycin concentrations, respectively, than the vehicle group. A significant correlation was observed between the D_t/D₀ glucose ratios and residual vancomycin ratios in the peritoneal fluid 2 or 6 h after intraperitoneal injection. A good correlation was observed between the D₂/D₀ glucose and residual vancomycin ratios 6 h after intraperitoneal vancomycin injection. Thus, PET score can predict residual intraperitoneal vancomycin, aiding in dosing decisions.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"80-85"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078561","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":"Longitudinal Trend in Antimicrobial Susceptibility among Haemophilus influenzae: A Single-Centre Study in Japan.","authors":"Takeaki Wajima, Naoki Hara, Emi Tanaka, Atsuko Shirai, Kei-Ichi Uchiya","doi":"10.1248/bpb.b24-00715","DOIUrl":"https://doi.org/10.1248/bpb.b24-00715","url":null,"abstract":"<p><p>Haemophilus influenzae presents significant concerns regarding antimicrobial resistance. The circumstances surrounding H. influenzae have been changing owing to changes in antimicrobial usage. In the present study, to determine the current situation of H. influenzae, the antimicrobial susceptibility trends were investigated. In total, 21 clinical isolates were analyzed. Antimicrobial susceptibility measured using the broth dilution method was compared with that reported in previous studies at the same hospital. Quinolone low-susceptible isolates were further characterized by multi-locus sequence typing. Upon comparing the susceptibility data in 2022 with those in the past 15 years, the number of β-lactamase nonproducing ampicillin-resistant isolates was decreased. Regarding recent changes, β-lactam-susceptible isolates were found to have gradually increased every year. However, β-lactamase-producing isolates did not decrease. In particular, the ratio of β-lactamase-producing amoxicillin and clavulanic acid-resistant isolates in 2022 was the highest among all the years studied. Moreover, quinolone low-susceptible isolates were still present, suggesting that these isolates could have been indigenized in the community. Furthermore, a β-lactamase-producing amoxicillin and clavulanic acid-resistant isolate was found to have emerged among the quinolone low-susceptibility isolates. At first glance, these findings indicate that antimicrobial resistance has decreased among H. influenzae in clinical settings. However, β-lactamase-producing isolates and quinolone low-susceptible isolates have remained at a constant rate in the community.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"60-64"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078576","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":"https://doi.org/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}

{"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":"https://doi.org/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":"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":"https://doi.org/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":"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":"Molecular Epidemiological Features of Methicillin-Resistant Staphylococcus aureus in Japan.","authors":"Hidemasa Nakaminami","doi":"10.1248/bpb.b23-00685","DOIUrl":"https://doi.org/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":"Identification of Bioactive Compounds and Potential Mechanisms of Fuzi in the Treatment of Ulcerative Colitis by Integrating Network Pharmacology and Experimental Validation.","authors":"Miaomiao Ma, Leshi Liang, Meihong Lin, Canhua Luo, Xingfeng Deng, Changhui Yu","doi":"10.1248/bpb.b24-00590","DOIUrl":"https://doi.org/10.1248/bpb.b24-00590","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease without efficient treatment. Fuzi has anti-inflammatory and immunomodulatory properties. However, the bioactive compounds and mechanisms of fuzi in the treatment of UC are not completely understood. The active components of fuzi were retrieved from Traditional Chinese Medicine Database System Pharmacology and Analysis Platform; PharmMapper was used to predict the targets of the active components of fuzi; UC-related disease targets were obtained from Online Mendelian Inheritance in Man and Genecards databases, and Venny 2.1 was used to obtain common targets; Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on the common targets using R 4.0.2. STRING and Cytoscape 3.9.0 was used to construct a protein-protein interaction (PPI) network for the intersection targets. We then determined the role of the candidate molecule from fuzi, Higenamine (Hig), in a mouse model of dextran sulfate sodium (DSS)-induced colitis. In total, 21 active components and 420 corresponding targets of fuzi were obtained, of which 224 common targets were identified by intersecting with UC-related targets. The GO, KEGG, and PPI results suggested that fuzi and Hig may target RAC-alpha serine/threonine-protein kinase (AKT) to regulate the phosphoinositide-3-kinase (PI3K)/AKT pathway in UC. Animal experiments have shown that Hig treatment greatly reduced DSS-induced colitis, as measured by the disease activity index score, colonic inflammation, and intestinal barrier integrity. Mechanistically, Hig downregulated the DSS-induced PI3K-AKT signaling pathway by inhibiting AKT phosphorylation. Altogether, Hig alleviated DSS-induced colitis in mice, possibly by inhibiting colon inflammation and improving the intestinal barrier by regulating the PI3K-AKT signaling pathway. The active component Hig from fuzi is likely to play a role in the treatment of UC.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"246-261"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655970","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":"Evaluating the Efficacy of Premedication in Preventing Hypersensitivity Reactions to Nonionic Contrast Agents.","authors":"Shinya Suzuki, Shungo Imai, Akinori Omata, Tadamasa Kamimura, Hayato Kizaki, Takuma Koinuma, Satoko Hori","doi":"10.1248/bpb.b24-00808","DOIUrl":"https://doi.org/10.1248/bpb.b24-00808","url":null,"abstract":"<p><p>Iodine-based contrast agents can induce various acute hypersensitivity reactions ranging from mild itching or vomiting shortly after administration to severe hypotension or loss of consciousness. In Japan, steroid premedication is commonly used to prevent acute hypersensitivity reactions. However, little clear evidence supporting its efficacy is available. In this study, we evaluated the effectiveness of premedication for acute hypersensitivity reactions induced by nonionic iodine contrast agents using propensity score matching. The participants included patients who were administered nonionic iodine contrast agents at Yokohama City Minato Red Cross Hospital between April 1, 2016 and March 31, 2022. Only first-time patients with no history of hypersensitivity reactions to contrast agents were included. The patients were classified into premedication and non-premedication groups, and the incidence proportions of acute hypersensitivity reactions were compared after matching. Of the 19976 patients, 422 (211 in each group) were matched. In the premedication group, 7 cases (3.32%) of hypersensitivity reactions occurred. In contrast, only 2 cases (0.95%) were observed in the non-premedication group. The odds ratio for the occurrence of hypersensitivity reactions in the premedication group was 3.500 (95% confidence interval, 0.727-16.848), with no significant difference. Therefore, premedication did not demonstrate the efficacy in preventing acute hypersensitivity reactions induced by nonionic iodine contrast agents. Based on the results of this study and guidelines, a recommendation for premedication was not reached for patients with a history of allergies, including asthma and atopy, as well as those with a history of drug or food allergies.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"241-245"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613328","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":"Preventive Effects of Psoraleae Semen Extracts on Cognitive Dysfunction in Alzheimer's Disease Model App^NL-P-F Mice.","authors":"Genki Hiramatsu, Reina Mizutani, Kazufumi Toume, Yosuke Inada, Masahito Sawahata, Daisuke Uta, Katsuko Komatsu, Toshiaki Kume","doi":"10.1248/bpb.b24-00773","DOIUrl":"https://doi.org/10.1248/bpb.b24-00773","url":null,"abstract":"<p><p>Oxidative stress and neuroinflammation accompanied by microglial activation are increased in Alzheimer's disease (AD) and contribute to the pathogenesis of AD. Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a master transcription factor that acts as an endogenous defense mechanism against oxidative stress and inflammation and is a potential target for preventing AD. Psoraleae Semen (PS) reportedly has antioxidant and anti-inflammatory effects. This study aimed to examine the effects of PS extract (PSE) on Nrf2 activation and prevention of cognitive dysfunction in App^NL-P-F AD model mice. The effects of PSE on antioxidant response element (ARE) activity and cytoprotection in PC12 cells and on microglial activation in BV-2 cells were evaluated. PSE showed high ARE activity and prevented 6-hydroxydopamine-induced cytotoxicity in PC12 cells. Moreover, PSE suppressed lipopolysaccharide-induced nitric oxide production in BV-2 cells. Oral administration of PSE prevented cognitive dysfunction in App^NL-P-F mice without affecting motor function. Our results support that PSE can contribute to the development of new preventive and therapeutic agents for AD focusing on Nrf2 activation.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"75-79"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078580","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}