Biological & pharmaceutical bulletin最新文献_第3页

Involvement of Ca_v3.2 T-Type Ca²⁺ Channels and the Role of Endogenous Estrogen in Pruritus: Evidence from a Fundamental Study and Cross-Sectional Analysis of Pharmacy Claims Data. Cav3.2 t型Ca2+通道的参与和内源性雌激素在瘙痒症中的作用：来自基础研究和药学索赔数据横断面分析的证据

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00671

Shotaro Kurahashi, Tomoyoshi Miyamoto, Hiroyuki Nishikawa, Emiri Mishima, Seira Matsunaga, Shiori Kino, Tomoya Ashida, Rina Minamino, Iyo Nishiyama, Maki Yamaguchi, Takashi Yamamoto, Mikio Sakakibara, Takuya Okada, Naoki Toyooka, Maho Tsubota, Fumiko Sekiguchi, Atsufumi Kawabata

{"title":"Involvement of Cav3.2 T-Type Ca2+ Channels and the Role of Endogenous Estrogen in Pruritus: Evidence from a Fundamental Study and Cross-Sectional Analysis of Pharmacy Claims Data.","authors":"Shotaro Kurahashi, Tomoyoshi Miyamoto, Hiroyuki Nishikawa, Emiri Mishima, Seira Matsunaga, Shiori Kino, Tomoya Ashida, Rina Minamino, Iyo Nishiyama, Maki Yamaguchi, Takashi Yamamoto, Mikio Sakakibara, Takuya Okada, Naoki Toyooka, Maho Tsubota, Fumiko Sekiguchi, Atsufumi Kawabata","doi":"10.1248/bpb.b25-00671","DOIUrl":"https://doi.org/10.1248/bpb.b25-00671","url":null,"abstract":"To clarify the roles of Cav3.2 T-type Ca2+ channels and endogenous estrogen in pruritus, we conducted a fundamental study employing mice and clinical cross-sectional analyses of pharmacy claims data. In mice, intradermal injection of sulfide (Na2S), a Cav3.2 enhancer, caused itch responses, an effect blocked by KTtp38, a T-type Ca2+ channel inhibitor, and deletion of Cav3.2 gene. KTtp38 also suppressed itch responses following intradermal histamine or chloroquine. The sulfide-induced itch responses in female mice decreased by ovariectomy and/or repeated treatment with letrozole, an aromatase inhibitor. Cross-sectional analyses of pharmacy claims data of 357972 female patients aged 18 years and older, obtained from nationwide branches of a chain pharmacy group, showed significantly lower prescription rates of topical steroids used for treatment of pruritus and/or dermatitis in women 55 years and older than in women under 55 years, and in the users than non-users of estrogen suppressants. Multivariate logistic regression analysis in the users and non-users of estrogen suppressants after propensity score matching indicated significant negative association of topical steroid prescription with the use of estrogen suppressants. Together, the present fundamental and clinical studies suggest the involvement of Cav3.2 and the promotive role of estrogen in pruritus in mice and/or humans.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"480-490"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462658","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

Rapid Screening for Detecting Genetically Modified Wheat by Loop-Mediated Isothermal Amplification. 环介导等温扩增检测转基因小麦的快速筛选

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00586

Shinya Kimata, Takumi Daimon, Miwa Takahashi, Kiyoko Miyatake, Yoshiki Ishida, Ken Iijima, Reona Takabatake

{"title":"Rapid Screening for Detecting Genetically Modified Wheat by Loop-Mediated Isothermal Amplification.","authors":"Shinya Kimata, Takumi Daimon, Miwa Takahashi, Kiyoko Miyatake, Yoshiki Ishida, Ken Iijima, Reona Takabatake","doi":"10.1248/bpb.b25-00586","DOIUrl":"https://doi.org/10.1248/bpb.b25-00586","url":null,"abstract":"We developed a loop-mediated isothermal amplification (LAMP)-based detection method for screening glyphosate-tolerant genetically modified (GM) wheat by targeting nucleotide sequences of the cauliflower mosaic virus 35S promoter (P35S) and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) from Agrobacterium tumefaciens strain CP4. LAMP products were detected using a Genie II real-time fluorometer. The limit of detection (LOD) was found to be ≤0.05% corresponding to 14 copies of target DNA. We also designed primer sets for detecting the endogenous reference sequences of wheat, proline-rich protein (PRP), and Waxy-D1. The combination of two LAMP primer sets targeting the PRP and Waxy-D1 sequences was useful for distinguishing common wheat from durum wheat. Single-stranded tag hybridization (STH) on a chromatography printed-array strip (C-PAS) system, a lateral-flow DNA chromatography technology, was used to improve efficiency. LAMP amplification was clearly detected by the STH C-PAS system at the LOD level, and duplex detection of P35S and PRP, and EPSPS and PRP was successfully achieved. This simple and quick method for screening GM wheat will be useful for preventing food and environmental contamination by unauthorized GM crops.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"557-563"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509489","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

Strain-Dependent and Site-Specific Differences in Irinotecan-Induced Skin Pigmentation in Mice. 伊立替康诱导小鼠皮肤色素沉着的菌株依赖性和位点特异性差异。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00047

Masashi Imai, Keiichi Hiramoto, Kazuya Ooi

{"title":"Strain-Dependent and Site-Specific Differences in Irinotecan-Induced Skin Pigmentation in Mice.","authors":"Masashi Imai, Keiichi Hiramoto, Kazuya Ooi","doi":"10.1248/bpb.b26-00047","DOIUrl":"https://doi.org/10.1248/bpb.b26-00047","url":null,"abstract":"Skin pigmentation induced by irinotecan-an anticancer drug-is clinically recognized; however, strain-dependent and skin site-specific differences in its manifestation have not been sufficiently investigated in mice. In this study, we compared melanocyte activation in plantar and genital skin following repeated irinotecan administration in three mouse strains: ICR (Slc:ICR), C57BL/6 (C57BL/6JmsSlc), and C3H (C3H/HeSlc). Melanocyte activation was assessed by 3,4-dihydroxyphenylalanine (DOPA) staining and immunofluorescence staining for microphthalmia-associated transcription factor (MITF). Although no obvious macroscopic pigmentation was observed in any strain or skin site, DOPA staining revealed an increased number of DOPA-positive cells in the plantar skin of all three mouse strains. By contrast, marked strain-dependent differences were observed in the genital skin: DOPA-positive cells were detected in ICR (Slc:ICR) and C57BL/6 (C57BL/6JmsSlc) mice but not in C3H (C3H/HeSlc) mice. MITF immunofluorescence staining results were consistent with the DOPA staining findings, demonstrating enhanced MITF signals in skin sites exhibiting melanocyte activation. Notably, the induction of DOPA-positive cells in the genital skin of albino ICR mice was an unexpected finding, suggesting that drug-induced melanocyte activation may occur independently of intrinsic melanin-producing capacity and instead involve upstream regulatory pathways. Collectively, these findings demonstrate clear strain-dependent and skin site-specific differences in irinotecan-induced melanocyte responses and provide important insights into the heterogeneity of drug-induced skin pigmentation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"720-724"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687537","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

Claims-Based Identification of Urinary Tract Infections among Patients in Long-Term Care Wards: A Retrospective Validation Study. 长期护理病房患者尿路感染的基于索赔识别：一项回顾性验证研究。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00803

Kohei Kumagai, Ryo Inose, Asako Kimura, Yuichi Muraki

{"title":"Claims-Based Identification of Urinary Tract Infections among Patients in Long-Term Care Wards: A Retrospective Validation Study.","authors":"Kohei Kumagai, Ryo Inose, Asako Kimura, Yuichi Muraki","doi":"10.1248/bpb.b25-00803","DOIUrl":"https://doi.org/10.1248/bpb.b25-00803","url":null,"abstract":"Claims data can be a resource for epidemiological evaluations in long-term care patients at increased risk of urinary tract infections (UTI) from antimicrobial-resistant bacteria. However, as claims data are primarily collected for administrative purposes, validating diagnostic accuracy is required. This study evaluated the validity of claims-based UTI identification in this patient population. This retrospective study included patients in long-term care wards between January 2023 and December 2024. Using diagnoses from electronic medical records as the gold standard, we evaluated the positive predictive value (PPV) of claims-based identification of UTI and catheter-associated UTI (CAUTI). Diagnoses were identified using International Classification of Diseases, 10th Revision (ICD-10) codes or urinalysis with microscopy, urine culture, antibiotic prescriptions, or indwelling bladder catheter procedures. Sensitivity analysis excluding suspected diagnoses was performed. Among 523 patients, 200 with at least one ICD-10 code for UTI were randomly selected. The PPV for identifying UTI using ICD-10 codes improved from 66.0 to 77.8% when additional codes were combined, and that for CAUTI improved from 45.5 to 86.8% with indwelling bladder catheter procedures. Excluding suspected diagnoses further improved the accuracy. Integrating ICD-10 codes, urinalysis with microscopy, urine culture, antibiotic prescriptions, and, when relevant, indwelling bladder catheter procedures while excluding suspected diagnoses enhances the validity of claims-based UTI identification and may be applicable to database studies using claims data.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"738-742"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761227","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

Ninjurin-1 Negatively Regulates Humoral and Cellular Immune Responses Induced by the Saponin-Based Adjuvant Quil-A in Mice. 忍尿素-1负向调控皂素基佐剂quila诱导的小鼠体液和细胞免疫反应。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00786

Meigui Shao, Michihiro Takahama, Naoki Takemura, Tatsuya Saitoh

{"title":"Ninjurin-1 Negatively Regulates Humoral and Cellular Immune Responses Induced by the Saponin-Based Adjuvant Quil-A in Mice.","authors":"Meigui Shao, Michihiro Takahama, Naoki Takemura, Tatsuya Saitoh","doi":"10.1248/bpb.b25-00786","DOIUrl":"https://doi.org/10.1248/bpb.b25-00786","url":null,"abstract":"Adjuvants are co-administered with antigens to enhance vaccine-induced protection. Saponins are plant-derived compounds with adjuvant properties, some of which are used in licensed vaccines. Macrophages and dendritic cells (DCs) exposed to saponin-based adjuvants have been reported to exhibit NLRP3-dependent interleukin-1 beta (IL-1β) release, and NLRP3 signaling has been shown to limit their adjuvant activity. Saponin-based adjuvants also induce plasma membrane rupture (PMR) and the release of high-molecular-weight intracellular molecules; however, the molecular mechanisms that mediate PMR and its impact on adjuvant-induced immune responses remain unclear. Here, we investigated the involvement of Ninjurin-1 (NINJ1), a key executor of PMR, in Quil-A-induced PMR and its immunological consequences. Upon stimulation with the saponin mixture Quil-A, peritoneal macrophages and bone marrow-derived dendritic cells (BMDCs) showed NLRP3-independent PMR but NLRP3-dependent IL-1β release. Quil-A-induced PMR was almost completely suppressed in Ninj1-/- peritoneal macrophages and BMDCs compared with wild-type cells, whereas IL-1β release remained unaffected by NINJ1 deficiency. Immunization with Quil-A and ovalbumin (OVA) increased OVA-specific serum immunoglobulin G (IgG), IgG2b, and IgG2c levels in Ninj1-/- mice compared with wild-type mice. Splenocytes from Ninj1-/- mice produced higher levels of interferon-gamma upon stimulation with class I- and class II-restricted OVA peptides than those from wild-type mice. Ninj1-/- mice also showed a higher frequency of OVA-bearing cells, particularly monocyte-derived DCs, in the draining lymph nodes. These results demonstrate that NINJ1 is critical for Quil-A-induced PMR and that NINJ1-mediated PMR negatively regulates Quil-A-induced humoral and cellular immune activation by restricting antigen delivery via antigen-presenting cells.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"371-379"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302053","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 Oxygen-Permeable Plates on Cytochrome P450 and Flavin-Containing Monooxygenase in HepaRG Spheroid Cultures. 透氧板对HepaRG球形培养细胞色素P450和含黄素单加氧酶的影响

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00489

Naoki Takaoka, Momoka Morita, Jun Takahashi, Katsuhiro Esashika, Shigeru Ohta, Seigo Sanoh

{"title":"Effects of Oxygen-Permeable Plates on Cytochrome P450 and Flavin-Containing Monooxygenase in HepaRG Spheroid Cultures.","authors":"Naoki Takaoka, Momoka Morita, Jun Takahashi, Katsuhiro Esashika, Shigeru Ohta, Seigo Sanoh","doi":"10.1248/bpb.b25-00489","DOIUrl":"https://doi.org/10.1248/bpb.b25-00489","url":null,"abstract":"Three-dimensional (3D) hepatocyte spheroid cultures offer an advanced in vitro model for investigating liver function and drug metabolism; however, oxygen diffusion limitations restrict spheroid size and functionality. In the present study, we developed a 3D spheroid culture system using HepaRG, a human hepatoma-derived cell line that retains drug-metabolizing enzymes, and oxygen-permeable plates composed of 4-polymethyl-1-pentene (PMP) to improve oxygen availability and metabolic performance. Morphological analysis showed enhanced spheroid circularity and compactness in the PMP culture, implying enhanced cell-cell adhesion. Hypoxic imaging revealed that PMP plate-based cultures markedly reduced central hypoxia, enabling the formation of spheroids with up to 20000 cells. Using clozapine, a low-clearance antipsychotic drug with limited metabolic elimination that is metabolized by monooxygenases, including CYP3A4 and flavin-containing monooxygenase (FMO), we observed an enhanced decline in clozapine levels in PMP plates compared with the clozapine levels seen in the conventional polystyrene plates. Furthermore, the mRNA and protein-expression levels of CYP3A4 and FMO3 were upregulated in the spheroids cultured on PMP plates. These results suggest that improved oxygenation enhances hepatic functionality in 3D cultures by maintaining cell viability and promoting the expression of drug-metabolizing enzymes. Therefore, the PMP plate-based spheroid model offers a practical and physiologically relevant platform for investigating drug metabolism and hepatotoxicity.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"90-98"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984334","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

Survey of Pharmacy Students' Awareness of Medication Overuse Headache. 药学专业学生对药物滥用头痛意识的调查。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00412

Shiori Yamada, Koki Takeda, Nobuhito Shibata, Asako Nishimura

{"title":"Survey of Pharmacy Students' Awareness of Medication Overuse Headache.","authors":"Shiori Yamada, Koki Takeda, Nobuhito Shibata, Asako Nishimura","doi":"10.1248/bpb.b25-00412","DOIUrl":"https://doi.org/10.1248/bpb.b25-00412","url":null,"abstract":"Medication overuse headache (MOH) is a condition in which excessive analgesic use induces headache. Recent studies have reported that simple advice significantly reduces the number of days patients use analgesics and the frequency of headaches. Pharmacists are expected to support patient self-medication and contribute to the prevention and treatment of MOH. This study was conducted at Doshisha Women's College of Liberal Arts and Osaka Medical and Pharmaceutical University with the aim of clarifying the current state of pharmacy students' awareness of MOH and related issues. The survey consisted of 28 items, including true or false, open-ended, and multiple-choice questions on MOH. Of the 341 students who responded, 49.9% had heard of the term MOH, and 84.5% recognized the importance of pharmacists in preventing and mitigating MOH. The correct answer rate for the true or false questions was 78.3%, but only 16.4% of the students responded that their current understanding of MOH allows them to provide care to patients, and only 7.9% reported having learned about ways to support patients with MOH. These findings indicate that the knowledge about MOH is not yet fully connected to patient support. Therefore, opportunities to learn about the practical aspects of pharmacist involvement in MOH management on campus may be limited. In the future, universities may consider providing more structured opportunities for pharmacy students to learn the practical aspects of pharmacist-led patient support.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"467-472"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376037","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

The Differences in Gut Microbiota Due to Dietary Habits Affect the Onset of Disease Pathology in a Dextran Sulfate Sodium-Induced Colitis Model. 饮食习惯引起的肠道菌群差异影响葡聚糖硫酸钠诱导结肠炎模型的发病病理

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00399

Chiho Takahara, Norihiko Tabuchi, Hirofumi Inoue, Honoka Itoh, Yuka Koike, Kazuyoshi Kawazoe, Kento Takayama

{"title":"The Differences in Gut Microbiota Due to Dietary Habits Affect the Onset of Disease Pathology in a Dextran Sulfate Sodium-Induced Colitis Model.","authors":"Chiho Takahara, Norihiko Tabuchi, Hirofumi Inoue, Honoka Itoh, Yuka Koike, Kazuyoshi Kawazoe, Kento Takayama","doi":"10.1248/bpb.b25-00399","DOIUrl":"10.1248/bpb.b25-00399","url":null,"abstract":"Ulcerative colitis (UC), an inflammatory bowel disease (IBD) involving colon ulceration and erosion, is challenging to prevent or stop. The findings highlighted the crucial role of gut microbiota imbalance in IBD development. This study aimed to investigate the influence of five dietary patterns on the onset or progression of UC in a dextran sulfate sodium (DSS)-induced colitis model by altering the gut microbiota. The results showed that the disease condition worsened most significantly in the high-protein diet group, followed by the high-fiber diet group. Before UC induction, these severely affected groups exhibited a higher proportion of Bacteroidota (Bacteroidetes) and a lower proportion of Bacillota (Firmicutes) than the groups in which the condition did not worsen. A reduced Firmicutes/Bacteroidetes ratio has been linked to the onset and progression of IBD. Upon DSS administration, the abundance of Bacteroidota increased in all dietary groups. Analyses revealed that as the disease progressed, the levels of the inflammatory cytokine tumor necrosis factor-α (TNF-α) increased. Specifically, the high-protein group showed elevated expression of interleukin-6 (IL-6) and transforming growth factor β1 (TGF-β1), which are involved in Th17 cell induction, and increased IL-17A secretion, indicating an amplified Th17-mediated inflammatory response. The expression of the tight junction protein occludin was reduced in the high-fiber and high-protein groups. These groups also demonstrated a significant decrease in beneficial short-chain fatty acids, acetate, and propionate. These findings suggest that dietary habits significantly impact the onset and progression of UC, and that the gut microbiota composition before disease onset may play a crucial role in this process.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"438-451"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353502","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

Chronotropic, Inotropic, and Lusitropic Effects of Flavonoids. 黄酮类化合物的变时、变肌和变肌作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00486

Kazuo Noguchi, Chinami Ueda, Saki Umeda, Haruna Kanae, Maika Seki, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka

{"title":"Chronotropic, Inotropic, and Lusitropic Effects of Flavonoids.","authors":"Kazuo Noguchi, Chinami Ueda, Saki Umeda, Haruna Kanae, Maika Seki, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka","doi":"10.1248/bpb.b25-00486","DOIUrl":"https://doi.org/10.1248/bpb.b25-00486","url":null,"abstract":"We summarized the recent findings on the acute myocardial effects of several flavonoids, whose long-term beneficial effects through antioxidant activity has attracted attention. Polymethoxyflavones, such as sudachitin, demethoxysudachitin, and nobiletin, showed chronotropic and inotropic effects; the effects were milder than those of β-adrenoceptor agonists. Their strength of action appeared to be related to the number of methoxy groups in the chemical structure. Sudachitin also showed strong vasorelaxant effect causing full relaxation. Quercetin showed positive lusitropic effects in both normal and diabetic myocardium; this was probably mediated by enhancement of Ca2+ sequestration into the sarcoplasmic reticulum by the Ca2+ ATPase. Hesperetin inhibited the spontaneous firing of action potential in the pulmonary vein myocardium; the chronotropic inotropic and lusitropic effects were weak or not observed. Thus, each flavonoid compound has characteristic pharmacological effects probably through their action on specific cellular targets. Further investigation of their effects would provide insights for the development of therapeutic agents for heart diseases such as heart failure and arrhythmia.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"12-23"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899166","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

Antiarrhythmic Potential of the β-Adrenoceptor Blocker Metoprolol against Dofetilide-Induced Torsades de Pointes in Anesthetized Bradycardic Rabbits. β-肾上腺素受体阻滞剂美托洛尔对麻醉心动过缓兔多非利特诱发的点扭转的抗心律失常电位。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00450

Satoshi Kawakami, Yuki Ishimaru, Megumi Aimoto, Yoshinobu Nagasawa, Akira Takahara

{"title":"Antiarrhythmic Potential of the β-Adrenoceptor Blocker Metoprolol against Dofetilide-Induced Torsades de Pointes in Anesthetized Bradycardic Rabbits.","authors":"Satoshi Kawakami, Yuki Ishimaru, Megumi Aimoto, Yoshinobu Nagasawa, Akira Takahara","doi":"10.1248/bpb.b25-00450","DOIUrl":"https://doi.org/10.1248/bpb.b25-00450","url":null,"abstract":"We have established a proarrhythmic rabbit model of acute atrioventricular block (AVB) with severe bradycardia to detect delayed rectifier K+ channel current (IKr) blocker-induced torsade de pointes (TdP). To better understand the role of β-adrenoceptors in this model, we investigated the effect of the β-adrenoceptor blocker metoprolol against an IKr blocker dofetilide-induced TdP. AVB was induced by catheter ablation under isoflurane anesthesia, and the ventricles were electrically paced at a constant rate of 60 beats/min throughout the experiments. Monophasic action potentials (MAPs) were recorded from the right ventricle. In the non-treated control rabbits (n = 5), intravenous administration of an IKr blocker dofetilide (25 µg/kg) prolonged the MAP duration (MAP90) by 90 ± 38 ms, which led to the induction of TdP in four of the five animals. In rabbits receiving the β-adrenoceptor blocker metoprolol (10 µg/kg/min, n = 5), the same dose of dofetilide prolonged MAP90 by 205 ± 31 ms, whereas TdP did not occur in this group. Meanwhile, the incidence of dofetilide-induced R-on-T-type premature ventricular contractions, representing an arrhythmogenic trigger, was lower in metoprolol-treated rabbits than in non-treated control rabbits. These results indicate that metoprolol exerted an overall antiarrhythmic effect by strongly suppressing TdP generation induced by dofetilide, despite its proarrhythmic action of enhancing repolarization prolongation. This highlights the critical role of β-adrenoceptors in facilitating arrhythmogenic triggers under conditions of excessive repolarization delay.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"34-39"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899184","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