Basic & Clinical Pharmacology & Toxicology最新文献_第6页

Levothyroxine Treatment During Pregnancy: A Metabolomics Study. 妊娠期间左旋甲状腺素治疗：代谢组学研究。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-07-01 DOI: 10.1111/bcpt.70246

Olli Kärkkäinen, Heidi Sahlman, Leea Keski-Nisula, Jaana Rysä

{"title":"Levothyroxine Treatment During Pregnancy: A Metabolomics Study.","authors":"Olli Kärkkäinen, Heidi Sahlman, Leea Keski-Nisula, Jaana Rysä","doi":"10.1111/bcpt.70246","DOIUrl":"10.1111/bcpt.70246","url":null,"abstract":"Levothyroxine is one of the most prescribed drugs during pregnancy. Our aim was to determine levothyroxine treatment-associated changes in the metabolite profiles and link these to the health of the newborn. Metabolite profiles of 118 levothyroxine-treated and 118 healthy control pregnancies were determined with nuclear magnetic resonance-based metabolomics from (1) umbilical cord blood samples, (2) samples collected during the first trimester and (3) during delivery from the pregnant women. There was a modest negative correlation between cord blood thyroid stimulating hormone (CBTSH) concentrations and Apgar scores at the 1 and 5 min time points in levothyroxine-treated pregnancies. Furthermore, the concentrations of cord serum metabolites linked with anaerobic glycolysis, for example, lactate, citrate and glycerol, as well as all measured amino acids were negatively associated with Apgar scores. Moreover, cord serum concentrations of lactate, glycerol and alanine were modestly correlated with CBTSH concentrations in the levothyroxine-treated pregnancies. In the during delivery samples, there was small but significant decrease in cholesteryl esters, cholesterol and phospholipids in small very low-density lipoprotein in the levothyroxine-treated pregnancies. In conclusion, levothyroxine treatment during pregnancy was associated with relatively small alterations in the blood metabolite profiles during pregnancy and labour.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":"e70246"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986284","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

Xiao-Jie-An Capsule Attenuates Oestrogen- and Progestogen-Induced Mammary Gland Hyperplasia by Modulating Sex Hormone Levels and Reducing Inflammatory Response. 小洁安胶囊通过调节性激素水平和减少炎症反应来减轻雌激素和孕激素诱导的乳腺增生。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-07-01 DOI: 10.1111/bcpt.70252

Kecheng Tang, Yi Ying, Feng Lu, Jihan Liu, Yiru Chen, Hang Zhang, Nannan Li, Zhizhen Huang, Baoxue Yang, Min Li

{"title":"Xiao-Jie-An Capsule Attenuates Oestrogen- and Progestogen-Induced Mammary Gland Hyperplasia by Modulating Sex Hormone Levels and Reducing Inflammatory Response.","authors":"Kecheng Tang, Yi Ying, Feng Lu, Jihan Liu, Yiru Chen, Hang Zhang, Nannan Li, Zhizhen Huang, Baoxue Yang, Min Li","doi":"10.1111/bcpt.70252","DOIUrl":"10.1111/bcpt.70252","url":null,"abstract":"Xiao-Jie-An capsule (XJA), a traditional Chinese medicine formulation consisting of six herbal components, has been used to treat MGH for a long time. Aim of this study was to determine the therapeutical impact of XJA on an MGH rat model and the underlying mechanism. The MGH model was established by daily intramuscular injections of estradiol benzoate (0.5 mg/kg) for 25 days, then progesterone (5 mg/kg) for 5 days. Network pharmacological analysis and molecular biological assays were conducted to determine the pharmacological targets of XJA. XJA significantly reduced nipple height and diameter and effectively suppressed histopathological hallmarks of MGH. Additionally, XJA markedly decreased the expression of Ki67 and the expression of proliferating cell nuclear antigen, increased the terminal deoxynucleotidyl transferase dUTP nick-end labelling and lowered the Bcl-2/Bax ratio in mammary tissue of MGH rats. Furthermore, XJA modulated endocrine disorder by reducing blood follicle-stimulating hormone and estradiol (E2), while increasing luteinising hormone and androgen concentrations. Concomitant anti-inflammatory effects were found by decreased pro-inflammatory cytokines IL-1β, IL-2, IL-6 and TNF-α; inhibited TLR4 expression and attenuated NF-κB phosphorylation. Our experimental results suggest that XJA effectively mitigated oestrogen- and progesterone-induced MGH by modulating sex hormone levels and reducing inflammatory response.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":"e70252"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013257","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

Pharmacological Inhibition of Cav2.2 Channels by Recombinant Phα1β Toxin (CTK01512-2) 重组Phα1β毒素（CTK01512-2）对Cav2.2通道的药理抑制作用

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-07-01 DOI: 10.1111/bcpt.70268

Natália Virtude Carobin, Thamyris Reis Moraes, Luana Assis Ferreira, Christopher Kushmerick, Marcus Vinícius Gomez, Célio José Castro Junior

{"title":"Pharmacological Inhibition of Cav2.2 Channels by Recombinant Phα1β Toxin (CTK01512-2)","authors":"Natália Virtude Carobin, Thamyris Reis Moraes, Luana Assis Ferreira, Christopher Kushmerick, Marcus Vinícius Gomez, Célio José Castro Junior","doi":"10.1111/bcpt.70268","DOIUrl":"10.1111/bcpt.70268","url":null,"abstract":"Phα1β is a peptide toxin originally isolated from the venom of the Brazilian spider Phoneutria nigriventer, known for its potent analgesic effects in preclinical models of acute and chronic pain. However, clinical translation has been limited by production constraints. A recombinant analogue, CTK01512-2, was developed and has demonstrated antinociceptive efficacy comparable to the native toxin in diverse experimental models. In this study, we examined the effects of CTK01512-2 on N-type voltage-gated calcium channels (Cav2.2) expressed in transiently transfected HEK-293 cells and confirmed its antinociceptive action in a mouse model of neuropathic pain. CTK01512-2 induced a partial (~50%) and reversible inhibition of Cav2.2-mediated calcium currents, with a calculated half-maximal inhibitory concentration (IC50) of 3.94 nM. In contrast to ω-conotoxin MVIIA, a clinically approved irreversible Cav2.2 blocker, CTK01512-2 allowed current recovery after washout, indicating reversible binding. Notably, the toxin did not significantly alter the voltage dependence or kinetics of channel activation. These findings identify CTK01512-2 as a selective and reversible Cav2.2 channel modulator, underscoring its therapeutic potential as a novel analgesic agent for chronic pain management.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Medication Burden: Beyond Counts to Recognize Polypharmacy as an Inherent Part of Living With Chronic Kidney Disease 药物负担：认识到多重用药是慢性肾病患者生活的固有部分。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-07-01 DOI: 10.1111/bcpt.70260

Morten Baltzer Houlind, Helle Gybel Juul-Larsen, Charlotte Strandhave, Niels Westergaard, Anne Estrup Olesen

{"title":"Medication Burden: Beyond Counts to Recognize Polypharmacy as an Inherent Part of Living With Chronic Kidney Disease","authors":"Morten Baltzer Houlind, Helle Gybel Juul-Larsen, Charlotte Strandhave, Niels Westergaard, Anne Estrup Olesen","doi":"10.1111/bcpt.70260","DOIUrl":"10.1111/bcpt.70260","url":null,"abstract":"Medication burden in older patients with chronic kidney disease (CKD) is substantial, and simple medication counts are insufficient for identifying those at elevated risk of inappropriate prescribing. This study characterized medication burden by assessing the number of medications, potentially inappropriate medications (PIMs) and anticholinergic burden in dialysis and non-dialysis patients with CKD aged ≥ 65 years. This retrospective study included patients with a CKD diagnosis who had hospital contact at the Department of Nephrology, Aalborg University Hospital, Denmark, between January and December 2022. Patients were classified as receiving dialysis or not, and polypharmacy and hyper-polypharmacy were defined as ≥ 5 and ≥ 10 medications, respectively. PIMs were identified using the EU(7)-PIM list, and anticholinergic burden was evaluated using the ACB scale with a cut-off of ≥ 3 points. In total, 140 dialysis patients and 534 non-dialysis patients were included. Polypharmacy was present in all dialysis patients and in 83% of non-dialysis patients, whereas hyper-polypharmacy affected 89% and 56%, respectively. Dialysis patients had a higher median number of PIMs (3 vs. 2) and a greater proportion with an ACB score ≥ 3 (44% vs. 27%). Proton pump inhibitors (PPIs), opioids and non-benzodiazepine hypnotics (Z-drugs) were identified as common PIMs, whereas bladder antimuscarinics (tolterodine and solifenacin), sedating antihistamines (clemastine and promethazine) and antipsychotics with anticholinergic properties (quetiapine) were the most frequently used medications with strong anticholinergic properties. In conclusion, medication burden in patients with CKD is high, and incorporating PIMs and ACB scores may identify prescribing risks not captured by medication counts alone.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Contribution of Countries and International Collaboration in Clinical Pharmacology Research. A Cross-Sectional Bibliometric Study of Six Top Ranked Specialty Society Journals 临床药理学研究的国家贡献和国际合作。六种排名靠前的专业学会期刊的横断面文献计量研究。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-07-01 DOI: 10.1111/bcpt.70269

Rafael Dal-Ré, Lucía Llanos, Ignacio Mahillo-Fernández

{"title":"Contribution of Countries and International Collaboration in Clinical Pharmacology Research. A Cross-Sectional Bibliometric Study of Six Top Ranked Specialty Society Journals","authors":"Rafael Dal-Ré, Lucía Llanos, Ignacio Mahillo-Fernández","doi":"10.1111/bcpt.70269","DOIUrl":"10.1111/bcpt.70269","url":null,"abstract":"<div>\u0000 \u0000 There are no bibliometrics analyses on articles published in clinical pharmacology journals. We aimed to determine the countries in which authors of original investigations or meta-analyses were based and their international collaboration. This is a cross-sectional study conducted in six journals linked to learned clinical pharmacology societies/associations. For each journal, we started with the June-2025 issue and searched backward for articles meeting the selection criteria until 100 were identified or the January-2024 issue was reached. To calculate the credit by country, we used the complete fractionalized counting (CFC) method for assessing authors' contribution considering only the country of the authors included in the byline. CFC awards 1 credit among all authors and countries. A total of 503 articles were included in the analysis: 100 from four journals and 79 and 24 from the other two. Investigators from 66 countries from all continents contributed as authors; 46 countries provided lead authors. All but one were multi-authored articles; 9% were authored by international teams (range among the six journals: 16%–41%). Of the 503 credits, top countries were the United States (99.14), China (76.14), Japan (31.65), Denmark (28.69) and the Netherlands (27.29). The 17 EU countries obtained 151.86 credits (30.2% of the total). Among the top 25 countries, only five were not high-income countries. This exploratory analysis showed that with limited international collaboration, the authors of these studies worked mainly in wealthy countries, except for China.\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366557","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

Identifying Current Needs in Paediatric Pharmacoepidemiology: Insights From the NorPEN 2025 Workshop 确定儿科药物流行病学的当前需求：来自NorPEN 2025研讨会的见解。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-07-01 DOI: 10.1111/bcpt.70270

Elin Kimland, Rikke Wesselhoeft, Jenny Kindblom, Elin Dahlén

引用次数: 0

Modulation of Respiratory Diseases by the Endocannabinoid System: A Therapeutic Perspective 内源性大麻素系统对呼吸系统疾病的调节：一个治疗的角度

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-06-27 DOI: 10.1111/bcpt.70267

Shiyuan Qin, Siyang Shen, Xiaoqin Chen, Pengfei Yi, Bendong Fu, Luyuan Peng

{"title":"Modulation of Respiratory Diseases by the Endocannabinoid System: A Therapeutic Perspective","authors":"Shiyuan Qin, Siyang Shen, Xiaoqin Chen, Pengfei Yi, Bendong Fu, Luyuan Peng","doi":"10.1111/bcpt.70267","DOIUrl":"https://doi.org/10.1111/bcpt.70267","url":null,"abstract":"Respiratory system diseases represent a major global health burden, characterized by high prevalence and significant morbidity and mortality. The respiratory tract's direct and continuous exposure to the external environment makes it particularly vulnerable to pathogens, pollutants and other injurious agents. This exposure often triggers excessive inflammatory responses and compromises the integrity of the air-blood barrier, leading to impaired gas exchange, hypoxia and respiratory failure. Therefore, modulating pulmonary inflammation and enhancing barrier function are critical therapeutic objectives. The endocannabinoid system, a ubiquitous signalling network comprising cannabinoid receptors, endogenous ligands and metabolic enzymes, has emerged as a crucial modulator of these processes. This review summarizes the role of the ECS in major respiratory diseases, including asthma, pulmonary fibrosis, respiratory syncytial virus infection and acute lung injury. The evidence highlights the therapeutic potential of targeting the ECS through strategies such as receptor-specific ligands and inhibitors of endocannabinoid-degrading enzymes. However, the context-dependent nature of ECS modulation necessitates precise intervention. Future efforts should focus on developing selective therapeutics and validating their efficacy in clinical settings, positioning the ECS as a sophisticated target for innovative respiratory disease management.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association Between Urinary Heavy Metals and Developmental Disorders in Children Aged 6–15 Years: A Study Based on the NHANES Database 6-15岁儿童尿液重金属与发育障碍的关系：基于NHANES数据库的研究

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-06-25 DOI: 10.1111/bcpt.70266

Yanping Liao, Lingling Zhan, Hong Li

{"title":"Association Between Urinary Heavy Metals and Developmental Disorders in Children Aged 6–15 Years: A Study Based on the NHANES Database","authors":"Yanping Liao, Lingling Zhan, Hong Li","doi":"10.1111/bcpt.70266","DOIUrl":"https://doi.org/10.1111/bcpt.70266","url":null,"abstract":"<div>\u0000 \u0000 This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2018, enrolling a total of 4525 children and adolescents aged 6–15 years. Weighted logistic regression, weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) models were applied to explore the associations between nine urinary heavy metals (UHMs) and developmental disorders (DDs). After full covariate adjustment, urinary lead (Pb) (OR = 1.30, 95% CI: 1.10–1.54) and urinary antimony (Sb) (OR = 1.41, 95% CI: 1.18–1.69) were found to be positively correlated with DDs. Combined exposure models further identified a positive joint relationship between the mixture of UHMs and DDs, with Pb and Sb serving as the major contributing components. Sensitivity analyses that defined DDs solely based on receipt of special education or early intervention services yielded consistent findings. Given the limitations inherent to the cross-sectional design, single-spot urine sampling and heterogeneous outcome definitions, the present findings can only demonstrate correlational relationships, and further longitudinal investigations are required for conclusive validation.\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148324611","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

Making Transparency and Reproducibility a Hallmark of Nordic Real-World Evidence 使透明度和可重复性成为北欧真实世界证据的标志

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-06-21 DOI: 10.1111/bcpt.70265

Anton Pottegård

引用次数: 0

The Effect of Dopaminergic Medication on Impulse Control and Compulsive Behaviour: A Translational Perspective 多巴胺能药物对冲动控制和强迫行为的影响：一个翻译的视角。

IF 3.6 4区医学

Basic & Clinical Pharmacology & Toxicology Pub Date : 2026-06-14 DOI: 10.1111/bcpt.70264

Mirjam Wolfschlag, Elena Espa, Kevin Oliveira Hauer, Jonathan Timpka, Ruben Smith, Per Odin, Maria Angela Cenci, Anders Håkansson

{"title":"The Effect of Dopaminergic Medication on Impulse Control and Compulsive Behaviour: A Translational Perspective","authors":"Mirjam Wolfschlag, Elena Espa, Kevin Oliveira Hauer, Jonathan Timpka, Ruben Smith, Per Odin, Maria Angela Cenci, Anders Håkansson","doi":"10.1111/bcpt.70264","DOIUrl":"10.1111/bcpt.70264","url":null,"abstract":"Dopaminergic medication used in disorders like Parkinson's disease (PD) and restless legs syndrome can cause impulsive-compulsive behaviour (ICB), often with strong negative effects on patients' quality of life. This narrative review presents translational evidence on iatrogenic ICB, taking findings from epidemiological, clinical, neuroimaging and preclinical studies into consideration. Epidemiological and clinical studies find dopamine agonists with high D2/3-selectivity to be most strongly linked to ICB. Their effect on ICB has often been shown to be dose-dependent, but the impact of combining different dopaminergic drugs or applying extended-release formulations is less clear. Intervention studies support tapering or replacing dopamine agonists for ICB reduction, whereas no efficacious pharmacotherapy has been identified for ICB treatment specifically. Adequate animal models for mimicking different types of ICB are available, and point, in line with human neuroimaging studies, towards an involvement of striatum and prefrontal cortex in iatrogenic ICB. Overall, complementary research designs have led to profound evidence regarding the occurrence of ICB in PD and establishing methods transferable to other, less-studied patient populations. A combined approach integrating insights from human studies and animal models could contribute to developing dopaminergic drugs with lower ICB risk but also specific pharmacotherapies for impulsivity or compulsivity in the future.","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"139 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0