Pharmacology Research & Perspectives最新文献_第8页

Co-created in vivo pharmacology practical classes using the novel organism Lumbriculus variegatus 利用新型生物 Lumbriculus variegatus 共同创建体内药理学实践课程

IF 2.6 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-08 DOI: 10.1002/prp2.1158

Julanta J. Carriere, Nia A. Davies, Margaret R. Cunningham, Melisa J. Wallace, Aidan Seeley

{"title":"Co-created in vivo pharmacology practical classes using the novel organism Lumbriculus variegatus","authors":"Julanta J. Carriere, Nia A. Davies, Margaret R. Cunningham, Melisa J. Wallace, Aidan Seeley","doi":"10.1002/prp2.1158","DOIUrl":"https://doi.org/10.1002/prp2.1158","url":null,"abstract":"Co-creation within higher education emphasizes learner empowerment to promote collaboration between the students and staff, enabling students to become active participants in their learning process and the construction of resources with academic staff. Concurrently, a diminishing number of higher education institutions offer in vivo practical classes, resulting in an in vivo skills shortage. To address this, and to actively engage students in their own learning, we describe the co-creation of a student-led drug trial using Lumbriculus variegatus. Under blinded conditions, final-year undergraduate biomedical science students, under the tutelage of academic staff and fellow students, were involved in the co-creation of an in vivo practical class to determine the effects of histamine and histamine receptor inverse agonists mepyramine and loratadine. Throughout this process, undergraduate- and masters-level students played key roles in every aspect of practical delivery and data analysis. Herein, students demonstrated the test compounds, both in isolation and in combination, resulted in reduced stereotypical movements of L. variegatus (p < .05, n ≥ 6). 15% of students in the class responded to a feedback survey (n = 8) after the class. Students reported the class provided “real life” insights into in vivo research and enabled the development of hands-on skills which would be useful in applying in their future careers. All students reported that they enjoyed the class with 25% (n = 2) reporting concerns about animal use in research, enabling useful discussions about animals in research. Moreover, these student-led in vivo trials add to the pharmacological knowledge of L. variegatus promoting education-led research.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138554935","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

Evaluating signaling bias for synthetic cannabinoid receptor agonists at the cannabinoid CB₂ receptor. 评估合成大麻素受体激动剂对大麻素CB2受体的信号偏倚。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1157

Monica Patel, Natasha L Grimsey, Samuel D Banister, David B Finlay, Michelle Glass

{"title":"Evaluating signaling bias for synthetic cannabinoid receptor agonists at the cannabinoid CB2 receptor.","authors":"Monica Patel, Natasha L Grimsey, Samuel D Banister, David B Finlay, Michelle Glass","doi":"10.1002/prp2.1157","DOIUrl":"10.1002/prp2.1157","url":null,"abstract":"The rapid structural evolution and emergence of novel synthetic cannabinoid receptor agonists (SCRAs) in the recreational market remains a key public health concern. Despite representing one of the largest classes of new psychoactive substances, pharmacological data on new SCRAs is limited, particularly at the cannabinoid CB2 receptor (CB2 ). Hence, the current study aimed to characterize the molecular pharmacology of a structurally diverse panel of SCRAs at CB2 , including 4-cyano MPP-BUT7AICA, 4F-MDMB-BUTINACA, AMB-FUBINACA, JWH-018, MDMB-4en-PINACA, and XLR-11. The activity of SCRAs was assessed in a battery of in vitro assays in CB2 -expressing HEK 293 cells: G protein activation (Gαi3 and GαoB ), phosphorylation of ERK1/2, and β-arrestin 1/2 translocation. The activity profiles of the ligands were further evaluated using the operational analysis to identify ligand bias. All SCRAs activated the CB2 signaling pathways in a concentration-dependent manner, although with varying potencies and efficacies. Despite the detection of numerous instances of statistically significant bias, compound activities generally appeared only subtly distinct in comparison with the reference ligand, CP55940. In contrast, the phytocannabinoid THC exhibited an activity profile distinct from the SCRAs; most notably in the translocation of β-arrestins. These findings demonstrate that CB2 is able to accommodate a structurally diverse array of SCRAs to generate canonical agonist activity. Further research is required to elucidate whether the activation of CB2 contributes to the toxicity of these compounds.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452110","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

Experimental pharmacology in precision medicine. 精准医学中的实验药理学。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1147

Alicja Urbaniak, Kenneth E Thummel, Ayoade N Alade, Allan E Rettie, Bhagwat Prasad, Amedeo De Nicolò, Jennifer H Martin, David N Sheppard, Michael F Jarvis

引用次数: 0

The role of plasma concentrations and drug characteristics of beta-blockers in fall risk of older persons. β受体阻滞剂的血浆浓度和药物特性在老年人跌倒风险中的作用。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1126

K J Ploegmakers, E P van Poelgeest, L J Seppala, S C van Dijk, L C P G M de Groot, S Oliai Araghi, N M van Schoor, B Stricker, K M A Swart, A G Uitterlinden, R A A Mathôt, N van der Velde

{"title":"The role of plasma concentrations and drug characteristics of beta-blockers in fall risk of older persons.","authors":"K J Ploegmakers, E P van Poelgeest, L J Seppala, S C van Dijk, L C P G M de Groot, S Oliai Araghi, N M van Schoor, B Stricker, K M A Swart, A G Uitterlinden, R A A Mathôt, N van der Velde","doi":"10.1002/prp2.1126","DOIUrl":"10.1002/prp2.1126","url":null,"abstract":"Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta-blockers are associated with an increased risk of falls in older beta-blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta-blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B-PROOF cohort. The associations between the beta-blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11-2.16], p = .01). No association was found for nonselective beta-blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta-blockers users. This might be caused by a decreased β1-selectivity in high plasma concentrations. In the future, beta-blocker concentrations could potentially help clinicians estimate fall risk in older beta-blockers users and personalize treatment.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/66/PRP2-11-e01126.PMC10603288.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230534","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

Time to treat the climate and nature crisis as one indivisible global health emergency. 是时候将气候和自然危机视为一个不可分割的全球卫生紧急事件。

IF 2.6 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1156

Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski

引用次数: 0

Development and evaluation of an escape room based on general pharmacokinetics: Students' perceptions of its motivational climate. 基于一般药代动力学的密室逃生的开发和评价:学生对其动机气氛的感知。

IF 2.6 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1155

Anneke van Houwelingen, Freija Ter Heegde, Wendy Boschloo, Leonie Piek, Theo Wubbels

{"title":"Development and evaluation of an escape room based on general pharmacokinetics: Students' perceptions of its motivational climate.","authors":"Anneke van Houwelingen, Freija Ter Heegde, Wendy Boschloo, Leonie Piek, Theo Wubbels","doi":"10.1002/prp2.1155","DOIUrl":"10.1002/prp2.1155","url":null,"abstract":"We designed an escape room based on the basic principles of pharmacokinetics for undergraduate bachelor students and explored its effect on students' perceived motivational climate and usefulness as a formative assessment via a mixed-method design. The effect on students' perceptions of the motivational climate was measured using pre- and post-test measurements of the MUSIC® inventory. Students' experiences with the escape room and suggestions for improvement were collected by open-ended survey questions. Forty-one students initially joined the study while 28 students completed both the pre- and post-test MUSIC® inventory. Data from the MUSIC® inventory revealed the effect of playing the escape room on students' situational interest was positive with medium to large effect (Cohen's dav = 0.63). Data from the open-ended questions confirmed the outcome of the MUSIC® inventory. While there was a positive effect on situational interest, students found the escape room not very useful as a tool for formative assessment. Further research should include a control group and focus on the effect of the escape room on academic success and work toward increasing the capacity of the escape room for large-scale courses.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452106","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

Quantitative analysis of the UDP-glucuronosyltransferase transcriptome in human tissues. 人组织中udp -葡萄糖醛基转移酶转录组的定量分析。

IF 2.6 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1154

Lucas Zhou, Abelardo D Montalvo, Joseph M Collins, Danxin Wang

{"title":"Quantitative analysis of the UDP-glucuronosyltransferase transcriptome in human tissues.","authors":"Lucas Zhou, Abelardo D Montalvo, Joseph M Collins, Danxin Wang","doi":"10.1002/prp2.1154","DOIUrl":"10.1002/prp2.1154","url":null,"abstract":"UDP-glucuronosyltransferases (UGTs) are phase II drug metabolizing enzymes that play important roles in the detoxification of endogenous and exogenous substrates. The 22 human UGTs belong to four families (UGT1, UGT2, UGT3, and UGT8) and differ in their expression, substrate specificity, UDP-sugar preference, and physiological functions. Differential expression/activity of the UGTs contributes to interperson variability in drug responses and toxicity, hormone homeostasis, and disease/cancer risks. However, in normal tissues, the tissue-specific expression profiles and transcriptional regulation of the UGTs are still not fully understood. In this study, we comprehensively analyzed the transcriptome of 22 UGTs in 54 human tissues/regions using RNAseq data from GTEx. We then validated the findings in the liver and small intestine samples using real-time PCR. Our results showed large interindividual variability across tissues in the expression of each UGT and the overall composition of UGT pools, consisting of different UGTs and their splice isoforms. Our results also revealed coexpression of the UGTs, Cytochrome P450s, and many transcription factors in the liver, suggesting potential coregulation or functional coordination. Our results provide the groundwork for future studies to detail further the regulation of the expression and activity of the UGTs.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138177021","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

Investigation of the human metabolism and disposition of the prolyl hydrolase inhibitor daprodustat using IV microtracer with Entero-Test bile string. 使用IV微量示踪剂和肠试验胆汁管柱研究脯氨酰水解酶抑制剂达普罗达的人体代谢和处置。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1145

Guoying Tai, Fangming Xia, Cathy Chen, Adrian Pereira, Jill Pirhalla, Xiusheng Miao, Graeme Young, Claire Beaumont, Liangfu Chen

{"title":"Investigation of the human metabolism and disposition of the prolyl hydrolase inhibitor daprodustat using IV microtracer with Entero-Test bile string.","authors":"Guoying Tai, Fangming Xia, Cathy Chen, Adrian Pereira, Jill Pirhalla, Xiusheng Miao, Graeme Young, Claire Beaumont, Liangfu Chen","doi":"10.1002/prp2.1145","DOIUrl":"10.1002/prp2.1145","url":null,"abstract":"Daprodustat is an oral small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI) approved in Japan and the United States for the treatment of anemia associated with chronic kidney disease. This phase 1, nonrandomized, 2-period, crossover study in 6 healthy men characterized and quantified the metabolites generated after a microtracer IV infusion of 50 μg (125 nCi) [14 C]-daprodustat administered concomitantly with a nonradiolabeled therapeutic dose of a 6-mg daprodustat tablet, followed by a single oral solution dose of 25 mg (62.5 μCi) [14 C]-daprodustat. High-performance liquid chromatography (HPLC) coupled with radioactivity detection (TopCount or AMS) and HPLC-tandem mass spectrometry (HPLC-MSn ) were used for quantitative measurement and structural identification of radioactive metabolites in plasma, urine, feces, and bile. Following oral administration of [14 C]-daprodustat, unchanged daprodustat was the principal circulating drug-related component, accounting for 40% of plasma radioactivity. Predominant oxidative metabolites M2, M3, M4, and M13 individually represented 6-8% of the plasma radioactivity and together accounted for the majority of radioactivity in urine and feces (53% in both matrices; 12% and 41% of dose, respectively). Unchanged daprodustat was not detected in urine and was only 0.7% of total radioactivity in feces (<0.5% of dose), with the remainder of the dose accounted for by oxidative metabolites. The radio-metabolic profile of duodenal bile following IV infusion of [14 C]-daprodustat was similar to that observed in feces after oral administration. The data suggested that oral daprodustat was extensively absorbed, cleared exclusively by oxidative metabolism, and eliminated via hepatobiliary (primary) and urinary (secondary) excretion.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230532","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

The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β-eudesmol in human liver: Reaction phenotyping and enzyme kinetics. CYP2C19和CYP3A4在人肝脏中β-去氨醇体外代谢中的作用：反应表型和酶动力学。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1149

Nadda Muhamad, Kesara Na-Bangchang

{"title":"The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β-eudesmol in human liver: Reaction phenotyping and enzyme kinetics.","authors":"Nadda Muhamad, Kesara Na-Bangchang","doi":"10.1002/prp2.1149","DOIUrl":"10.1002/prp2.1149","url":null,"abstract":"β-eudesmol is a major bioactive component of Atractylodes lancea (AL). AL has been developed as the capsule formulation of standardized AL extract for treating cholangiocarcinoma (CCA). However, the complex constituents of herbal products increase the risk of adverse drug interactions. β-eudesmol has demonstrated inhibitory effects on rCYP2C19 and rCYP3A4 in the previous research. This study aimed to identify the cytochrome P450 (CYP) isoforms responsible for the metabolism of β-eudesmol and determine the enzyme kinetic parameters and the metabolic stability of β-eudesmol metabolism in the microsomal system. Reaction phenotyping using human recombinant CYPs (rCYPs) and selective chemical inhibitors of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was performed, and enzyme kinetics and metabolic stability were investigated using human liver microsome (HLM). The results suggest that CYP2C19 and CYP3A4 play significant roles in β-eudesmol metabolism. The disappearance half-life (t1/2 ) and intrinsic clearance (CLint ) of β-eudesmol were 17.09 min and 0.20 mL/min·mg protein, respectively. Enzyme kinetic analysis revealed the Michaelis-Menten constant (Km ) and maximum velocity (Vmax ) of 16.76 μM and 3.35 nmol/min·mg protein, respectively. As a component of AL, β-eudesmol, as a substrate and inhibitor of CYP2C19 and CYP3A4, has a high potential for drug-drug interactions when AL is co-administered with other herbs or conventional medicines.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413469","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

A systematic review of knowledge, attitude and practice of pharmacogenomics in pediatric oncology patients. 儿童肿瘤患者药物基因组学知识、态度和实践的系统回顾。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2023-12-01 DOI: 10.1002/prp2.1150

Claire Moore, Smaro Lazarakis, Tayla Stenta, Marliese Alexander, Rachel Phan Nguyen, David A Elliott, Rachel Conyers

{"title":"A systematic review of knowledge, attitude and practice of pharmacogenomics in pediatric oncology patients.","authors":"Claire Moore, Smaro Lazarakis, Tayla Stenta, Marliese Alexander, Rachel Phan Nguyen, David A Elliott, Rachel Conyers","doi":"10.1002/prp2.1150","DOIUrl":"10.1002/prp2.1150","url":null,"abstract":"Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence-based guidelines. This systematic review aims to understand enablers and barriers to pharmacogenomics implementation in pediatric oncology by assessing the knowledge, attitudes, and practice of healthcare professionals and consumers. Medline, Embase, Emcare, and PsycINFO database searches identified 146 relevant studies of which only three met the inclusion criteria. These studies reveal that consumers were concerned with pharmacogenomic test costs, insurance discrimination, data sharing, and privacy. Healthcare professionals possessed mostly positive attitudes toward pharmacogenomic testing yet identified lack of experience and training as barriers to implementation. Education emerged as the key enabler, reported in all three studies and both healthcare professionals and consumer groups. However, despite the need for education, no studies utilizing a pediatric oncology consumer or healthcare professional group have reported on the implementation or analysis of a pharmacogenomic education program in pediatric oncology. Increased access to guidelines, expert collaborations and additional guidance interpreting results were further enablers established by healthcare professionals. The themes identified mirror those reported in broader pediatric genetic testing literature. As only a small number of studies met inclusion criteria for this review, further research is warranted to elicit implementation determinants and advance pediatric pharmacogenomics.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445694","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