Fundamental & Clinical Pharmacology最新文献

{"title":"Mechanism research on microRNA-669f-5p/deoxycytidylate deaminase axis mediating sevoflurane-induced cognitive dysfunction in aged mice","authors":"Yuan-Ping Zhong,&nbsp;Chao Zhang,&nbsp;Xue Zheng,&nbsp;Dong-Qin Chen,&nbsp;Xu Fang,&nbsp;Yu Zhang,&nbsp;Zhao-Qiong Zhu","doi":"10.1111/fcp.13023","DOIUrl":"10.1111/fcp.13023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the role of the microRNA (miRNA)-669f-5p/deoxycytidylate deaminase (Dctd) axis in sevoflurane inducing cognitive dysfunction in aged mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty-six C57BL/6J mice were used in the experiment model and were randomly divided into the sevoflurane group and the control group. The mice in the sevoflurane group were anesthetised with 3.4% sevoflurane, whereas those in the control group were air-treated for the same period. The study was then performed using bioinformatics sequencing, as well as in vitro and in vivo validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mice in the sevoflurane group showed significant cognitive impairments in terms of a decrease in both spatial learning and memory abilities. Experimental doses of miR-669f-5p agonist exhibited no obvious effect on cognitive function following sevoflurane inhalation, but inhibiting the expression of miR-669f-5p could alleviate the impairments. Based on the results of the bioinformatics sequencing, miR-669f-5p/Dctd and the toll-like receptor (TLR) signalling pathway could be the key miRNA, gene and pathway leading to postoperative cognitive dysfunction following sevoflurane inhalation. The aged mice showed significantly increased expression of miR-669f-5p in the hippocampus following sevoflurane inhalation, and upregulating/inhibiting its expression could increase/decrease TLR expression in the hippocampus. Furthermore, miR-669f-5p could reduce the expression of the Dctd gene by binding to its 3′untranslated region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The miR-669f-5p/Dctd axis plays an important role in sevoflurane inducing cognitive dysfunction in aged mice, providing a new direction for further development of therapeutic strategies concerning the prevention and treatment of cognitive dysfunction associated with sevoflurane anaesthesia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 6","pages":"1031-1044"},"PeriodicalIF":2.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534178","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":"Vortioxetine improved schizophrenia-like behavioral deficits in a Poly I:C-induced maternal immune activation model of schizophrenia in rats","authors":"Mehmet Taskiran,&nbsp;Sacide Yildiz Taskiran,&nbsp;Gokhan Unal,&nbsp;Nuh Mehmet Bozkurt,&nbsp;Asuman Golgeli","doi":"10.1111/fcp.13028","DOIUrl":"10.1111/fcp.13028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Several studies provide clear evidence that exposure to various infections during pregnancy are linked with an increased risk for schizophrenia. In preclinical studies, administration of polyinosinic-polycytidylic acid (Poly I:C) in pregnant rodents can induce maternal immune activation leading to impairments in brain function in the offspring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The aim of this study was to investigate the effect of vortioxetine, a multimodal selective serotonin reuptake inhibitor (SSRI), in the pathophysiology of Poly I:C-induced schizophrenia-like model in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this purpose, Poly I:C (8 mg/kg, ip) was injected into pregnant animals 14 days after mating, and tail blood was taken for determination of IL-6 levels after 2 h. At postnatal days 83–86, behavioral tests were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results revealed that Poly I:C caused impairments in prepulse inhibition, novel object recognition, social interaction, and open-field tests. Chronic administration of vortioxetine (2.5, 5, and 10 mg/kg, ip, postnatal days 69–83) caused significant improvements in these deficits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, our findings indicate that vortioxetine may provide new therapeutic approaches for the treatment of schizophrenia. We think that increased serotonergic activity in frontal brain regions may provide the ameliorative effect of vortioxetine, especially on negative and cognitive symptoms. Therefore, it will be useful to determine the efficacy of vortioxetine with combined drugs with further studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 6","pages":"1069-1079"},"PeriodicalIF":2.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497845","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":"The β2-adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury","authors":"Natalia V. Naryzhnaya,&nbsp;Sergey V. Logvinov,&nbsp;Boris K. Kurbatov,&nbsp;Ivan A. Derkachev,&nbsp;Liliia R. Mustafina,&nbsp;Aleksandr S. Gorbunov,&nbsp;Maria A. Sirotina,&nbsp;Mikhail Kilin,&nbsp;Svetlana V. Gusakova,&nbsp;Leonid N. Maslov","doi":"10.1111/fcp.13026","DOIUrl":"10.1111/fcp.13026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β₂-adrenergic receptor (β₂-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β₂-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β₂-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 6","pages":"1116-1130"},"PeriodicalIF":2.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491684","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":"Sodium-glucose cotransporter-2 inhibitor (SGLT2i) plus glucagon-like peptide type 1 receptor combination is more effective than SGLT2i plus dipeptidyl peptidase-4 inhibitor combination in treating obese mice metabolic dysfunction-associated steatotic liver disease (MASLD)","authors":"Pedro H. Reis-Barbosa,&nbsp;Carlos A. Mandarim-de-Lacerda","doi":"10.1111/fcp.13024","DOIUrl":"10.1111/fcp.13024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Monotherapy to treat obesity-associated liver insult is limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>In diet-induced obese mice showing metabolic dysfunction-associated steatotic liver disease (MASLD), we aimed to compare the combinations of sodium-glucose cotransporter-2 inhibitor (SGLT2i, empagliflozin, E), dipeptidyl peptidase-4 inhibitor (DPP4i, linagliptin, L), and glucagon-like peptide type 1 receptor agonist (GLP1RA, dulaglutide, D).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male 3-month-old C57BL/6J mice were fed for 12 weeks in a control (C, <i>n</i> = 10) or high-fat (HF, <i>n</i> = 30) diet. Then, mice were followed for three additional weeks: C, HF, HF E + L, and HF E + D (<i>n</i> = 10/group).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HF versus C showed higher hepatic triacylglycerol (TAG, +82%), steatosis (+850%), glucose intolerance (+71%), insulin (+98%), and insulin resistance (+68%). Compared to the HF group, HF E + L showed lower glucose intolerance (−60%), insulin (−61%), insulin resistance (−46%), TAG (−61%), and steatosis (−58%), and HF E + D showed lower glucose intolerance (−71%), insulin (−58%), insulin resistance (−62%), TAG (−61%), and steatosis (−82%). The principal component analysis (PCA) placed the HF group and the HF E + D group on opposite sides, while the HF E + L group was placed between C and HF E + D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PCA separated the groups considering the metabolism-related genes (glucose and lipid), mitochondrial biogenesis, and steatosis. The two pharmacological combinations showed beneficial effects in treating obesity and MASLD. However, the combination of SGLT2i and GLP1RA showed more potent beneficial effects on MASLD than SGLT2i and DPP4i and, therefore, should be the recommended combination.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 6","pages":"1059-1068"},"PeriodicalIF":2.1,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456294","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":"Population pharmacokinetics of mycophenolate in patients treated for interstitial lung disease (EVER-ILD study)","authors":"Yan-Min Xu,&nbsp;David Ternant,&nbsp;Martine Reynaud-Gaubert,&nbsp;Théodora Bejan-Angoulvant,&nbsp;Sylvain Marchand-Adam","doi":"10.1111/fcp.13021","DOIUrl":"10.1111/fcp.13021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mycophenolate mofetil (MMF) has been used to treat interstitial lung disease (ILD), but mycophenolate (MPA) pharmacokinetics was not reported for this use. This ancillary study of the EVER-ILD protocol aimed at describing the pharmacokinetic variability of MPA using population modelling in ILD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Concentrations of MPA were measured during an 8-h course for 27 ILD patients treated with 1000 mg MMF b.i.d. Absorption, distribution and elimination of MPA were described using population compartment models with first-order transfer and elimination rate constants, while accounting for both absorption peaks using gamma absorption models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The pharmacokinetics of MPA was best described using a two-compartment model and two gamma absorption models, model performances of this model were still similar to those of a one gamma absorption model. This pharmacokinetics seemed to be notably influenced by body weight, renal function and inflammatory status. The distribubtion value area under the concentration curve between two administrations of MMF was AUC₁₂ = 52.5 mg.h/L in median (interquartile range: 42.2–58.0 mg.h/L).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This is the first study reporting MPA pharmacokinetics in ILD. This pharmacokinetics appears to be similar to other indications and should be further investigated in future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 5","pages":"1008-1016"},"PeriodicalIF":2.1,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.13021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330720","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}

{"title":"Pharmacological treatment for mental health illnesses in adults receiving dialysis: A scoping review","authors":"Jenny Wichart,&nbsp;Peter Yoeun,&nbsp;Tracy Chin,&nbsp;Christopher Evernden,&nbsp;Charlotte Berendonk,&nbsp;Jodi Kerr,&nbsp;Alexandra Birchall,&nbsp;Belinda Boschee,&nbsp;Kimberly Defoe,&nbsp;Jasleen Dhaliwal,&nbsp;Tasia KarisAllen,&nbsp;Megan Kennedy,&nbsp;Alexis McDonald,&nbsp;Monika K. Mierzejewski,&nbsp;Kara Schick-Makaroff","doi":"10.1111/fcp.13022","DOIUrl":"10.1111/fcp.13022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pharmacologic management of mental health illnesses in patients receiving dialysis is complex and lacking data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Our objective was to synthesize published data for the treatment of depression, bipolar and related disorders, schizophrenia or psychotic disorders, and anxiety disorders in adults receiving hemodialysis or peritoneal dialysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We undertook a scoping review, searching the following databases: Medline, Embase, CINAHL, PsycINFO, Cochrane Library, Scopus, and Web of Science. Data on patients who received only short-term dialysis, a kidney transplant, or non-pharmacologic treatments were excluded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-three articles were included: 41 focused on depression, 16 on bipolar disorder, 13 on schizophrenia and psychotic disorders, 1 on anxiety disorders, and 2 addressing multiple mental health illnesses. The majority of depression studies reported on selective serotonin reuptake inhibitors (SSRIs) as a treatment. Sertraline had the most supporting data with use of doses from 25 to 200 mg daily. Among the remaining SSRIs, escitalopram, citalopram, and fluoxetine were studied in controlled trials, whereas paroxetine and fluvoxamine were described in smaller reports and observational trials. There are limited published data on other classes of antidepressants and on pharmacological management of anxiety. Data on treatment for patients with bipolar disorder or schizophrenia and related disorders are limited to case reports.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Over half of the studies included were case reports, thus limiting conclusions. More robust data are required to establish effect sizes of pharmacological treatments prior to providing specific recommendations for their use in treating mental health illnesses in patients receiving dialysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 5","pages":"862-882"},"PeriodicalIF":2.1,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.13022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320834","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}

{"title":"Oral communication abstracts","authors":"","doi":"10.1111/fcp.13012","DOIUrl":"10.1111/fcp.13012","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 S1","pages":"6-40"},"PeriodicalIF":2.9,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293326","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":"Master 2 award","authors":"","doi":"10.1111/fcp.13013","DOIUrl":"10.1111/fcp.13013","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 S1","pages":"41-42"},"PeriodicalIF":2.9,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293327","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":"Drug news and therapeutic news","authors":"","doi":"10.1111/fcp.13011","DOIUrl":"10.1111/fcp.13011","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 S1","pages":"3-5"},"PeriodicalIF":2.9,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293325","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":"Discussed Poster Abstracts – PM2","authors":"","doi":"10.1111/fcp.13016","DOIUrl":"10.1111/fcp.13016","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"38 S1","pages":"68-93"},"PeriodicalIF":2.9,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293330","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}