{"title":"Theme and main topic index","authors":"","doi":"10.1111/fcp.70024","DOIUrl":"https://doi.org/10.1111/fcp.70024","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339596","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}
Chien-Chou Su, Tsai-Kuei Huang, Ching-Sen Shih, Yi-Chia Su
{"title":"Risk Factors and Multiple Interaction Effects for Hyperammonemia in Patients Receiving Valproic Acid","authors":"Chien-Chou Su, Tsai-Kuei Huang, Ching-Sen Shih, Yi-Chia Su","doi":"10.1111/fcp.70030","DOIUrl":"https://doi.org/10.1111/fcp.70030","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Valproic acid (VPA) use is associated with an increased risk of hyperammonemia (HA); however, the specific interactions between HA risk factors in VPA-treated patients remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to identify and assess the effects of multiple interactions between different risk factors affecting HA to improve clinical risk stratification in patients undergoing VPA therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study by reviewing the medical records of patients treated with VPA at a single center from January 2019 to December 2021. The SHapley Additive exPlanations (SHAP) method was used to interpret model predictions, revealing the relative importance and interactions of factors affecting HA risk. SHAP interaction scores were used to assess the effects of multiple interactions between features, providing a comprehensive analysis of how risk factors interact.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study identified the Top 15 predictors of HA, ranked by importance: patient age, VPA blood concentration, VPA dose, epilepsy, VPA treatment duration, levetiracetam use, hypertension, mental disorders, and number of medications. Notable multiple interaction effects were observed, particularly between age and factors including VPA concentration, epilepsy, and treatment duration. Younger patients and those with elevated VPA concentrations were at increased risk of developing HA, especially when epilepsy or polypharmacy were present.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study highlights several critical factors potentially influencing HA development in VPA-treated patients, particularly younger patients, those with epilepsy, or those undergoing polypharmacy. However, as a single-center retrospective study, these findings necessitate further validation through additional research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339208","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":"Fluvoxamine Attenuates Liver Injury in Lipopolysaccharide-Induced Sepsis: Via Nrf2/HO-1 Pathway","authors":"Rahime Aslankoc, Ozlem Ozmen, Pınar Karabacak, Cahide Aslan, Oguzhan Kavrik, Okan Sancer","doi":"10.1111/fcp.70031","DOIUrl":"https://doi.org/10.1111/fcp.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>The search for new treatments for sepsis is a pivotal subject of survey owing to the high mortality of sepsis. Sepsis can cause serious injury to many vital organs, including the liver. This study investigated the potential therapeutic impacts of fluvoxamine (FLV) against liver injury in a lipopolysaccharide (LPS)-induced sepsis model. Thirty-two female Wistar Albino rats were divided into four equal groups: control, LPS (5 mg/kg, i.p., single dose), LPS + FLV(5 mg/kg, i.p., single dose+50 mg/kg, i.p., single dose, 30 min before LPS application) and FLV(50 mg/kg, i.p., single dose). Six hours after LPS application, blood and liver tissues were gathered under anesthesia for biochemical, histopathological, and immunohistochemical analyses. The RT-qPCR analyzed the mRNA expression of nuclear factor erythroid 2–related factor 2 (Nrf2), glycogen synthase kinase-3 (GSK3ß), kelch-like ECH–associated protein 1 (Keap1), and heme oxygenase-1 (HO-1). LPS administration caused significant histopathological changes in the liver and increased oxidative stress. It increased the number of TNF-α, osteopontin (OPN), and serum amyloid A (SAA) immune positive cells associated with inflammation and decreased Nrf2, GSK3ß, Keap1, and HO-1 gene expressions associated with antioxidant defense. Additionally, serum alanine aminotransferase (ALT) level significantly increased. In the LPS + FLV and FLV groups, improvement in histopathological findings and a significant decrease in oxidative stress were detected. TNF-α, OPN, and SAA expression decreased, and Nrf2, GSK3ß, Keap1, and HO-1 gene expressions increased. The decrease in serum aspartate aminotransferase (AST) and ALT was found to be significant only in the FLV group. Our findings therefore provide new evidence that FLV reduces LPS-induced liver injury.</p>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331879","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}
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