{"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}
Marie-Laure Laroche, Marion Labetoulle, Emilie Jouanjus, Edeltraut Kröger, Arsène Zongo
{"title":"Cannabinoids and Adverse Convulsive Effects: A Pharmacovigilance and Addictovigilance Analysis of Cases Reported in France","authors":"Marie-Laure Laroche, Marion Labetoulle, Emilie Jouanjus, Edeltraut Kröger, Arsène Zongo","doi":"10.1111/fcp.70028","DOIUrl":"https://doi.org/10.1111/fcp.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Seizures after the use of cannabinoids are reported, but no precise descriptions of the characteristics of subjects and factors that may trigger seizures are available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To study the characteristics and circumstances associated with the occurrence of seizures in individuals using cannabinoids for medical or recreational purposes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis of spontaneous reports of adverse drug effects issued by the French pharmacovigilance and addictovigilance systems, and by manufacturers, extracted data from the Eudravigilance database (01/01/1985–21/07/2023). The request used the broad MedDRA SMQ term ‘convulsive’, with all products containing cannabinoids (THC, CBD, cannabis or natural cannabinoids).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 4296 notifications with cannabinoids, 130 (3%) reports of convulsive effects were analysed: 29 cases (23.3%) related to medical use (27 CBD, 1 THC and 2 combined THC/CBD preparations) and 98 (75.4%) related to recreational use. The median age was 29.0 years (min-max: 3–75), 78.7% were men and 81.1% were serious cases. Among the recreational users, 38.8% used <i>Cannabis sativa</i> with a history of epilepsy, and 68.4% of them were taking antiepileptics. In total, 67.7% of individuals had at least one risk factor for seizures, i.e., 31.0% among medical users and 78.6% among recreational users. The main risk factors with medical use were inefficacy of CBD (17.2%), fatigue (13.8%) and concomitant epileptogenic medications (10.3%). The main risk with recreational use was concomitant epileptogenic medications (39.8%), consumption of illicit drugs (33.7%) and alcohol (32.7%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This analysis demonstrates the importance of alerting cannabinoid users, particularly recreational cannabis users and those with a history of epilepsy, about seizure-associated risks. Moreover, educational information should be provided together with the prescription of licensed cannabinoids and medical cannabis.</p>\u0000 </section>\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":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331806","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}
Gökçe Sevim Öztürk Fincan, Ayşe Kübra Kibar Güzin, Atiye Seda Yar Sağlam
{"title":"Hydrogen Sulfide Treatment Enhanced Paclitaxel's Anticancer Effect on the ID8 Murine Epithelial Ovarian Cancer Cell Line","authors":"Gökçe Sevim Öztürk Fincan, Ayşe Kübra Kibar Güzin, Atiye Seda Yar Sağlam","doi":"10.1111/fcp.70029","DOIUrl":"https://doi.org/10.1111/fcp.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Paclitaxel is a potent agent against ovarian cancer. Hydrogen sulfide (H<sub>2</sub>S) is of particular interest in cancer treatment research. It is known that H<sub>2</sub>S has apoptotic and antiproliferative effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to examine the potential effects of H<sub>2</sub>S donor NaHS and paclitaxel, both individually and when co-administered, on the ID8 murine epithelial ovarian cancer cell line.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined the effects of the co-administration of paclitaxel and NaHS on cell viability, cytotoxicity, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), apoptosis, and proliferation in the ID8 ovarian cancer cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase tests were performed to ascertain the effect of NaHS and paclitaxel on cell viability and cytotoxicity. Caspase 3/7 levels were quantified in order to detect whether apoptosis is caspase dependent. Quantitative real-time polymerase chain reaction (qPCR) method was used to ascertain relative mRNA levels of Bcl-2, Bcl-xL, Bax, and Bak genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The viability of ID-8 cells showed a significant reduction following the co-administration of paclitaxel and NaHS, compared to the paclitaxel administration only. The results of qPCR analysis demonstrated significant alterations in the Bcl-2, Bcl-xL, Bax, Bak, Casp3, Casp8, and Casp9 genes' mRNA levels following cotreatment. In contrast to paclitaxel alone, its co-administration with NaHS resulted in increased apoptosis and decreased ROS levels. The presence of NaHS has been observed to enhance the apoptotic impact of paclitaxel by amplifying the decline in MMP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These data indicate that co-administration of H<sub>2</sub>S with paclitaxel could be useful as a potential agent in the treatment of ovarian cancer. We found that the presence of H<sub>2</sub>S enhanced the antitumor efficacy of paclitaxel.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273242","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}