BMC Pharmacology & Toxicology最新文献

{"title":"Effect of combination therapy of methylfolate with antidepressants in patients with depressive disorder.","authors":"Afifa Siddique, Muhammad Masood Khokhar, Akbar Waheed, Uzma Naeem, Shahzad Akhtar Aziz","doi":"10.1186/s40360-025-00846-x","DOIUrl":"10.1186/s40360-025-00846-x","url":null,"abstract":"<p><strong>Objective: </strong>To determine the relative effectiveness of combination therapy of antidepressants with low-dose methylfolate versus antidepressant monotherapy in patients with depressive disorder.</p><p><strong>Methods: </strong>In an open-label clinical trial, forty-four patients with depressive disorder (6A70, 6A71, and 6A72 according to ICD-11) received an evidence-based antidepressant therapy (either escitalopram 10-20 mg, sertraline 50-100 mg, fluoxetine 20-40 mg, duloxetine 30-60 mg, mirtazapine 15-30 mg, venlafaxine 75-150 mg, trazodone 50-100 mg, amitriptyline 25-75 mg, or clomipramine 25-75 mg orally daily for 4 weeks). The experimental group, Group B was additionally given a dose of methylfolate 800 µg daily for four weeks. The psychometric testing of depression was achieved through administration of Patient Health Questionnaire-9 (PHQ-9) on days 0, 14, and 28, to find the improvement in the depressive score on day 28, the remission rate on day 28, and decrease in the time lag on day 14. Adverse effects were analyzed by self-assessment questionnaire to observe the tolerability. The paired sample t-test and the independent sample t-test were applied for analysis by using SPSS v27.0. The p-value ≤ 0.05 was considered statistically significant.</p><p><strong>Results: </strong>On day 28, patients on low dose methylfolate and antidepressant combination therapy showed a 40.33% improvement in depression symptoms, compared to 26.43% in patients on antidepressant monotherapy (p-value < 0.05). This treatment strategy had no effect on the time-lag of outcomes on day 14 and the remission rate on day 28 was not found statistically significant. Only one patient reported insomnia, while another mentioned irritability.</p><p><strong>Conclusion: </strong>Combination therapy of antidepressants with low-dose methylfolate may provide a safe and effective treatment strategy for patients with depressive disorder.</p><p><strong>Clinical trial identifier: </strong>NCT05931965.</p><p><strong>Clinicaltrials: </strong>gov. https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/NCT05931965.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"14"},"PeriodicalIF":2.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of cypermethrin exposure on learning and memory functions and anxiety-like behavior in rats.","authors":"Mansour Nazari, Mohammadmahdi Sabahi, Arash Salehipour, Sara Ami Ahmadi, Azin Kazemi, Shahab Razipour, Nafiseh Faraji, Alireza Komaki","doi":"10.1186/s40360-025-00840-3","DOIUrl":"10.1186/s40360-025-00840-3","url":null,"abstract":"<p><strong>Background: </strong>Cypermethrin (CYP), a synthetic pyrethroid widely used to control plant pests, has been associated with various diseases in humans exposed to pesticides, either directly or indirectly. This study aimed to examine the effects of CYP on learning and memory functions, as well as anxiety-like behavior.</p><p><strong>Methods: </strong>Forty male Wistar rats (8 weeks old) were randomly assigned to 4 groups: The first group served as the control, while the other three groups received different doses of CYP (5, 20, and 80 mg/kg) via gavage once daily for one month. Passive avoidance learning (PAL) and memory were assessed using the shuttle box test, cognitive memory was evaluated using the novel object recognition (NOR) test, and spatial memory was measured with the Morris water maze (MWM) test. The elevated plus-maze (EPM) and open field tests were used to assess locomotor activity and anxiety levels.</p><p><strong>Results: </strong>In the PAL test, significant differences were observed in the time spent in the dark compartment (TDC) and step-through latency in the retention trial (STLr) in rats receiving 80 mg/kg of CYP. MWM results indicated memory impairment in rats treated with 20 and 80 mg/kg of CYP. Additionally, rats treated with the highest dose of CYP (80 mg/kg) showed a reduction in the number of entries into the open arms of the EPM compared to the control group.</p><p><strong>Conclusion: </strong>This study demonstrates that CYP negatively affects learning and memory retention. Further research is needed to explore the precise mechanisms by which this toxin impacts cognitive functions.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"12"},"PeriodicalIF":2.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical observation of none-promyelocytic AML patients inducted with idarubicin or daunorubicin included standard regimens: a tertiary care center experience.","authors":"Jianhui Xu, Chaoyang Song, Yanjie He, Rui Huang, Sanfang Tu","doi":"10.1186/s40360-025-00839-w","DOIUrl":"10.1186/s40360-025-00839-w","url":null,"abstract":"<p><strong>Background: </strong>Few Chinese study compared the impacts of idarubicin and daunorubicin based \"3+7\" intensive chemotherapies on early and long-term outcomes of AML patients through exploring their real-world data.</p><p><strong>Patients and methods: </strong>Our none promyelocytic AML patients inducted with \"3+7\" regimens were studied to find out the factors relating with induction response and long term survival.</p><p><strong>Results: </strong>Idarubicin induction was related with less chemotherapy refractory rate comparing with daunorubicin induction (10% vs 25%, P = 0.02). But cytogenetic molecular risk classification was the only independent factor relating with achieving CR after initial induction or chemotherapy refractory (P = 0.000 and 0.036). Both to overall survival (OS) and progress free survival (PFS), having transplantation and chemotherapy refractory were independent factors related, MLL rearrangement and DNA methylating related genes' mutations as well. CR at time of transplantation and MLL rearrangement were independent factors relating both with OS after transplantation and relapse free survival after transplantation.</p><p><strong>Conclusion: </strong>Traditional \"3+7\" chemotherapy regimen with idarubicin plays better in CR induction than that with daunorubicin. But the patient's long-term survival related with clinical practice aspects, like having stem cell transplantation, as well as genetic alterations equally, like MLL rearrangement and DNA methylating related genes' mutations.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"10"},"PeriodicalIF":2.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse events associated with IL-23 and IL-12/23 inhibitors in the clinical management of psoriasis: a comprehensive pharmacovigilance analysis.","authors":"Wentao Shi, Ziyi Zhao, Yinghong Zhai, Xiaofei Ye, Feng Xu","doi":"10.1186/s40360-025-00837-y","DOIUrl":"10.1186/s40360-025-00837-y","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-23 (IL-23) inhibitors and the IL-12/23 inhibitor ustekinumab constitute a pivotal class of therapeutic agents employed in the clinical management of Psoriasis, a chronic immune-mediated skin disorder. Notwithstanding their therapeutic efficacy, concerns have arisen due to the emergence of multiple adverse events (AEs) associated with their usage. This study aims to provide a comprehensive examination of the distribution and characteristics of these AEs concerning IL-23 and IL-12/23 inhibitors, with a specific focus on guselkumab, tildrakizumab, risankizumab, and ustekinumab.</p><p><strong>Methods: </strong>In this research endeavor, we conducted an extensive analysis of data extracted from the FDA Adverse Event Reporting System (FAERS), spanning the timeframe from January 1, 2014, to September 30, 2022. To identify potential signals of AEs, we rigorously applied disproportionality analysis, utilizing both reporting odds ratio (ROR) and information component (IC) metrics. A signal was considered present when the lower limit of the 95% confidence interval (CI) for ROR (ROR025) exceeded one or when IC (IC025) surpassed zero, with a minimum requirement of three or more reported cases.</p><p><strong>Results: </strong>Our investigation encompassed a substantial dataset, comprising a total of 41,408,408 reports detailing drug-AE associations and involving 13,271,168 individuals. Among these, 704, 13,164, and 11,399 patients were identified as users of the IL-23 inhibitors tildrakizumab, guselkumab, and risankizumab, respectively, while 62,853 patients were identified as users of the IL-12/23 inhibitor ustekinumab. The analysis revealed the presence of 8, 20, 107, and 115 signals for these respective drugs. Significantly, the System Organ Class (SOC) exhibiting the highest incidence was \"infections and infestations,\" with documented occurrences in tildrakizumab (6/8), guselkumab (5/20), ustekinumab (50/107), and risankizumab (25/115).</p><p><strong>Conclusion: </strong>Our pharmacovigilance analysis has brought to light a substantial frequency of AEs linked to IL-23 and IL-12/23 inhibitors. These findings underscore the pivotal role of IL-23 and IL-12/23 inhibitors in modulating immune function and raise concerns regarding their potential to heighten susceptibility to infections and malignancies. However, limitations inherent to the FAERS database, including underreporting, lack of denominator data, potential duplicate records, and inability to confirm causality, should be acknowledged of particular significance is risankizumab, which, despite having fewer reported cases and a later market introduction compared to ustekinumab, exhibited a higher incidence of AEs. These results emphasize the necessity for ongoing vigilance, further investigation, and a reevaluation of the safety profile of IL-23 and IL-12/23 inhibitors in the clinical management of Psoriasis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"11"},"PeriodicalIF":2.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous dexmedetomidine for delirium prevention in elderly patients following orthopedic surgery: a meta-analysis of randomized controlled trials.","authors":"Jing Sun, Duo Wang, Yue Zhao, Ying Bai, Shufang Wang, Chang Meng, Guobin Miao, Peng Liu","doi":"10.1186/s40360-025-00841-2","DOIUrl":"10.1186/s40360-025-00841-2","url":null,"abstract":"<p><strong>Objectives: </strong>We conducted a meta-analysis to investigate the effect of dexmedetomidine on postoperative delirium in elderly orthopedic surgery patients.</p><p><strong>Methods: </strong>A meta-analysis was conducted to identify randomized controlled trials of dexmedetomidine in elderly patients undergoing orthopedic surgery. The data was published on October 25, 2024. PubMed, Embase, and Cochrane Library databases were searched. Outcome measures included incidence of delirium, length of hospital stay, visual analogue scale, and postoperative complications. Estimates are expressed as relative risk (RR) or mean difference (MD) with a 95% confidence interval (CI). The publications were reviewed according to the guidelines of the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).</p><p><strong>Results: </strong>This study was registered with INPLASY (number INPLASY2024110004). A total of 3159 patients were included in 9 randomized controlled trials. The results showed that dexmedetomidine exhibited a preventive effect on delirium compared with the control group in elderly patients after orthopedic surgery (RR: 0.55, 95% CI: 0.45-0.66, P < 0.01, I² = 0%). Subgroup analysis suggested that dexmedetomidine was significantly different from saline(RR: 0.56; 95% CI: 0.44-0.73, P<0.01, I²=31%) and propofol(RR: 0.52; 95% CI: 0.39-0.70, P<0.01, I²=0%) in reducing postoperative delirium in elderly fracture patients. No statistically significant differences were observed in length of hospital stay, visual analogue scale, and postoperative complications (P > 0.05). Certainty of evidence for postoperative delirium was moderate.</p><p><strong>Conclusions: </strong>Dexmedetomidine has been shown to have a protective effect on postoperative delirium in elderly patients following orthopedic surgery.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"8"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential antihyperlipidemic effects of myrcenol and curzerene in high-fat fed rats.","authors":"Sana Tahir, Abdullah Abdo, Aisha Mobashar, Arham Shabbir, Komal Najam, Aisha Ibrahim, Khalid Hussain, Yousef A Bin Jardan, Samir Ibenmoussa, Youssouf Ali Younous","doi":"10.1186/s40360-025-00838-x","DOIUrl":"10.1186/s40360-025-00838-x","url":null,"abstract":"<p><p>The study evaluated the anti-hyperlipidemic effects of myrcenol and curzerene on a high fat diet induced hyperlipidemia rat model. Thirty male albino rats were fed on a high-fat diet for four months. The HFD-induced hyperperlipidemia rats were treated with rosuvastatin (10 mg/kg), curzerene (130 mg/kg) and myrcenol (100 mg/kg) for four weeks. Blood samples were collected for further analysis. Aorta and heart were harvested for histopathological evaluation. Hepatic lipase and HMG-CoA reductase were determined by ELISA. FST and Y-maze tests were performed to assess the stress level in hyperlipidemia rats. The phytochemical compounds (Curzerene and Myrcenol) and the standard drug (Rosuvastatin) resulted in decreased body weight as well as reduced levels of LDL, TG, TC, AST and ALT as compared to the diseased group. Additionally, the treated groups displayed improved HDL levels and less depressed behavior. The ELISA results revealed that the Curzerene and myrcenol had significantly increased the protein concentration of hepatic lipase than the diseased group whereas both compounds significantly lowered the HMG-CoA reductase concentrations compared to the diseased group. The findings suggested that myrcenol and curzerene had the potential to be therapeutic agents for managing hyperlipidemia and reducing the risk of heart-related conditions associated with high lipid levels.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"9"},"PeriodicalIF":2.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and interactions between piperine and ezetimibe in their Anti-hyperlipidemic efficacy using Biopharmaceutics and Pharmacokinetics.","authors":"Kavitha Marati, Sujatha Palatheeya, Ananda Kumar Chettupalli, Sarad Pawar Naik Bukke","doi":"10.1186/s40360-025-00836-z","DOIUrl":"10.1186/s40360-025-00836-z","url":null,"abstract":"<p><strong>Background: </strong>Piperine, a secondary metabolite, affects the antihyperlipidemic effect of Ezetimibe (EZ). Hyperlipidemia is one of the independent risk factors for cardiovascular disorders such as atherosclerosis. Antihyperlipidemic drugs are essential for reducing cardiovascular events and patient mortality. Our study aimed to improve the solubility of EZ, a lipid-lowering drug that belongs to BCS II and has low solubility. Piperine, a bioenhancer, can increase the bioavailability of other pharmaceuticals without modifying their fundamental characteristics or enhancing their efficacy. The objective of this study was to increase the bioavailability of EZ while also improving its potency and reducing its toxicity by using piperine as a bioenhancer. Therefore, rats were given piperine combined with EZ, and their antihyperlipidemic activity was assessed while fed a high-fat diet.</p><p><strong>Method: </strong>The in vivo antihyperlipidemic effect of EZ with piperine was assessed at doses of 10 and 5-20 mg/kg b.w. The evaluation was conducted using propylthiouracil-induced and triton X-100-induced hyperlipidemia in rats. Give 400 mg/kg body weight of propylthiouracil along with piperine. Serum levels of total cholesterol (TC) (p < 0.01), triglycerides (TG) (p < 0.01), low-density lipoprotein (LDL) (p < 0.01), and very low-density lipoprotein (VLDL) (p < 0.01) all went up significantly. Additionally, it led to the induction of high-density lipoprotein (HDL) (p < 0.01). Administration of Triton X-100 via intraperitoneal injection at a single dose resulted in an elevation of lipid levels.</p><p><strong>Results: </strong>Lower levels of high-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), and very low-density lipoprotein (VLDL) were significantly reduced by EZ at 10 mg/kg b.w. and piperine at 20 mg/kg b.w., respectively (p < 0.01 and p < 0.05). Liver histology studies provided further evidence supporting the present findings. Areas of concentrated periportal lymphocytes and hepatocytes formed a cord pattern in rats with hyperlipidaemia. It seemed like the hepatocytes, periportal area, and centrilobular part of the liver were all normal in the group who had the treatment. An analysis of the EZ plasma drug concentration with time was carried out in a research. The medication's most effective concentration (Cmax) was determined to be within 4 h after delivery, and The quantified concentration of the active medication was detectable in the bloodstream for 24 h.</p><p><strong>Conclusion: </strong>In combination with piperine, EZ has demonstrated significant antioxidant and antihyperlipidemic effects. This indicates that EZ could be further utilised for treating hyperlipidemia and atherosclerosis due to its potential to boost the bioavailability and oral absorption of the drug.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"7"},"PeriodicalIF":2.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boswellic acid synergizes with low-dose ionizing radiation to mitigate thioacetamide-induced hepatic encephalopathy in rats.","authors":"Dina E Saad, Somaya Z Mansour, Eman I Kandil, Asmaa Hassan, Fatma S M Moawed, Mustafa M M Elbakry","doi":"10.1186/s40360-024-00831-w","DOIUrl":"10.1186/s40360-024-00831-w","url":null,"abstract":"<p><p>Hepatic encephalopathy (HE) is a syndrome that arises from acute or chronic liver failure. This study was devised to assess the impact of a combination of boswellic acid (BA) and low doses of gamma radiation (LDR) on thioacetamide (TAA)-induced HE in an animal model. The effect of daily BA treatment (175 mg/kg body weight, for four weeks) and/or fractionated low-dose γ-radiation (LDR; 0.25 Gy, twice the total dose of 0.5 Gy) was evaluated against TAA (200 mg/kg, intraperitoneal) twice-weekly for four weeks to induce liver damage and HE in rats. TAA-exposed rats exhibited a significant elevation in serum activities of liver enzymes (GGT, ALP) and plasma ammonia levels at P < 0.05 (Duncan's test) compared to the control group. Moreover, there was an increase in the levels of proinflammatory cytokines (IL6, IL12, IL18) in the TAA-exposed animals accompanied by a depletion in the activities of paraoxonase-1 and neurotransmitter contents compared with normal control rats (P < 0.05). However, the administration of BA alone or in combination with LDR led to improvements in liver and brain parameter indices. Furthermore, the histopathological assessments of liver and brain tissues supported the findings of the biochemical investigations. From the statistical analysis, it can be concluded that the combined administration of BA and exposure to LDR may possess potential hepatoprotective effects against hepatic encephalopathy-associated hyperammonemia and the consequent damage to the liver and brain. This study proposes that a combination of therapeutic approaches, LDR and BA could be a new therapeutic candidate for the management of hepatic encephalopathy.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"6"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics, risk factors and a risk prediction model of tocilizumab-induced hypofibrinogenemia: a retrospective real-world study of inpatients.","authors":"Le Cai, Xiao Wen, Zihan Qiu, An Fu, Daihong Guo, Man Zhu","doi":"10.1186/s40360-024-00827-6","DOIUrl":"10.1186/s40360-024-00827-6","url":null,"abstract":"<p><strong>Objective: </strong>The occurrence of hypofibrinogenemia after tocilizumab treatment has attracted increasing attention, which may cause bleeding and even life-threatening. This study aims to explore the risk factors for tocilizumab-induced hypofibrinogenemia (T-HFIB) and construct a risk prediction model.</p><p><strong>Methods: </strong>A total of 221 inpatients that received tocilizumab from 2015 to 2023 were retrospectively collected and divided into T-HFIB group or control group. The risk factors for T-HFIB were obtained by logistic regression equation and used to establish the nomogram.</p><p><strong>Results: </strong>T-HFIB was observed in 121 of 221 patients (54.75%). Multifactorial logistic regression analysis revealed that infection (OR = 2.002, 95%CI:1.018 ~ 3.935), COVID-19 (OR = 3.752, 95%CI:1.264 ~ 11.139), CAR-T therapy (OR = 4.409, 95%CI:2.017 ~ 0.894), and concomitant glucocorticoids (OR = 5.303, 95%CI:0.227 ~ 0.894) were identified as independent risk factors for T-HFIB, while high baseline fibrinogen level (OR = 0.813, 95%CI:0.670 ~ 0.988) and concomitant antirheumatic drugs (OR = 0.451, 95%CI:0.227 ~ 0.894) were identified as protective factors. A nomogram was established, and area under the curve (AUC) of prediction model was 0.772 (95%CI:0.709 ~ 0.836). Calibration curve showed a good prediction accuracy for the occurrence of T-HFIB.</p><p><strong>Conclusion: </strong>The infection, COVID-19, CAR-T therapy, and concomitant glucocorticoids were independent risk factors for T-HFIB, while high baseline fibrinogen and concomitant antirheumatic drugs were protective factors. This nomogram can help early identify the patients at potential high risk of developing T-HFIB.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"5"},"PeriodicalIF":2.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of different antiplatelet therapy drugs on platelet activation and platelet-leukocyte aggregate formation in early septic ARDS.","authors":"Lu Wang, Liang-Yu Mi, Xiang-Yu Chen, Huai-Wu He, Yun Long","doi":"10.1186/s40360-024-00806-x","DOIUrl":"https://doi.org/10.1186/s40360-024-00806-x","url":null,"abstract":"<p><strong>Background: </strong>In patients with sepsis, platelets are activated and adhere to neutrophils, forming platelet-leukocyte aggregates (PLAs) that lead to the development of MODS. ARDS is one of the main manifestations of septic MODS. We designed this study to explore the effects of different anti-plate therapy drugs on platelet activation and platelet-leukocyte aggregate (PLA) formation in the early stage of septic ARDS.</p><p><strong>Methods: </strong>Sixty adult male SD rats were randomly divided into: Control group; ARDS group, ARDS + aspirin group, ARDS + clopidogrel group and ARDS + tirofiban group. ARDS was performed via instill lipopolysaccharide (LPS) intratracheally at a dose of 5 mg/kg. Aspirin or clopidogrel were given by gavage immediately after modeling. Tirofiban were given by intraperitoneal injection immediately after modeling. Rats in every group were euthanized by rapid decapitation 6 h after modeling. Platelet activation and PLA were assessed using flow cytometry and immunofluorescence staining. Histology of lung was performed by hematoxylin and eosin staining.</p><p><strong>Results: </strong>Aspirin, clopidogrel and tirofiban decreased CRP, IL-1 and TNF-α significantly in septic ARDS (P < 0.05). Aspirin, clopidogrel and tirofiban decreased platelet function and ratio of wet/dry significantly in septic ARDS (P < 0.05). Aspirin, clopidogrel and tirofiban increased PaO₂ significantly in septic ARDS (P < 0.05). Platelet activation and PLA in the ARDS + aspirin group, ARDS + clopidogrel group and ARDS + tirofiban group decreased significantly compared to the ARDS group (P < 0.05). At 6 h after ARDS operation, obvious histological damage was observed in the lungs. All of these histological changes were quantitatively evaluated using injury scores. Aspirin, clopidogrel and tirofiban reduced the histological damages in ARDS group (P < 0.05).</p><p><strong>Conclusions: </strong>Aspirin, clopidogrel and tirofiban alleviated the inflammatory response and pulmonary edema, reduced platelet function, and alleviated hypoxemia in early septic ARDS. Aspirin, clopidogrel and tirofiban reduced platelet activation and PLA formation in early septic ARDS. Aspirin, clopidogrel and tirofiban ultimately alleviated lung injury in early septic ARDS.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"4"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}