Drug Design, Development and Therapy最新文献

{"title":"Factors Affecting Vancomycin Trough Concentration; a Population Pharmacokinetic Model in Non-Critical Care Saudi Patients.","authors":"Aymen Ali Alqurain, Laila Nasser Alrashidi, Shatha Khalid Aloraifej, Moayd Alkhalifah, Hawra Ali Alsayed, Salah Abohelaika, Mohammad A Alshabeeb, Amal Shibak Aldhafeeri, Moyad Almuslim, Thuraya Nasser Bumozah, Mukhtar Jawad Alomar, Azhar Abdullah Alshehab, Ahmed AbdulWahab Alamer, Jenan Al-Matouq, Keshore R Bidasee, Fadhel A Alomar","doi":"10.2147/DDDT.S496512","DOIUrl":"10.2147/DDDT.S496512","url":null,"abstract":"<p><strong>Background and objective: </strong>Vancomycin is commonly prescribed in treatment of methicillin-resistant Staphylococcus aureus infections. While, vancomycins' pharmacokinetic vary among older patients, there is a paucity of data regarding specific characteristics influencing pharmacokinetics in Saudi adult patients. This study aims to establish a population-pharmacokinetic (Pop-PK) model for vancomycin in patients admitted to medical wards, with the focus on identification of patient characteristics influencing vancomycin trough concentrations.</p><p><strong>Methods: </strong>A multicenter retrospective study was conducted involving patients aged ≥40 years admitted to medical wards in the Eastern Province, Saudi Arabia and initiated on vancomycin, between January to December 2022. Non-linear mixed-effects modelling (Monolix) was employed to develop the Pop-PK model. A base model was selected based on the Akaike information criterion. Covariates considered included age, sex, body weight, C-reactive protein (CRP), serum creatinine, creatinine clearance (CrCl), and albumin levels. A <i>P</i>-value of <0.05 was considered statistically significant for inclusion of covariates in the final model by stepwise addition. The simulation performance of the model was assessed by visual predictive check plot. The final model was simulated using Simulx software to assess the effect of the included covariates on vancomycin trough concentration.</p><p><strong>Results: </strong>A total of 172 vancomycin trough concentrations from 124 patients were analyzed. The final Pop-PK model characterized vancomycin trough concentrations was one compartment distribution with linear elimination. CrCl and CRP were the only covariates included in the final model, as they reduced the between-subject variability (BSV) for clearance (from 173% to 81%). The simulated model demonstrated that high CRP value and low CrCl contributed to increased vancomycin trough concentrations.</p><p><strong>Conclusion: </strong>This study highlights large BSV in trough concentrations among patients and emphasizes the influencing of CrCl and CRP on vancomycin pharmacokinetics in medical care settings.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6185-6198"},"PeriodicalIF":4.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Intravenous Lidocaine on EC50 of Remifentanil for Preventing Cough During Emergence in Female for Thyroid Surgery Anesthesia.","authors":"Zheng-Lun Lin, Li Liu, Kai Shi, Tian-Jie Chen, Lin-Ming Chen, Hong-da Cai","doi":"10.2147/DDDT.S496608","DOIUrl":"10.2147/DDDT.S496608","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the effect of intravenous lidocaine injection on the half-maximum effective concentration (EC50) of remifentanil in preventing cough due to tracheal extubation in female patients undergoing thyroid surgery by Dixon's sequential method.</p><p><strong>Methods: </strong>A total of 50 female patients underwent elective thyroidectomy were randomly divided into two groups of a 1:1 ratio. Group L (lidocaine group) was given intravenous lidocaine (1.5 mg/kg) and then continuous infusion (2 mg/kg/h) until the end of surgery. Group C (control group) received 0.9% sodium chloride solution infusion in the same way. The primary outcome was effective concentration EC50 of remifentanil in preventing cough due to tracheal extubation in female patients undergoing thyroid surgery. The secondary outcomes were as follows: mean arterial pressure (MAP), oxygen saturation (SpO₂), heart rate (HR), PetCO₂ and respiratory rate at the time of tracheal extubation. The incidence of postoperative nausea and vomiting, and symptoms associated with lidocaine toxicity.</p><p><strong>Results: </strong>Finally, 44 subjects completed the study. The EC50 values of remifentanil calculated using probit regression were 1.40 ng/mL (95% CI, 1.15-1.65 ng/mL) in Group C and 0.83 ng/mL (95% CI, 0.58-1.08 ng/mL) in Group L. A lower concentration of remifentanil can inhibit the cough reaction during intravenous lidocaine infusion. PetCO₂ in the lidocaine group was lower than that in the control group (Z=-2.162, <i>P</i> < 0.05). The respiratory rate of the lidocaine group after extubation was higher than that of the control group (Z=-3.287, <i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Intravenous injection of lidocaine can reduce the effective concentration EC50 of remifentanil in preventing tracheal extubation cough in female patients undergoing thyroid surgery.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6165-6172"},"PeriodicalIF":4.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Position-Based Dosing Strategy for Metaraminol on Neonatal Acid-Base Status During Elective Caesarean Delivery: A Noninferiority Randomised Controlled Trial.","authors":"Tianyu Liu, Hua Jiang, Chao Xu, Lei Li, Hong Zhang, Yi Feng","doi":"10.2147/DDDT.S492254","DOIUrl":"10.2147/DDDT.S492254","url":null,"abstract":"<p><strong>Background: </strong>The 15° left tilt position during caesarean delivery has been recommended by guidelines for many years, but recent studies have questioned the clinical benefit of left tilt position. We hypothesize that using a higher starting dose of metaraminol in the supine position will result in a non-inferior umbilical arterial pH, compared to the 15° left tilt position.</p><p><strong>Methods: </strong>Healthy women undergoing elective caesarean delivery were randomized to the supine position (n = 62) or 15° left tilt position (n = 62) after spinal anaesthesia (0.5% bupivacaine 9 mg). Different starting doses of metaraminol infusion were initiated at 2.7 μg kg^-1 min^-1 for the supine position group and 2.0 μg kg^-1 min^-1 for the tilt position group. The infusion rates were then adjusted using a fixed algorithm to maintain systolic blood pressure. The primary outcome was the pH of the umbilical artery.</p><p><strong>Results: </strong>Compared with tilt group, pH (supine group: 7.325 (7.29, 7.35) vs tilt group: 7.33 (7.3, 7.35), P = 0.76) and base excess (tilt group: -0.98 (2.59) mM vs supine group: -0.92 (2.77) mM, P = 0.9) of the umbilical artery are non-inferior. There was no difference in SBP (P = 0.16) or incidence of hypotension (P = 0.75) between the two groups. The incidence of reactive hypertension was greater in the supine position group (P < 0.001).</p><p><strong>Conclusion: </strong>If maternal blood pressure is maintained using the higher starting dose of metaraminol, the left tilted position may not be necessary among healthy patients (BMI less than 35 kg/m²) undergoing elective caesarean delivery with spinal anaesthesia.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6209-6219"},"PeriodicalIF":4.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Quaternary Ammonium N-Propylamiodarone Bromide Provides Long-Lasting Analgesia Against Corneal Pain.","authors":"Yumi Kotoda, Sohei Hishiyama, Jaehoon Shim, Hiroki Kobayashi, Ayasa Takamino, Masako Abe, Kenji Kashiwagi, Takashi Matsukawa, Masakazu Kotoda","doi":"10.2147/DDDT.S486031","DOIUrl":"10.2147/DDDT.S486031","url":null,"abstract":"<p><strong>Purpose: </strong>Corneal pain is one of the most common eye symptoms caused by various types of epithelial injuries, including traumatic abrasion, chemical injury, ulcers, ultraviolet exposure, and infection. However, current therapeutic options for corneal pain are limited. In this study, we synthesized a novel quaternary ammonium compound, N-propylamiodarone bromide (NPA), and employed a rodent model of corneal injury to investigate whether NPA offers prolonged corneal analgesia through transient receptor potential vanilloid 1 (TRPV1) channel-mediated selective cellular entry, without hindering corneal epithelial recovery.</p><p><strong>Methods: </strong>In the corneal injury model, 24 adult Wistar rats received a topical application of normal saline, oxybuprocaine, or NPA (n = 8 each), and corneal pain sensitivity was assessed using the von Frey technique. Another set of 32 rats with intact corneas received oxybuprocaine, capsaicin (a TRPV1 agonist), or NPA with or without capsaicin (n = 8 each), followed by a mechanical sensitivity evaluation. Potential adverse effects on normal epithelial recovery were evaluated using fluorescence and hematoxylin-eosin staining in an additional 8 rats with corneal injury.</p><p><strong>Results: </strong>In the corneal injury model, NPA produced significantly longer-lasting analgesia than oxybuprocaine (duration of the maximum effect: 215 ± 11 vs 25 ± 2 min, P < 0.001). None of the animals presented any signs of eye irritability. In contrast to injured eyes, NPA alone did not significantly increase mechanical sensitivity in naïve eyes. However, the co-administration of NPA and capsaicin produced significantly longer-lasting corneal anesthesia than oxybuprocaine (duration of the maximum effect: 165 ± 15 vs 31 ± 2 min, P < 0.001). NPA did not hamper wound healing.</p><p><strong>Conclusion: </strong>The novel quaternary ammonium NPA produced long-lasting analgesia against corneal injury without hampering corneal recovery, suggesting that it is a potential candidate for analgesic medicine targeting corneal pain.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6199-6208"},"PeriodicalIF":4.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyroptosis the Emerging Link Between Gut Microbiota and Multiple Sclerosis.","authors":"Hua Fan, Ruile Shen, Junqiang Yan, Yongjie Bai, Qizhi Fu, Xiaofei Shi, Ganqin Du, Dongmei Wang","doi":"10.2147/DDDT.S489454","DOIUrl":"10.2147/DDDT.S489454","url":null,"abstract":"<p><p>This review elucidates the pivotal role of pyroptosis, triggered by gut microbiota, in the development of multiple sclerosis (MS), emphasizing its significance within the gut-brain axis. Our comprehensive analysis of recent literature reveals how dysbiosis in the gut microbiota of MS patients-characterized by reduced microbial diversity and shifts in bacterial populations-profoundly impacts immune regulation and the integrity of the central nervous system (CNS). Pyroptosis, an inflammatory form of programmed cell death, significantly exacerbates MS by promoting the release of inflammatory cytokines and causing substantial damage to CNS tissues. The gut microbiota facilitates this detrimental process through metabolites such as short-chain fatty acids and neuroactive compounds, or self-structural products like lipopolysaccharides (LPS), which modulate immune responses and influence neuronal survival. This review highlights the potential of modulating gut microbiota to regulate pyroptosis, thereby suggesting that targeting this pathway could be a promising therapeutic strategy to mitigate inflammatory responses and preserve neuronal integrity in patients with MS.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6145-6164"},"PeriodicalIF":4.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cubosomes as Delivery System to Repositioning Nitrofurantoin in Breast Cancer Management.","authors":"Dina Louis, Christianne Mounir Zaki Rizkalla, Amira Rashad","doi":"10.2147/DDDT.S499068","DOIUrl":"10.2147/DDDT.S499068","url":null,"abstract":"<p><strong>Purpose: </strong>Nitrofurantoin (NITRO), a long-standing antibiotic to treat urinary tract infections, is activated by Nitro reductases. This activation mechanism has led to its exploration for repositioning applications in controlling and treating breast cancer, which express a Nitro reductase gene.</p><p><strong>Methods: </strong>NITRO Cubosomes were developed using hot homogenization according to 2³-full factorial design. The factors studied included the ratio of drug to oily phase (1:10 and 2:10), the ratio of oily to aqueous phase (1:10 and 1:5), and the ratio of Glyceryl mono-oleate (GMO) to Poloxamer 407 (PX407) (0.25:1 and 0.5:1). A total of 8 systems were proposed and evaluated by measuring particle size, zeta potential, polydispersity index, and percentage of entrapment efficiency.</p><p><strong>Results: </strong>S6 (1:10 drug: oily phase, 1:5 oily: aqueous phase and 0.5:1 GMO: PX407) with particle size 45.5 ±c1.1 nm and an entrapment efficiency of 98.6 ± 1.8% exhibited highest desirability and was selected for further analysis. The morphology of S6 was examined using TEM microscopy. The activation of NITRO from S6 reflected on intracellular viability of MCF-7 breast cancer cell line was investigated by an MTT assay. The findings indicated that S6 had the lowest IC50 value (83.99 ± 0.15 μg g/mL) compared to Free NITRO (174.54 ± 1.36 μg g/mL), suggesting enhanced efficacy compared to free NITRO.</p><p><strong>Conclusion: </strong>Nitrofurantoin cubosomes can be candidates for repositioning in breast cancer management after encouraging further stability and in-vivo studies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6173-6184"},"PeriodicalIF":4.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Panax notoginseng</i> Saponins Improve Angiogenesis in Coronary Heart Disease Based on the microRNA 200a Methylation Pathway.","authors":"Jie Wang, Yan Dong, Zhaoling Li, Yun Zhang, Lanchun Liu, Guang Yang, Yongmei Liu, Jun Li, Lian Duan","doi":"10.2147/DDDT.S488036","DOIUrl":"10.2147/DDDT.S488036","url":null,"abstract":"<p><strong>Background: </strong>Improving angiogenesis in the ischemic myocardium is a therapeutic strategy for preventing, reducing, and repairing myocardial injury of coronary artery disease (CAD). <i>Panax notoginseng</i> saponins (PNS) have been widely used in the clinical treatment of cardiovascular diseases, demonstrating excellent efficacy, and can potentially improve angiogenesis in the ischemic myocardium. However, the effects of PNS on angiogenesis and its underlying mechanism of action remain unclear.</p><p><strong>Purpose: </strong>In this study, we aimed to evaluate the role of PNS in improving angiogenesis after myocardial infarction (MI) and explain the mechanism of PNS in improving angiogenesis in CAD from an epigenetic perspective.</p><p><strong>Study design: </strong>The MI rat model was established by ligating the left anterior descending coronary artery permanently. The in vitro model comprised hypoxic human coronary artery endothelial cells (HCEACs). The mice and cells were then treated with PNS.</p><p><strong>Methods: </strong>Blood tests, histomorphology, polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and MassARRAY targeted methylation detection analyses were conducted in vivo and in vitro to investigate the potential mechanisms of PNS.</p><p><strong>Results: </strong>Oral PNS significantly improved myocardial injury and activated angiogenesis in MI rats. DNA methylation analysis in vitro revealed that PNS decreased the hypermethylation of microRNA 200a (miR200a). PNS improved angiogenesis in hypoxic human coronary artery endothelial cells (HCEACs) by regulating the vascular endothelial growth factor (VEGF) pathway.</p><p><strong>Conclusion: </strong>Our research shows that PNS can improve angiogenesis in rats with MI and hypoxic HCEACs and affect the level of miR200a promoter methylation and miR200a and VEGF molecular pathways.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6075-6087"},"PeriodicalIF":4.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ciprofol Ameliorates Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis Through Upregulating HIF-1α.","authors":"Jun Ding, Bi-Ying Wang, Yu-Fan Yang, Ling-Yu Kuai, Jing-Jie Wan, Mian Zhang, Hai-Yan Xia, Yao Wang, Zhong Zheng, Xiao-Wen Meng, Ke Peng, Fu-Hai Ji","doi":"10.2147/DDDT.S480514","DOIUrl":"10.2147/DDDT.S480514","url":null,"abstract":"<p><strong>Purpose: </strong>Ciprofol is a novel intravenous anesthetic that has been increasingly used in clinical anesthesia and sedation. Studies suggested that ciprofol reduced oxidative stress and inflammatory responses to alleviate cerebral ischemia/reperfusion (I/R) injury, but whether ciprofol protects the heart against I/R injury and the mechanisms are unknown. Herein, we assessed the effects of ciprofol on ferroptosis during myocardial I/R injury.</p><p><strong>Methods: </strong>Experimental models of myocardial I/R injury in mice (ischemia for 30 min and reperfusion for 24 h) and hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes (hypoxia for 6 h followed by 6 h of reoxygenation) were established. Ciprofol was used prior to ischemia or hypoxia. Echocardiography, myocardial TTC staining, HE staining, DAB-enhanced Perl's staining, transmission electron microscopy, FerroOrange staining, Liperfluo staining, JC-1 staining, Rhodamine-123 staining, DCFH-DA staining, and Western blot were performed. Cell viability, serum cardiac enzymes, and oxidative- and ferroptosis-related biomarkers were measured. HIF-1α siRNA transfection and the specific inhibitor BAY87-2243 were utilized for mechanistic investigation.</p><p><strong>Results: </strong>Ciprofol treatment reduced myocardial infarct area and myocardium damage, alleviated oxidative stress and mitochondrial injury, suppressed Fe²⁺ accumulation and ferroptosis, and improved cardiac function in mice with myocardial I/R injury. Ciprofol also increased cell viability, attenuated mitochondrial damage, and reduced intracellular Fe²⁺ and lipid peroxidation in cardiomyocytes with H/R injury. Ciprofol enhanced the protein expression of HIF-1α and GPX4 and reduced the expression of ACSL4. Specifically, the protective effects of ciprofol against I/R or H/R injury were abolished by downregulating the expression of HIF-1α using siRNA transfection or the inhibitor BAY87-2243.</p><p><strong>Conclusion: </strong>Ciprofol ameliorated myocardial I/R injury in mice and H/R injury in cardiomyocytes by inhibiting ferroptosis via the upregulation of HIF-1α expression.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6115-6132"},"PeriodicalIF":4.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrathecal Morphine and Ropivacaine for Quality of Recovery After Laparoscopic Colorectal Surgery: A Randomized Controlled Trial.","authors":"Ying Yang, Wenjun Lin, Yifen Zhuo, Yuxin Luo, Xiaoyan Wu, Junyu Li, Yusheng Yao","doi":"10.2147/DDDT.S500316","DOIUrl":"10.2147/DDDT.S500316","url":null,"abstract":"<p><strong>Purpose: </strong>Intrathecal morphine is increasingly used for pain management in laparoscopic colorectal surgery. While ropivacaine shows advantages of reduced cardiotoxicity and faster motor recovery compared to bupivacaine, the impact of intrathecal morphine-ropivacaine combination on postoperative recovery quality remains unclear. This study aimed to evaluate this combination's effect on recovery outcomes after laparoscopic colorectal surgery.</p><p><strong>Patients and methods: </strong>In this randomized, double-blind, placebo-controlled trial, 78 patients undergoing laparoscopic colorectal surgery received either preservative-free intrathecal morphine 250 μg with ropivacaine 15 mg (Intrathecal group) or a sham subcutaneous saline injection (Control group). The primary outcome was the Quality of Recovery-15 (QoR-15) score 24 hours after surgery. Secondary outcomes included pain scores, opioid consumption, and adverse effects.</p><p><strong>Results: </strong>The intrathecal group showed significantly higher QoR-15 scores 24 hours postoperatively compared to the control group (median [IQR]: 121 [109-128] vs 111 [102-116], p < 0.001), with improvements in pain management (p < 0.001), physical comfort (p = 0.001), and physical independence (p = 0.002). The intrathecal group had lower pain scores at rest (area under the curve 0-48 h: 66 [59-90] vs 107 [89-126], p < 0.001) and during coughing (152 [137-172] vs 191 [166-213], p < 0.001), particularly from 0.5 to 24 hours. They also required less postoperative morphine (0-48 h: 10 [6-20] vs 26 [22-36] mg, p < 0.001). While hypotension (43.6% vs 17.9%, p = 0.014) and pruritus (35.9% vs 2.6%, p < 0.001) were more frequent in the intrathecal group, but no respiratory depression occurred in either group.</p><p><strong>Conclusion: </strong>Intrathecal morphine-ropivacaine administration improves 24-hour postoperative recovery quality and provides superior pain relief after laparoscopic colorectal surgery, despite increased but manageable side effects. Further research should focus on dose optimization and comparative studies of different intrathecal local anesthetic combinations.</p><p><strong>Trial registration: </strong>The Chinese Clinical Trial Registry, ChiCTR2100052337.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6133-6143"},"PeriodicalIF":4.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on the Anti-Liver Cancer Mechanism and Toxicity of Rhubarb Anthraquinone.","authors":"Linyuan Yu, Jinxing Qin, Mei Zhang, Yawen Gao, Yongli Zhao","doi":"10.2147/DDDT.S489377","DOIUrl":"10.2147/DDDT.S489377","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Rhubarb has the effect of breaking blood stasis and abnormal mass, and was often used to treat various tumor diseases including liver cancer in ancient China. Recipes containing rhubarb have anti-liver cancer properties and are still used today. However, the main components and mechanism of action of rhubarb against liver cancer are still unclear.</p><p><strong>Aim of the review: </strong>To conduct a review of the anti-liver cancer effects and toxicity of rhubarb anthraquinones (AQs).</p><p><strong>Materials and methods: </strong>This article reviewed the effects of rhubarb AQs in the treatment of liver cancer and the signaling pathways involved, and discussed the toxicity and pharmacokinetics of rhubarb AQs by searching the Web of Science, PubMed and CNKI databases.</p><p><strong>Results: </strong>Rhubarb (Rhei Radix et Rhizoma) is a traditional Chinese medicine that has been existed for thousands of years and is used as an anti-cancer drug. Modern pharmacological research shows that rhubarb AQs, as the main component of rhubarb, contains emodin, rhein, chrysophanol, physcione and aloe-emodin, which has anti-liver cancer effects and can be considered as a potential therapeutic drug for liver cancer. However, many modern studies have shown that rhubarb AQs have certain toxicity, which hinders in-depth research on rhubarb AQs.</p><p><strong>Conclusion: </strong>Rhubarb AQs can be used as a potential anti-liver cancer drug, but its research still has many limitations. Strengthening research on related experiments and finding a balance between toxicity and efficacy are all directions worth studying in the future.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6089-6113"},"PeriodicalIF":4.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}