Current Therapeutic Research-clinical and Experimental最新文献

{"title":"Alpha-Lipoic Acid-Mediated Inhibition of LTB4 Synthesis Suppresses Epithelial-Mesenchymal Transition, Modulating Functional and Tumorigenic Capacities in Non-Small Cell Lung Cancer A549 Cells","authors":"María José Torres PhD ,&nbsp;Juan Carlos Ríos PhD ,&nbsp;Alexandra Valle MSc ,&nbsp;Sebastián Indo PhD ,&nbsp;Kevin Brockway GV MSc ,&nbsp;Fernanda López-Moncada PhD ,&nbsp;Mario Faúndez PhD ,&nbsp;Enrique A. Castellón PhD ,&nbsp;Héctor R. Contreras PhD","doi":"10.1016/j.curtheres.2024.100765","DOIUrl":"10.1016/j.curtheres.2024.100765","url":null,"abstract":"<div><h3>Background</h3><div>Leukotriene B₄ (LTB₄) plays a crucial role in carcinogenesis by inducing epithelial-mesenchymal transition (EMT), a process associated with tumor progression. The synthesis of LTB₄ is mediated by leukotriene A₄ hydrolase (LTA₄H), and it binds to the receptors BLT₁ and BLT₂. Dysregulation in LTB₄ production is linked to the development of various pathologies. Therefore, the identification or design of inhibitors of LTB₄ synthesis or receptor antagonists represents an ongoing challenge. In this context, our laboratory previously demonstrated that alpha-lipoic acid (ALA) inhibits LTA₄H. The objective of this study was to evaluate the effect of ALA on the expression of canonical EMT markers and the functional and tumorigenic capacities induced by LTB₄ in A549 cells.</div></div><div><h3>Methods</h3><div>The expression of cPLA₂, 5LOX, FLAP, LTA₄H, BLT1, and LTB₄ production in human adenocarcinomic alveolar basal epithelial A549 cells was assessed using Western blot, RT-qPCR, and ELISA, respectively. Subsequently, the expression of canonical EMT markers was evaluated by Western blot. Functional assays were performed to assess cell viability, proliferation, invasion, migration, and clonogenicity using MTT, Western blot, Transwell assays, and colony formation assays, respectively. Results were expressed as median with interquartile range (n≥3) and analyzed using the Kruskal-Wallis or Tukey multiple comparisons tests.</div></div><div><h3>Results</h3><div>A549 cells express key proteins involved in LTB₄ synthesis and receptor binding, including LTA₄H and BLT₁, and ALA inhibits the production of LTB₄. Additionally, LTA₄H and BLT1 were detected in lung adenocarcinoma tissue samples. LTB₄ was found to induce EMT, whereas ALA treatment enhanced the expression of epithelial markers and reduced the expression of mesenchymal markers. Furthermore, ALA treatment resulted in a decrease in LTB₄ levels and attenuated the functional and tumorigenic capacities of A549 cells, including their viability, migration, invasion, and clonogenic potential.</div></div><div><h3>Conclusions</h3><div>These findings suggest that ALA may offer therapeutic potential in the context of lung cancer, as it could be integrated into conventional pharmacological therapies to enhance treatment efficacy and mitigate the adverse effects associated with chemotherapy. Further studies are warranted to confirm the clinical applicability of ALA as an adjunctive treatment in lung cancer.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100765"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Anthocyanin Supplementation on Pro-Inflammatory Biomarkers in Patients With Metabolic Disorders: A Grade-Assessed Systematic Review and Meta-Analysis","authors":"Fatemeh Babaee Kiadehi MSc ,&nbsp;Pegah Samani MSc ,&nbsp;Sanaz Barazandeh MSc ,&nbsp;Pedram Pam MSc ,&nbsp;Ali Hajipour MSc ,&nbsp;Narges Goli MSc ,&nbsp;Ali Asadi PhD","doi":"10.1016/j.curtheres.2024.100772","DOIUrl":"10.1016/j.curtheres.2024.100772","url":null,"abstract":"<div><h3>Introduction and Aim</h3><div>Patients with metabolic disorders benefit from using anthocyanins. Nevertheless, the findings drawn from extant trials remain contentious. Thus, this meta-analysis evaluated anthocyanin's effect on inflammatory biomarkers in patients with metabolic disorders.</div></div><div><h3>Materials and Methods</h3><div>We comprehensively searched electronic databases, including PubMed, Scopus, Web of Science, and CENTRAL, from their inception to June 14, 2024.</div></div><div><h3>Findings</h3><div>A total of 11 randomized controlled clinical trials with 14 arms were analyzed. There was no significant effect of anthocyanin supplementation on interleukin (IL)-1β levels (standardized mean difference [SMD] = –0.01, 95% CI: –0.33, 0.31; <em>P</em> = 0.941, <em>I</em>² = 62.4%, <em>P</em> = 0.031), tumor necrosis factor-α (TNF-α) (SMD = –0.49, 95% CI: –1.07, 0.09; <em>P</em> = 0.098, <em>I</em>² = 94.0%, <em>P</em> &lt; 0.001) and IL-6 (SMD = –0.69, 95% CI: –1.45, 0.06; <em>P</em> = 0.073, <em>I</em>² = 95.2%, <em>P</em> &lt; 0.001), respectively. A significant between-study heterogeneity was identified, which was reduced when subgrouping by sample size, dosage, and study population. However, subgroup analysis showed that it might decrease TNF-α and IL-6 in patients with hypertension, and if the intervention lasted less than 12 weeks.</div></div><div><h3>Conclusions</h3><div>There was no significant impact of anthocyanin supplementation on IL-1β, TNF-α, and IL-6; however, it should be noted that the intervention has a decreasing impact on individuals with hypertension. Our observed effect sizes on IL-1β, TNF-α, and IL-6 are not clinically important.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100772"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Events and Heart Failure in Patients With Type 2 Diabetes Treated With Dipeptidyl Peptidase-4 Inhibitors: A Meta-Analysis","authors":"Adili Tuersun PhD ,&nbsp;Shufen Cui BS ,&nbsp;Li Han BS ,&nbsp;Alimu Aikebaier BS ,&nbsp;Yanyan Shi BS ,&nbsp;Gang Cheng PhD ,&nbsp;Lei Cheng BS ,&nbsp;Guo Ma PhD","doi":"10.1016/j.curtheres.2025.100804","DOIUrl":"10.1016/j.curtheres.2025.100804","url":null,"abstract":"<div><h3>Background</h3><div>The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise, with patients facing significantly elevated risks of cardiovascular complications, particularly heart failure (HF).</div></div><div><h3>Objective</h3><div>This examination sought to methodically examine cardiovascular sequelae, notably heart failure, among users of dipeptidyl peptidase 4 (DPP-4) inhibitors when compared with nonusers.</div></div><div><h3>Methods</h3><div>Cochrane, Embase, and PubMed databases, which compared the use of DPP-4 inhibitors and reported cardiovascular outcomes and heart failure events in patients with type 2 diabetes mellitus (T2DM), were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: they were randomized trials comparing DPP-4 inhibitor use in patients with T2DM; study duration was longer than 24 weeks; and they reported cardiovascular outcomes as their main or secondary end points. Stata 15 MP (StataCorp LLC, College Station, Texas, USA) was used to analyze the data, and odds ratios (ORs) with 95% CIs were used to represent the results.</div></div><div><h3>Results</h3><div>A total of 79,010 participants with T2DM were included. A total of 37,895 patients were assigned to the DPP-4 inhibitor group, whereas 41,115 patients were assigned to the control group. Results of the analysis showed that during a mean follow-up period ranging from 24 to 302 weeks, heart failure incidence did not differ significantly between T2DM patients treated with DPP-4 inhibitors and those who were not (OR = 1.06; 95% CI, 0.96–1.18; <em>P</em> = 0.452). Major adverse cardiovascular events (including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death; OR = 1.01; 95% CI, 0.95–1.08; <em>P</em> = 0.354), stroke (OR = 1.01; 95% CI, 0.78–1.30; <em>P</em> = 0.968), myocardial infarction (OR = 0.89; 95% CI, 0.73–1.07; <em>P</em> = 0.49), and all-cause mortality (OR = 1.03; 95% CI, 0.96–1.11; <em>P</em> = 0.309) were also similarly manifested in both groups.</div></div><div><h3>Conclusions</h3><div>The present analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes and heart failure in these patients with T2DM, indicating that these drugs may be safe to use in terms of cardiovascular events.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100804"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis of the Efficacy and Safety of Sintilimab in Combination With Chemotherapy for Advanced Non–Small-Cell Lung Cancer","authors":"Liling Pan MPharm ,&nbsp;Qiongqing Chen MPharm ,&nbsp;Ningsheng Liang PhD ,&nbsp;Jinying Liang MBBS ,&nbsp;Youjia Guo MMed","doi":"10.1016/j.curtheres.2025.100796","DOIUrl":"10.1016/j.curtheres.2025.100796","url":null,"abstract":"<div><h3>Objective</h3><div>Sintilimab is an innovative immune checkpoint inhibitor (ICI), domestically produced in China, that exhibits significant efficacy in the treatment of lung cancer. However, due to the delayed initiation of ICI development in China, its use is currently restricted to domestic markets, resulting in a limited volume of clinical data, which poses a challenge in postmarketing evaluation. This study aimed to assess the safety and efficacy of sintilimab through a meta-analysis.</div></div><div><h3>Methods</h3><div>We conducted independent searches for relevant articles in both Chinese and international databases, followed by independent screening, after which the data were extracted from the selected studies. Statistical analysis was performed using RevMan software, version 5.4, and the results were estimated using the risk ratio with 95% confidence interval.</div></div><div><h3>Results</h3><div>Efficacy analysis revealed that sintilimab, when combined with chemotherapy, significantly enhanced the objective response rate and disease control rate in patients with non-small-cell lung cancer (NSCLC) while reducing the risk of disease progression. Evaluation of the safety of sintilimab revealed that the risks of hypothyroidism, pneumonia, and rash in patients with advanced NSCLC following treatment were higher than those of the control group by 3.70-fold, 2.22-fold, and 1.58-fold, respectively. There were no significant differences between the combination therapy and chemotherapy groups in terms of the incidence of blood system toxicity, impairment of liver function, and fever; however, nausea, vomiting, and diarrhea appeared to be less severe in the combination therapy group.</div></div><div><h3>Conclusions</h3><div>Sintilimab, combined with chemotherapy, demonstrates promising efficacy in the treatment of advanced NSCLC; however, it is imperative to closely monitor for adverse events, particularly immune-related adverse events.</div></div><div><h3>Clinical trial registration</h3><div>Not available.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100796"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Bioavailability of Nitrates and Nitrites in 3 Species of Amaranthus: A Randomized, Double-Blind, Placebo-Controlled, 4-Way Crossover Study in Healthy Subjects Under Fasting Conditions","authors":"Deepa Suhag ,&nbsp;Aparna Nilesh Kodre","doi":"10.1016/j.curtheres.2025.100789","DOIUrl":"10.1016/j.curtheres.2025.100789","url":null,"abstract":"<div><h3>Background</h3><div><em>Amaranthus</em> is a significant source of dietary nitrates, which have been known to improve aerobic capacity and exercise performance in physically active individuals. There is a significant data gap on nonpartitive pharmacokinetics and bioequivalence studies of nitrate and nitrite from 3 species of Amaranth (<em>A. hybridus, A. hypochondriacus</em>, and <em>A. tricolor</em>).</div></div><div><h3>Objective</h3><div>This study aimed to assess the bioavailability of nitrates and nitrites from 3 <em>Amaranthus</em> species in a randomized, placebo-controlled design, thereby filling this gap.</div></div><div><h3>Methods</h3><div>A double-blinded, 4-way crossover study was conducted in 16 healthy participants. Each participant enrolled in the study received a single dose of 2000 mg of <em>Amaranthus</em> extract or a placebo. The plasma and saliva samples were collected at specific intervals over 24 hours. Nitrate and nitrite concentrations were analyzed using a validated LCMS/MS method.</div></div><div><h3>Results</h3><div>After the administration of amaranth extracts, both plasma and saliva samples were observed significantly higher levels of nitrate and nitrite compared with the placebo group. Pharmacokinetic variables (C_max, AUC_0-t24, and AUC0-∞) found a similar pattern for nitrite and nitrate in the 3 amaranth products but were significantly different from placebo (<em>P</em> &lt; 0.05), in both plasma and saliva samples. Bioequivalence analysis confirmed significant bioequivalence among the 3 amaranth extracts for nitrite and nitrate.</div></div><div><h3>Conclusions</h3><div>This study concludes that the 3 species of <em>Amaranthus</em>—<em>A. hybridus, A. hypochondriacus</em>, and <em>A. tricolor</em> are bioequivalent in terms of plasma and saliva nitrate and nitrite levels from a single dose of 2000 mg amaranth extract and have higher bioavailability than placebo. These findings report that <em>Amaranthus</em> extracts could potentially act as a daily diet supplement for improving the cardiovascular and neurogenerative health of the body, particularly aging people.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100789"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unleashing the Potential of Givinostat: A Novel Therapy for Duchenne Muscular Dystrophy","authors":"Ahmad Furqan Anjum MBBS, BSc ,&nbsp;Muhammad Burhan Anjum MBBS ,&nbsp;Raza ur Rehman MBBS, Bsc","doi":"10.1016/j.curtheres.2025.100787","DOIUrl":"10.1016/j.curtheres.2025.100787","url":null,"abstract":"<div><h3>Purpose</h3><div>Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder with limited treatment options beyond corticosteroids, which have significant adverse effects. Givinostat, a histone deacetylase inhibitor, has recently emerged as a promising disease-modifying therapy. This commentary examines the therapeutic potential of givinostat, its mechanism of action, and the clinical evidence supporting its role in DMD treatment.</div></div><div><h3>Methods</h3><div>A review of the EPIDYS Phase 3 trial and supporting clinical studies was conducted. The study included boys aged 6 to 17 years with genetically confirmed DMD, assessing givinostat's efficacy and safety over 18 months. Key endpoints included the North Star Ambulatory Assessment (NSAA), MRI-based muscle preservation, and adverse event (AE) profiles.</div></div><div><h3>Findings</h3><div>Givinostat-treated patients demonstrated a 1.9-point higher NSAA score compared to placebo (<em>P</em> = 0.03), with significant reductions in muscle fat infiltration (40% lower than placebo; <em>P</em> &lt; 0.05). Functional tests showed trends toward improved stair-climbing ability, though not statistically significant. AEs included thrombocytopenia (20%) and hypertriglyceridemia (10%), necessitating monitoring but remaining manageable.</div></div><div><h3>Implications</h3><div>Givinostat represents a paradigm shift in DMD management, offering benefits beyond corticosteroids by reducing fibrosis and promoting muscle regeneration. While its long-term safety and cost-effectiveness require further evaluation, its combination potential with gene therapies highlights its importance in future DMD treatment strategies. Ongoing studies aim to refine its role in broader neuromuscular disorders.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100787"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Effect of Reducing the Signs and Symptoms of Lid Wiper Epitheliopathy in Patients With Dry Eye Disease With Perfluorohexyloctane","authors":"Chris Lievens OD, MS, PhD, FNAP, FAAO ,&nbsp;Andrew D. Pucker OD, PhD, FAAO ,&nbsp;Quentin Franklin BS ,&nbsp;Stephen M. Montaquila OD, FAAO ,&nbsp;Brad Giedd OD, MS, FAAO ,&nbsp;Gina Wesley OD, MS, FAAO ,&nbsp;Morgan Bromley PhD ,&nbsp;Zackarias Coker MS ,&nbsp;John Meyers MS ,&nbsp;Marta Vianya-Estopa PhD","doi":"10.1016/j.curtheres.2025.100786","DOIUrl":"10.1016/j.curtheres.2025.100786","url":null,"abstract":"<div><h3>Background</h3><div>Perfluorohexyloctane (PFHO) acts to prevent the evaporation of the tear film. It has the potential to limit friction related issues between the eye lid margin and the ocular surface. Prior to the present work, this had not yet been evaluated.</div></div><div><h3>Objective</h3><div>To examine the potential of using perfluorohexyloctane for reducing the signs and symptoms of lid wiper epitheliopathy (LWE).</div></div><div><h3>Methods</h3><div>Data were collected at 4 visits spanning 2 months. Patients who had symptomatic dry eye and a LWE score of ≥1.0 on the Korb LWE scale were recruited. Participants were randomized to PFHO 4 times a day or no treatment. Lid wiper epitheliopathy was graded at each visit with the Korb and photographic LWE (PLWE) scales. Symptoms were assessed using the Standard Patient Evaluation of Eye Dryness questionnaire and visual analog scales (0–100).</div></div><div><h3>Results</h3><div>A total of 52 participants were enrolled (mean ± SD age, 49.7 ± 15.7 years; 79% female). Right eyes in the treatment group were significantly more likely to show an improvement of ≥0.5-units in PLWE scores at 2 months than the no treatment group (<em>P</em> = 0.04), but no left eye differences were noted. Korb and PLWE scores were significantly better in the treatment group compared with the no treatment group starting at 2 weeks and remained so for the duration of the study (all <em>P</em> &lt; 0.001). Standard Patient Evaluation of Eye Dryness scores and dry eye symptoms were significantly better in the treatment than in the no treatment group at the 2-month visit (all <em>P</em> ≤ 0.01).</div></div><div><h3>Conclusions</h3><div>Perfluorohexyloctane significantly reduced LWE and improved dry eye symptoms compared with no treatment, suggesting that PFHO may enhance ocular lubrication and reduce friction-related damage. Masked, randomized, trials are still needed to compare PFHO to other treatments in participants with LWE to support generalizability of results. ClinicalTrials.gov study NCT06671041.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100786"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy","authors":"Tahereh Eteraf-Oskouei Phd ,&nbsp;Adel Mahmoudi Gharehbaba Phd ,&nbsp;Solmaz Asnaashari Phd ,&nbsp;Zahra Fazli Phd ,&nbsp;Bohloul Habibi Asl Phd","doi":"10.1016/j.curtheres.2025.100783","DOIUrl":"10.1016/j.curtheres.2025.100783","url":null,"abstract":"<div><h3>Background</h3><div>The treatment of chronic pain presents a considerable difficulty, particularly due to opioid dependence, which is marked by tolerance and withdrawal symptoms. Opioids primarily target mu (μ) opioid receptors, providing pain relief while also leading to various side effects. This research aimed to examine the effectiveness of cetirizine and green tea hydroalcoholic extract (EXT) in altering morphine tolerance and improving analgesic effects.</div></div><div><h3>Methods</h3><div>Adult male mice were divided into nine groups. In order to investigate the analgesic tolerance, animals received morphine on 14 consecutive days. Cetirizine (5, 10, 20 mg/kg, i.p.) and EXT (50, 100, 200 mg/kg, i.p.) were given before a test dose of morphine (9 mg/kg, i.p.). The analgesic effects were evaluated by the hot plate test.</div></div><div><h3>Results</h3><div>Cetirizine with doses of 5, 10, 20 mg/kg, and 10 mg/kg showed a significant effect in reducing morphine tolerance 30 min (<em>P</em> &lt; 0.0001) and 45 to 60 min (<em>P</em> &lt; 0.0001) after test dose of morphine (9 mg/kg, i.p.) respectively. While the injection of different doses of the extract did not show any effect on tolerance to morphine. In the combined injection of these two drugs, there was no reduction in tolerance to morphine.</div></div><div><h3>Conclusions</h3><div>Cetirizine but not EXT reversed morphine tolerance. Furthermore, the co-administration of cetirizine and EXT did not yield any significant benefits compared to the individual treatments.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100783"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Cyclosporine Treatment for Four Pediatric Patients With Toxic Epidermal Necrolysis That Showed No Response to High-dose Corticosteroids in Combination With Intravenous Immunoglobulin: A Case Series","authors":"Peijing Li MD ,&nbsp;Qin Yao MD ,&nbsp;Yuanyuan Wang MD ,&nbsp;Xipeng Xu MD","doi":"10.1016/j.curtheres.2024.100767","DOIUrl":"10.1016/j.curtheres.2024.100767","url":null,"abstract":"<div><h3>Background</h3><div>Immunosuppressive agents like cyclosporine have proven effective in some pediatric cases, although there are limited case reports considering potential risks such as secondary infections.</div></div><div><h3>Objective</h3><div>This study investigated the safety and efficacy of Cyclosporine A in children who did not respond to high-dose corticosteroids combined with intravenous immunoglobulin (IVIG).</div></div><div><h3>Methods</h3><div>We reported four pediatric patients diagnosed with toxic epidermal necrolysis (TEN) received treatment at our institution. All patients were previously healthy children with a median age of 7 years, comprising three boys and one girl (<span><span>Table 1</span></span>). Epidermal exfoliation and vesicular lesions ranged from 32.5% to 54.5% of the body surface area (BSA). Despite the administration of treatment comprising high-dose corticosteroids and intravenous immunoglobulin (IVIG), new cutaneous herpes continually emerged. This prompted a transition to cyclosporine treatment (3–5 mg/kg/d) administered in 1–2 oral doses.</div></div><div><h3>Results</h3><div>Lesions stopped progressing, and bullous lesions started epithelialization after 13–27 days of hospitalization. Cases 1 and 2 faced secondary bacterial and fungal infections, respectively, and their temperatures stabilized after administration of antibiotics. Cases 3 and 4 experienced fever again when the dosage of corticosteroids was tapered off, with no discernible evidence of infection. The patients’ temperatures normalized upon the continuation of cyclosporine therapy. Among the patients, three presented asymptomatic elevated serum amylase, one of which met the diagnostic criteria for acute pancreatitis. Two children showed mildly raised aminotransferases, with one experiencing mild coronary artery dilation, two contracted onychomadesis, and three developed corneal ulceration/keratitis and atretoblepharia, which eventually resolved after vigorous ophthalmologic treatment. None of the children had any permanent sequelae after being discharged from the hospital for six months.</div></div><div><h3>Conclusions</h3><div>Cyclosporine A is generally safe and effective for children who fail to respond to high-dose corticosteroids in combination with IVIG.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100767"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Solutions for Multidrug-Resistant Organisms’ Infections in Intensive Care Unit: A Joint Efficacy Evaluation of Multidisciplinary Team and SHEL (Software, Hardware, Environment, Liveware) Model","authors":"Xiaoyan Kang MD ,&nbsp;Ping Zhang DNP ,&nbsp;Qing Xu MD ,&nbsp;Zhengqun Feng MD ,&nbsp;Bei Yin MD","doi":"10.1016/j.curtheres.2024.100766","DOIUrl":"10.1016/j.curtheres.2024.100766","url":null,"abstract":"<div><h3>Background</h3><div>The escalating threat of multidrug-resistant organisms (MDROs) in intensive care unit (ICU) demands innovative management strategies to curb the rising infection rates and associated clinical challenges.</div></div><div><h3>Objective</h3><div>To assess the effectiveness of integrating the multidisciplinary team (MDT) approach with the SHEL (Software, Hardware, Environment, Liveware) model in reducing MDRO infections within ICU settings.</div></div><div><h3>Methods</h3><div>From January 2021 to April 2024, a prospective, randomized controlled study was conducted in the ICU of Nantong Fourth People's Hospital, enrolling 411 patients with MDRO infections. These patients were randomly assigned into 3 groups: the MDT group, the SHEL model group, and a combined group. The intervention lasted for 4 weeks, during which the effects on the MDRO detection rate, infection rate, health care staff's infection control execution scores, and the rationality of antibiotic use were assessed, aiming to determine the efficacy of each approach in managing MDROs in the ICU setting.</div></div><div><h3>Results</h3><div>The overall infection rate of MDROs in the ICU of our hospital from 2021 to 2024 was 60.18%, with sputum infection sources accounting for 68.37% of the total sources, making it the primary source of infection. The detection rate of MDROs in the combined group was significantly higher than that in the MDT and the SHEL groups, with the SHEL group having a higher detection rate than the MDT group (<em>P</em> &lt; 0.05). The infection rate of MDROs in the combined group was significantly lower than that in both the MDT and the SHEL groups, with the SHEL group having a lower detection rate than the MDT group (<em>P</em> &lt; 0.05). The implementation scores of the combination group in standard prevention, hand hygiene, antibiotic management, and isolation measures were significantly higher than those of the MDT and SHEL groups, with the SHEL group scoring higher than the MDT group (<em>P</em> &lt; 0.05). The rational use of antibiotics in the combined group was also higher than in both the MDT and the SHEL groups, with the SHEL group having a higher level than the MDT group (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>The integrated MDT and SHEL model significantly reduced MDRO infections in ICU, improved health care workers' infection prevention and nursing quality, and promoted the appropriate use of antibiotics, advocating for its clinical application.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100766"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}