Current Therapeutic Research-clinical and Experimental最新文献

{"title":"Efficacy and Safety of Nebulized Sodium Bicarbonate in Adults with COVID-19 (SODIC): A Randomized, Single-Center, Double-Blinded, Controlled Trial","authors":"Mohammad Khairy El-Badrawy MD ,&nbsp;Rehab Ahmad Elmorsey MD ,&nbsp;Mahmoud Mostafa Elhosiny MD ,&nbsp;Mohammed Shehta MD ,&nbsp;Tamer Ali El-Hadidy MD ,&nbsp;Ibrahim El-Said Abdelwahab MD ,&nbsp;Adel El-Badrawy MD ,&nbsp;Ahmed A. Shokeir MD","doi":"10.1016/j.curtheres.2025.100801","DOIUrl":"10.1016/j.curtheres.2025.100801","url":null,"abstract":"<div><h3>Background</h3><div>Entry of severe acute respiratory syndrome coronavirus 2 into a host cell is pH-dependent. Hence, intracellular alkalinization by nebulized sodium bicarbonate could elevate endosomal pH and then block viral entry into the host cells.</div></div><div><h3>Objective</h3><div>To study the efficacy of nebulized sodium bicarbonate as an adjuvant treatment for coronavirus disease 2019 (COVID-19).</div></div><div><h3>Methods</h3><div>A prospective, randomized, double-blinded trial was conducted in Mansoura University Hospital, Egypt. Eligible patients were &gt;18 years old with all COVID-19 severities. Patients were electronically randomly assigned (1:1) to receive standard treatment only (control group) (274 patients) or standard treatment plus nebulized sodium bicarbonate (272 patients). The primary end points were time to clinical improvement, defined as number of days from diagnosis until reporting of a better feeling by the patients; length of hospital stay for admitted patients; and mortality. This study was registered at ClinicalTrials.gov (NCT05035524) on September 2, 2021, and has been completed.</div></div><div><h3>Results</h3><div>Between September 2, 2021, and April 30, 2022, 546 patients (215 men and 331 women) were enrolled and randomly allocated for treatment. Mean (SD) age was 50.7 (16.8) years. Study showed a significantly shorter time to clinical improvement and length of hospital stay in the study group (<em>P</em> &lt; 0.001), and the number of deaths was significantly low only in the severe grade of the study group (11 cases in the study group vs 22 cases in the control group, <em>P</em> = 0.014). C-reactive protein and D-dimer levels measured at 1 week were significantly lower in the severe cases of the study group (<em>P</em> = 0.001). The overall median computed tomography score was significantly better in the study group at all points of follow-up (<em>P</em> &lt; 0.05). All patients reported mild irritative cough initially with sodium bicarbonate inhalation. No serious treatment adverse events were observed.</div></div><div><h3>Conclusions</h3><div>Nebulized sodium bicarbonate (8.4%) could be a possible adjuvant therapy for patients with moderate and severe COVID‑19. ClinicalTrials.gov identifier: NCT05035524.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100801"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470634","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":"Real-World Utilization Patterns, Safety, and Efficacy of Tafamidis in Patients With Hereditary Transthyretin Amyloidosis in Japan","authors":"Hiroaki Konishi PharmD ,&nbsp;Hajime Abe MD, PhD ,&nbsp;Noriko Matsumoto ,&nbsp;Yutaka Endo ,&nbsp;Yoshiki Sekijima MD, PhD ,&nbsp;Mitsuharu Ueda MD, PhD ,&nbsp;Yukio Ando MD, PhD","doi":"10.1016/j.curtheres.2025.100793","DOIUrl":"10.1016/j.curtheres.2025.100793","url":null,"abstract":"<div><h3>Purpose</h3><div>Patients with hereditary transthyretin (ATTRv) amyloidosis experience progressive degeneration of the somatic and peripheral nervous system that can impair ambulation, autonomy, and quality of life (QOL). Tafamidis meglumine (tafamidis) is the first pharmacotherapy approved to slow the progression of peripheral neurological impairment in ATTRv amyloidosis and was well tolerated and efficacious in clinical trials; however, longer-term safety in Japanese patients with ATTRv amyloidosis has not been fully elucidated. Consequently, the present study was conducted to understand the safety and efficacy of long-term use (up to 156 weeks) of tafamidis meglumine under postmarketing conditions in Japan.</div></div><div><h3>Methods</h3><div>This single-arm observational study (conducted from November 2013 to May 2021) included all patients prescribed tafamidis (20 mg/day) for the treatment of ATTRv amyloidosis in routine clinical practice. The observation period was 156 weeks (3 years) following tafamidis initiation (78 weeks [1.5 years] for patients who initiated treatment after May 2018). The outcomes of interest were clinical characteristics of patients, tafamidis utilization patterns, adverse drug reactions (ADRs), serious ADRs (safety analysis set), and efficacy (Neuropathy Impairment Score–Lower Limbs [NIS-LL] score, total QOL [TQOL] score, modified body mass index [mBMI], and ambulatory status; efficacy analysis set).</div></div><div><h3>Findings</h3><div>A total of 400 and 397 patients were included in the safety and efficacy analysis sets, respectively. The mean ± standard deviation (SD) age was 61.5 ± 15.0 years, 65.5% were male, 57.3% were aged ≥50 years at disease onset, 71.0% were from nonendemic areas, and 10.3% had Karnofsky Performance Status 40 to 10. A total of 212 (53.0%) patients were treated with tafamidis for &gt;156 weeks (mean ± SD treatment duration: 120.8 ± 56.4 weeks) and 145 (36.3%) patients discontinued the study, with the reasons for discontinuation (duplicate) being adverse events (<em>n</em> = 46), hospital transfer (<em>n</em> = 33), loss to follow-up (<em>n</em> = 15), insufficient clinical response (<em>n</em> = 9), and others (<em>n</em> = 62). ADRs and serious ADRs were reported in 58 (14.5%) and 12 (3.0%) patients, respectively. In the efficacy analysis set, NIS-LL score, TQOL score, mBMI, and ambulatory status after 156 weeks of treatment were comparable to those reported prior to tafamidis initiation.</div></div><div><h3>Implications</h3><div>The findings of this study indicate that late-onset cases of ATTRv amyloidosis and those that originate from nonendemic areas may be more prevalent in Japan than historically believed. The safety profile of tafamidis was largely consistent with that obtained from previous research, and no new safety concerns were identified. The efficacy of tafamidis was also demonstrated in the real-world clinical setting.</div></div><div><h3>Clinical trial registration","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100793"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116671","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":"Exploring the Use of Mobile Health Applications in Palestinian Community Pharmacy Practice","authors":"Ahmed Nouri PharmD, MSc","doi":"10.1016/j.curtheres.2025.100782","DOIUrl":"10.1016/j.curtheres.2025.100782","url":null,"abstract":"<div><h3>Background</h3><div>Mobile health applications have become essential tools in modern healthcare, enabling professionals to access real-time drug information, clinical guidelines, and patient management resources. While globally embraced, the adoption of these apps in resource-limited settings like Palestine remains under-researched, particularly among community pharmacists, who are pivotal to the healthcare system.</div></div><div><h3>Aims</h3><div>This study explores the perceptions, awareness, and challenges faced by Palestinian community pharmacists regarding mobile health applications. It aims to assess the feasibility of integrating these tools into their practice to improve pharmaceutical care and patient outcomes.</div></div><div><h3>Methods</h3><div>A cross-sectional online survey was conducted in 2023 among community pharmacists in Palestine. A self-administered electronic questionnaire was distributed via social media, targeting registered pharmacists. Data were collected using a structured, validated questionnaire addressing demographics, app usage patterns, perceived benefits, and barriers. Descriptive and inferential analyses were performed using SPSS® software, with P-values ≤0.05 considered statistically significant.</div></div><div><h3>Results</h3><div>The study included 400 community pharmacists, predominantly female (65.8%). Pharmacists frequently used information resources for verifying drug interactions (89%) and dosages (98%), citing quick access to reliable information as a major advantage. Barriers included time constraints (92.3%) and concerns about patient trust (77.8%). No significant associations were found between demographics (e.g., gender, years of experience) and perceptions of app usefulness or trust. A strong positive correlation (<em>P</em> &lt; 0.001) was observed between community pharmacists’ support for mobile health applications and their perception of the applications’ reliability. This indicates that pharmacists who perceive mobile apps as reliable are more likely to support their use in practice.</div></div><div><h3>Conclusion</h3><div>Limited app use among Palestinian community pharmacists impacts medication safety, patient trust, and care quality. Adopting mobile tools can improve efficiency, reduce errors, and align pharmacy practice with modern standards, highlighting the need for future research.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100782"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684679","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":"Assessing the Impact of Frailty Interventions on Older Patients With Frailty","authors":"Miaoyu Zhang,&nbsp;Lingling Zhong","doi":"10.1016/j.curtheres.2024.100769","DOIUrl":"10.1016/j.curtheres.2024.100769","url":null,"abstract":"<div><h3>Background</h3><div>As the global population ages, frailty-marked by diminished physiological reserves and increased vulnerability, poses significant health risks such as falls, hospitalization, and mortality. Exercise therapy, enhancing muscle strength and balance, has shown promise in mitigating frailty's effects, while nursing interventions ensure tailored, comprehensive care. However, the combined impact of these interventions remains underexplored. This study investigates the clinical effectiveness of integrating active exercise with nursing interventions to manage frailty in elderly patients, aiming to improve their physical function and quality of life.</div></div><div><h3>Methods</h3><div>This retrospective study analyzed 100 elderly patients (≥80 years) admitted to our hospital with mild to moderate frailty. Participants were randomly assigned to either a control group (n = 50), receiving a standard exercise program, or an experimental group (n = 50), receiving the same program with personalized interventions under nursing assistance. Assessments were conducted at baseline and at 1, 3, 6, and 12 months. Outcome measures included assessing functional mobility, physical dependence in activities of daily living (ADLs), balance, muscle strength, degree of frailty and patient satisfaction with the nursing care.</div></div><div><h3>Results</h3><div>There were no significant differences in the baseline characteristics between the two groups (<em>P</em> ˃ 0.05). However, both groups exhibited significant improvements from baseline in functional mobility (<em>P</em> &lt; 0.001), physical dependence in ADLs (<em>P</em> &lt; 0.001), balance (<em>P</em> &lt; 0.001), muscle strength (<em>P</em> &lt; 0.001), and degree of frailty (<em>P</em> &lt; 0.001). Importantly, from 3 months onward, the experimental group showed significantly greater improvements in all these parameters compared to the control group (<em>P</em> &lt; 0.001 for each measure). Additionally, patient satisfaction was higher in the experimental group, with a satisfaction rate of 94.0% compared to 72.0% in the control group (<em>P</em> = 0.013).</div></div><div><h3>Conclusions</h3><div>This study demonstrates that combining active exercise with nursing interventions significantly improves physical performance, independence, balance, muscle strength, and reduces frailty in elderly patients. Furthermore, the high levels of patient satisfaction underscore the effectiveness and favorable reception of this intervention. These findings suggest that the implemented interventions can be a valuable approach in improving the overall health and well-being of elderly patients with frailty.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100769"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068429","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":"Anti-Gastric Cancer Activity of Mixed-Region Iranian Propolis Nanoparticles: Potential Therapeutic Applications","authors":"Sara Aravand MSc ,&nbsp;Azam J. Esfahani PhD ,&nbsp;Nematollah Gheibi PhD ,&nbsp;Saeideh G. Khoei PhD ,&nbsp;Shaghayegh P. Dibazar MSc ,&nbsp;Leila Zolghadr PhD ,&nbsp;Hossein Ahmadpour_Yazdi PhD","doi":"10.1016/j.curtheres.2025.100806","DOIUrl":"10.1016/j.curtheres.2025.100806","url":null,"abstract":"<div><h3>Background</h3><div>Propolis holds great potential in therapeutic development due to the presence of flavonoids, phenolic acids, and esters. However, its chemical composition has restricted its solubility and bioaccessibility. Here, we synthesized responsive Iranian propolis nanoparticles derived from 3 distinct regions of Iran, representing the first comparative investigation of their anticancer effects against AGS gastric cancer cells.</div></div><div><h3>Methods</h3><div>Propolis was collected from 3 different regions of Iran. Iranian propolis extract (IPE) was prepared using Bosio method. Quantitative and qualitative analyses were performed. Using the probe sonication, Iranian propolis nanoparticles (IPNs) were prepared. Identification tests of IPNs were performed with dynamic light scattering (DLS)-Zetasizer methods. Next, the anticancer potential of IPNs was analyzed by measuring the cell survival rate on the AGS gastric cancer cell line by MTT assay. Also, the IPNs apoptotic activity was evaluated using Annexin V/FITC-propidium iodide (PI) flow cytometry.</div></div><div><h3>Results</h3><div>Analysis of the IPE showed the presence of paracoumaric acid and caffeic acid predominantly. An average IPNs size was obtained from 8 to 15 nm with good stability and cellular uptake. Compared with IPE, IPNs showed a greater effect on AGS gastric cancer cell survival inhibition after 24 and 48 h. The IC50 values of cancer cells treated with IPE and IPNs were calculated as 76.55 and 43.26 µg/ml for 24 h and 63.26 and 12.14 µg/ml for 48 h respectively. The flow cytometry results showed that the apoptosis induced by IPNs was greater than the control cells.</div></div><div><h3>Conclusions</h3><div>Our study indicated that the IPNs can be more effective than IPE in reducing AGS cell viability and increasing apoptosis. These results suggest the potential of IPNs as low-toxicity nanocarriers for gastric cancer therapy, although further in vivo studies are required to validate their therapeutic potential and assess their pharmacokinetic properties.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100806"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780887","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":"The Effect of Stem Cell Secretome on the Improvement of Diabetic Wound Recovery: A Systematic Review and Meta-Analysis of In Vivo Studies","authors":"Cecep Suhandi MSc ,&nbsp;Gofarana Wilar PhD ,&nbsp;Khaled M. Elamin PhD ,&nbsp;Audry Rahma Dewayani BSc ,&nbsp;Salsabil Ghaliya BSc ,&nbsp;Astriani Abdullah BSc ,&nbsp;Nasrul Wathoni PhD","doi":"10.1016/j.curtheres.2025.100778","DOIUrl":"10.1016/j.curtheres.2025.100778","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic wounds, characterized by their chronic nature, represent a critical challenge for patients with diabetes, often leading to amputation and mortality. Although stem cells show great promise, their use is limited by challenges related to stability and tumorigenicity. The secretome of stem cells, comprising molecules released by these cells, offers a potential alternative to the challenges associated with stem cell therapy and provides a promising solution for diabetic wound healing.</div></div><div><h3>Objective</h3><div>We conducted a systematic review and meta-analysis of relevant preclinical studies to evaluate the effectiveness of stem cell secretomes in treating diabetic wounds.</div></div><div><h3>Methods</h3><div>The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023473726). Databases were searched from their inception until November 20, 2023. The quality assessment of the included studies was performed utilizing the CAMARADES 10-item Quality Checklist. Statistical analyses were conducted using a random-effects model to calculate standardized mean differences (SMD) and 95% confidence intervals (CI), with heterogeneity assessed via the <em>I²</em> statistic. The primary outcome evaluated was the wound closure rate, while secondary outcomes included parameters such as the number of fibroblasts, neutrophils, and macrophages.</div></div><div><h3>Results</h3><div>Twenty studies were included, comprising 382 animal subjects, and five of which were eligible for quantitative evaluation in a meta-analysis. The stem cell secretome significantly improved the wound closure rate (SMD = 9.63; 95% CI = 2.01 −17.25; <em>P</em> = 0.01, I² = 76%) and reduced the number of neutrophils (SMD =  −8.47; 95% CI =  −13.05 to −3.90; <em>P</em> = 0.0003) and macrophages (SMD = −5.32; 95% CI = −9.09 to −1.55; <em>P</em> = 0.006).</div></div><div><h3>Conclusion</h3><div>This review suggests that stem cell secretomes have potential as a novel therapeutic strategy for diabetic wound healing, enhancing wound closure rates and reducing inflammation. These findings support the use of stem cell secretomes as a safer and more stable alternative to direct stem cell therapy, but further clinical studies are needed to confirm these results in human patients.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100778"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526717","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":"Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics","authors":"Haruno Oku BS ,&nbsp;Saki Yoshida BS ,&nbsp;Takumi Hotta BS ,&nbsp;Hirohito Muroi BS ,&nbsp;Keizo Fukushima PhD ,&nbsp;Kei Irie PhD ,&nbsp;Tatsuya Hirano BS ,&nbsp;Yoshimitsu Shimomura MD ,&nbsp;Takayuki Ishikawa MD, PhD ,&nbsp;Hiroaki Ikesue PhD ,&nbsp;Nobuyuki Muroi PhD ,&nbsp;Tohru Hashida PhD ,&nbsp;Nobuyuki Sugioka PhD","doi":"10.1016/j.curtheres.2024.100775","DOIUrl":"10.1016/j.curtheres.2024.100775","url":null,"abstract":"<div><h3>Objectives</h3><div>Treatment with tacrolimus requires strict control of the whole-blood concentration in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In patients undergoing cord blood transplantation (CBT), there is a negative correlation between volume of distribution of tacrolimus and hemoglobin levels, which reflect the red blood cell (RBC) count. In this study, we evaluated the influence of the conditioning regimen (myeloablative and reduced-intensity conditioning) or donor source (cord blood, bone marrow, and peripheral blood stem cells) on the pharmacokinetics of tacrolimus in patients undergoing HSCT, including those undergoing CBT. We also examined applicability of dosing strategy of tacrolimus considering the RBC count.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed clinical data—including whole-blood tacrolimus concentrations—from patients with HSCT. The observation period spanned from first continuous intravenous infusions until switch to oral medication, transfer to another hospital, relapse, or death. Population pharmacokinetic analysis was performed on whole-blood tacrolimus concentrations obtained from therapeutic drug monitoring during the observation period. Patient characteristics and laboratory data were evaluated as covariates.</div></div><div><h3>Results</h3><div>We enrolled 91 patients undergoing HSCT (CBT: <em>n</em> = 56; bone marrow transplantation: <em>n</em> = 22; and peripheral blood stem cell transplantation: <em>n</em> = 13); 58 and 33 patients received myeloablative conditioning and reduced-intensity conditioning, respectively. Whole-blood tacrolimus concentrations were accurately captured (<em>n</em> = 1,658 measurements) using a one-compartment and additive error model. The conditioning regimen and donor source did not have an impact on the pharmacokinetics of tacrolimus. Therefore, these factors were not considered when forming the dosing strategy. Nevertheless, a negative correlation between volume of distribution and hemoglobin level was confirmed, indicating that monitoring the RBC count is useful in assessing the dosing strategy.</div></div><div><h3>Conclusions</h3><div>A tacrolimus dosing strategy that considers the variability in hemoglobin levels applies to all patients undergoing HSCT.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100775"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122229","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":"Effect of a Pleuran-Based Supplement on Salivary IgA Secretion in Children With Recurrent Respiratory Infections","authors":"Peter Kunc MD, PhD ,&nbsp;Jaroslav Fabry MD, PhD ,&nbsp;Michaela Matiscakova MD ,&nbsp;Katarina Istvankova DVM ,&nbsp;Zuzana Diamant MD, PhD ,&nbsp;Juraj Majtan PhD, DSc ,&nbsp;Milos Jesenak MD, PhD","doi":"10.1016/j.curtheres.2025.100780","DOIUrl":"10.1016/j.curtheres.2025.100780","url":null,"abstract":"<div><h3>Background</h3><div>ß-glucans isolated from natural sources have demonstrated pluripotent immunomodulatory potential, making them a promising supportive treatment for the management of recurrent respiratory infections (RRIs) in children. This study aimed to evaluate the effects of a pleuran-based supplement (ß-glucan isolated from <em>Pleurotus ostreatus</em> in combination with vitamin D and zinc) on mucosal immunity –through modulating salivary secretory immunoglobulin A (sIgA) levels –in children with RRIs.</div></div><div><h3>Methods</h3><div>This monocentric, prospective, open-label pilot study investigated the effect of an orally administered pleuran/vitamin D/zinc supplement (1–2 chewable tablets daily depending on body weight) on the dynamics of sIgA secretion measured in saliva samples collected at three timepoints: at baseline and after 4–6 and 8–10 days.</div></div><div><h3>Results</h3><div>This study included 49 children aged 6-11 years (mean age: 8.2 ± 1.6 years) with a history of one or more of the following conditions in the inclusion criteria: RRIs, allergy, and asthma. After 8–10 days with daily administration of the chewable pleuran/vitamin D/zinc supplement, children exhibited a statistically significant increase in salivary sIgA concentrations compared with baseline (227 ± 211 µg/mL; <em>P</em> = 0.045). No adverse events were observed during the course of the study in relation to the administration of pleuran-based supplement.</div></div><div><h3>Conclusions</h3><div>We demonstrated the beneficial effects of the short-term administration of a pleuran-based chewable supplement on mucosal immunity through increasing salivatory sIgA levels. This study confirms the favourable safety profile of this pleuran/vitamin D/zinc combination, which could be beneficial for children with acute or recurrent respiratory infections, including children with allergies and/or asthma. Moreover, the significant increases in salivary sIgA concentrations that were observed after a few days of supplementation support the use of pleuran in not only the prevention but also the treatment of acute respiratory infections.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100780"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576715","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":"Randomized, Double-Blind, Crossover Study Comparing the Bioavailability of 4 Ashwagandha (Withania somnifera (L.) Dunal) Extracts in Healthy Adults Under Fasting Condition","authors":"Priyank Rathi MD ,&nbsp;Se-Kwon Kim PhD","doi":"10.1016/j.curtheres.2025.100805","DOIUrl":"10.1016/j.curtheres.2025.100805","url":null,"abstract":"<div><h3>Background</h3><div><em>Withania somnifera</em> (L.) Dunal, commonly known as ashwagandha, is a well-known plant in ayurvedic medicine, widely valued for its therapeutic potential. Although numerous clinical studies have explored its diverse health benefits, limited data are available on the pharmacokinetic (PK) properties and comparative bioavailability of its key bioactive constituents in humans.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate and compare the oral bioavailability of 4 commercially standardized ashwagandha extracts under fasting conditions in healthy adults.</div></div><div><h3>Methods</h3><div>This randomized, double-blind, 4-treatment, 4-period, 4-sequence, single dose, 4-way crossover study was conducted in 16 healthy human volunteers. Participants received a single oral dose of 1 of 4 ashwagandha extracts, with varying compositions of 35% (<em>Withania somnifera</em> [WS]-35) or 10% (WS-10) withanolide glycosides, or 5% (WS-5) or 2.5% (WS-2.5) withanolides, each standardized to deliver 185 mg of total withanolides. Seventeen blood samples were collected over a 24-hour period after dose administration. Plasma concentrations of withanolide A, withanoside IV, withaferin A, and total withanolides were quantified, and PK parameters were calculated.</div></div><div><h3>Results</h3><div><em>Withania somnifera</em>-35 had significantly superior bioavailability compared with the other extracts. The AUC_0–t for total withanolides per gram of WS-35 was 118.28, 226.11, and 267.83 times better than WS-10, WS-5, and WS-2.5 respectively. <em>Withania somnifera</em>-35 exhibited a significantly higher C_max, longer half-life, extended mean residence time, and lower systemic clearance, attributable to its higher withanolide glycoside content.</div></div><div><h3>Conclusions</h3><div>These findings emphasize the critical role of withanolide glycosides in determining the PK performance of ashwagandha supplements. The enhanced bioavailability of WS-35 supports its preferential use in therapeutic applications and provides a strong rationale for further investigation into dose-response relationships and the long-term efficacy of standardized, high-bioavailability formulations. Clinical Trial Registry of India identifier: CTRI/2020/10/028397.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100805"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738188","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":"A Clinical Nomogram for Predicting Substandard Serum Valproic Acid Concentrations in Chinese Patients With Epilepsy","authors":"Zi-Hao Duan MS ,&nbsp;Chun-Yuan He MS ,&nbsp;Jie Chen BS ,&nbsp;Jun-Jie Jiang BS ,&nbsp;Zhi-Xiang Zhu PhD ,&nbsp;Jing Li MS ,&nbsp;Fa-Cai Wang MD","doi":"10.1016/j.curtheres.2024.100771","DOIUrl":"10.1016/j.curtheres.2024.100771","url":null,"abstract":"<div><h3>Background</h3><div>It is well-known that substandard serum valproic acid (VPA) concentrations may lead to treatment failure of epilepsy. However, there is still a lack of a quick method to predict whether a patient's serum VPA concentration will reach the standard.</div></div><div><h3>Objective</h3><div>The aims of this study were to investigate the factors leading to substandard serum VPA concentrations in Chinese patients with epilepsy and develop a related nomogram for risk prediction.</div></div><div><h3>Methods</h3><div>From January 2019 to March 2022, a total of 1143 serum VPA concentrations were collected from 630 hospitalized Chinese patients with epilepsy who were monitored by the Department of Pharmacy of Lu'an People's Hospital, and complete clinical data were collected from the corresponding patients for retrospective analysis. All monitored serum VPA concentrations were further divided into a training cohort and a validation cohort. For the training cohort, serum VPA concentrations below 50 µg/mL and between 50 and 100 µg/mL were classified into the subtherapeutic group and therapeutic group, respectively. The variables were selected from the clinical data, and differences between the variables of the subtherapeutic and therapeutic groups were analyzed. The influencing factors leading to substandard serum VPA concentrations were screened via logistic regression analysis, and the screened influencing factors were used to establish the nomogram prediction model.</div></div><div><h3>Results</h3><div>Multivariate logistic regression analysis revealed that the daily dose per unit of body weight (mg/kg/d), route of administration, presence of hepatic lesions, hypoalbuminemia, and combination with carbapenems or barbiturates were independent factors influencing the occurrence of substandard serum VPA concentrations. On the basis of the results of the multivariate logistic regression analysis, a nomogram risk prediction model for substandard serum VPA concentration was established. The values of the C-index and internal verification results indicated that the nomogram model had good accuracy and discrimination. The decision curve revealed that the nomogram that predicted the risk of substandard serum VPA concentration had a greater net benefit value (ranging from 12% to 94%), indicating that the model had a wide prediction interval.</div></div><div><h3>Conclusions</h3><div>Our study established a nomogram risk prediction model for substandard serum VPA concentrations in Chinese patients with epilepsy, which can help doctors or patients control the serum VPA concentration within the target concentration range as soon as possible.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100771"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078876","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}