Die Pharmazie最新文献

{"title":"Therapeutic Potential of Water-Soluble Resveratrol-Loaded Polyethylene Glycol Monostearate Micelles in a Mouse Model of Dry Eye Disease.","authors":"Aoi Machida, Kengo Banshoya, Riko Okada, Yuki Kameda, Yui Kawamoto, Sachi Shibata, Yoshiharu Kaneo, Tetsuro Tanaka, Masatoshi Ohnishi","doi":"10.31083/Pharmazie53494","DOIUrl":"https://doi.org/10.31083/Pharmazie53494","url":null,"abstract":"<p><strong>Background: </strong>Dry eye disease (DED) is a multifactorial ocular surface condition that causes damage and discomfort, significantly impairing the quality of life of patients. Recently, phytochemicals such as trans-resveratrol (Res) have attracted growing interest due to their potential therapeutic effects against the DED-related pathophysiology. To enable the therapeutic application of water-insoluble Res, this study aimed to evaluate the efficacy of a previously developed water-soluble micelle formulation (stPEG/Res) containing polyethylene glycol monostearate (stPEG) in treating DED.</p><p><strong>Methods: </strong>The antioxidant activity of stPEG/Res was assessed using the 2,2-diphenyl-1-picrylhydrazyl radical-scavenging assay, and its cytotoxicity was evaluated in a human corneal epithelial cell line. Furthermore, an <i>in vivo</i> efficacy study was performed using a mouse model of DED induced by lacrimal gland excision. Tear volume, corneal histopathological changes, inflammatory responses, and apoptosis in the cornea were evaluated.</p><p><strong>Results: </strong>The stPEG/Res formulation exhibited antioxidant activity and a cytotoxicity profile against corneal epithelial cells comparable to that of free Res. Furthermore, in the mouse model of DED, stPEG/Res alleviated dry eye symptoms not by restoring tear volume, but by suppressing inflammation and apoptosis in the cornea.</p><p><strong>Conclusions: </strong>These findings indicate that stPEG/Res has potential as a novel therapeutic option for corneal disorders associated with DED.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 7","pages":"53494"},"PeriodicalIF":0.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623825","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":"Clinical and Biochemical Determinants of the Systemic Inflammation Response Index During Vancomycin Therapy.","authors":"Mohammad A Alfhili, Sahar A Alazmi, Jawaher Alsughayyir","doi":"10.31083/Pharmazie51565","DOIUrl":"10.31083/Pharmazie51565","url":null,"abstract":"<p><strong>Background: </strong>Vancomycin (VAN) is the standard of care for Gram-positive infections. The systemic inflammation response index (SIRI) has been associated with infections and sepsis across various clinical settings; however, the correlates and determinants of the SIRI during VAN therapy remain unexplored. This retrospective cross-sectional study aimed to identify the determinants of the SIRI among adults treated with VAN.</p><p><strong>Methods: </strong>Medical records of 299 patients who received VAN were analyzed consecutively. Prevalence rates were calculated; Spearman's correlation and regression models were employed to evaluate associations; risk assessment was conducted using prevalence ratios and odds ratios; diagnostic potential was assessed using receiver operating characteristic curves.</p><p><strong>Results: </strong>The SIRI was significantly higher in intensive care unit (ICU) patients than in non-ICU patients receiving VAN therapy (<i>p</i> < 0.0001). Age, blood pressure, creatinine, Na⁺, CO₂, albumin, aspartate transaminase (AST), gamma-glutamyl transferase (GGT), bilirubin, coefficient of variation in red cell distribution width (RDW-CV), and platelet count were significantly and differentially correlated with the SIRI. In the adjusted analysis, ICU requirement emerged as the strongest independent predictor of SIRI, with ICU patients showing a 2.13-fold higher SIRI(<i>p</i> < 0.0001). Moreover, the prevalence of ICU requirement was 1.61 times higher in individuals with increased SIRI (<i>p</i> = 0.0018), whose odds of ICU requirement were 2.16 times higher (<i>p</i> = 0.0016). The SIRI also demonstrated moderate discriminatory ability, with the highest performance observed in patients younger than 50 years (area under the curve [AUC] = 0.731, <i>p</i> = 0.0001).</p><p><strong>Conclusions: </strong>The SIRI is a novel and cost-effective marker that is correlated with distinct demographic and clinical variables and independently associated with ICU requirement in VAN-treated patients and may aid in the risk stratification and management of this vulnerable patient cohort.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 6","pages":"51565"},"PeriodicalIF":0.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400372","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":"Assessment of the Quality of Finished Intravenous Infusions Using Failure Mode and Effects Analysis.","authors":"Yani Ma, Wei Chen, Jirong Li, Yanping Yang, Dangli Bai, Meng Gao, Yulian Hu, Fangyun Zhao","doi":"10.31083/Pharmazie52007","DOIUrl":"10.31083/Pharmazie52007","url":null,"abstract":"<p><strong>Background: </strong>The post-dispensing process of Pharmacy Intravenous Admixture Services (PIVAS), including verification, packaging, transportation, nurse receipt and verification, and clinical administration, involves multiple high-risk steps associated with intravenous medication safety. However, existing risk management studies have primarily focused on internal preparation procedures within PIVAS, with limited attention to the external circulation processes after admixture preparation.</p><p><strong>Methods: </strong>Failure mode and effects analysis (FMEA) was applied to systematically identify, evaluate, and prioritize potential risks in the post-dispensing workflow of finished intravenous infusions. Risk priority numbers (RPNs) were calculated based on severity, occurrence, and detectability scores. High-risk failure modes were defined as those with an RPN ≥120 or a severity score ≥8. Targeted corrective interventions were subsequently implemented for these high-risk processes.</p><p><strong>Results: </strong>A total of six high-risk failure modes were identified across the post-dispensing workflow. Following FMEA-based interventions, the total RPN score of these six high-risk failure modes decreased from 707 to 394, representing a 44.3% reduction. In addition, the incidence of real-world risk events decreased significantly between 2020 and 2022 (<i>p</i> < 0.001), indicating substantial improvements in medication safety and process quality.</p><p><strong>Conclusion: </strong>FMEA is an effective and practical tool for extending quality control from internal admixture preparation to the complete post-dispensing process in PIVAS. The implementation of FMEA facilitated the establishment of a closed-loop risk management framework and improved the safety of intravenous medication administration.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 6","pages":"52007"},"PeriodicalIF":0.0,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400342","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":"Ferulenol, a Prenylated Coumarin, Suppresses Collagen-Induced Platelet Activation via PLCγ2-Mediated cPLA2 Signaling in Humans.","authors":"Wei-Chieh Huang, Yi Chang, Chia-Yau Chang, Yui-Xi Lee, Chia-Yuan Hsu, Chih-Wei Hsia, Thanasekaran Jayakumar, Chao-Chien Chang, Joen-Rong Sheu","doi":"10.31083/Pharmazie52496","DOIUrl":"10.31083/Pharmazie52496","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide and are strongly associated with atherothrombotic events. Thrombus formation results from the interplay between platelet activation and the coagulation cascade. While anticoagulant systems are essential for maintaining hemostasis, these systems can also increase the risk of bleeding complications. Coumarins led to the development of clinically important oral anticoagulants such as warfarin, which inhibits vitamin K epoxide reductase complex subunit 1 (VKORC1), a key enzyme in vitamin K recycling and normal blood clotting. Ferulenol, a prenylated coumarin derived from &lt;i&gt;Ferula communis&lt;/i&gt;, has been reported to inhibit VKORC1, indicating a similar anticoagulant mechanism. Indeed, the close interplay between coagulation and platelet activation suggests that ferulenol may also modulate platelet function. However,the role of ferulenol in platelet activation has not yet been fully clarified.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, washed platelets obtained from healthy human donors were used to examine whether ferulenol suppresses platelet activation. To further clarify the underlying mechanisms, this study performed immunoblotting and confocal microscopy. In addition, this study evaluated the &lt;i&gt;in vivo&lt;/i&gt; antithrombotic and hemostatic effects of ferulenol using a vascular thrombosis model and a tail bleeding time assay in mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Collagen (2 μg/mL)-induced platelet aggregation was reduced by ferulenol in a concentration-dependent manner from 10 to 40 μM, with near-complete inhibition at 40 μM. Ferulenol produced only moderate inhibition of arachidonic acid (AA, 60 μM)-induced aggregation at 80 μM and did not significantly affect by thrombin (0.02 U/mL)-induced platelet responses. Moreover, ferulenol markedly reduced collagen-induced platelet activation markers, including P-selectin expression, intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; mobilization, and adenosine triphosphate (ATP) release. These inhibitory effects were accompanied by reduced phosphorylation of phospholipase Cγ2 (PLCγ2), cytosolic phospholipase A2 (cPLA2), and mitogen-activated protein kinase (MAPK) family members, including extracellular signal-regulated kinase, p38 MAPK, and c-Jun N-terminal kinase. Ferulenol also suppressed activation of the phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) signaling pathway. In mice, ferulenol extended the time to thrombotic platelet plug formation, without significantly increasing bleeding time.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study, provides the first evidence that ferulenol inhibits platelet activation. Mechanistically, ferulenol may inhibit collagen-induced platelet activation, at least in part, by suppressing PLCγ2 activation, thereby reducing phosphorylation of cPLA2, MAPKs, and PI3K/Akt/GSK3β signaling proteins. These inhibitory effects were reflected by reduced","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 6","pages":"52496"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400385","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":"Postmarketing Safety Concerns With Caplacizumab: A Real-World Pharmacovigilance Study Based on the FDA Adverse Event Reporting System Database.","authors":"Juan Shao, Jing Lin, Hong-Yan Xu, Xiao-Xia Yang","doi":"10.31083/Pharmazie52100","DOIUrl":"10.31083/Pharmazie52100","url":null,"abstract":"<p><strong>Objective: </strong>To analyze data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to characterize the adverse effects of caplacizumab, including associated adverse events (AEs) and safety signals in real-world clinical practice. and obtain evidence to support the rational use of this drug in the treatment of thrombotic thrombocytopenic purpura (TTP).</p><p><strong>Methods: </strong>Postmarketing AE reports associated with caplacizumab were retrieved from the FAERS database. Safety signals were identified using four disproportionality analysis methods: the reporting odds ratio, proportional reporting ratio, Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker. The Weibull distribution was used to analyze the onset time of AEs, and subgroup analyses were performed according to sex, age group, and reporter type.</p><p><strong>Results: </strong>In total, 1144 reports involving caplacizumab were analyzed. Most AEs were nonserious. Among the 401 reports with documented onset times, 162 (40.4%) described AEs occurring within 7 days of administration. Common bleeding-related events (e.g., epistaxis, gingival bleeding, gastrointestinal hemorrhage, heavy menstrual bleeding, and vaginal hemorrhage) were consistent with product labeling. Decreases in platelet count and in disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) activity were interpreted as manifestations of the underlying disease (acquired TTP) rather than drug-induced AEs. Newly identified safety signals included contusion, injection site pain, injection site bruising, injection site erythema, injection site haemorrhage, pruritus and rash.</p><p><strong>Conclusions: </strong>These findings underscore the importance of pharmacovigilance and postmarketing surveillance for caplacizumab. Clinicians should closely monitor bleeding events and injection site reactions during treatment. To ensure the safe use of caplacizumab, the mechanisms underlying these potential signals should be elucidated, and targeted monitoring strategies should be developed.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 6","pages":"52100"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400310","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":"Guggulsterone Alleviates Atherosclerosis in ApoE^-/- Mice by Modulating Lipid Metabolism and Inflammatory Responses Associated with Modulation of the <i>Srebp2</i>/<i>Hmgcr</i> Signaling Axis.","authors":"Jialin Liang, Jingfang Zhang, Xun Huang, Jiahui Xu, Xinyu Luo, Jiaying Zhang, Cheng Huang, Kunhui He","doi":"10.31083/Pharmazie52690","DOIUrl":"https://doi.org/10.31083/Pharmazie52690","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Atherosclerosis (AS) is a chronic inflammatory vascular disease characterized by dysregulated lipid homeostasis and plaque formation. Consequently, there is an ongoing need for therapies with high efficacy and low toxicity. Thus, this study aimed to investigate the effects of guggulsterone (GS) on atherosclerotic plaques in mice and to elucidate the molecular mechanisms underlying the beneficial effects of GS in this pathological context.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 53 male ApoE&lt;sup&gt;-/-&lt;/sup&gt; knockout mice were fed on a high-fat Western-type diet for 8 consecutive weeks to induce atherosclerotic lesions; three mice were randomly selected for model validation by serum lipid analysis and histopathological examination, and were excluded from subsequent grouping. The remaining 50 mice were randomly assigned to five groups (n = 10 per group): model group, low/medium/high-dose GS treatment groups (35/70/140 mg/kg GS, respectively), and an atorvastatin (AT) group (2.6 mg/kg). An additional 10 C57BL/6J mice served as the normal control group. After 8 weeks of intragastric treatment, serum lipid levels (Total cholesterol [TC], Triglycerides [TG], Low-density lipoprotein-cholesterol [LDL], High-density lipoprotein-cholesterol [HDL]) and a composite AS index were analyzed using standard biochemical methods. Serum nitric oxide (NO), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and prostacyclin (PGI2) levels were measured by enzyme-linked immunosorbent assay (ELISA). Aortic pathological changes were evaluated by hematoxylin and eosin staining, while monocyte/macrophage-specific monoclonal antibody 2 (MOMA-2) and α-smooth muscle actin (α-SMA) expression were evaluated by immunohistochemistry; Aortic Hmgcr and Srebp2 mRNA levels were quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Outcome assessments were conducted in a blinded manner.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with the control group, the model group exhibited poorer general status, increased body weight, abnormal lipid levels, elevated levels of inflammatory factors, and typical aortic AS pathological changes (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05), together with the upregulation of aortic &lt;i&gt;Srebp2&lt;/i&gt; and &lt;i&gt;Hmgcr&lt;/i&gt; mRNA levels (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). In contrast, mice in the medium- and high-dose GS groups and the AT treatment group exhibited improved general status, reduced body weight, normalized lipid levels and inflammatory factors, and ameliorated aortic pathological damage, along with the reversal of the molecular changes observed in AS model mice (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). Notably, high-dose GS exerted comparable or even superior regulatory effects versus AT on the levels of TC, TG, LDL, NO, PGI&lt;sub&gt;2&lt;/sub&gt;, IL-6 and MOMA-2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;GS treatment reduces atherosclerotic plaque area and delays AS progression in mice, potentially through the regulation of &lt;i&gt;Srebp2&lt;/i&gt;/&lt;i&gt;Hmgc","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 6","pages":"52690"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400368","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":"Effectiveness of the Clinical Decision Support System Upgrade in the Automated Unit Dose Drug Dispensing System.","authors":"Kui Zhao, Jianglin Li, Mianwei Chen, Xian Zou, Lin Cheng","doi":"10.31083/Pharmazie51382","DOIUrl":"https://doi.org/10.31083/Pharmazie51382","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate the effectiveness of the clinical decision support system (CDSS) upgrade in the automated unit-dose drug dispensing system (AUDDS), which comprises both the pre-review CDSS software of the automated drug unit-dose dispensing machine (ADDM) and the pre-verify CDSS software of the medication detection machine (MDM). The ultimate goal of these coordinated enhancements is to improve the overall dispensing efficiency of the AUDDS.</p><p><strong>Methods: </strong>A multidisciplinary collaboration involving pharmacists and the AUDDS engineer was established to implement two upgrades: the rule-based pre-review CDSS software in ADDM and the pre-verify CDSS software in MDM. The upgraded CDSS software of ADDM was configured to automatically identify and intercept three categories of clinically inappropriate inpatient medication orders (IMOs) based on real-time patient data from the hospital information system: duplicate IMOs, IMOs of excessive doses, and non-splittable IMOs. Upon detection, the CDSS software in ADDM generates an alert to notify the managing pharmacist, who conducts a telephone consultation with the prescribing doctor for timely resolution. The pre-verify CDSS software in MDM was upgraded to improve image acquisition and recognition accuracy and reduce the error rate in automatically identifying mismatched unit-dose medication bags (UMBs).</p><p><strong>Results: </strong>Pre-post comparisons revealed improvements in both workload and efficiency metrics and safety metrics. After the upgrade, total order volume (TOV) and order volume per pharmacist (OVP) showed a 7.54% mean increase, and the monthly total number of pre-verified unit-dose medication bags (MTN) revealed a 31.84% mean increase. The monthly volume of duplicate IMOs (MVDI) displayed a 11.62% mean reduction, and the ratio of duplicate IMOs (RDI) displayed a 19.32% mean reduction. The monthly volume of IMOs with excessive doses (MVIE) revealed a 35.20% mean reduction, and the ratio of IMOs with excessive doses (RIE) displayed a 41.78% mean reduction. The monthly true-positive error rate (MTER) displayed a 16.29% mean reduction. However, the monthly false-positive error rate (MFER) was higher after the upgrade. Non-splittable IMOs were rare in the study, so they were excluded from the comparison.</p><p><strong>Conclusion: </strong>This study demonstrates that the upgrade was associated with improvement of the appropriateness of long-term IMOs and the dispensing efficiency of AUDDS, thereby enhancing medication safety in hospital pharmacies.</p>","PeriodicalId":524122,"journal":{"name":"Die Pharmazie","volume":"81 6","pages":"51382"},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400374","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}