Background Doxorubicin (DOX) is a powerful anthracycline anti-neoplastic agent, and its therapeutic application is frequently restricted because of its liver-damaging effects. In this study, we found that DOX induces acute liver toxicity in rats, and the mechanisms underlying these effects were investigated. Purpose This study aimed to assess the hepatoprotective effects of 2,3-dichloro-6-(trifluoromethoxy) quinoxaline (DTQ) against DOX-induced acute liver toxicity in rats and to investigate the underlying mechanisms involved. Materials and Methods Male Wistar rats were administered an intraperitoneal dose of DOX on days 12–14 of the experiment to induce acute liver toxicity. The rats received DTQ (30 and 60 mg/kg, orally) continuously from day 1 for 14 days, along with DOX on days 12–14. Different biochemical parameters (liver function enzymes, lipid peroxidation, and oxidative stress) were measured. Results DOX treatment increased the levels of liver function enzymes, lipid peroxidation, and oxidative stress by suppressing the production of antioxidant enzymes. Additionally, DOX treatment triggered the expression of pro-inflammatory cytokines and inflammatory mediators in the liver. Histological analysis further confirmed the structural liver damage resulting from DOX treatment. Conclusion DTQ administration offered protection against the harmful effects of DOX on the liver, as indicated by the normalization of altered biochemical parameters and reduction in oxidative stress and inflammation. The results of this study indicate that DTQ exerts liver-protective effects against DOX-induced acute liver toxicity, likely due to its strong antioxidant and anti-inflammatory properties, which modulate the cellular signaling pathways.
Background Prescribing errors are a major cause of preventable medication-related harm. Although educational interventions such as pharmacotherapy teaching, prescription audits and objective structured practical examination (OSPE)/objective structured clinical examination-based assessments improve prescribing competence, most rely on simulated rather than authentic clinical prescribing experiences. Purpose To evaluate the educational impact of integrating real-world electronic prescription (e-prescription) audits into undergraduate pharmacology teaching using the hospital’s medical records, administration and electronic prescribing software (Medical Information Archiving Software [MIAS]), with a focus on improving rational prescribing competence. Materials and Methods A quasi-experimental pre- and post-test design was implemented among 249 second-year Bachelor of Medicine, Bachelor of Surgery students, grouped into seven batches. Participants received structured training, completed a formative OSPE, performed MIAS-based real-world e-prescription audits, and subsequently undertook a summative OSPE. Performance differences across batches and genders were examined using paired t -tests, analysis of variance and multivariate analysis of variance. Student perceptions were collected to examine their learning experiences. Reporting followed the Transparent Reporting of Evaluations with Nonrandomized Designs guidelines for non-randomised intervention studies. Results Summative OSPE scores were significantly higher than formative scores (mean ± standard deviation: 7.30 ± 0.93 vs 5.72 ± 1.11; p < .001), with a large effect size (Cohen’s d = 1.43). All batches demonstrated consistent improvement, with no significant disparities. MIAS audit scores displayed moderate variation across batches, with one batch performing relatively lower than the other batches. There were no gender differences identified across any method of assessment, confirming the equity and fairness of the intervention. Students’ feedback reflected enhanced skills in prescribing, clinical reasoning, confidence and identification of prescribing errors. Conclusions Integrating real-world e-prescription audits using MIAS in conjunction with structured OSPE-based assessment significantly enhances the competencies of rational prescribing. The intervention elicited consistently significant gains across all batches, without any gender disparities. This highlights the effectiveness of MIAS-based real - world e-prescription audits as an impactful and equitable intervention within a competency-based medical curriculum.
Background Depression is a common psychiatric disorder frequently associated with gastrointestinal (GI) symptoms, reflecting the complex bidirectional interaction of the gut–brain axis. Disturbances in gut–brain communication may contribute to both depressive symptom severity and GI dysfunction. Purpose To evaluate the association between depression severity and GI symptom burden and to identify domain-specific GI symptom patterns among patients with depression. Materials and Methods A hospital-based cross-sectional observational study was conducted among 100 adult patients diagnosed with depression. Depression severity was assessed using the Hamilton Depression Rating Scale-17 (HAM-D-17), while GI symptoms were evaluated using the Gastrointestinal Symptom Rating Scale. Statistical analyses included correlation analysis, the Kruskal–Wallis test, chi-square test, and multiple linear regression analysis. Results A significant positive association was observed between depression severity and overall GI symptom burden. Among the assessed GI domains, constipation, diarrhea, and indigestion demonstrated the strongest correlations with depressive severity. Multiple linear regression analysis identified the HAM-D score as an independent predictor of GI symptom burden. Conclusion Greater depression severity was associated with increased GI symptom burden, particularly constipation, diarrhea, and indigestion. Although the cross-sectional design precludes causal inference, these findings highlight the clinical relevance of the gut–brain axis and support the integration of GI symptom assessment into routine psychiatric evaluation for comprehensive, patient-centered management.
Muscular dystrophies (MDs) are genetic disorders marked by progressive myofibre loss, impaired regeneration and weakness that eventually involves cardiac and respiratory muscle. Multidisciplinary care has extended survival, and gene- and ribonucleic acid (RNA)-directed therapies now address the underlying molecular lesions. We propose a stage-specific framework that matches therapeutic modality to mechanism, disease stage and organ burden and identify the practical barriers to translating gene- and RNA-targeted therapies into routine care. We reviewed pivotal clinical trials, regulatory decisions, care guidelines and mechanism-defining studies across Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophies, facioscapulohumeral muscular dystrophy, myotonic dystrophies (DM1/DM2) and selected congenital forms, prioritising modality-to-mechanism fit over exhaustive cataloguing. DMD has led the field, with exon-skipping oligonucleotides and adeno-associated virus micro-dystrophin gene transfer approved in some jurisdictions. Benefit is nonetheless constrained in advanced disease and in cardiac and diaphragmatic rescue, and depends on early initiation, immune compatibility and demonstrable functional gain. Other dystrophies require different logic, such as suppression of toxic RNA or aberrant transcription, or control of inflammation and fibrosis. No single modality serves every patient or every stage. The most practical way forward combines exemplary multidisciplinary care with mechanism-matched intervention delivered at the right time, supported by decision-linked biomarkers and safer, more equitable long-term access.
Background Biosimilar drugs are essential to expanding access to affordable treatments for chronic autoimmune diseases, yet regulatory requirements remain complex, with distinct pathways applied by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and India’s Central Drugs Standard Control Organization (CDSCO). Purpose This study compares EMA, FDA, and CDSCO regulatory guidelines for biosimilars, examining analytical and non-clinical comparability, clinical pharmacology, immunogenicity studies, comparative clinical trials, and the principles of extrapolation of indications and interchangeability, using the monoclonal antibody infliximab as a case study. Materials and Methods Publicly available regulatory guidelines, scientific literature, and official agency documents from EMA, FDA, and CDSCO were systematically reviewed and compared across a structured framework of key regulatory elements, supported by an in-depth analysis of infliximab biosimilar approvals across the three agencies. Results All three agencies emphasize comprehensive analytical and non-clinical characterization as the foundation for biosimilar approval, and require comparative pharmacokinetic (PK) and pharmacodynamic (PD) studies and immunogenicity assessments, with a shared shift toward reducing or eliminating comparative clinical efficacy and safety trials when robust analytical and PK/PD data adequately establish biosimilarity. All three broadly accept extrapolation of indications. However, considerable variation persists in interchangeability: the FDA maintains specific, higher-evidence requirements for “interchangeable biosimilars,” the EMA leaves interchangeability decisions to individual member states, and CDSCO lacks a formal interchangeability designation. Further differences exist in clinical trial waiver criteria, analytical comparability acceptance thresholds, and immunogenicity data interpretation. Conclusion While progress has been made in aligning scientific principles for biosimilar approval, further cooperation through enhanced international regulatory collaboration, standardized data requirements, integrated use of real-world evidence, and transparent communication policies is needed to bridge remaining gaps, facilitate global development, and improve patient access to safe and effective biosimilars worldwide.
