Tamil Nadu Dr. M.G.R. Medical University

Although 5-fluorouracil (5-FU) is still a vital chemotherapeutic treatment for several types of cancers, especially in gastrointestinal cancers like colorectal cancer (CRC), pancreatic cancer and gastric cancer, its long-term therapeutic effectiveness is severely limited by both innate and acquired resistance. Overexpression of thymidylate synthase (TYMS), elevation of dihydropyrimidine dehydrogenase (DPD), epithelial–mesenchymal transition (EMT), increased drug efflux through ABC transporters, and dysregulation of apoptotic signalling pathways are important mechanisms of resistance. With increasing data demonstrating their significance in modifying important molecular targets to overcome or mitigate resistance, recent studies have highlighted the potential of vitamins, herbal remedies, and nutritional supplements as adjuncts to conventional 5-FU therapy. Vitamin D, C, curcumin, allicin, EGCG, and omega-3 fatty acids have been shown to suppress TYMS expression, inhibit NF-κB signaling, reduce oxidative stress-mediated survival signaling, modulate apoptosis regulators (Bcl-2, Bax), and reduce drug efflux mechanisms in preclinical cancer models. Incorporating such supplementary strategies may improve patient quality of life, decrease treatment-related toxicities, and increase the effectiveness of 5-FU. This review presents integrated approaches for improving therapeutic outcomes in cancer care by synthesising current knowledge of 5-FU resistance mechanisms and critically analyzing the supportive roles of dietary supplements, vitamins, and phytochemicals in minimising the adverse effects related to 5-FU resistance.

Cancer is characterized by the uncontrolled proliferation of abnormal cells that escape the body's standard regulatory mechanisms. Under normal conditions, cells grow, divide, and die in an orderly manner, but cancerous cells lose this control, growing uncontrollably and invading surrounding tissues. Poly(ADP-ribose) polymerase 1 (PARP1) is a crucial enzyme in this DNA repair process, helping to fix single-strand breaks. PARP inhibitors (PARPi) are a class of drugs that target and block the activity of the PARP1 enzyme, impairing its ability to repair DNA damage. By inhibiting PARP1, these drugs lead to an accumulation of DNA damage in cancer cells, which eventually becomes overwhelming and leads to cell death. This mechanism is particularly effective in cancers with deficiencies in other DNA repair pathways, such as those with BRCA1 and BRCA2 gene mutations. Several PARPi, including Olaparib, Niraparib, and Rucaparib, have been approved by the U.S. Food and Drug Administration (FDA) for use in treating cancers like breast, ovarian, and prostate cancer, particularly in patients with BRCA mutations. The evolution and development of PARP inhibitors have focused on modifying their chemical structure to increase their effectiveness. The design of PARPi also aims to improve their bioavailability, ensuring that the drugs are effectively absorbed into the body and can reach the tumor site in sufficient concentrations. Further developments may also involve combining PARPi with other treatments, such as chemotherapy or immunotherapy, to enhance their overall efficacy.

Patients with chronic kidney disease undergoing hemodialysis are at an increased risk of cardiovascular complications due to volume overload. Lung ultrasound (LUS) has emerged as a non-invasive tool to assess extravascular lung water (EVLW) and manage fluid excess. This study aimed to validate LUS in a relatively asymptomatic day-care dialysis population and to correlate it with clinical parameters, ECHO/IVC metrics. This prospective pre-post intervention study was conducted in a dialysis unit, enrolling 93 eligible hemodialysis patients. The fluid status of all patients was evaluated by clinical examination, lung ultrasound, inferior vena cava (IVC) indices, and echocardiography pre and post-dialysis. The mean age was 48.20 ± 13.81 years with male predominance (n = 66,71

Recent advances in pediatric pharmacokinetics highlight substantial age-dependent physiological changes that require specialised approaches to optimise efficacy and minimise adverse effects in children. This review compares pharmacokinetic differences between adults and children, traditional dosing approaches, and recent developments in Model-Informed Precision Dosing (MIPD), with a focus on Population Pharmacokinetic (PopPK) and Physiologically Based Pharmacokinetic (PBPK) modeling strategies. Recent advances in Bayesian forecasting and the integration of artificial intelligence and machine learning are highlighted for their potential to improve dosing accuracy and clinical decision-making. This article examines current regulatory perspectives on pharmacometric approaches in pediatric medication development and offers insights into evolving standards and guidelines. It also addresses key technical, logistical, and regulatory challenges and potential solutions. Based on these insights, future strategies to improve model-based precision in pediatric dosing are discussed.

Recent guidelines have introduced the concept of early gestational glucose intolerance (EGGI), necessitating timely intervention to prevent GDM and its complications. This study aimed to evaluate whether early intervention with medical nutritional therapy (MNT) and metformin in women with postprandial blood glucose (PPBG) ≥ 110 mg/dl at 8–9 weeks gestation (EGGI) could reduce the progression to GDM and associated complications. This prospective, longitudinal study included pregnant women with singleton pregnancies and PPBG ≥ 110 mg/dl < 9 weeks gestation. Participants were divided into two groups: the intervention group (MNT + Metformin 250 mg twice daily) and the control group (MNT only). Metformin group had a significant reduction in PPBG levels by 11 weeks (p < 0.0001) thus preventing fetal hyperinsulinemia. Only 2.6