👤 Nikola Ilić

Familial hypertriglyceridemia (FHTG) is a rare inherited lipid disorder that may present with severe phenotypes when caused by compound heterozygous or biallelic APOA5 variants. We report a male child diagnosed at 2.5 years of age with severe hypertriglyceridemia, who exhibited serum triglyceride levels persistently above 10 mmol/L (≈ 885 mg/dl) despite adherence to a low-fat diet and pharmacotherapy including fibrates, omega-3 fatty acids, and statins. Representative triglycerides at presentation were 11.6 mmol/L (≈ 1029 mg/dl). During follow up, the patient experienced an acute abdominal pain episode with triglycerides nearing 20 mmol/L (≈ 1770 mg/dL), managed conservatively under suspicion of pancreatitisOral glucose tolerance testing showed a high-normal insulin response (peak 84.5 mIU/L, below the insulin-resistance threshold of 100-150 mIU/L), which prompted addition of metformin. Over a decade, despite normal growth and clinical well-being, biochemical control remained suboptimal. This case illustrates the clinical utility of early genetic testing in pediatric dyslipidemias and highlights limitations of traditional treatments in monogenic severe FHTG. Emerging therapies, including antisense oligonucleotides and ANGPTL3 inhibitors, may hold future promise. Show less

Cholesteryl ester transfer protein (CETP) belongs to the group of enzymes which inhibition have the application in the treatment of cardiovascular diseases. This study presents QSAR modeling for a set of compounds acting as CETP inhibitors based on the Monte Carlo optimization with SMILES notation and molecular graph-based descriptors, and field-based 3D modeling. A 3D QSAR model was developed for one random split into the training and test sets, whereas conformation independent QSAR models were developed for three random splits, with the results suggesting there is an excellent correlation between them. Various statistical approaches were used to assess the statistical quality of the developed models, including robustness and predictability, and the obtained results were very good. This study used a novel statistical metric known as the index of ideality of correlation for the final assessment of the model, and the results that were obtained suggested that the model was good. Also, molecular fragments which account for the increases and/or decreases of a studied activity were defined and then used for the computer-aided design of new compounds as potential CETP inhibitors. The final assessment of the developed QSAR model and designed inhibitors was done using molecular docking, which revealed an excellent correlation with the results from QSAR modeling.Communicated by Ramaswamy H. Sarma. Show less