Metabolomics profiling for diagnosis of acute renal failure after cardiopulmonary bypass.

RATIONALE: Acute renal failure (ARF) is one of the most serious complications of cardiopulmonary bypass (CPB) surgery. Serum creatinine level is a key compound examined to understand whether renal function is normal. However, its level may vary based on age, gender, race, muscle mass, nutrition, and drugs taken by an individual. In addition, it may not be detected without a 50% reduction in renal function and may lead to delays in treatment. New markers are needed for early diagnosis of ARF. They were determined for early diagnosis of ARF after CPB. Metabolic differences in plasma samples of individuals who developed and did not develop ARF after cardiopulmonary bypass were determined. METHODS: This study was the first to perform an untargeted metabolomics analysis for early diagnosis of ARF after CPB surgery. Plasma samples were taken from 105 patients (9 ARF patients) at five time points to identify the time at which a more accurate ARF diagnosis can be made. A total of 687 samples, including quality control samples, were analyzed. RESULTS: Two hundred twenty-six metabolites were identified using retention index libraries. Based on the statistical evaluations, tryptophan, threonine, and methionine were found in lower concentrations in patients with ARF compared to the control group at all time points. Whereas gluconic acid, hypoxanthine, and lactic acid showed a decreasing trend over time, longitudinal analysis showed that cysteine, hippuric acid, and uric acid levels increased over time in the ARF group. CONCLUSIONS: These metabolites are candidate biomarkers for early diagnosis of ARF as well as biomarkers for tracking the recovery of ARF patients.

Comparative Metabolomic Profiles of Vascular Involvement in Behçet's Disease.

BACKGROUND: Behçet's disease is a systemic, inflammatory disease affecting multiple organs. Vascular involvement is the main cause of morbidity and mortality in Behçet's disease patients. Though clinically well-defined, there is limited information related to disease pathogenesis and vascular incidence in this patient group. The aim of this study is to investigate the unique metabolic signatures of Behçet's disease patients with vascular involvement. METHODS: Metabolomic profiling was performed on serum samples of 48 Behçet's disease patients (18 with vascular involvement) and 40 healthy controls using gas chromatography-mass spectrometrybased untargeted metabolomics analysis. Multivariate and univariate statistical analyses were performed to find altered metabolites and pathways. RESULTS: Untargeted metabolomics results showed that a total of 168 metabolites were identified. The comparison between the groups of Behçet's disease, vascular involvement in Behçet's disease, and the healthy control group showed that altered amino acid and oxidative stress pathways, especially with glutathione synthesis, could be an important stage for developing Behçet's disease. CONCLUSION: In the present work, the untargeted metabolomics approach provided new molecular insights for a better understanding of Behçet's disease pathogenesis and also developing vascular involvement in Behçet's disease at the metabolite level. The results showed that vascular involvement in Behçet's disease could be highly linked with amino acid metabolism and also the antioxidant system, and these disease-related pathways could be evaluated with further experiments for diagnosis and prognosis of Behçet's disease and also for vascular involvement in Behçet's disease.

A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies.

Antiviral drugs have gained much more attention in recent years due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and many drug candidates are currently under investigation in order to end pandemic. Molnupiravir, a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, is one of the promising candidates for SARS-CoV-2 treatment. In this study, a RP-HPLC method was developed for the determination of Molnupiravir and applied for in vitro permeability studies of self-emulsifying drug delivery system (SEDDS) formulations using Caco-2 cell line. Discovery® HS C18 Column (75 ×4.6 mm, 3 µm) was used at 30 °C. Isocratic elution was performed with ACN:water (20:80 v/v) mixture. The flow rate was 0.5 mL/min and UV detection was at 240 nm. Molnupiravir eluted within 5 min. Molnupiravir was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions. Peak homogeneity data of Molnupiravir in the stressed samples peak obtained using photodiode array detector, in the stressed sample chromatograms, demonstrated the specificity of the method for their estimation in presence of degradants. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines and found to be linear within the range 0.1-60.0 µg/mL. The method was simple, rapid, selective, sensitive, accurate, precise, robust and rugged. Thus, it was applied successfully for permeability quantitation of Molnupiravir in nanoformulations. The apparent permeability of Molnupiravir in SEDDS formulations, which have droplet size under 350 nm, was calculated as 3.20 ± 0.44 × 10-6 cm/s.