An increase of pyroglutamic acid, or 5-oxoproline plasmatic concentration was reported in metabolic acidosis observed after chronic intake of some drugs, as acetaminophen. We developed a simple, fast and reproducible method by capillary zone electrophoresis using a commercial Anion Analysis Kit to quantify pyroglutamic acid, in plasma after acetonitrile precipitation, and after simple dilution in urines. Fumaric acid was used as internal standard in both. In less than 7 min, the method separates pyroglutamic acid from other organic and inorganic anions. The method is linear between 0.25 and 10 mmol/L in plasma, and 0.15 and 10 mmol/L in urines. The quantification limits are 0.25 mmol/L and 0.15 mmol/L for plasma and urines, respectively. For repeatability and intermediate precision, the variation coefficients are less than 15% and the bias values are between ± 10%. For the 2 matrices, the recoveries are between 88% and 101%. The method does not interfere with physiological organic and inorganic anions. Pyroglutamic acid concentrations measured in 9 children were between 0.45 and 3.96 mmol/L in the plasma and between 0.15 and 3.2 mmol/L in the urine. No correlation between pyroglutamic acid and acetaminophen concentrations were found, regardless of the biological media. In conclusion, our method measures pathophysiological concentrations of pyroglutamic acid and highlights the increase in other organic acids that may explain metabolic acidosis due to chronic acetaminophen intake.
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http://dx.doi.org/10.1684/abc.2021.1689 | DOI Listing |
Chem Asian J
December 2024
CSIR National Chemical Laboratory, Center for Materials Characterization, INDIA.
We present a comprehensive account of our efforts directed towards the synthesis of sacubitril, a neprilysin inhibitor used in combination with valsartan and marketed as Entresto™. Our initial approach to the formal synthesis of sacubitril employed a chiral pool strategy, utilizing (S)-pyroglutamic acid as a key building block and Cu(I)-mediated Csp2-Csp3 cross-coupling as a key transformation. Further investigations led to the development of chiral amine transfer (CAT) reagents-based stereoselective synthesis.
View Article and Find Full Text PDFChem Biodivers
December 2024
Kitasato University: Kitasato Daigaku, Ōmura Satoshi Memorial Institute and Graduate School of Infection Control Sciences, 5-9-1 Shirokane, 1088641, Minato-ku, JAPAN.
The discovery of novel natural products through the exploration of distinct microorganisms is crucial for advancing drug discovery research. In this study, we focus on a unique environmental resource, microbial masses known as "Tengu-no-Mugimeshi." From the culture broth of Lecanicillium aphanocladii FKI-9593, isolated from Tengu-no-Mugimeshi collected at Mount Kurohime, Nagano Prefecture, Japan, we report the isolation of two novel tetrapeptides, tengupeptins A (1) and B (2), as well as the known compound oosporein.
View Article and Find Full Text PDFBiomed Pharmacother
December 2024
Research and Innovation Hub, Alamein International University, Alamein, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Alamein International University, Alamein, Egypt. Electronic address:
Mild cognitive impairment is increasingly recognized as a complication of type 2 diabetes (T2D). Although currently no disease-modifying treatments for cognitive disorders exist, interest surged in potential neuroprotective effects of newer anti-diabetic drugs. This study investigates the impact of newer anti-diabetic drug classes, dipeptidyl peptidase-4 (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) - on cognitive decline in T2D patients on metformin therapy.
View Article and Find Full Text PDFA 60-year-old polymorbid patient developed severe metabolic acidosis during weeks of treatment with flucloxacillin and paracetamol. The acidosis was triggered by an accumulation of 5-oxoproline due to pre-existing risk factors for glutathione deficiency as well as a ketoacidosis due to starvation. After treatment with N-acetylcysteine and hemofiltration, the acidosis completely resolved.
View Article and Find Full Text PDFPestic Biochem Physiol
December 2024
National Biopesticide Engineering Research Centre, Hubei Biopesticide Engineering Research Centre, Hubei Academy of Agricultural Science, Wuhan 430064, PR China. Electronic address:
The brown planthopper Nilaparvata lugens is one of the most economically important rice crop pests in Asia. Entomopathogenic fungi (EPF) have been developed as a biological control of N. lugens.
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