On the degradation of metformin and carbamazepine residues in sewage sludge compost

ArticleRecent decades have shown intensive studies devoted to the fate of pharmaceuticals in the environment. These studies have involved the development of analytical tools, determination of pharmaceuticals in different compartments, composting technologies, and plant uptake of pharmaceuticals. The presence of organic pollutants in sewage sludge, including pharmaceuticals, is a problem of major concern. The r e - use of sewage sludge should be encouraged since it represents a long - term solution provided that the quality of the sludge re - used is compatible with public health and environmental protection requirements. Composting is a widely recognized way of making the soil application of sewage sludge safer. In this study, the impact of sewage sludge composting on the degradation of metformin (MET), by far the most often prescribed antidiabetic drug worldwide, and carbamazepine (CBZ), a poorly biodegradable but wid ely used as an anticonvulsant drug to cure depression and seizures, were analysed. The anaerobically digested and dewatered sewage sludge samples were collected from municipal wastewater treatment plant. Composting experiments were performed under fixed co nditions during 30 days. The results of the experiment showed that during a 1 - month composting period more than 90% of MET residues degraded, but no degradation of CBZ took place during the composting period. The half - life of MET was 3 days for the compost mixture with the ratios of 1:3 and 1:2 (v:v). The results of this study show that composting maylead to the efficient degradation of MET, whereas for the elimination of CBZ from sewage sludge different means should be used

SELENIUM TREATMENT UNDER FIELD CONDITIONS AFFECTS MINERAL NUTRITION, YIELD AND ANTIOXIDANT PROPERTIES OF BULB ONION (Allium cepa L.)

The aim of the research was to find out how foliar selenium (Se) treatment in open field conditions affects plant nutrition, yield and bulb bioactive properties. 10, 50 or 100 μg·mL-1 Se, referred to as Se10, Se50 and Se100 treatments, was applied to onion ‘Hercules’ in 2008 and 2009. Bulb weight, total yield, content of total Se, free selenomethionine and selenomethylselenocysteine, total S, N, P, K, Ca and Mg, content of total phenolics, pungency and total antioxidant capacity (TAC) were determined. All Se treatments significantly reduced bulb S content. The Se100 treatment had a tendency to decrease bulb size and yield. The Se50 treatment increased total Se content, total phenolics and TAC and had a tendency to increase the yield. A larger proportion of total Se was converted into organic compounds in the Se50 than in the Se100 treatment. In Se 10 treatment, bulb TAC was the highest among treatments in 2009. Considering both agronomic and human health benefits, Na2SeO4 solution at the rate of 50 μg·mL-1 Se can be recommended for bulb onion

C-reaktiivse valgu dünaamika ennustamine meropeneemravi ajal vastsündinutel ja imikutel

Eesti Arst 2024; 103(10):52

Small-Molecule Inhibitors of the RNA M6A Demethylases FTO Potently Support the Survival of Dopamine Neurons

The fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase, is an important regulator of central nervous system development, neuronal signaling and disease. We present here the target-tailored development and biological characterization of small-molecule inhibitors of FTO. The active compounds were identified using high-throughput molecular docking and molecular dynamics screening of the ZINC compound library. In FTO binding and activity-inhibition assays the two best inhibitors demonstrated Kd = 185 nM; IC50 = 1.46 µM (compound 2) and Kd = 337 nM; IC50 = 28.9 µM (compound 3). Importantly, the treatment of mouse midbrain dopaminergic neurons with the compounds promoted cellular survival and rescued them from growth factor deprivation induced apoptosis already at nanomolar concentrations. Moreover, both the best inhibitors demonstrated good blood-brain-barrier penetration in the model system, 31.7% and 30.8%, respectively. The FTO inhibitors demonstrated increased potency as compared to our recently developed ALKBH5 m6A demethylase inhibitors in protecting dopamine neurons. Inhibition of m6A RNA demethylation by small-molecule drugs, as presented here, has therapeutic potential and provides tools for the identification of disease-modifying m6A RNAs in neurogenesis and neuroregeneration. Further refinement of the lead compounds identified in this study can also lead to unprecedented breakthroughs in the treatment of neurodegenerative diseases

Ampitsilliini farmakokineetika enneaegsetel ja ajalistel vastsündinutel esimesel elunädalal

Eesti Arst 2022; 101(2):12

Accumulation of sulfonamides and fluoroquinolones from soil to plants

Saabunud / Received 12.12.2022 ; Aktsepteeritud / Accepted 29.06.2023 ; Avaldatud veebis / Published online 15.08.2023 ; Vastutav autor / Corresponding author Merike Lillenberg ; [email protected] current study was conducted to determine the potential for some antibiotics to be taken up by food plants from soil fertilized with manure, sewage sludge or its compost containing antibiotic residues. The plants (potato – Solanum tuberosum L., carrot – Daucus carota L., and wheat – Triticum aestivum L.) were cultivated in greenhouse under natural light conditions in the presence of three fluoroquinolones (ciprofloxacin, ofloxacin, and norfloxacin), and two sulfonamides (sulfadimethoxine and sulfamethoxazole). The uptake of antibiotics was demonstrated from two different soils (loamy and loamy sand). The concentrations of each antibiotic in soil were 0.01, 0.1, 0.5, 1.0, and 10 mg kg–1. The antibiotics were extracted from the plants using the liquid extraction (LE) and cleaned up by the solid phase extraction (SPE). The extracts were analyzed by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The accumulation range depended on antibiotic con- centration in soil, chemical properties of the antibiotic, soil type, plant species and parts (overground or below-ground). At soil concentrations of 10 mg kg–1 antibiotics accumulated in edible parts of most plants in amounts, which exceeded their maximum residue levels (MRL) set for food of animal origin – 100 μg kg–1. The highest average content of antibiotics was detected in potato tubers and carrot roots grown in the loamy sand soil – 3897 μg kg–1 and 3400 μg kg–1 sulfamethoxazole. Plants accumulated antibiotics (ciprofloxacin and ofloxacin) from soil even at soil concentration of 0.01 mg kg–1. Mostly the highest concentrations of antibiotics were detected in below-ground parts of the plants grown in the loamy-sand soil

Utilization of data below the analytical limit of quantitation in pharmacokinetic analysis and modeling: promoting interdisciplinary debate

Traditionally, bioanalytical laboratories do not report actual concentrations for samples with results below the LOQ (BLQ) in pharmacokinetic studies. BLQ values are outside the method calibration range established during validation and no data are available to support the reliability of these values. However, ignoring BLQ data can contribute to bias and imprecision in model-based pharmacokinetic analyses. From this perspective, routine use of BLQ data would be advantageous. We would like to initiate an interdisciplinary debate on this important topic by summarizing the current concepts and use of BLQ data by regulators, pharmacometricians and bioanalysts. Through introducing the limit of detection and evaluating its variability, BLQ data could be released and utilized appropriately for pharmacokinetic research

Matrix interference in LC-ESI-MS/MS analysis of metanephrines in protein precipitated plasma samples

Metanephrine and normetanephrine are measured in blood plasma to diagnose different diseases. Simpler sample preparation procedures are preferred but tend to yield less purified extracts. Therefore, thorough investigation of matrix effects is required. In this work, several sample preparation methods and chromatographic modes were compared for liquid chromatography tandem mass spectrometric (with electrospray ionization; LC-ESI-MS/MS) analysis of metanephrine and normetanephrine in blood plasma. Protein precipitation with methanol was found to be sufficient for sample preparation and pentafluorophenyl column provided adequate chromatographic separation. A new cheaper and less labor-intensive approach is proposed where necessary quantitation limits are achieved through a sample preparation containing only protein precipitation and dilution of the sample extract. Matrix effects for different sample preparation methods and the use of isotope-labeled internal standards were evaluated. Unusual interference to D3-labeled internal standard of normetanephrine was discovered – signal of interfering compound increased while the matrix effects were reduced by dilution, e.g. dilution eliminates matrix suppression on interfering compound. The results stress the need to monitor interfering compounds and evaluate matrix effects at every step of method development. Matrix effects and interferences can be different for analytes and their corresponding isotopically labeled internal standards. This means that the use of isotopically labeled internal standards cannot guarantee accuracy of obtained results. New method allows quantification of the low nanomolar concentrations of metanephrine and normetanephrine in plasma samples. </jats:p