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

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

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

Ampitsilliini farmakokineetika enneaegsetel ja ajalistel vastsündinutel esimesel elunädalal

Eesti Arst 2022; 101(2):12

Shallow and Deep Groundwater Moderate Methane Dynamics in a High Arctic Glacial Catchment

Glacial groundwater can mobilize deep-seated methane from beneath glaciers and permafrost in the Arctic, leading to atmospheric emissions of this greenhouse gas. We present a temporal, hydro-chemical dataset of methane-rich groundwater collected during two melt seasons from a high Arctic glacial forefield to explore the seasonal dynamics of methane emissions. We use methane and ion concentrations and the isotopic composition of water and methane to investigate the sources of groundwater and the origin of the methane that the groundwater transports to the surface. Our results suggest two sources of groundwater, one shallow and one deep, which mix, and moderate methane dynamics. During summer, deep methane-rich groundwater is diluted by shallow oxygenated groundwater, leading to some microbial methane oxidation prior to its emergence at the surface. Characterization of the microbial compositions in the groundwater shows that microbial activity is an important seasonal methane sink along this flow-path. In the groundwater pool studied, we found that potential methane emissions were reduced by an average of 29% (±14%) throughout the summer due to microbial oxidation. During winter, deep groundwater remains active while many shallow systems shut down due to freezing, reducing subsurface methane oxidation, and potentially permitting larger methane emissions. Our results suggest that ratios of the different groundwater sources will change in the future as aquifer capacities and recharge volumes increase in a warming climate

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

HIV Replication Is Increased by RNA Methylation METTL3/METTL14/WTAP Complex Activators

The N6-methyladenosine (m(6)A) modifications in both viral and host cell RNAs play an important role in HIV-1 virus genome transcription and virus replication. We demonstrate here that activators of the METTL3/METTL14/WTAP RNA methyltransferase complex enhance the production of virus particles in cells harboring HIV-1 provirus. In parallel, the amount of m(6)A residues in the host cell mRNA was increased in the presence of these activator compounds. Importantly, the m(6)A methylation of the HIV-1 RNA was also enhanced significantly (about 18%). The increase of virus replication by the small-molecule activators of the METTL3/METTL14/WTAP complex excludes them as potential anti-HIV-1 drug candidates. However, the compounds may be of large interest as activators for the latent HIV-1 provirus copies deposited in host cells' genome and the subsequent virus eradication by an antiviral compound.Peer reviewe

Human Biomonitoring in the Oil Shale Industry Area in Estonia : Overview of Earlier Programmes and Future Perspectives

Ida-Viru County, in Eastern Estonia, features industrially contaminated sites–where oil shale has been mined and used for electricity generation, and shale oil extraction. Higher prevalence of respiratory and cardiovascular disease has been found in the region due to high quantities of air pollution. Within the framework of “Studies of the health impact of the oil shale sector—SOHOS,” this analysis aimed to map earlier human biomonitoring (HBM) studies and identify the suitable biomarkers for upcoming HBM in Estonia. Altogether, three studies have been conducted among residents: first, among adults in the 1980's; second, among children in the 1990's; and third, among employees, with a focus on workers and miners in the oil shale chemistry industry in the late 1990's and 2000's. In some of those studies, increased levels of biomarkers in blood and urine (heavy metals, 1-OHP) have appeared; nevertheless, in last 20 years, there has been no population-wide HBM in Estonia. According to air pollution monitoring and emission analysis, the pollutants of concern are benzene, PM10, PM2.5, and PAHs. In general, there is a decreasing trend in air pollutant levels, with the exception of a slight increase in 2018. One of the aims of HBM is to be analyzed if this trend can be identified in HBM, using similar biomarkers as applied earlier. The future perspective HBM could be divided into two Tiers. Tier 1 should focus on exposure biomarkers as heavy metals, PAH, and BTEX metabolites and Tier 2, in later stage, on effect biomarkers as Ox LDL, TBARS, etc

Free Amino Acids and Biogenic Amines Profiling and Variation in Wild and Sub-Endemic Cardueae Species from Sardinia and Corse

The cardueae are a common species in the Mediterranean area where they grow spontaneously and are traditionally employed as food and for health purposes. In this work, five Cardueae, including two sub-endemic species (four Carduus and three Ptilostemon casabonae (L.) Greuter samples from different locations) were collected from Sardinia and the Corse islands. All the considered plants are characteristic of the area, in particular the sub-endemic species C. cephalanthus and P. casabonae. This work aims to obtain, for the first time, the amino compounds profile (primary metabolites) of these little-studied species to detect for any similarities and differences among the different samples using statistical analyses. A recently developed method was employed, where diethyl ethoxymethylenemalonate (DEEMM) derivatives are detected in a neutral loss scan mode using high performance liquid chromatography in tandem with a mass spectrometry technique. In total, 42 amino compounds were detected, of which 33 were fully identified and semi-quantified. Overall, the results show that DEEMM-derivatized amino compounds are qualitatively similar among the considered samples. Nonetheless, a discrimination at the genus level is possible. This work adds more information regarding the phytochemical composition regarding the primary metabolites of the considered samples, their discriminations and the search for compounds with potential health benefits