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Environmental Science and Pollution... Aug 2021From 2001 to 2014, 13 surveys were conducted in the Baltic Sea, to determine its pollution of 50 micropollutants. The investigations focused mostly on the German western...
From 2001 to 2014, 13 surveys were conducted in the Baltic Sea, to determine its pollution of 50 micropollutants. The investigations focused mostly on the German western Baltic Sea; in 2008, one survey covered the entire Baltic Sea. Various groups of herbicides (such as triazines, phenoxyacetic acid, phenylurea), perfluoroalkyl substances, pharmaceuticals, and industrial products were analyzed during these surveys. The highest concentrations (median 1 to 4 ng/L) were observed for atrazine, simazine, chloridazone, 2,4-dichlorophenoxyacetic acid, benzotriazole, primidone, and carbamazepine. Most micropollutants exhibited a relatively homogenous spatial distribution, though some herbicides show elevated concentrations in certain regions (e.g., Odra estuary), indicating a riverine input. The data set was analyzed, both for seasonal influences and long-time trends. Some herbicides exhibited higher concentrations during summertime. Both upward- and downward-directed time trends could be identified for some herbicides and perfluorinated compounds. For most of the detected compounds, a low-risk quotient was calculated. Only the occurrence of carbendazim could potentially pose a higher risk to the Baltic Sea.
Topics: Baltic States; Environmental Monitoring; Estuaries; Risk Assessment; Seasons; Water Pollutants, Chemical
PubMed: 33755886
DOI: 10.1007/s11356-021-13254-5 -
Journal of Hazardous Materials Jul 2021Understanding and acquiring knowledge about the adsorption of pharmaceuticals on carbon-based nanomaterials (CNMs) is imperative to the chemical engineering applications...
Understanding and acquiring knowledge about the adsorption of pharmaceuticals on carbon-based nanomaterials (CNMs) is imperative to the chemical engineering applications of CNMs, as well as to risk assessment and pollution control of both CNMs and pharmaceuticals. A computational assessment of the mechanism and thermodynamics of the adsorption of 18 most common pharmaceuticals (acetaminophen, acetylsalicylic acid, atenolol, caffeine, carbamazepine, clofibric acid, diclofenac, fenofibric acid, fluoxetine, gemfibrozil, ibuprofen, ketoprofen, naproxen, phenazone, primidone, propranolol, salicylic acid, tramadol) on four different CNMs (pristine/functionalised graphene and carbon nanotube) in two different solvents (water and n-octanol) was provided. We show that the adsorption of pharmaceuticals on pristine CNMs is controlled by dispersion forces, π-interactions and hydrophobic interaction. On the other hand, adsorption on functionalised CNMs is controlled by hydrogen bonding and Coulombic interactions. Furthermore, we demonstrate how functionalization of CNM, CNM curvature and background solution properties modulate the intensity of non-covalent interactions and their contribution towards adsorption free energy. With this knowledge, we pinpoint functionalised graphene at environmental pH as the most effective setting for the removal of a given set of pharmaceuticals from water and wastewater. Finally, we show that CNMs may transport pharmaceuticals into living organisms and release them in nonpolar mediums such as cellular membranes and fat cells.
Topics: Adsorption; Nanostructures; Pharmaceutical Preparations; Wastewater; Water Pollutants, Chemical; Water Purification
PubMed: 33684815
DOI: 10.1016/j.jhazmat.2021.125554 -
Epilepsy & Behavior : E&B Apr 2021Treatment with antiseizure medications (ASMs) confers a risk of drug-induced liver injury (DILI), especially for older ASMs. We sought to quantify recent reports of DILI...
PURPOSE
Treatment with antiseizure medications (ASMs) confers a risk of drug-induced liver injury (DILI), especially for older ASMs. We sought to quantify recent reports of DILI attributed to both older and newer generation ASMs and survey newly marketed ASMs for hepatotoxicity in a large post-marketing database.
METHODS
We queried over 2.6 million adverse event reports made to the FDA Adverse Event Reporting System (FAERS) database between July 1, 2018 and March 31, 2020 for DILI due to ASMs commonly used in clinical practice. Patient characteristics and outcomes were assessed. We calculated the reporting odds ratio (ROR) of DILI for each individual ASM versus all non-ASM reports.
RESULTS
A total of 2175 DILI cases were attributed to an ASM during the study period. 97.2% of these were designated as serious reactions, which include death, hospitalization, disability, and other life-threatening outcomes. A number of older and newer generation ASMs were associated with DILI, specifically: carbamazepine (ROR 2.92), phenobarbital (ROR 2.91), oxcarbazepine (ROR 2.58), phenytoin (ROR 2.40), valproate (ROR 2.22), lamotrigine (ROR 2.06), clobazam (ROR 1.67), levetiracetam (ROR 1.56), and diazepam (ROR 1.53). However, increased odds of DILI were not seen with zonisamide, perampanel, stiripentol, lacosamide, clonazepam, pregabalin, felbamate, eslicarbazepine, cannabidiol, topiramate, gabapentin, ethosuximide, brivaracetam, or primidone. Vigabatrin, tiagabine, and rufinamide all had zero reports of DILI.
CONCLUSIONS
The majority of newer generation ASMs were not significantly associated with DILI. Future studies utilizing FAERS in conjunction with other data sources will be critical for the ongoing surveillance of DILI, particularly as newly marketed ASMs continue to enter into widespread clinical use.
Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Humans; Lamotrigine; Levetiracetam; Phenytoin; United States
PubMed: 33626490
DOI: 10.1016/j.yebeh.2021.107832 -
Scientific Reports Feb 2021Trace organic compounds (TrOCs) enter rivers with discharge of treated wastewater. These effluents can contain high loads of dissolved organic matter (DOM). In a 48 h...
Trace organic compounds (TrOCs) enter rivers with discharge of treated wastewater. These effluents can contain high loads of dissolved organic matter (DOM). In a 48 h field study, we investigated changes in molecular composition of seven DOM compound classes (FTICR-MS) and attenuation of 17 polar TrOCs in a small urban stream receiving treated wastewater. Correlations between TrOCs and DOM were used to identify simultaneous changes in surface water and the hyporheic zone. Changes in TrOC concentrations in surface water ranged between a decrease of 29.2% for methylbenzotriazole and an increase of 152.2% for the transformation product gabapentin-lactam. In the hyporheic zone, only decreasing TrOC concentrations were observed, ranging from 4.9% for primidone to 93.8% for venlafaxine . TrOC attenuation coincided with a decline of molecular diversity of easily biodegradable DOM compound classes while molecular diversity of poorly biodegradable DOM compound classes increased. This concurrence indicates similar or linked attenuation pathways for biodegradable DOM and TrOCs. Strong correlations between TrOCs and DOM compound classes as well as high attenuation of TrOCs primarily occurred in the hyporheic zone. This suggests high potential for DOM turnover and TrOC mitigation in rivers if hyporheic exchange is sufficient.
PubMed: 33603043
DOI: 10.1038/s41598-021-83750-8 -
The Science of the Total Environment Jun 2021In this work, the occurrences of bacteria families and relevant pharmaceuticals in municipal wastewater effluents from Bogotá (Colombia), and their treatment by the...
In this work, the occurrences of bacteria families and relevant pharmaceuticals in municipal wastewater effluents from Bogotá (Colombia), and their treatment by the photo-electro-Fenton process were studied. Twenty-five representative pharmaceuticals (azithromycin, carbamazepine, ciprofloxacin, clarithromycin, diclofenac, enalapril, gabapentin, iopromide, metoprolol, sulfamethoxazole, trimethoprim, valsartan, clindamycin, erythromycin, levamisole, lincomycin, norfloxacin, oxolinic acid, phenazone, primidone, salbutamol, sulfadiazine, tetracycline, tramadol, and venlafaxine) were quantified in the effluent by LC-MS/MS analysis. Four of these target compounds (azithromycin, diclofenac, trimethoprim, norfloxacin) were found at concentrations that represent an environmental risk. In addition, several bacteria families related to water and foodborne diseases were identified in such effluents (e.g., Pseudomonadaceae, Campylobacteraceae, Aeromonadaceae, Enterobacteriaceae, and Bacteroidaceae), via shotgun-metagenomic technique. Then, a bench-scale photo-electro-Fenton (PEF) system equipped with a DSA anode (Ti/IrO-SnO) and a GDE cathode was applied to treat such effluents. After 60 min, this treatment led to a decrease in the ratio of the bacterial content in the original samples, ~150 thousand times, and a pondered removal of 66.12% for the pharmaceuticals. The study of the process pathways indicated that the bacteria and pharmaceuticals elimination mainly occurred through attacks of hydroxyl and chlorine radicals. Interestingly, in the case of pharmaceuticals, their environmental risk quotients were diminished after the PEF application. Furthermore, the prolonged action of this electrochemical process induced ~15% of mineralization and a significant reduction of the total DNA (removal >85%). Hence, the photo-electro-Fenton process showed to be a promising alternative to deal with municipal effluents for limiting the waterborne diseases, pollution by pharmaceuticals, and mobility/availability of genetic material coming from microorganisms.
Topics: Bacteria; Chromatography, Liquid; Colombia; Humans; Hydrogen Peroxide; Iron; Oxidation-Reduction; Pharmaceutical Preparations; Tandem Mass Spectrometry; Wastewater; Water Pollutants, Chemical
PubMed: 33578165
DOI: 10.1016/j.scitotenv.2020.144890 -
The Science of the Total Environment Apr 2021This work critically compared the removal of fluorescing PARAFAC components and selected pharmaceuticals (carbamazepine, fluoxetine, gemfibrozil, primidone,...
Comparison of the new Cl/O/UV process with different ozone- and UV-based AOPs for wastewater treatment at pilot scale: Removal of pharmaceuticals and changes in fluorescing organic matter.
This work critically compared the removal of fluorescing PARAFAC components and selected pharmaceuticals (carbamazepine, fluoxetine, gemfibrozil, primidone, sulfamethoxazole, trimethoprim) from a tertiary wastewater effluent by different UV- and ozone-based advanced oxidation processes (AOPs) operated at pilot-scale. Investigated AOPs included UV/HO, UV/Cl, O, O/UV, HO/O/UV, and the new Cl/O/UV. AOPs comparison was accomplished using various ozone doses (0-9 mg/L), UV fluences (191-981 mJ/cm) and radical promoter concentrations of Cl = 0.04 mM and HO = 0.29 mM. Chlorine-based AOPs produced radical species that reacted more selectively with pharmaceuticals than radical species and oxidants generated by other AOPs. Tryptophan-like substances and humic-like fluorescing compounds were the most degraded components by all AOPs, which were better removed than microbial products and fulvic-like fluorescing substances. Removal of UV absorbance at 254 (UV) nm was always low. Overall, chlorine-based AOPs were more effective to reduce fluorescence intensities than similar HO-based AOPs. The Cl/O/UV process was the most effective AOP to degrade all target micro-pollutants except primidone. On the other hand, the oxidation performance of pharmaceuticals by other ozone-based AOPs followed the order HO/O/UV > O/UV > O. UV/Cl process outcompeted UV/HO only for the removal of trimethoprim and sulfamethoxazole. Correlations between the removal of pharmaceuticals and spectroscopic indexes (PARAFAC components and UV) had unique regression parameters for each compound, surrogate parameter and oxidation process. Particularly, a diverse PARAFAC component for each investigated AOP resulted to be the most sensitive surrogate parameter able to monitor small changes of pharmaceuticals removal.
Topics: Hydrogen Peroxide; Oxidation-Reduction; Ozone; Pharmaceutical Preparations; Ultraviolet Rays; Water Pollutants, Chemical; Water Purification
PubMed: 33572038
DOI: 10.1016/j.scitotenv.2020.142720 -
European Journal of Drug Metabolism and... Mar 2021Therapeutic drug monitoring (TDM) of antiepileptic drugs (AED) using blood is well established but limited by its invasiveness, accessibility, cost, interpretation... (Review)
Review
Therapeutic drug monitoring (TDM) of antiepileptic drugs (AED) using blood is well established but limited by its invasiveness, accessibility, cost, interpretation errors, and related disturbances in protein binding. TDM using oral fluid (OF) could overcome these limitations. This paper provides a summary of the current evidence for using OF as a matrix to perform TDM of AEDs, as well as practical considerations. A literature search of MEDLINE, EMBASE, and the Cochrane Library was conducted on April 9, 2018 (and then updated on May 20, 2020) using all AEDs as keywords along with "oral fluid," "saliva," "salivary," "seizure," "epilepsy," "antiepileptic," and "anticonvulsant." A total of 18 relevant articles were found and included in this review. There is evidence to suggest that AED TDM using OF is feasible and that reference ranges can be calculated for the following drugs: carbamazepine, ethosuximide, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and valproic acid. For all other AEDs, there is either a lack of evidence on the feasibility of TDM using OF or the evidence indicates that TDM using OF is not feasible. Practical considerations should include the timing and method of OF collection (stimulated or unstimulated) due to their probable impact on the reliability of AED TDM. Using OF may improve the acceptability and accessibility and reduce the cost of AED TDM. Clinical implementation requires standardized collection protocols, more rigorously defined OF reference ranges, and further studies to determine the relevance to clinically important outcomes.
Topics: Anticonvulsants; Drug Monitoring; Epilepsy; Feasibility Studies; Humans; Reproducibility of Results; Saliva; Time Factors
PubMed: 33569746
DOI: 10.1007/s13318-020-00661-1 -
European Journal of Pharmacology Apr 2021Niemann-Pick disease type C (NPC) is caused by a loss of function of either NPC1 or NPC2 protein, resulting in the accumulation of unesterified, free-cholesterol... (Comparative Study)
Comparative Study
Beneficial effects of primidone in Niemann-Pick disease type C (NPC)-model cells and mice: Reduction of unesterified cholesterol levels in cells and extension of lifespan in mice.
Niemann-Pick disease type C (NPC) is caused by a loss of function of either NPC1 or NPC2 protein, resulting in the accumulation of unesterified, free-cholesterol (free-C) in cells/tissues and thus leading to cell/tissue damage. In the brain of patients/animals with NPC, as a consequence of the accumulation of free-C in late endosomes/lysosomes (LE/LY) in cells, multiple lipids including complex sphingolipids are accumulated, and almost all patients/animals ultimately develop progressive/fatal neurodegeneration. Several reagents that are considered to act in the brain show beneficial effects on NPC-model animals. In the present study, we investigated the effects of antiepileptic drugs, such as primidone and valproic acid, on the accumulation of free-C in NPC1-null CHO cells and NPC1* fibroblasts, human fibroblasts established from a patient with NPC1 mutation. Like valproic acid, treatment with primidone reduced free-C levels in LE/LY in NPC1-null/mutant cells. Down-regulation of cholesterol ester levels in NPC1-null cells and up-regulation of HMG-CoA reductase and low-density lipoprotein receptor mRNA levels in NPC1* cells were partially recovered by primidone treatment. Thus, primidone was suggested to enhance free-C trafficking from LE/LY to endoplasmic reticulum in NPC1-null/mutant cells. In NPC1-null mice, oral application of primidone (100 mg/kg/day) extended lifespan by approximately 5 days, although the first days showing ataxia, a typical symptom of neuromotor dysfunction, were not affected. Our findings suggest the potential of primidone for the treatment of NPC.
Topics: Animals; Biological Transport; CHO Cells; Cholesterol; Cricetulus; Disease Models, Animal; Endoplasmic Reticulum; Endosomes; Fibroblasts; Humans; Intracellular Signaling Peptides and Proteins; Longevity; Lysosomes; Mice, Inbred BALB C; Mice, Knockout; Motor Activity; Niemann-Pick C1 Protein; Niemann-Pick Disease, Type C; Primidone; Time Factors; Valproic Acid; Mice
PubMed: 33503462
DOI: 10.1016/j.ejphar.2021.173907 -
The Journal of Neuroscience : the... Mar 2021Transient receptor potential melastatin 3 (TRPM3) is a heat-activated ion channel in primary sensory neurons of the dorsal root ganglia (DRGs). Pharmacological and...
Transient receptor potential melastatin 3 (TRPM3) is a heat-activated ion channel in primary sensory neurons of the dorsal root ganglia (DRGs). Pharmacological and genetic studies implicated TRPM3 in various pain modalities, but TRPM3 inhibitors were not validated in TRPM3 mice. Here we tested two inhibitors of TRPM3 in male and female wild-type and TRPM3 mice in nerve injury-induced neuropathic pain. We found that intraperitoneal injection of either isosakuranetin or primidone reduced heat hypersensitivity induced by chronic constriction injury (CCI) of the sciatic nerve in wild-type, but not in TRPM3 mice. Primidone was also effective when injected locally in the hindpaw or intrathecally. Consistently, intrathecal injection of the TRPM3 agonist CIM0216 reduced paw withdrawal latency to radiant heat in wild-type, but not in TRPM3 mice. Intraperitoneal injection of 2 mg/kg, but not 0.5 mg/kg isosakuranetin, inhibited cold and mechanical hypersensitivity in CCI, both in wild-type and TRPM3 mice, indicating a dose-dependent off-target effect. Primidone had no effect on cold sensitivity, and only a marginal effect on mechanical hypersensitivity. Genetic deletion or inhibitors of TRPM3 reduced the increase in the levels of the early genes c-Fos and pERK in the spinal cord and DRGs in CCI mice, suggesting spontaneous activity of the channel. Intraperitoneal isosakuranetin also inhibited spontaneous pain related behavior in CCI in the conditioned place preference assay, and this effect was eliminated in TRPM3 mice. Overall, our data indicate a role of TRPM3 in heat hypersensitivity and in spontaneous pain after nerve injury. Neuropathic pain is a major unsolved medical problem. The heat-activated TRPM3 ion channel is a potential target for novel pain medications, but the pain modalities in which it plays a role are not clear. Here we used a combination of genetic and pharmacological tools to assess the role of this channel in spontaneous pain, heat, cold, and mechanical hypersensitivity in a nerve injury model of neuropathic pain in mice. Our findings indicate a role for TRPM3 in heat hyperalgesia, and spontaneous pain, but not in cold and mechanical hypersensitivity. We also find that not only TRPM3 located in the peripheral nerve termini, but also TRPM3 in the spinal cord or proximal segments of DRG neurons are important for heat hypersensitivity.
Topics: Animals; Female; Hot Temperature; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuralgia; Peripheral Nerve Injuries; TRPM Cation Channels
PubMed: 33478988
DOI: 10.1523/JNEUROSCI.1551-20.2020 -
Epilepsy Research Feb 2021This study aimed at providing valid estimates for the risk of clinically relevant seizure aggravation by recommended anti-seizure medications in patients with Genetic...
This study aimed at providing valid estimates for the risk of clinically relevant seizure aggravation by recommended anti-seizure medications in patients with Genetic Generalized Epilepsy (GGE). To this aim, treatment response, side effects and paradoxical reactions to anti-seizure treatment were retrospectively assessed in a near-population based cohort comprising 471 adult GGE patients. A total of 1046 treatment attempts were analyzed (lamotrigine: 351, valproic acid: 295, levetiracetam: 249, primidone/phenobarbital: 94, zonisamide: 57). Under lamotrigine, seizure aggravation was observed in 15 patients (two patients during levetiracetam, one patient during zonisamide, none during phenobarbital and valproic acid). All but two patients with paradoxical reactions to lamotrigine were diagnosed with juvenile myoclonic epilepsy (JME), otherwise, the clinical and electroencephalographic characteristics of patients with paradoxical reactions did not differ. At treatment start, the estimated risk of a paradoxical reaction to lamotrigine was 7.9 % in JME patients (n = 190). For all GGE patients (incl. JME), the estimated risk of clinically relevant seizure aggravation under treatment with lamotrigine was 3.7 % (1.8 % for zonisamide and 0.8 % for levetiracetam). In conclusion, clinical significant aggravation of seizure frequency is common in lamotrigine-treated JME patients but rare in patients with other GGE subsyndromes or under treatment with other recommended anti-seizure medication.
Topics: Adult; Anticonvulsants; Epilepsy, Generalized; Humans; Lamotrigine; Levetiracetam; Myoclonic Epilepsy, Juvenile; Phenobarbital; Retrospective Studies; Risk Factors; Seizures; Valproic Acid; Zonisamide
PubMed: 33421702
DOI: 10.1016/j.eplepsyres.2020.106547