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Analytical Methods : Advancing Methods... May 2024The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is an important environmental contaminant occurring in surface waters all over the world, because,...
The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is an important environmental contaminant occurring in surface waters all over the world, because, after excretion, it is not adequately removed from wastewater in sewage treatment plants. To be able to monitor this pollutant, highly efficient analytical methods are needed, including immunoassays. In a medical research project, monoclonal antibodies against diclofenac and its metabolites had been produced. Based on this monoclonal anti-DCF antibody, a new indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed and applied for environmental samples. The introduction of a spacer between diclofenac and the carrier protein in the coating conjugate led to higher sensitivity. With a test midpoint of 3 μg L and a measurement range of 1-30 μg L, the system is not sensitive enough for direct analysis of surface water. However, this assay is quite robust against matrix influences and can be used for wastewater. Without adjustment of the calibration, organic solvents up to 5%, natural organic matter (NOM) up to 10 mg L, humic acids up to 2.5 mg L, and salt concentrations up to 6 g L NaCl and 75 mg L CaCl are tolerated. The antibody is also stable in a pH range from 3 to 12. Cross-reactivity (CR) of 1% or less was determined for the metabolites 4'-hydroxydiclofenac (4'-OH-DCF), 5-hydroxydiclofenac (5-OH-DCF), DCF lactam, and other NSAIDs. Relevant cross-reactivity occurred only with an amide derivative of DCF, 6-aminohexanoic acid (DCF-Ahx), aceclofenac (ACF) and DCF methyl ester (DCF-Me) with 150%, 61% and 44%, respectively. These substances, however, have not been found in samples. Only DCF-acyl glucuronide with a cross-reactivity of 57% is of some relevance. For the first time, photodegradation products were tested for cross-reactivity. With the ELISA based on this antibody, water samples were analysed. In sewage treatment plant effluents, concentrations in the range of 1.9-5.2 μg L were determined directly, with recoveries compared to HPLC-MS/MS averaging 136%. Concentrations in lakes ranged from 3 to 4.4 ng L and were, after pre-concentration, determined with an average recovery of 100%.
Topics: Diclofenac; Antibodies, Monoclonal; Water Pollutants, Chemical; Enzyme-Linked Immunosorbent Assay; Anti-Inflammatory Agents, Non-Steroidal; Environmental Monitoring; Wastewater
PubMed: 38742423
DOI: 10.1039/d3ay01333b -
Langmuir : the ACS Journal of Surfaces... Aug 2023To unveil the intricacies surrounding the interaction between microplastics (MPs) and pollutants, diligent investigation is warranted to mitigate the environmental...
To unveil the intricacies surrounding the interaction between microplastics (MPs) and pollutants, diligent investigation is warranted to mitigate the environmental perils they pose. This exposition delves into the sorption behavior and mechanism of diclofenac sodium (DCF), a contaminant, upon two distinct materials: polystyrene (PS) and poly(butylene adipate--terephthalate) (PBAT). Experimental adsorption endeavors solidify the observation that the adsorption capacity of DCF onto the designated MPs amounts to = 9.26 mg g and = 9.03 mg g, respectively. An exploration of the factors governing these discrepant adsorption phenomena elucidates the influence of MPs and DCF properties, environmental factors, as well as surfactants. Fitting procedures underscore the suitability of the pseudo-second-order kinetic and Freundlich models in capturing the intricacies of the DCF adsorption process onto MPs, corroborating the notion that the mentioned process is characterized by non-homogeneous chemisorption. Moreover, this inquiry unveils that the primary adsorption mechanisms of DCF upon MPs encompass electrostatic interaction, hydrogen bonding, and halo hydrogen bonding. An additional investigation concerns the impact of commonly encountered surfactants in aqueous environments on the adsorption of DCF onto MPs. The presence of surfactants elicits modifications in the surface charge properties of MPs, consequently influencing their adsorption efficacy vis-à-vis DCF.
PubMed: 37581507
DOI: 10.1021/acs.langmuir.3c01536 -
Scientific Reports Sep 2023The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a...
The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins/peptides, which ultimately leads to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer's disease, diabetes, AL/AA amyloidosis, and amyotrophic lateral sclerosis can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the β-amyloid (1-42) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of the diclofenac-mediated repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. Together, this work suggests that the A-body machinery may be linked to a subset of pathological amyloidosis, and highlights the utility of this model system in the identification of new small molecules that could treat these debilitating diseases.
Topics: Humans; Diclofenac; Amyloidogenic Proteins; Amyloidosis; Prostaglandin-Endoperoxide Synthases; Immunoglobulin Light-chain Amyloidosis
PubMed: 37660155
DOI: 10.1038/s41598-023-41712-2 -
ADMET & DMPK 2024Diclofenac (DCF) is a non-steroidal anti-inflammatory drug possessing analgesic and antipyretic properties. It is used for the treatment of rheumatoid arthritis pain,... (Review)
Review
BACKGROUND AND PURPOSE
Diclofenac (DCF) is a non-steroidal anti-inflammatory drug possessing analgesic and antipyretic properties. It is used for the treatment of rheumatoid arthritis pain, osteoarthritis, and acute muscle pain conditions and can be administrated orally, topically or intravenously. Because of its widespread use, hydrophilicity, stability and poor degradation (bioaccumulation in the food chain), DCF is an emerging chemical contaminant that can cause adverse effects in the ecosystems. Taking into account the consumption of DCF in pharmaceutical formulations and its negative impact on the environment, the development of new sensitive, selective, cheap, fast, and online capable analytical devices is needed for on-site applications.
EXPERIMENTAL APPROACH
This brief review attempts to cover the recent developments related to the use of nanomaterials as catalysts for electrochemical determination of DCF in pharmaceutical formulations, biological fluids and environmental samples.
KEY RESULTS
The article aims to prove how electrochemical sensors represent reliable alternatives to conventional methods for DCF analysis.
CONCLUSION
The manuscript highlights the progress in the development of electrochemical sensors for DCF detection. We have analyzed numerous recent papers (mainly since 2019) on sensors developed for the quantitative determination of DCF, indicating the limit of detection, linear range, stability, reproducibility, and analytical applications. Current challenges related to the sensor design and future perspectives are outlined.
PubMed: 38560716
DOI: 10.5599/admet.2116 -
Medicine Oct 2023In this study, interscalene brachial plexus block (ISB) with superficial cervical plexus block added and general anesthesia (GA) application were evaluated in terms of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In this study, interscalene brachial plexus block (ISB) with superficial cervical plexus block added and general anesthesia (GA) application were evaluated in terms of intraoperative hemodynamics, operative time and postoperative analgesia need in patients who underwent rotator cuff tear repair.
METHODS
70 patients aged between 18 and 75 years were included in this prospective study. Arthroscopic rotator cuff tear repair surgery was performed in all patients. The patients were randomized into 2 groups, namely Group ISB who received a combination of superficial cervical plexus block added to the Interscalene Nerve Block, and Group GA, for those who received GA. Duration of operation, waiting times, intraoperative hemodynamic data, postoperative visual analog scale (VAS), analgesic requirement, as well as patient and surgeon satisfaction levels, were compared between the 2 groups.
RESULTS
While VAS values at the post-anesthesia care unit were lower in ISB group at 2 and 24 hours (P < .05), there was no significant difference between VAS values measured at 6th and 12th hours (P ≥ .05). In the GA group, postoperative morphine and diclofenac consumption was higher, and rescue analgesia was needed earlier (P < .05). The hospital stay was shorter (P < .05), and surgeon and patient satisfaction were higher in the ISB group (P < .05).
CONCLUSION SUBSECTIONS
In rotator cuff tear repair anesthesia, ISB with superficial cervical plexus block provides adequate intraoperative anesthesia, low postoperative VAS level, reduced and deferred consumption of opioids and nonsteroidal anti-inflammatory drugs, higher patient and surgeon satisfaction and early discharge.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Prospective Studies; Anesthetics, Local; Rotator Cuff Injuries; Rotator Cuff; Cervical Plexus Block; Pain, Postoperative; Brachial Plexus Block; Anesthesia, General; Arthroscopy
PubMed: 37861492
DOI: 10.1097/MD.0000000000035522 -
International Journal of Nanomedicine 2024Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and...
BACKGROUND
Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events.
METHODS
We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA.
RESULTS
Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations.
CONCLUSION
Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.
Topics: Humans; Rats; Animals; Methotrexate; Rats, Wistar; Arthritis, Rheumatoid; Nanoparticles; Inflammation; Arthritis, Experimental; Lipids; Diclofenac
PubMed: 38482519
DOI: 10.2147/IJN.S439359 -
PeerJ 2023Amultigenerational study on was carried out by exposing three subsequent generations to pharmaceuticals chlorpromazine (CPZ) and diclofenac (DCF), and two lanthanide...
Amultigenerational study on was carried out by exposing three subsequent generations to pharmaceuticals chlorpromazine (CPZ) and diclofenac (DCF), and two lanthanide chlorides, gadolinium as GdCl and europium as EuCl. As the treatments, environmentally relevant concentrations were chosen (0.001, 0.01 and 0.1 mg/L for CPZ; 0.1, 1 and 10 mg/L for DCF; 0.425, 4.25 and 42.5 µg/L for Gd and 0.41, 4.1 and 41 µg/L for Eu). Survival, population growth and reproduction success were evaluated at 21 and 30 days of exposure, and the whole observation period lasted 40 days. The least sensitive to all selected substances was the first daphnid generation (F1). Within 21-day exposure, no significant effects of the psychotropic drug CPZ on survival were observed in generations F1-F3. The anti-inflammatory drug DCF did not affect survival in the F1 generation; however, it significantly reduced survival in the F3 generation at 1-10 mg/L. Both lanthanides did not affect survival in the F1 and F2 generations of but considerably decreased survival in the F3 at 4-42 µg/L. Both pharmaceuticals stimulated the reproduction of in the F1 generation, while inhibition occurred at the highest tested concentrations in generations F2 and F3. The inhibitory effect on the reproductive success of lanthanides in the F2 generation resembled that for CPZ but not for DCF. The dynamics of adverse effects during the 21-30-day period revealed that despite increased mortality in the controls (up to 30%), concentrations used in the study minified, in most instances, the survival and aggravated population growth and reproduction success of . Our data suggest that as a test organism can be used for 21 days in multigenerational investigations, especially when testing close to environmental concentrations. In this respect, the standard chronic toxicity assay seems limited since prolonged observations and several generations of daphnids are required to obtain reliable information for the risk assessment of potentially aggressive chemicals.
Topics: Animals; Chlorpromazine; Cladocera; Diclofenac; Lanthanoid Series Elements
PubMed: 38025671
DOI: 10.7717/peerj.16472 -
ACS Omega Oct 2023Much research has been carried out to remove emerging contaminants using diverse materials. Furthermore, studies related to pollutant degradation have increased over the...
Much research has been carried out to remove emerging contaminants using diverse materials. Furthermore, studies related to pollutant degradation have increased over the past decade. Mechanochemical degradation can successfully decompose molecules that are persistent in the environment. In this study, the biochar of fique bagasse with mixtures SiO, Al, AlO, and Al-AlO was treated with a mechanochemical technique using a planetary ball mill to investigate the degradation of caffeine and diclofenac. These tests resulted in the transformation of caffeine and diclofenac due to the use of Al employing mechanochemistry. In fact, through the use of liquid chromatography coupled with mass spectrometry, eight and six subproducts were identified for caffeine and diclofenac, respectively. Additionally, analysis of the molecules proposed for caffeine and diclofenac transformation suggested hydroxylation, demethylation, decarboxylation, oxidation reactions, and cleavage of the C-C and C-N bonds in the pollutants studied. The formation of these transformation products could be possible by reductant oxygen species generated from the molecular oxygen in the presence of aluminum and the energy delivered for ball milling. The results obtained show the potential application in the environmental management of mechanochemical treatment in the elimination of emerging contaminants caffeine and diclofenac.
PubMed: 37901549
DOI: 10.1021/acsomega.3c03051 -
Ecotoxicology (London, England) Sep 2023Soil contamination with micropollutants is an important global problem and the impact of these pollutants on living organisms cannot be underestimated. The effects of...
Soil contamination with micropollutants is an important global problem and the impact of these pollutants on living organisms cannot be underestimated. The effects of diclofenac (DCF) and sulfamethoxazole (SMX), their mixture (MIX), and wastewater containing these drugs on the mortality and reproduction of Eisenia fetida were investigated. The impact on the activities of antioxidant enzymes in earthworm cells was also assessed. Furthermore, the influence of the following parameters of the vertical flow constructed wetlands on wastewater toxicity was investigated: the dosing system, the presence of pharmaceuticals and the plants Miscanthus giganteus. The compounds and their mixture significantly affected the reproduction and mortality of earthworms. The calculated values of LC values were 3.4 ± 0.3 mg kg for DCF, 1.6 ± 0.3 mg kg for SMX, and 0.9 ± 0.1 mg kg for MIX. The EC (reproduction assay) for DCF was 1.2 ± 0.2 mg kg, whereas for SMX, it was 0.4 ± 0.1 mg kg, and for MIX, it was 0.3 ± 0.1 mg kg, respectively. The mixture toxicity index (MTI) was calculated to determine drug interactions. For both E. fetida mortality (MTI = 3.29) and reproduction (MTI = 3.41), the index was greater than 1, suggesting a synergistic effect of the mixture. We also observed a negative effect of wastewater (raw and treated) on mortality (32% for raw and 8% for treated wastewater) and fertility (66% and 39%, respectively) of E. fetida. It is extremely important to analyze the harmfulness of microcontaminants to organisms inhabiting natural environments, especially in the case of wastewater for irrigation of agricultural fields.
Topics: Animals; Diclofenac; Wastewater; Sulfamethoxazole; Oligochaeta; Wetlands; Fertility; Soil; Oxidative Stress; Soil Pollutants
PubMed: 37633869
DOI: 10.1007/s10646-023-02690-3 -
Polymers Aug 2023The emerging pharmaceutical contaminants diclofenac (DCF) and salicylic acid (SA) pose potential hazards to humans and living organisms due to their persistence in water...
The emerging pharmaceutical contaminants diclofenac (DCF) and salicylic acid (SA) pose potential hazards to humans and living organisms due to their persistence in water environments. In this work, the conductive polymers polypyrrole (PPY) and polyaniline (PANI) were successfully coated on cotton fabrics, as confirmed by FTIR and SEM measurements. The coated fabrics efficiently removed DCF at pH 5.3 and SA at pH 4, with removal efficiencies that exceeded 90% and 70%, respectively. Adsorption was rapid for most of the tested contaminant-fabric systems and reached equilibrium within 20-30 min. The best adsorption performance for both contaminants was shown on the PPY-coated fabrics, which yielded adsorption capacities of about 65 and 21 mg/g for DCF and SA, respectively. This could be explained by molecular modeling simulations, which mostly estimated higher total cohesive energy densities for adsorption on the PPY-coated fabrics than on the PANI-coated ones. The adsorption mechanism involved both coulombic electrostatic attractions and non-coulombic van der Waals and π-π stacking. The fabrics could be reused for three adsorption-desorption cycles. Immobilization of the conductive polymers on cotton fabrics provides a facile method for their handling and collection during adsorption and regeneration cycles while maintaining their multi-functionality in adsorbing different contaminants.
PubMed: 37688189
DOI: 10.3390/polym15173563