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BioRxiv : the Preprint Server For... May 2024causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the...
causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant . Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a nonsteroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant clinical strains to colistin, and in a murine model of pneumonia. Diclofenac also reduced the colistin MIC of and isolates. Transcriptomic and proteomic analyses revealed an upregulation of oxidative stress-related genes and downregulation of type IV pili induced by the combination treatment. Notably, the concentrations of colistin and diclofenac effective in the murine model were substantially lower than those determined , implying a stronger synergistic effect compared to . A mutant strain, lacking the primary component of the type IV pili, became sensitive to colistin in the absence of diclofenac. This suggest that the downregulation of type IV pili is key for the synergistic activity of these drugs and indicates that colistin and diclofenac exert an anti-virulence effect. Together, these results suggest that the diclofenac can be repurposed with colistin to treat MDR .
PubMed: 38798593
DOI: 10.1101/2024.05.17.594771 -
Pharmaceuticals (Basel, Switzerland) May 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.
PubMed: 38794197
DOI: 10.3390/ph17050627 -
Materials (Basel, Switzerland) May 2024The global presence of pharmaceutical pollutants in water sources represents a burgeoning public health concern. Recent studies underscore the urgency of addressing this...
The global presence of pharmaceutical pollutants in water sources represents a burgeoning public health concern. Recent studies underscore the urgency of addressing this class of emerging contaminants. In this context, our work focuses on synthesizing a composite material, FeO/MAF-32, through a streamlined one-pot reaction process, as an adsorbent for diclofenac, an emerging environmental contaminant frequently found in freshwater environments and linked to potential toxicity towards several organisms such as fish and mussels. A thorough characterization was performed to elucidate the structural composition of the composite. The material presents magnetic properties attributed to its superparamagnetic behavior, which facilitates the recovery efficiency of the composite post-diclofenac adsorption. Our study further involves a comparative analysis between the FeO/MAF-32 and a non-magnetic counterpart, comprised solely of 2-ethylimidazolate zinc polymer. This comparison aims to discern the relative advantages and disadvantages of incorporating magnetic iron oxide nanoparticles in the contaminant removal process facilitated by a coordination polymer. Our findings reveal that even a minimal incorporation of iron oxide nanoparticles substantially enhanced the composite's overall performance in pollutant adsorption.
PubMed: 38793334
DOI: 10.3390/ma17102269 -
Medicina (Kaunas, Lithuania) May 2024: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation,...
: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. : We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp () and cultured in vitro, as well as their effects on the expression of angiogenic growth factors ( and ) and selected genes in apoptosis signalling pathways (, , , , and 2). : Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of , while the expression of remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of and , with decreased expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. : Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.
Topics: Humans; Dental Pulp; Diclofenac; Apoptosis; Ibuprofen; Cell Survival; Anti-Inflammatory Agents, Non-Steroidal; Stem Cells; Mesenchymal Stem Cells; Cells, Cultured
PubMed: 38792973
DOI: 10.3390/medicina60050787 -
Molecules (Basel, Switzerland) May 2024CYP2A7 is one of the most understudied human cytochrome P450 enzymes and its contributions to either drug metabolism or endogenous biosynthesis pathways are not...
CYP2A7 is one of the most understudied human cytochrome P450 enzymes and its contributions to either drug metabolism or endogenous biosynthesis pathways are not understood, as its only known enzymatic activities are the conversions of two proluciferin probe substrates. In addition, the CYP2A7 gene contains four single-nucleotide polymorphisms (SNPs) that cause missense mutations and have minor allele frequencies (MAFs) above 0.5. This means that the resulting amino acid changes occur in the majority of humans. In a previous study, we employed the reference standard sequence (called CYP2A7*1 in P450 nomenclature). For the present study, we created another CYP2A7 sequence that contains all four amino acid changes (Cys311, Glu169, Gly479, and Arg274) and labeled it CYP2A7-WT. Thus, it was the aim of this study to identify new substrates and inhibitors of CYP2A7 and to compare the properties of CYP2A7-WT with CYP2A7*1. We found several new proluciferin probe substrates for both enzyme variants (we also performed in silico studies to understand the activity difference between CYP2A7-WT and CYP2A7*1 on specific substrates), and we show that while they do not act on the standard CYP2A6 substrates nicotine, coumarin, or 7-ethoxycoumarin, both can hydroxylate diclofenac (as can CYP2A6). Moreover, we found ketoconazole, 1-benzylimidazole, and letrozole to be CYP2A7 inhibitors.
Topics: Humans; Substrate Specificity; Aryl Hydrocarbon Hydroxylases; Enzyme Inhibitors; Polymorphism, Single Nucleotide
PubMed: 38792050
DOI: 10.3390/molecules29102191 -
The Science of the Total Environment Aug 2024Freshwater systems are facing a number of pressures due to the inputs of polar organic contaminants from a range of sources including agriculture, domestic and industry....
Freshwater systems are facing a number of pressures due to the inputs of polar organic contaminants from a range of sources including agriculture, domestic and industry. The River Itchen and River Test are two sensitive chalk streams in Southern England that are experiencing a decline in invertebrate communities. We used Chemcatcher passive samplers to measure time-weighted average concentrations (14 days) of polar pollutants at nine sites on the River Itchen and eight sites on the River Test over a 12-month period. Sampler extracts were analysed using a targeted LC/MS method. In total, 121 plant protection products and pharmaceutical and personal care products were quantified (range of log K from - 1.5 to 7). Concentrations (sub ng L to >500 ng L) in both rivers showed spatial and temporal variations. A greater number of compounds and higher concentrations were found in the River Test. The chemical profile was dominated by inputs from wastewater treatment plants and legacy plant protection products. On the River Itchen, high concentrations (∼100 ng L) of caffeine were observed directly downstream of a fish farm. Using the NORMAN database, the predicted no effect concentration (PNEC) freshwater values were exceeded by only five contaminants (2-hydroxy-terbuthylazine, alprazolam, azithromycin, diclofenac and imidacloprid). In addition, venlafaxine was detected above its EU Watch List concentration. These exceedances were mainly downstream of direct inputs from treatment plants. These compounds are known to have ecotoxicological effects on a range of aquatic biota including macroinvertebrates. Of concern is the ubiquitous presence of the ectoparasiticide imidacloprid, highlighting the need to control its use. The impact of the cocktail of pollutants found in this study on the long-term effects on chalk stream ecosystems remains unknown and needs further investigation.
Topics: Water Pollutants, Chemical; Rivers; Environmental Monitoring; Risk Assessment; England
PubMed: 38782290
DOI: 10.1016/j.scitotenv.2024.173316 -
Biomaterials Advances Jul 2024Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral...
Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.
Topics: Diclofenac; Animals; Needles; Rats; Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Drug Delivery Systems; Nanoparticles; Male; Skin; Skin Absorption; Transdermal Patch; Rats, Sprague-Dawley
PubMed: 38781739
DOI: 10.1016/j.bioadv.2024.213889 -
Chemosphere Aug 2024This study focuses on the removal and risk assessment of twenty emerging contaminants (ECs) and heavy metals in a REMIX water treatment plant (RWTP) that produces...
This study focuses on the removal and risk assessment of twenty emerging contaminants (ECs) and heavy metals in a REMIX water treatment plant (RWTP) that produces drinking water from combination of wastewater reuse and desalination. The membrane biological reactor (MBR) exhibit removal rates exceeding 95% of pharmaceuticals like acetaminophen, trimethoprim, diclofenac, naproxen, and emtricitabine. The efficiency of brackish reverse osmosis (BWRO) in removing ECs is highlighted, showing substantial efficacy with reduction rates of 99.5%, 75.5%, and 51.2% for sulfamethoxazole, venlafaxine, and benzotriazole, respectively. The advanced oxidation process based on Fenton process reveals removal (>95%) of emtricitabine, efavirenz, and carbamazepine. The study confirms that the combination of treatment units within the RWTP effectively removes heavy metals (>90%), complying with acceptable limits. Risk quotient (RQ) calculations indicate the efficiency of the RWTP in EC removal, serving as benchmarks for public acceptance of reclaimed water. In the context of heavy metals, the study concludes negligible cancer risks associated with reclaimed water consumption over a lifetime. Quantitative structure-activity relationship and occurrence, persistence, bioaccumulation and toxicity (OPBT) models were used to assess EC risk. The study screened and identified potential persistant, bio accumulating and toxic PBT ECs. Critical control points (CCPs) in the RWTP are identified, with brackish and seawater reverse osmosis (BWRO and SWRO) and advanced oxidation process (AOP) recognized as pivotal in hazard management. The study provides valuable insights on the removal of ECs and heavy metals in a wastewater reuse process and demonstrates potential of adopted process configuration in supplying safe drinking water from wastewater recycling.
Topics: Water Pollutants, Chemical; Metals, Heavy; Wastewater; Risk Assessment; Water Purification; Drinking Water; Humans; Waste Disposal, Fluid
PubMed: 38777194
DOI: 10.1016/j.chemosphere.2024.142396 -
Journal of Applied Oral Science :... 2024To compare the effect of submucosal cryotherapy using cold saline to dexamethasone sodium phosphate and diclofenac sodium injections on substance P and interleukin 6... (Comparative Study)
Comparative Study
Effect of submucosal cryotherapy compared with steroids and NSAIDs injections on Substance P and Interleukin 6 pulpal release in experimentally induced pulpal inflammation in rabbits.
OBJECTIVE
To compare the effect of submucosal cryotherapy using cold saline to dexamethasone sodium phosphate and diclofenac sodium injections on substance P and interleukin 6 release in experimentally induced pulpal inflammation in rabbits' molar teeth.
METHODOLOGY
Fifteen rabbits were randomly classified into 3 groups according to the submucosal injection given: cold saline, dexamethasone sodium phosphate, and diclofenac sodium. A split-mouth design was adopted, the right mandibular molars were experimental, and the left molars served as the control without injections. Intentional pulp exposures were created and left for 6 hours to induce pulpitis. Pulpal tissue was extracted and examined for SP and IL-6 levels using ELISA. Within each group, the level of cytokines released was measured for both control and experimental groups for intragroup comparison to determine the effect of injection. The percentage reduction of each mediator was calculated compared with the control side for intergroup comparison then the correlation between SP and IL-6 levels was analyzed using Spearman's rank order correlation coefficient. Statistical analysis was performed, and the significance level was set at p<0.05.
RESULTS
Submucosal cryotherapy, dexamethasone sodium phosphate, and diclofenac sodium significantly reduced SP and IL-6 pulpal release. Submucosal cryotherapy significantly reduced SP more than and IL-6 more than dexamethasone sodium phosphate and diclofenac sodium. Pulpal reduction of SP and IL-6 showed a strong positive significant correlation.
CONCLUSIONS
Submucosal cryotherapy reduces the pulpal release of SP and IL-6 and could be tested as an alternative to premedication to potentiate the effect of anesthesia and control postoperative endodontic pain.
Topics: Animals; Rabbits; Pulpitis; Diclofenac; Dexamethasone; Interleukin-6; Random Allocation; Cryotherapy; Substance P; Anti-Inflammatory Agents, Non-Steroidal; Dental Pulp; Enzyme-Linked Immunosorbent Assay; Time Factors; Reproducibility of Results; Treatment Outcome; Male; Statistics, Nonparametric; Disease Models, Animal; Anti-Inflammatory Agents; Saline Solution; Reference Values
PubMed: 38775598
DOI: 10.1590/1678-7757-2024-0017 -
Frontiers in Pharmacology 2024Basil is a widely used herb in Persian medicine and is gaining recognition as a functional food worldwide.
BACKGROUND
Basil is a widely used herb in Persian medicine and is gaining recognition as a functional food worldwide.
AIM OF THE STUDY
This trial aimed to assess the effectiveness of a traditional formulation of basil oil in comparison with diclofenac gel in treating knee osteoarthritis, considering its established anti-inflammatory, anti-nociceptive, and anti-oxidative properties.
MATERIALS AND METHODS
One hundred eligible patients were equally randomized to the traditional basil oil (containing sesame oil) and diclofenac gel groups. They used their respective topical treatments thrice daily for 4 weeks. Various measurements were taken at the beginning of the study, 2, and 4 weeks after starting the intervention, including the 8-m walk test, knee pain (based on visual analog scale), flexion angle of the knee joint, analgesic consumption, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire.
RESULTS
No significant differences were observed between the basil oil and diclofenac gel groups in any of the measured outcomes. However, significant improvements were noted within each group for most variables.
CONCLUSION
Topical application of the traditional formulation of basil oil appears to improve clinical symptoms and certain functional indicators of knee osteoarthritis to a similar extent as diclofenac gel. This suggests that basil oil could be considered an effective management option for this condition. https://irct.behdasht.gov.ir/, identifier IRCT2017081711341N7.
PubMed: 38769995
DOI: 10.3389/fphar.2024.1377527