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Antioxidants (Basel, Switzerland) May 2024The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and...
Preliminary Investigation of subsp. : LC-MS/MS Chemical Profiling, In Vitro Evaluation of Antioxidant, Anti-Inflammatory Properties, Cytotoxicity, and In Silico Analysis against COX-2.
The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and MD simulation of the identified phenolic compounds in the subsp. extract (AAH). The analysis revealed substantial levels of total phenolic content (TPC), with a measured value of 191 ± 0.03 mg GAE/g DM. This high TPC was primarily attributed to two key phenolic compounds: total flavonoid content (TFC) and total tannin content (TTC), quantified at 80.82 ± 0.02 mg QE/g DM and 51.91 ± 0.01 mg CE/g DM, respectively. LC-MS/MS analysis identified 28 phenolic compounds, with gallic acid, protocatechuic acid, catechin, and others. In the DPPH scavenging assay, the IC value for the extract was determined to be 19.44 ± 0.04 μg/mL, comparable to standard antioxidants like BHA, BHT, ascorbic acid, and α-tocopherol. Regarding anti-inflammatory activity, the extract demonstrated a notably lower IC value compared to both diclofenac and ketoprofen, with values of 35.73 µg/mL, 63.78 µg/mL, and 164.79 µg/mL, respectively. Cytotoxicity analysis revealed significant cytotoxicity of the extract, with an LC value of 28.84 µg/mL, which exceeded that of potassium dichromate (15.73 µg/mL), indicating its potential as a safer alternative for various applications. Molecular docking studies have highlighted chrysin as a promising COX-2 inhibitor, with favorable binding energies and interactions. Molecular dynamic simulations further support chrysin's potential, showing stable interactions with COX-2, comparable to the reference ligand S58. Overall, the study underscores the pharmacological potential of extract, particularly chrysin, as a source of bioactive compounds with antioxidant and anti-inflammatory properties. Further research is warranted to elucidate the therapeutic mechanisms and clinical implications of these natural compounds.
PubMed: 38929093
DOI: 10.3390/antiox13060654 -
Journal of Endodontics Jun 2024This prospective, randomized, double-blind clinical trial investigated the impact of diclofenac potassium, prednisolone, and placebo as oral premedication on...
Influence of Diclofenac Potassium versus Prednisolone on Post-endodontic Pain and Pulpal Interleukin-8 expression in Symptomatic Irreversible Pulpitis Cases: A Randomized Placebo-Controlled Trial.
AIM
This prospective, randomized, double-blind clinical trial investigated the impact of diclofenac potassium, prednisolone, and placebo as oral premedication on post-endodontic pain and pulpal interleukin (IL)-8 expression in patients with irreversible pulpitis.
METHODS
Thirty-six patients undergoing conventional endodontic treatment were assigned into one of three groups (n= 12). Pulpal blood samples were taken after access cavity preparation and stored until they were analyzed using ELISA for quantification of IL-8. Post-endodontic pain was scored using the visual analogue scale. Outcome data were statistically analyzed using one-way ANOVA, Kruskal-Wallis, Friedman's, Dunn's, Chi-square, and Fisher's exact tests and Spearman's correlation coefficient. The significance level (α) was set at 0.05.
RESULTS
Apart from pre-operative pain scores, all groups had similar baseline characteristics (P > .05). Immediate post-endodontic pain scores had a significant difference between all groups (P < .05) where placebo group showed the highest score. There was no significant difference between all groups at 6 and 12 hours post-operatively (P > .05). Furthermore, there was no significant difference in the incidence of post-endodontic pain and in mean IL-8 levels between the three groups (P > .05).
CONCLUSIONS
The only impact the premedications had was on the immediate post-endodontic pain intensity, and they had no influence on the later time points, incidence of post-endodontic pain or pulpal IL-8 levels.
PubMed: 38925367
DOI: 10.1016/j.joen.2024.05.019 -
The Journal of Biological Chemistry Jun 2024Transthyretin (TTR) is a homotetrameric protein involved in the transport of thyroxine. More than 150 different mutations have been described in the TTR gene, several of...
Transthyretin (TTR) is a homotetrameric protein involved in the transport of thyroxine. More than 150 different mutations have been described in the TTR gene, several of them associated with familial amyloid cardiomyopathy (FAC). Recently, our group described a new variant of TTR in Brazil, namely A39D-TTR, which causes a severe cardiac condition. Position 39 is in the AB loop, a region of the protein that is located within the thyroxine-binding channels and is involved in tetramer formation. In the present study we solved the structure and characterize the thermodynamic stability of this new variant of TTR using urea and high hydrostatic pressure (HHP). Interestingly, during the process of purification, A39D-TTR turned out to be a dimer and not a tetramer, a variation that might be explained by the close contact of the four aspartic acids at position 39, where they face each other inside the thyroxine channel. In the presence of sub-denaturing concentrations of urea, bis-ANS binding and dynamic light scattering revealed A39D-TTR in the form of a molten-globule dimer. Co-expression of A39D and WT isoforms in the same bacterial cell did not produce heterodimers or heterotetramers, suggesting that somehow a negative charge at the AB loop precludes tetramer formation. A39D-TTR proved to be highly amyloidogenic, even at mildly acidic pH values where WT-TTR does not aggregate. Interestingly, despite being a dimer, aggregation of A39D-TTR was inhibited by diclofenac, which binds to the thyroxine channel in the tetramer, suggesting the existence of other pockets in A39D-TTR able to accommodate this molecule.
PubMed: 38925327
DOI: 10.1016/j.jbc.2024.107495 -
European Journal of Pharmacology Jun 2024Preeclampsia (PE) is often associated with multiple organ damage that remains noticeable postnatally. Here, we tested the hypotheses that antenatal therapy with...
Preeclampsia (PE) is often associated with multiple organ damage that remains noticeable postnatally. Here, we tested the hypotheses that antenatal therapy with nonsteroidal antiinflammatory drugs (NSAIDs) refashions liver damage induced by PE in weaning rats and that the high mobility group box 1 (HMGB1) signaling modulates this interaction. PE was induced by pharmacologic nitric oxide deprivation during the last week of gestation (N-nitro-L-arginine methyl ester, L-NAME, 50 mg/kg/day, oral gavage). Compared with control rats, weaning PE rats revealed substantial rises in serum transaminases together with histopathological signs of hepatic cytoplasmic changes, portal inflammation, and central vein dilation. While gestational NSAIDs reversed the elevated transaminases, they had no effects (celecoxib, naproxen) or even worsened (diclofenac) the structural damage. Molecularly, celecoxib was the most effective NSAID in (i) reversing PE-evoked upregulation of hepatic HMGB1 gene expression and concomitant increments and decrements in mitogen-activated protein kinases MAPK and MAPK expression, respectively, and (ii) elevating and suppressing serum interleukin-10 and tumor necrosis factor-α, respectively. Alternatively, rises in serum interleukin-1β and shifts in macrophage polarization towards an inflammatory phenotype caused by PE were comparably diminished by all NSAIDs. The data disclose an advantageous therapeutic potential for gestational celecoxib over diclofenac or naproxen in controlling hepatic dysfunction and HMGB1-interrelated inflammatory and oxidative sequels of PE.
PubMed: 38925287
DOI: 10.1016/j.ejphar.2024.176769 -
Pharmacy (Basel, Switzerland) Jun 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, fever, and inflammation. Although most are usually classified as prescription-only...
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, fever, and inflammation. Although most are usually classified as prescription-only medicines, in many countries they are frequently purchased for self-medication purposes. This study explores NSAID-usage patterns in Kosovo, aiming for a safer and more effective medicinal use. The study employed a dual approach to collect data. First, NSAID sales were analyzed in a convenience sample of ten community pharmacies across diverse regions in Kosovo in 2023. Second, data on NSAID-usage patterns and patient awareness were systematically gathered from 410 patients during routine pharmacist-patient interactions. The four most commonly purchased NSAIDs according to sales analysis were diclofenac (33.1%), ketoprofen (27.6%), ibuprofen (17.0%) and nimesulide (12.7%). A significant 74.8% of NSAIDs were bought without prescriptions, particularly among younger adults (20-39 years), who accounted for 82.8% of such purchases. The predominant reason for NSAID use was headache (43.8%). Although many of the patients suffered from occasional (33.7%) or frequent (12.6%) stomachaches and took acid-lowering medicines, the majority (85.9%) could not recall any NSAID adverse reactions. This study exposes widespread self-medication and a significant lack of awareness regarding potential risks of NSAIDs, particularly among young adults. To address these issues, it is critical to improve dispensing practices through increased pharmacist awareness and stricter law enforcement.
PubMed: 38921969
DOI: 10.3390/pharmacy12030093 -
ACS Applied Materials & Interfaces Jun 2024A peroxymonosulfate oxidation system was developed via modification of β-cyclodextrin (β-CD) on the surface of Fe-doped ZIF-67 (CD/Fe@ZIF-67) as an activator. The...
A peroxymonosulfate oxidation system was developed via modification of β-cyclodextrin (β-CD) on the surface of Fe-doped ZIF-67 (CD/Fe@ZIF-67) as an activator. The 99.7% carbamazepine, 91.3% bisphenol A (BPA), and 95.4% diclofenac (DCF) degradation efficiency were achieved within 10 min, 60, and 1 min, respectively. The hydrophobicity of these three pollutants is positively correlated with their adsorption kinetic constants by CD/Fe@ZIF-67 due to the introduction of β-CD. Scavenger experiments and electron spin resonance spectra confirmed that carbamazepine was preferentially oxidized by SO [λ(SO)(70.5%) > λ(OH)(28.2%) > λ(O)(1.3%)], where SO and O played dominant roles in the degradation of BPA [λ(SO)(71.7%) > λ(O)(22.8%) > λ(OH)(5.5%)], and O was responsible for DCF removal [λ(O) = 93.2%]. Additionally, the particulate catalyst was immobilized in the shell side of a ceramic membrane in a membrane reactor for catalyst recovery. This reactor achieved nearly 100% removal efficiency under optimal conditions: 0.036 wt % catalyst loading, 0.5 mM peroxymonosulfate concentration, 1 L inflow, 10 mg/L initial carbamazepine concentration, and 0.012 L/min hydraulic retention time. In summary, this study elucidates the active role of β-CD in a polymetallic/peroxymonosulfate system and provides valuable insights into the development of effective oxidation methods for pharmaceutical and personal care products in wastewater.
PubMed: 38918892
DOI: 10.1021/acsami.4c05315 -
ACS Applied Materials & Interfaces Jun 2024
PubMed: 38910290
DOI: 10.1021/acsami.4c09703 -
Effectiveness of Mesotherapy in Post-COVID Pain Syndrome: Retrospective Cohort Study of 96 Patients.Clinical Therapeutics Jun 2024Musculoskeletal pain may occur after becoming infected with SARS-Cov2. This study was designed to evaluate the efficacy of mesotherapy in treating chronic pain following...
PURPOSE
Musculoskeletal pain may occur after becoming infected with SARS-Cov2. This study was designed to evaluate the efficacy of mesotherapy in treating chronic pain following COVID-19 infection.
METHODS
A retrospective review was conducted of the records of 96 patients with post-COVID pain syndrome. Those who were eligible for oral therapy or mesotherapy, included in the study. Patients receiving oral treatment with diclofenac potassium, thiocolchicoside and cyanocobalamin were included in one group (n = 46), and patients receiving intradermal mesotherapy with 2% lidocaine + cyanocobalamin were included in another group (n = 50). The results of the Visual Analogue Scale (VAS) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were individually assessed before and one week after the treatment.
FINDINGS
The participants were 40.2 ± 11.1 years old on average. Of the participants, 35.4% (n = 34) were male and 64.6% (n = 62) were female. Before treatment, there was no statistically significant difference between the patients in terms of VAS and LANSS scores. Following the treatment, a notable positive response was observed in both groups. Nevertheless, when compared to the oral treatment group, the mesotherapy group exhibited a more pronounced enhancement in VAS and LANSS scores (P < 0.001, P < 0.001, respectively).
IMPLICATIONS
While both mesotherapy and oral therapy offer benefits in reducing pain and alleviating neuropathic symptoms in post-COVID pain syndrome, mesotherapy stands out as an especially effective and well-tolerated treatment method, surpassing the efficacy of the oral alternative.
PubMed: 38910071
DOI: 10.1016/j.clinthera.2024.05.004 -
JAMA Network Open Jun 2024Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM...
IMPORTANCE
Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM and recommend alternative prescribing, but the complexity of available lists limits their applicability and the amount of data available on PIM prescribing.
OBJECTIVE
To determine PIM prevalence and the most frequently prescribed PIMs according to 6 well-known PIM lists and to develop a best practice synthesis for clinicians.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used anonymized electronic health record data of Swiss primary care patients aged 65 years or older with drug prescriptions from January 1, 2020, to December 31, 2021, extracted from a large primary care database in Switzerland, the FIRE project. Data analyses took place from October 2022 to September 2023.
EXPOSURE
PIM prescription according to PIM criteria operationalized for use with FIRE data.
MAIN OUTCOMES AND MEASURES
The primary outcomes were PIM prevalence (percentage of patients with 1 or more PIMs) and PIM frequency (percentage of prescriptions identified as PIMs) according to the individual PIM lists and a combination of all 6 lists. The PIM lists used were the American 2019 Updated Beers criteria, the French list by Laroche et al, the Norwegian General Practice Norwegian (NORGEP) criteria, the German PRISCUS list, the Austrian list by Mann et al, and the EU(7) consensus list of 7 European countries.
RESULTS
This study included 115 867 patients 65 years or older (mean [SD] age, 76.0 [7.9] years; 55.8% female) with 1 211 227 prescriptions. Among all patients, 86 715 (74.8%) were aged 70 years or older, and 60 670 (52.4%) were aged 75 years or older. PIM prevalence among patients 65 years or older was 31.5% (according to Beers 2019), 15.4% (Laroche), 16.1% (NORGEP), 12.7% (PRISCUS), 31.2% (Mann), 37.1% (EU[7]), and 52.3% (combined list). PIM prevalence increased with age according to every PIM list (eg, according to Beers 2019, from 31.5% at age 65 years or older to 37.4% for those 75 years or older, and when the lists were combined, PIM prevalence increased from 52.3% to 56.7% in those 2 age groups, respectively). PIM frequency was 10.3% (Beers 2019), 3.9% (Laroche), 4.3% (NORGEP), 2.4% (PRISCUS), 6.7% (Mann), 9.7% (EU[7]), and 19.3% (combined list). According to the combined list, the 5 most frequently prescribed PIMs were pantoprazole (9.3% of all PIMs prescribed), ibuprofen (6.9%), diclofenac (6.3%), zolpidem (4.5%), and lorazepam (3.7%). Almost two-thirds (63.5%) of all PIM prescriptions belonged to 5 drug classes: analgesics (26.9% of all PIMs prescribed), proton pump inhibitors (12.1%), benzodiazepines and benzodiazepine-like drugs (11.2%), antidepressants (7.0%), and neuroleptics (6.3%).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of adults aged 65 or older, PIM prevalence was high, varied considerably depending on the criteria applied, and increased consistently with age. However, only few drug classes accounted for the majority of all prescriptions that were PIM according to any of the 6 PIM lists, and by considering this manageable number of drug classes, clinicians could essentially comply with all 6 PIM lists. These results raise awareness of the most common PIMs and emphasize the need for careful consideration of their risks and benefits and targeted deprescribing.
Topics: Humans; Switzerland; Aged; Cross-Sectional Studies; Primary Health Care; Potentially Inappropriate Medication List; Female; Male; Inappropriate Prescribing; Aged, 80 and over; Prevalence; Practice Patterns, Physicians'
PubMed: 38904960
DOI: 10.1001/jamanetworkopen.2024.17988 -
International Journal of Toxicology Jun 2024These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5 mg/mL) formulation containing povidone K12 (80 mg/mL)...
These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5 mg/mL) formulation containing povidone K12 (80 mg/mL) as the key excipient in Wistar rats. This formulation was tested at doses of 3, 7, and 15 mg/kg/day and was administered daily for 28 days by intravenous route. Toxicokinetic estimation revealed a dose-proportional increase in plasma exposure to diclofenac. The formulation was well tolerated in males; however, mortality was observed in females (2/15) at the highest dose (15 mg/kg/day). Adverse gastrointestinal events related to NSAIDS and a few other treatment-related effects on clinical and anatomic pathology were noted at the 15 mg/kg/day dose, which normalized at the end of the 2-week recovery period. In addition, the excipient povidone K12 was present in a higher amount than the approved Inactive Ingredient Database (IID) limit in the proposed novel formulation. It was qualified through a separate 28-day repeated dose toxicity study by intravenous route in Wistar rats. Povidone K12 was found to be well tolerated and safe up to a dose of 165 mg/kg/day. No treatment-related adverse effects were observed in this study. In conclusion, repeated administration of a novel intravenous formulation containing diclofenac sodium was found to be safe up to the dose of 7 mg/kg/day in female rats and 15 mg/kg/day in male rats.
PubMed: 38901831
DOI: 10.1177/10915818241261922